Dnmts and Tet target memory-associated genes after appetitive olfactory training in honey bees

PubMed Central

Biergans, Stephanie D.; Giovanni Galizia, C.; Reinhard, Judith; Claudianos, Charles

2015-01-01

DNA methylation and demethylation are epigenetic mechanisms involved in memory formation. In honey bees DNA methyltransferase (Dnmt) function is necessary for long-term memory to be stimulus specific (i.e. to reduce generalization). So far, however, it remains elusive which genes are targeted and what the time-course of DNA methylation is during memory formation. Here, we analyse how DNA methylation affects memory retention, gene expression, and differential methylation in stimulus-specific olfactory long-term memory formation. Out of 30 memory-associated genes investigated here, 9 were upregulated following Dnmt inhibition in trained bees. These included Dnmt3 suggesting a negative feedback loop for DNA methylation. Within these genes also the DNA methylation pattern changed during the first 24 hours after training. Interestingly, this was accompanied by sequential activation of the DNA methylation machinery (i.e. Dnmts and Tet). In sum, memory formation involves a temporally complex epigenetic regulation of memory-associated genes that facilitates stimulus specific long-term memory in the honey bee. PMID:26531238

The orexin component of fasting triggers memory processes underlying conditioned food selection in the rat.

PubMed

Ferry, Barbara; Duchamp-Viret, Patricia

2014-03-14

To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor-malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion of OXA or artificial cerebrospinal fluid (ACSF) 1 h before COA acquisition. An additional group of intact rats were food-deprived for 24 h before acquisition. Results showed that the increased olfactory sensitivity induced by fasting and by OXA infusion was accompanied by enhanced COA performance. The present results suggest that fasting-induced central OXA release influenced COA learning by increasing not only olfactory sensitivity, but also the memory processes underlying the odor-malaise association.

The orexin component of fasting triggers memory processes underlying conditioned food selection in the rat

PubMed Central

Ferry, Barbara; Duchamp-Viret, Patricia

2014-01-01

To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor–malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion of OXA or artificial cerebrospinal fluid (ACSF) 1 h before COA acquisition. An additional group of intact rats were food-deprived for 24 h before acquisition. Results showed that the increased olfactory sensitivity induced by fasting and by OXA infusion was accompanied by enhanced COA performance. The present results suggest that fasting-induced central OXA release influenced COA learning by increasing not only olfactory sensitivity, but also the memory processes underlying the odor–malaise association. PMID:24634353

IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

PubMed

Liu, Zhihui; Chen, Zijun; Shang, Congping; Yan, Fei; Shi, Yingchao; Zhang, Jiajing; Qu, Baole; Han, Hailin; Wang, Yanying; Li, Dapeng; Südhof, Thomas C; Cao, Peng

2017-07-05

During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca 2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. Copyright © 2017 Elsevier Inc. All rights reserved.

Direct neural pathways convey distinct visual information to Drosophila mushroom bodies

PubMed Central

Vogt, Katrin; Aso, Yoshinori; Hige, Toshihide; Knapek, Stephan; Ichinose, Toshiharu; Friedrich, Anja B; Turner, Glenn C; Rubin, Gerald M; Tanimoto, Hiromu

2016-01-01

Previously, we demonstrated that visual and olfactory associative memories of Drosophila share mushroom body (MB) circuits (Vogt et al., 2014). Unlike for odor representation, the MB circuit for visual information has not been characterized. Here, we show that a small subset of MB Kenyon cells (KCs) selectively responds to visual but not olfactory stimulation. The dendrites of these atypical KCs form a ventral accessory calyx (vAC), distinct from the main calyx that receives olfactory input. We identified two types of visual projection neurons (VPNs) directly connecting the optic lobes and the vAC. Strikingly, these VPNs are differentially required for visual memories of color and brightness. The segregation of visual and olfactory domains in the MB allows independent processing of distinct sensory memories and may be a conserved form of sensory representations among insects. DOI: http://dx.doi.org/10.7554/eLife.14009.001 PMID:27083044

Working Memory Systems in the Rat.

PubMed

Bratch, Alexander; Kann, Spencer; Cain, Joshua A; Wu, Jie-En; Rivera-Reyes, Nilda; Dalecki, Stefan; Arman, Diana; Dunn, Austin; Cooper, Shiloh; Corbin, Hannah E; Doyle, Amanda R; Pizzo, Matthew J; Smith, Alexandra E; Crystal, Jonathon D

2016-02-08

A fundamental feature of memory in humans is the ability to simultaneously work with multiple types of information using independent memory systems. Working memory is conceptualized as two independent memory systems under executive control [1, 2]. Although there is a long history of using the term "working memory" to describe short-term memory in animals, it is not known whether multiple, independent memory systems exist in nonhumans. Here, we used two established short-term memory approaches to test the hypothesis that spatial and olfactory memory operate as independent working memory resources in the rat. In the olfactory memory task, rats chose a novel odor from a gradually incrementing set of old odors [3]. In the spatial memory task, rats searched for a depleting food source at multiple locations [4]. We presented rats with information to hold in memory in one domain (e.g., olfactory) while adding a memory load in the other domain (e.g., spatial). Control conditions equated the retention interval delay without adding a second memory load. In a further experiment, we used proactive interference [5-7] in the spatial domain to compromise spatial memory and evaluated the impact of adding an olfactory memory load. Olfactory and spatial memory are resistant to interference from the addition of a memory load in the other domain. Our data suggest that olfactory and spatial memory draw on independent working memory systems in the rat. Copyright © 2016 Elsevier Ltd. All rights reserved.

No evidence for visual context-dependency of olfactory learning in Drosophila

NASA Astrophysics Data System (ADS)

Yarali, Ayse; Mayerle, Moritz; Nawroth, Christian; Gerber, Bertram

2008-08-01

How is behaviour organised across sensory modalities? Specifically, we ask concerning the fruit fly Drosophila melanogaster how visual context affects olfactory learning and recall and whether information about visual context is getting integrated into olfactory memory. We find that changing visual context between training and test does not deteriorate olfactory memory scores, suggesting that these olfactory memories can drive behaviour despite a mismatch of visual context between training and test. Rather, both the establishment and the recall of olfactory memory are generally facilitated by light. In a follow-up experiment, we find no evidence for learning about combinations of odours and visual context as predictors for reinforcement even after explicit training in a so-called biconditional discrimination task. Thus, a ‘true’ interaction between visual and olfactory modalities is not evident; instead, light seems to influence olfactory learning and recall unspecifically, for example by altering motor activity, alertness or olfactory acuity.

Visualizing the engram: learning stabilizes odor representations in the olfactory network.

PubMed

Shakhawat, Amin M D; Gheidi, Ali; Hou, Qinlong; Dhillon, Sandeep K; Marrone, Diano F; Harley, Carolyn W; Yuan, Qi

2014-11-12

The nature of memory is a central issue in neuroscience. How does our representation of the world change with learning and experience? Here we use the transcription of Arc mRNA, which permits probing the neural representations of temporally separated events, to address this in a well characterized odor learning model. Rat pups readily associate odor with maternal care. In pups, the lateralized olfactory networks are independent, permitting separate training and within-subject control. We use multiday training to create an enduring memory of peppermint odor. Training stabilized rewarded, but not nonrewarded, odor representations in both mitral cells and associated granule cells of the olfactory bulb and in the pyramidal cells of the anterior piriform cortex. An enlarged core of stable, likely highly active neurons represent rewarded odor at both stages of the olfactory network. Odor representations in anterior piriform cortex were sparser than typical in adult rat and did not enlarge with learning. This sparser representation of odor is congruent with the maturation of lateral olfactory tract input in rat pups. Cortical representations elsewhere have been shown to be highly variable in electrophysiological experiments, suggesting brains operate normally using dynamic and network-modulated representations. The olfactory cortical representations here are consistent with the generalized associative model of sparse variable cortical representation, as normal responses to repeated odors were highly variable (∼70% of the cells change as indexed by Arc). Learning and memory modified rewarded odor ensembles to increase stability in a core representational component. Copyright © 2014 the authors 0270-6474/14/3415394-08$15.00/0.

Steroid Hormone (20-Hydroxyecdysone) Modulates the Acquisition of Aversive Olfactory Memories in Pollen Forager Honeybees

ERIC Educational Resources Information Center

Geddes, Lisa H.; McQuillan, H. James; Aiken, Alastair; Vergoz, Vanina; Mercer, Alison R.

2013-01-01

Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on associative olfactory learning in the honeybee, "Apis mellifera." 20-E impaired the bees' ability to associate odors with punishment during aversive conditioning, but did not interfere with their ability to associate odors with a food reward (appetitive…

Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain.

PubMed

Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-01

In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca(2+) indicator in the MBs, we investigated synaptic transmission and plasticity at the AL-MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca(2+) responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca(2+) responses were mediated through Drosophila NMDA receptors (dNRs). AL-MB synaptic transmission was enhanced more than 2 h after the simultaneous 'associative-stimulation' of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL-MB synapses but not at the AFV-MB synapses. AL-MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL-MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL-MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL-MB LTE might be a relevant cellular model for olfactory memory.

Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain

PubMed Central

Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-01

In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca2+ indicator in the MBs, we investigated synaptic transmission and plasticity at the AL–MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca2+ responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca2+ responses were mediated through Drosophila NMDA receptors (dNRs). AL–MB synaptic transmission was enhanced more than 2 h after the simultaneous ‘associative-stimulation’ of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL–MB synapses but not at the AFV–MB synapses. AL–MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL–MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL–MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL–MB LTE might be a relevant cellular model for olfactory memory. PMID:23027817

Olfactory Context-Dependent Memory and the Effects of Affective Congruency.

PubMed

Hackländer, Ryan P M; Bermeitinger, Christina

2017-10-31

Odors have been claimed to be particularly effective mnemonic cues, possibly because of the strong links between olfaction and emotion processing. Indeed, past research has shown that odors can bias processing towards affectively congruent material. In order to determine whether this processing bias translates to memory, we conducted 2 olfactory-enhanced-context memory experiments where we manipulated affective congruency between the olfactory context and to-be-remembered material. Given the presumed importance of valence to olfactory perception, we hypothesized that memory would be best for affectively congruent material in the olfactory enhanced context groups. Across the 2 experiments, groups which encoded and retrieved material in the presence of an odorant exhibited better memory performance than groups that did not have the added olfactory context during encoding and retrieval. While context-enhanced memory was exhibited in the presence of both pleasant and unpleasant odors, there was no indication that memory was dependent on affective congruency between the olfactory context and the to-be-remembered material. While the results provide further support for the notion that odors can act as powerful contextual mnemonic cues, they call into question the notion that affective congruency between context and focal material is important for later memory performance. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

No Sensory Compensation for Olfactory Memory: Differences between Blind and Sighted People.

PubMed

Sorokowska, Agnieszka; Karwowski, Maciej

2017-01-01

Blindness can be a driving force behind a variety of changes in sensory systems. When vision is missing, other modalities and higher cognitive functions can become hyper-developed through a mechanism called sensory compensation. Overall, previous studies suggest that olfactory memory in blind people can be better than that of the sighted individuals. Better performance of blind individuals in other-sensory modalities was hypothesized to be a result of, among others, intense perceptual training. At the same time, if the superiority of blind people in olfactory abilities indeed results from training, their scores should not decrease with age to such an extent as among the sighted people. Here, this hypothesis was tested in a large sample of 94 blind individuals. Olfactory memory was assessed using the Test for Olfactory Memory, comprising episodic odor recognition (discriminating previously presented odors from new odors) and two forms of semantic memory (cued and free identification of odors). Regarding episodic olfactory memory, we observed an age-related decline in correct hits in blind participants, but an age-related increase in false alarms in sighted participants. Further, age moderated the between-group differences for correct hits, but the direction of the observed effect was contrary to our expectations. The difference between blind and sighted individuals younger than 40 years old was non-significant, but older sighted individuals outperformed their blind counterparts. In conclusion, we found no positive effect of visual impairment on olfactory memory. We suggest that daily perceptual training is not enough to increase olfactory memory function in blind people.

No Sensory Compensation for Olfactory Memory: Differences between Blind and Sighted People

PubMed Central

Sorokowska, Agnieszka; Karwowski, Maciej

2017-01-01

Blindness can be a driving force behind a variety of changes in sensory systems. When vision is missing, other modalities and higher cognitive functions can become hyper-developed through a mechanism called sensory compensation. Overall, previous studies suggest that olfactory memory in blind people can be better than that of the sighted individuals. Better performance of blind individuals in other-sensory modalities was hypothesized to be a result of, among others, intense perceptual training. At the same time, if the superiority of blind people in olfactory abilities indeed results from training, their scores should not decrease with age to such an extent as among the sighted people. Here, this hypothesis was tested in a large sample of 94 blind individuals. Olfactory memory was assessed using the Test for Olfactory Memory, comprising episodic odor recognition (discriminating previously presented odors from new odors) and two forms of semantic memory (cued and free identification of odors). Regarding episodic olfactory memory, we observed an age-related decline in correct hits in blind participants, but an age-related increase in false alarms in sighted participants. Further, age moderated the between-group differences for correct hits, but the direction of the observed effect was contrary to our expectations. The difference between blind and sighted individuals younger than 40 years old was non-significant, but older sighted individuals outperformed their blind counterparts. In conclusion, we found no positive effect of visual impairment on olfactory memory. We suggest that daily perceptual training is not enough to increase olfactory memory function in blind people. PMID:29276494

Self-grounding visual, auditory and olfactory autobiographical memories.

PubMed

Knez, Igor; Ljunglöf, Louise; Arshamian, Artin; Willander, Johan

2017-07-01

Given that autobiographical memory provides a cognitive foundation for the self, we investigated the relative importance of visual, auditory and olfactory autobiographical memories for the self. Thirty subjects, with a mean age of 35.4years, participated in a study involving a three×three within-subject design containing nine different types of autobiographical memory cues: pictures, sounds and odors presented with neutral, positive and negative valences. It was shown that visual compared to auditory and olfactory autobiographical memories involved higher cognitive and emotional constituents for the self. Furthermore, there was a trend showing positive autobiographical memories to increase their proportion to both cognitive and emotional components of the self, from olfactory to auditory to visually cued autobiographical memories; but, yielding a reverse trend for negative autobiographical memories. Finally, and independently of modality, positive affective states were shown to be more involved in autobiographical memory than negative ones. Copyright © 2017 Elsevier Inc. All rights reserved.

Pheromone-Induced Olfactory Memory in Newborn Rabbits: Involvement of Consolidation and Reconsolidation Processes

ERIC Educational Resources Information Center

Coureaud, Gerard; Languille, Solene; Schaal, Benoist; Hars, Bernard

2009-01-01

Mammary pheromone (MP)-induced odor memory is a new model of appetitive memory functioning early in a mammal, the newborn rabbit. Some properties of this associative memory are analyzed by the use of anisomycin as an amnesic agent. Long-term memory (LTM) was impaired by anisomycin delivered immediately, but not 4 h after either acquisition or…

Memory Consolidation and Gene Expression in "Periplaneta Americana"

ERIC Educational Resources Information Center

Strausfeld, Nicholas J.; Pinter, Marianna; Lent, David D.

2005-01-01

A unique behavioral paradigm has been developed for "Periplaneta americana" that assesses the timing and success of memory consolidation leading to long-term memory of visual-olfactory associations. The brains of trained and control animals, removed at the critical consolidation period, were screened by two-directional suppression subtractive…

Syngeneic Transplantation of Olfactory Ectomesenchymal Stem Cells Restores Learning and Memory Abilities in a Rat Model of Global Cerebral Ischemia.

PubMed

Veron, Antoine D; Bienboire-Frosini, Cécile; Girard, Stéphane D; Sadelli, Kevin; Stamegna, Jean-Claude; Khrestchatisky, Michel; Alexis, Jennifer; Pageat, Patrick; Asproni, Pietro; Mengoli, Manuel; Roman, François S

2018-01-01

Stem cells are considered as promising tools to repair diverse tissue injuries. Among the different stem cell types, the "olfactory ectomesenchymal stem cells" (OE-MSCs) located in the adult olfactory mucosa stand as one of the best candidates. Here, we evaluated if OE-MSC grafts could decrease memory impairments due to ischemic injury. OE-MSCs were collected from syngeneic F344 rats. After a two-step global cerebral ischemia, inducing hippocampal lesions, learning abilities were evaluated using an olfactory associative discrimination task. Cells were grafted into the hippocampus 5 weeks after injury and animal's learning abilities reassessed. Rats were then sacrificed and the brains collected for immunohistochemical analyses. We observed significant impairments in learning and memory abilities following ischemia. However, 4 weeks after OE-MSC grafts, animals displayed learning and memory performances similar to those of controls, while sham rats did not improve them. Immunohistochemical analyses revealed that grafts promoted neuroblast and glial cell proliferation, which could permit to restore cognitive functions. These results demonstrated, for the first time, that syngeneic transplantations of OE-MSCs in rats can restore cognitive abilities impaired after brain injuries and provide support for the development of clinical studies based on grafts of OE-MSCs in amnesic patients following brain injuries.

Vaginocervical stimulation enhances social recognition memory in rats via oxytocin release in the olfactory bulb.

PubMed

Larrazolo-López, A; Kendrick, K M; Aburto-Arciniega, M; Arriaga-Avila, V; Morimoto, S; Frias, M; Guevara-Guzmán, R

2008-03-27

The ability of vaginocervical stimulation (VCS) to promote olfactory social recognition memory at different stages of the ovarian cycle was investigated in female rats. A juvenile social recognition paradigm was used and memory retention tested at 30 and 300 min after an adult was exposed to a juvenile during three 4-min trials. Results showed that an intact social recognition memory was present at 30 min in animals with or without VCS and at all stages of the estrus cycle. However, whereas no animals in any stage of the estrus cycle showed retention of the specific recognition memory at 300 min, those in the proestrus/estrus phase that received VCS 10 min before the trial started did. In vivo microdialysis studies showed that there was a significant release of oxytocin after VCS in the olfactory bulb during proestrus. There was also increased oxytocin immunoreactivity within the olfactory bulb after VCS in proestrus animals compared with diestrus ones. Furthermore, when animals received an infusion of an oxytocin antagonist directly into the olfactory bulb, or a systemic administration of alpha or beta noradrenaline-antagonists, they failed to show evidence for maintenance of a selective olfactory recognition memory at 300 min. Animals with vagus or pelvic nerve section also showed no memory retention when tested after 300 min. These results suggest that VCS releases oxytocin in the olfactory bulb to enhance the social recognition memory and that this may be due to modulatory actions on noradrenaline release. The vagus and pelvic nerves are responsible for carrying the information from the pelvic area to the CNS.

Olfactory memory and maternal behaviour-induced changes in c-fos and zif/268 mRNA expression in the sheep brain.

PubMed

Da Costa, A P; Broad, K D; Kendrick, K M

1997-06-01

In sheep maternal behaviour and the formation of the selective olfactory, ewe/lamb bond are induced by feedback to the brain from stimulation of the vagina and cervix during parturition. In the present study, we have used in situ hybridization histochemistry to quantify changes in cellular expression of two immediately-early genes, c-fos and zif/268, in order to identify activated brain regions during the induction of maternal behaviour and olfactory bonding as well as regions where plastic changes are occurring during with the formation of the olfactory memory associated with bonding. Three different treatment groups were used. One group gave birth normally, became maternal and were allowed to interact with their lambs for 30 min. A second group received exogenous treatment with oestradiol and progesterone to induce lactation and then received a 5-min period of artificial stimulation of the vagina and cervix (VCS) which reliably induces maternal behaviour but could not interact with lambs. A final control group received exogenous hormone treatment but no VCS or interaction with lambs. Compared to the control group, post-partum animals and animals that had received VCS showed increased c-fos expression in a number of cortical regions (cingulate, entorhinal and somatosensory), the mediodorsal thalamic nucleus and the lateral habenula, the limbic system (bed nucleus of the stria terminalis, lateral septum, medial arnygdala, dentate gyrus and the CA3 region of the hippocampus) and the hypothalamus (medial preoptic area, mediobasal hypothalamus, paraventricular nucleus, supraoptic nucleus and periventricular complex). The group that gave birth and had contact with their lambs for 30 min had significantly enhanced c-fos mRNA expression in the cingulate cortex compared to those receiving VCS and additionally showed significantly increased c-fos mRNA expression in olfactory processing regions (olfactory bulb, piriform cortex and orbitofrontal cortex). Expression of zif/268 was significantly increased in the entorhinal cortex, orbitofrontal cortex and dentate gyrus of the parturition group compared to either the control or the VCS alone groups. These results show a clear differentiation between neural substrates controlling the expression of maternal behaviour and those involved in the olfactory memory process associated with selective recognition of offspring although at the level of the hippocampus and cingulate cortex there may be some degree of overlap. Alterations in zif/268 at tertiary processing sites for olfactory information (orbitofrontal cortex) and the entorhinal cortex and dentate gyrus may reflect plastic changes occurring during the early stages of olfactory memory formation.

Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory.

PubMed

Noack, Julia; Richter, Karin; Laube, Gregor; Haghgoo, Hojjat Allah; Veh, Rüdiger W; Engelmann, Mario

2010-11-01

When tested in the olfactory cued social recognition/discrimination test, rats and mice differ in their retention of a recognition memory for a previously encountered conspecific juvenile: Rats are able to recognize a given juvenile for approximately 45 min only whereas mice show not only short-term, but also long-term recognition memory (≥ 24 h). Here we modified the social recognition/social discrimination procedure to investigate the neurobiological mechanism(s) underlying the species differences. We presented a conspecific juvenile repeatedly to the experimental subjects and monitored the investigation duration as a measure for recognition. Presentation of only the volatile fraction of the juvenile olfactory signature was sufficient for both short- and long-term recognition in mice but not rats. Applying additional volatile, mono-molecular odours to the "to be recognized" juveniles failed to affect short-term memory in both species, but interfered with long-term recognition in mice. Finally immunocytochemical analysis of c-Fos as a marker for cellular activation, revealed that juvenile exposure stimulated areas involved in the processing of olfactory signals in both the main and the accessory olfactory bulb in mice. In rats, we measured an increased c-Fos synthesis almost exclusively in cells of the accessory olfactory bulb. Our data suggest that the species difference in the retention of social recognition memory is based on differences in the processing of the volatile versus non-volatile fraction of the individuals' olfactory signature. The non-volatile fraction is sufficient for retaining a short-term social memory only. Long-term social memory - as observed in mice - requires a processing of both the volatile and non-volatile fractions of the olfactory signature. Copyright © 2010 Elsevier Inc. All rights reserved.

Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice.

PubMed

Rey, Nolwen L; Jardanhazi-Kurutz, Daniel; Terwel, Dick; Kummer, Markus P; Jourdan, Francois; Didier, Anne; Heneka, Michael T

2012-02-01

Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits. Copyright © 2012 Elsevier Inc. All rights reserved.

Circadian modulation of short-term memory in Drosophila.

PubMed

Lyons, Lisa C; Roman, Gregg

2009-01-01

Endogenous biological clocks are widespread regulators of behavior and physiology, allowing for a more efficient allocation of efforts and resources over the course of a day. The extent that different processes are regulated by circadian oscillators, however, is not fully understood. We investigated the role of the circadian clock on short-term associative memory formation using a negatively reinforced olfactory-learning paradigm in Drosophila melanogaster. We found that memory formation was regulated in a circadian manner. The peak performance in short-term memory (STM) occurred during the early subjective night with a twofold performance amplitude after a single pairing of conditioned and unconditioned stimuli. This rhythm in memory is eliminated in both timeless and period mutants and is absent during constant light conditions. Circadian gating of sensory perception does not appear to underlie the rhythm in short-term memory as evidenced by the nonrhythmic shock avoidance and olfactory avoidance behaviors. Moreover, central brain oscillators appear to be responsible for the modulation as cryptochrome mutants, in which the antennal circadian oscillators are nonfunctional, demonstrate robust circadian rhythms in short-term memory. Together these data suggest that central, rather than peripheral, circadian oscillators modulate the formation of short-term associative memory and not the perception of the stimuli.

Olfactory imprinting is correlated with changes in gene expression in the olfactory epithelia of the zebrafish.

PubMed

Harden, Maegan V; Newton, Lucy A; Lloyd, Russell C; Whitlock, Kathleen E

2006-11-01

Odors experienced as juveniles can have significant effects on the behavior of mature organisms. A dramatic example of this occurs in salmon, where the odors experienced by developing fish determine the river to which they return as adults. Further examples of olfactory memories are found in many animals including vertebrates and invertebrates. Yet, the cellular and molecular bases underlying the formation of olfactory memory are poorly understood. We have devised a series of experiments to determine whether zebrafish can form olfactory memories much like those observed in salmonids. Here we show for the first time that zebrafish form and retain olfactory memories of an artificial odorant, phenylethyl alcohol (PEA), experienced as juveniles. Furthermore, we demonstrate that exposure to PEA results in changes in gene expression within the olfactory sensory system. These changes are evident by in situ hybridization in the olfactory epithelium of the developing zebrafish. Strikingly, our analysis by in situ hybridization demonstrates that the transcription factor, otx2, is up regulated in the olfactory sensory epithelia in response to PEA. This increase is evident at 2-3 days postfertilization and is maintained in the adult animals. We propose that the changes in otx2 gene expression are manifest as an increase in the number of neuronal precursors in the cells olfactory epithelium of the odor-exposed fish. Thus, our results reveal a role for the environment in controlling gene expression in the developing peripheral nervous system. Copyright 2006 Wiley Periodicals, Inc.

A Fully Automated Drosophila Olfactory Classical Conditioning and Testing System for Behavioral Learning and Memory Assessment

PubMed Central

Jiang, Hui; Hanna, Eriny; Gatto, Cheryl L.; Page, Terry L.; Bhuva, Bharat; Broadie, Kendal

2016-01-01

Background Aversive olfactory classical conditioning has been the standard method to assess Drosophila learning and memory behavior for decades, yet training and testing are conducted manually under exceedingly labor-intensive conditions. To overcome this severe limitation, a fully automated, inexpensive system has been developed, which allows accurate and efficient Pavlovian associative learning/memory analyses for high-throughput pharmacological and genetic studies. New Method The automated system employs a linear actuator coupled to an odorant T-maze with airflow-mediated transfer of animals between training and testing stages. Odorant, airflow and electrical shock delivery are automatically administered and monitored during training trials. Control software allows operator-input variables to define parameters of Drosophila learning, short-term memory and long-term memory assays. Results The approach allows accurate learning/memory determinations with operational fail-safes. Automated learning indices (immediately post-training) and memory indices (after 24 hours) are comparable to traditional manual experiments, while minimizing experimenter involvement. Comparison with Existing Methods The automated system provides vast improvements over labor-intensive manual approaches with no experimenter involvement required during either training or testing phases. It provides quality control tracking of airflow rates, odorant delivery and electrical shock treatments, and an expanded platform for high-throughput studies of combinational drug tests and genetic screens. The design uses inexpensive hardware and software for a total cost of ~$500US, making it affordable to a wide range of investigators. Conclusions This study demonstrates the design, construction and testing of a fully automated Drosophila olfactory classical association apparatus to provide low-labor, high-fidelity, quality-monitored, high-throughput and inexpensive learning and memory behavioral assays. PMID:26703418

A fully automated Drosophila olfactory classical conditioning and testing system for behavioral learning and memory assessment.

PubMed

Jiang, Hui; Hanna, Eriny; Gatto, Cheryl L; Page, Terry L; Bhuva, Bharat; Broadie, Kendal

2016-03-01

Aversive olfactory classical conditioning has been the standard method to assess Drosophila learning and memory behavior for decades, yet training and testing are conducted manually under exceedingly labor-intensive conditions. To overcome this severe limitation, a fully automated, inexpensive system has been developed, which allows accurate and efficient Pavlovian associative learning/memory analyses for high-throughput pharmacological and genetic studies. The automated system employs a linear actuator coupled to an odorant T-maze with airflow-mediated transfer of animals between training and testing stages. Odorant, airflow and electrical shock delivery are automatically administered and monitored during training trials. Control software allows operator-input variables to define parameters of Drosophila learning, short-term memory and long-term memory assays. The approach allows accurate learning/memory determinations with operational fail-safes. Automated learning indices (immediately post-training) and memory indices (after 24h) are comparable to traditional manual experiments, while minimizing experimenter involvement. The automated system provides vast improvements over labor-intensive manual approaches with no experimenter involvement required during either training or testing phases. It provides quality control tracking of airflow rates, odorant delivery and electrical shock treatments, and an expanded platform for high-throughput studies of combinational drug tests and genetic screens. The design uses inexpensive hardware and software for a total cost of ∼$500US, making it affordable to a wide range of investigators. This study demonstrates the design, construction and testing of a fully automated Drosophila olfactory classical association apparatus to provide low-labor, high-fidelity, quality-monitored, high-throughput and inexpensive learning and memory behavioral assays. Copyright © 2015 Elsevier B.V. All rights reserved.

PKA Increases in the Olfactory Bulb Act as Unconditioned Stimuli and Provide Evidence for Parallel Memory Systems: Pairing Odor with Increased PKA Creates Intermediate- and Long-Term, but Not Short-Term, Memories

ERIC Educational Resources Information Center

Grimes, Matthew T.; Harley, Carolyn W.; Darby-King, Andrea; McLean, John H.

2012-01-01

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and…

What a Nostril Knows: Olfactory Nerve-Evoked AMPA Responses Increase while NMDA Responses Decrease at 24-h Post-Training for Lateralized Odor Preference Memory in Neonate Rat

ERIC Educational Resources Information Center

Yuan, Qi; Harley, Carolyn W.

2012-01-01

Increased AMPA signaling is proposed to mediate long-term memory. Rat neonates acquire odor preferences in a single olfactory bulb if one nostril is occluded at training. Memory testing here confirmed that only trained bulbs support increased odor preference at 24 h. Olfactory nerve field potentials were tested at 24 h in slices from trained and…

AKAPS Act in a Two-Step Mechanism of Memory Acquisition

PubMed Central

Scheunemann, Lisa; Skroblin, Philipp; Hundsrucker, Christian; Klussmann, Enno; Efetova, Marina

2013-01-01

Defining the molecular and neuronal basis of associative memories is based upon behavioral preparations that yield high performance due to selection of salient stimuli, strong reinforcement, and repeated conditioning trials. One of those preparations is the Drosophila aversive olfactory conditioning procedure where animals initiate multiple memory components after experience of a single cycle training procedure. Here, we explored the analysis of acquisition dynamics as a means to define memory components and revealed strong correlations between particular chronologies of shock impact and number experienced during the associative training situation and subsequent performance of conditioned avoidance. Analyzing acquisition dynamics in Drosophila memory mutants revealed that rutabaga (rut)-dependent cAMP signals couple in a divergent fashion for support of different memory components. In case of anesthesia-sensitive memory (ASM) we identified a characteristic two-step mechanism that links rut-AC1 to A-kinase anchoring proteins (AKAP)-sequestered protein kinase A at the level of Kenyon cells, a recognized center of olfactory learning within the fly brain. We propose that integration of rut-derived cAMP signals at level of AKAPs might serve as counting register that accounts for the two-step mechanism of ASM acquisition. PMID:24174675

Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression.

PubMed

Cook, A; Pfeiffer, L-M; Thiele, S; Coenen, V A; Döbrössy, M D

2017-10-01

Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity.

PubMed

Naganos, Shintaro; Ueno, Kohei; Horiuchi, Junjiro; Saitoe, Minoru

2016-04-06

Reduced insulin/insulin-like growth factor signaling (IIS) is a major cause of symmetrical intrauterine growth retardation (IUGR), an impairment in cell proliferation during prenatal development that results in global growth defects and mental retardation. In Drosophila, chico encodes the only insulin receptor substrate. Similar to other animal models of IUGR, chico mutants have defects in global growth and associative learning. However, the physiological and molecular bases of learning defects caused by chico mutations, and by symmetrical IUGR, are not clear. In this study, we found that chico mutations impair memory-associated synaptic plasticity in the mushroom bodies (MBs), neural centers for olfactory learning. Mutations in chico reduce expression of the rutabaga-type adenylyl cyclase (rut), leading to decreased cAMP synthesis in the MBs. Expressing a rut (+) transgene in the MBs restores memory-associated plasticity and olfactory associative learning in chico mutants, without affecting growth. Thus chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in the MBs. Our results suggest that some cognitive defects associated with reduced IIS may occur, independently of developmental defects, from acute reductions in cAMP signaling.

Olfactory identification deficits and associated response inhibition in obsessive-compulsive disorder: on the scent of the orbitofronto-striatal model.

PubMed

Bersani, Giuseppe; Quartini, Adele; Ratti, Flavia; Pagliuca, Giulio; Gallo, Andrea

2013-11-30

Olfactory identification ability implicates the integrity of the orbitofrontal cortex (OFC). The fronto-striatal circuits including the OFC have been involved in the neuropathology of Obsessive Compulsive Disorder (OCD). However, only a few studies have examined olfactory function in patients with OCD. The Brief Smell Identification Test (B-SIT) and tests from the Cambridge Neuropsychological Automated Battery (CANTAB) were administered to 25 patients with OCD and to 21 healthy matched controls. OCD patients showed a significant impairment in olfactory identification ability as well as widely distributed cognitive deficits in visual memory, executive functions, attention, and response inhibition. The degree of behavioural impairment on motor impulsivity (prolonged response inhibition Stop-Signal Reaction Time) strongly correlated with the B-SIT score. Our study is the first to indicate a shared OFC pathological neural substrate underlying olfactory identification impairment, impulsivity, and OCD. Deficits in visual memory, executive functions and attention further indicate that regions outside of the orbitofronto-striatal loop may be involved in this disorder. Such results may help delineate the clinical complexity of OCD and support more targeted investigations and interventions. In this regard, research on the potential diagnostic utility of olfactory identification deficits in the assessment of OCD would certainly be useful. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Requirement of the Combination of Mushroom Body ? Lobe and a/ß Lobes for the Retrieval of Both Aversive and Appetitive Early Memories in "Drosophila"

ERIC Educational Resources Information Center

Xie, Zhiyong; Huang, Cheng; Ci, Bo; Lianzhang, Wang; Zhong, Yi

2013-01-01

Extensive studies of "Drosophila" mushroom body in formation and retrieval of olfactory memories allow us to delineate the functional logic for memory storage and retrieval. Currently, there is a questionable disassociation of circuits for memory storage and retrieval during "Drosophila" olfactory memory processing. Formation…

Olfactory learning without the mushroom bodies: Spiking neural network models of the honeybee lateral antennal lobe tract reveal its capacities in odour memory tasks of varied complexities

PubMed Central

2017-01-01

The honeybee olfactory system is a well-established model for understanding functional mechanisms of learning and memory. Olfactory stimuli are first processed in the antennal lobe, and then transferred to the mushroom body and lateral horn through dual pathways termed medial and lateral antennal lobe tracts (m-ALT and l-ALT). Recent studies reported that honeybees can perform elemental learning by associating an odour with a reward signal even after lesions in m-ALT or blocking the mushroom bodies. To test the hypothesis that the lateral pathway (l-ALT) is sufficient for elemental learning, we modelled local computation within glomeruli in antennal lobes with axons of projection neurons connecting to a decision neuron (LHN) in the lateral horn. We show that inhibitory spike-timing dependent plasticity (modelling non-associative plasticity by exposure to different stimuli) in the synapses from local neurons to projection neurons decorrelates the projection neurons’ outputs. The strength of the decorrelations is regulated by global inhibitory feedback within antennal lobes to the projection neurons. By additionally modelling octopaminergic modification of synaptic plasticity among local neurons in the antennal lobes and projection neurons to LHN connections, the model can discriminate and generalize olfactory stimuli. Although positive patterning can be accounted for by the l-ALT model, negative patterning requires further processing and mushroom body circuits. Thus, our model explains several–but not all–types of associative olfactory learning and generalization by a few neural layers of odour processing in the l-ALT. As an outcome of the combination between non-associative and associative learning, the modelling approach allows us to link changes in structural organization of honeybees' antennal lobes with their behavioural performances over the course of their life. PMID:28640825

Olfactory learning without the mushroom bodies: Spiking neural network models of the honeybee lateral antennal lobe tract reveal its capacities in odour memory tasks of varied complexities.

PubMed

MaBouDi, HaDi; Shimazaki, Hideaki; Giurfa, Martin; Chittka, Lars

2017-06-01

The honeybee olfactory system is a well-established model for understanding functional mechanisms of learning and memory. Olfactory stimuli are first processed in the antennal lobe, and then transferred to the mushroom body and lateral horn through dual pathways termed medial and lateral antennal lobe tracts (m-ALT and l-ALT). Recent studies reported that honeybees can perform elemental learning by associating an odour with a reward signal even after lesions in m-ALT or blocking the mushroom bodies. To test the hypothesis that the lateral pathway (l-ALT) is sufficient for elemental learning, we modelled local computation within glomeruli in antennal lobes with axons of projection neurons connecting to a decision neuron (LHN) in the lateral horn. We show that inhibitory spike-timing dependent plasticity (modelling non-associative plasticity by exposure to different stimuli) in the synapses from local neurons to projection neurons decorrelates the projection neurons' outputs. The strength of the decorrelations is regulated by global inhibitory feedback within antennal lobes to the projection neurons. By additionally modelling octopaminergic modification of synaptic plasticity among local neurons in the antennal lobes and projection neurons to LHN connections, the model can discriminate and generalize olfactory stimuli. Although positive patterning can be accounted for by the l-ALT model, negative patterning requires further processing and mushroom body circuits. Thus, our model explains several-but not all-types of associative olfactory learning and generalization by a few neural layers of odour processing in the l-ALT. As an outcome of the combination between non-associative and associative learning, the modelling approach allows us to link changes in structural organization of honeybees' antennal lobes with their behavioural performances over the course of their life.

Serotonin is critical for rewarded olfactory short-term memory in Drosophila.

PubMed

Sitaraman, Divya; LaFerriere, Holly; Birman, Serge; Zars, Troy

2012-06-01

The biogenic amines dopamine, octopamine, and serotonin are critical in establishing normal memories. A common view for the amines in insect memory performance has emerged in which dopamine and octopamine are largely responsible for aversive and appetitive memories. Examination of the function of serotonin begins to challenge the notion of one amine type per memory because altering serotonin function also reduces aversive olfactory memory and place memory levels. Could the function of serotonin be restricted to the aversive domain, suggesting a more specific dopamine/serotonin system interaction? The function of the serotonergic system in appetitive olfactory memory was examined. By targeting the tetanus toxin light chain (TNT) and the human inwardly rectifying potassium channel (Kir2.1) to the serotonin neurons with two different GAL4 driver combinations, the serotonergic system was inhibited. Additional use of the GAL80(ts1) system to control expression of transgenes to the adult stage of the life cycle addressed a potential developmental role of serotonin in appetitive memory. Reduction in appetitive olfactory memory performance in flies with these transgenic manipulations, without altering control behaviors, showed that the serotonergic system is also required for normal appetitive memory. Thus, serotonin appears to have a more general role in Drosophila memory, and implies an interaction with both the dopaminergic and octopaminergic systems.

Neuronal Nitric-Oxide Synthase Deficiency Impairs the Long-Term Memory of Olfactory Fear Learning and Increases Odor Generalization

ERIC Educational Resources Information Center

Pavesi, Eloisa; Heldt, Scott A.; Fletcher, Max L.

2013-01-01

Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice…

G(o) Activation Is Required for Both Appetitive and Aversive Memory Acquisition in "Drosophila"

ERIC Educational Resources Information Center

Madalan, Adrian; Yang, Xiao; Ferris, Jacob; Zhang, Shixing; Roman, Gregg

2012-01-01

Heterotrimeric G(o) is an abundant brain protein required for negatively reinforced short-term associative olfactory memory in "Drosophila". G(o) is the only known substrate of the S1 subunit of pertussis toxin (PTX) in fly, and acute expression of PTX within the mushroom body neurons (MB) induces a reversible deficit in associative olfactory…

Inhibiting DNA methylation alters olfactory extinction but not acquisition learning in Apis cerana and Apis mellifera.

PubMed

Gong, Zhiwen; Wang, Chao; Nieh, James C; Tan, Ken

2016-07-01

DNA methylation plays a key role in invertebrate acquisition and extinction memory. Honey bees have excellent olfactory learning, but the role of DNA methylation in memory formation has, to date, only been studied in Apis mellifera. We inhibited DNA methylation by inhibiting DNA methyltransferase (DNMT) with zebularine (zeb) and studied the resulting effects upon olfactory acquisition and extinction memory in two honey bee species, Apis cerana and A. mellifera. We used the proboscis extension reflex (PER) assay to measure memory. We provide the first demonstration that DNA methylation is also important in the olfactory extinction learning of A. cerana. DNMT did not reduce acquisition learning in either species. However, zeb bidirectionally and differentially altered extinction learning in both species. In particular, zeb provided 1h before acquisition learning improved extinction memory retention in A. mellifera, but reduced extinction memory retention in A. cerana. The reasons for these differences are unclear, but provide a basis for future studies to explore species-specific differences in the effects of methylation on memory formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Loss of hfe function reverses impaired recognition memory caused by olfactory manganese exposure in mice.

PubMed

Ye, Qi; Kim, Jonghan

2015-03-01

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout (Hfe (-/-)) and wild-type (Hfe (+/+)) mice mice were intranasally-instilled with manganese chloride (MnCl2 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in Hfe (+/+) mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, Hfe (-/-) mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in Hfe (+/+) mice, but not in Hfe (-/-) mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson's disease.

PubMed

Prediger, Rui D S; Rojas-Mayorquin, Argelia E; Aguiar, Aderbal S; Chevarin, Caroline; Mongeau, Raymond; Hamon, Michel; Lanfumey, Laurence; Del Bel, Elaine; Muramatsu, Hisako; Courty, José; Raisman-Vozari, Rita

2011-08-01

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Activity-dependent expression of miR-132 regulates immediate-early gene induction during olfactory learning in the greater short-nosed fruit bat, Cynopterus sphinx.

PubMed

Mukilan, Murugan; Ragu Varman, Durairaj; Sudhakar, Sivasubramaniam; Rajan, Koilmani Emmanuvel

2015-04-01

The activity-dependent expression of immediate-early genes (IEGs) and microRNA (miR)-132 has been implicated in synaptic plasticity and the formation of long-term memory (LTM). In the present study, we show that olfactory training induces the expression of IEGs (EGR-1, C-fos, C-jun) and miR-132 at similar time scale in olfactory bulb (OB) of Cynopterus sphinx. We examined the role of miR-132 in the OB using antisense oligodeoxynucleotide (AS-ODN) and demonstrated that a local infusion of AS-ODN in the OB 2h prior to training impaired olfactory memory formation in C. sphinx. However, the infusion of AS-ODN post-training did not cause a deficit in memory formation. Furthermore, the inhibition of miR-132 reduced the olfactory training-induced expression of IEGs and post synaptic density protein-95 (PSD-95) in the OB. Additionally, we show that miR-132 regulates the activation of calcium/calmodulin-dependent protein kinase-II (CaMKII) and cAMP response element binding protein (CREB), possibly through miR-148a. These data suggest that olfactory training induces the expression of miR-132 and IEGs, which in turn activates post-synaptic proteins that regulate olfactory memory formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Aversive Olfactory Learning and Associative Long-Term Memory in "Caenorhabditis elegans"

ERIC Educational Resources Information Center

Amano, Hisayuki; Maruyama, Ichiro N.

2011-01-01

The nematode "Caenorhabditis elegans" ("C. elegans") adult hermaphrodite has 302 invariant neurons and is suited for cellular and molecular studies on complex behaviors including learning and memory. Here, we have developed protocols for classical conditioning of worms with 1-propanol, as a conditioned stimulus (CS), and hydrochloride (HCl) (pH…

Noradrenergic induction of odor-specific neural habituation and olfactory memories

PubMed Central

Shea, Stephen D.; Katz, Lawrence C.; Mooney, Richard

2008-01-01

For many mammals, individual recognition of conspecifics relies on olfactory cues. Certain individual recognition memories are thought to be stored when conspecific odor cues coincide with surges of noradrenaline (NA) triggered by intensely arousing social events. Such familiar stimuli elicit reduced behavioral responses, a change likely related to NA-dependent plasticity in the olfactory bulb (OB). In addition to its role in these ethological memories, NA signaling in the OB appears to be relevant for the discrimination of more arbitrary odorants as well. Nonetheless, no NA-gated mechanism of long-term plasticity in the OB has ever been directly observed in vivo. Here we report that NA release from locus coeruleus (LC), when coupled to odor presentation, acts locally in the main olfactory bulb (MOB) to cause a specific long-lasting suppression of respones to paired odors. These effects were observed for both food odors and urine, an important social recognition cue. Moreover, in subsequent behavioral tests, mice exhibited habituation to paired urine stimuli, suggesting that this LC-mediated olfactory neural plasticity, induced under anesthesia, can store an individual recognition memory that is observable upon recovery. PMID:18923046

Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx.

PubMed

Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Balamurugan, Krishnaswamy; Ragu Varman, Durairaj; Rajan, Koilmani Emmanuvel

2012-08-30

Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training. Our results showed that behavioral training significantly up-regulates immediate early gene (IEG) EGR-1 and key synaptic proteins Synaptotagmin-1(SYT-1), CaMKII and PSD-95, and phosphorylation of CaMKII in the OB at the protein level per se. Subsequently, we observed that egr-1 antisense-ODN infusion in the OB impaired olfactory memory and down regulates the expression of CaMKII and PSD-95, and the phosphorylation of CaMKII but not SYT-1. In contrast, NS-ODN or PBS had no effect on the expression of the PSDs CaMKII or PSD-95, or on the phosphorylation of CaMKII. When the egr-1 NS-ODN was infused in the OB after training for the novel odor there was no effect on olfactory memory. These findings suggest that egr-1 control the activation of CaMKII and PSD-95 during the process of olfactory memory formation. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of odor identification among amnestic and non-amnestic mild cognitive impairment, subjective cognitive decline, and early Alzheimer's dementia.

PubMed

Park, Sung-Jin; Lee, Jee-Eun; Lee, Kwang-Soo; Kim, Joong-Seok

2018-03-01

Olfactory impairment might be an important clinical marker and predictor of Alzheimer's disease (AD). In the present study, we aimed to compare the degree of olfactory identification impairment in each mild cognitive impairment (MCI) subtype, subjective memory impairment, and early AD dementia and assessed the relationship between olfactory identification and cognitive performance. We consecutively included 50 patients with amnestic MCI, 28 patients with non-amnestic MCI, 20 patients with mild AD, and 17 patients with subjective memory impairment (SMI). All patients underwent clinical and neuropsychological assessments. A multiple choice olfactory identification cross-cultural smell identification test was also utilized. Controlling for age and gender, olfactory impairment was significantly more severe in patients with AD and amnestic MCI compared with the results from the non-amnestic MCI and SMI groups. Higher scores on MMSE, verbal and non-verbal memory, and frontal executive function tests were significantly related to olfactory identification ability. In conclusion, olfactory identification is impaired in amnestic MCI and AD. These findings are consistent with previous studies. In amnestic MCI patients, this dysfunction is considered to be caused by underlying AD pathology.

Kinase activity in the olfactory bulb is required for odor memory consolidation.

PubMed

Tong, Michelle T; Kim, Tae-Young P; Cleland, Thomas A

2018-05-01

Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)-a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor-reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB. K252a is a partially selective inhibitor of tyrosine kinase (Trk) receptors, including the TrkB receptor for BDNF, though it also inhibits other plasticity-related kinases such as PKC and CaMKII/IV. K252a infusion into the OB did not impair odor acquisition or short-term (2 h) memory for the learned discriminations, but significantly impaired long-term (48 h) odor memory (LTM). This LTM deficit also was associated with reduced selectivity for the conditioned odorant in a reward-seeking digging task. Infusions of K252a immediately prior to testing did not impair LTM recall. These results indicate that kinase activation in the OB is required for the consolidation of odor memory of incrementally acquired information. © 2018 Tong et al.; Published by Cold Spring Harbor Laboratory Press.

Virtual vision system with actual flavor by olfactory display

NASA Astrophysics Data System (ADS)

Sakamoto, Kunio; Kanazawa, Fumihiro

2010-11-01

The authors have researched multimedia system and support system for nursing studies on and practices of reminiscence therapy and life review therapy. The concept of the life review is presented by Butler in 1963. The process of thinking back on one's life and communicating about one's life to another person is called life review. There is a famous episode concerning the memory. It is called as Proustian effects. This effect is mentioned on the Proust's novel as an episode that a story teller reminds his old memory when he dipped a madeleine in tea. So many scientists research why smells trigger the memory. The authors pay attention to the relation between smells and memory although the reason is not evident yet. Then we have tried to add an olfactory display to the multimedia system so that the smells become a trigger of reminding buried memories. An olfactory display is a device that delivers smells to the nose. It provides us with special effects, for example to emit smell as if you were there or to give a trigger for reminding us of memories. The authors have developed a tabletop display system connected with the olfactory display. For delivering a flavor to user's nose, the system needs to recognition and measure positions of user's face and nose. In this paper, the authors describe an olfactory display which enables to detect the nose position for an effective delivery.

DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees

PubMed Central

Biergans, Stephanie D.; Claudianos, Charles; Reinhard, Judith; Galizia, C. G.

2016-01-01

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., ‘correct’ (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes. PMID:27672359

DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees.

PubMed

Biergans, Stephanie D; Claudianos, Charles; Reinhard, Judith; Galizia, C G

2016-01-01

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., 'correct' (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes.

Plasticity in the olfactory bulb of the maternal mouse is prevented by gestational stress

PubMed Central

Belnoue, Laure; Malvaut, Sarah; Ladevèze, Elodie; Abrous, Djoher Nora; Koehl, Muriel

2016-01-01

Maternal stress is associated with an altered mother-infant relationship that endangers offspring development, leading to emotional/behavioral problems. However, little research has investigated the stress-induced alterations of the maternal brain that could underlie such a disruption of mother-infant bonding. Olfactory cues play an extensive role in the coordination of mother-infant interactions, suggesting that motherhood may be associated to enhanced olfactory performances, and that this effect may be abolished by maternal stress. To test this hypothesis, we analyzed the impact of motherhood under normal conditions or after gestational stress on olfactory functions in C57BL/6 J mice. We report that gestational stress alters maternal behavior and prevents both mothers’ ability to discriminate pup odors and motherhood-induced enhancement in odor memory. We investigated adult bulbar neurogenesis as a potential mechanism of the enhanced olfactory function in mothers and found that motherhood was associated with an increased complexity of the dendritic tree of newborn neurons. This motherhood-evoked remodeling was totally prevented by gestational stress. Altogether, our results may thus provide insight into the neural changes that could contribute to altered maternal behavior in stressed mothers. PMID:27886228

Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

PubMed

Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

2017-07-12

The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

Odors as effective retrieval cues for stressful episodes.

PubMed

Wiemers, Uta S; Sauvage, Magdalena M; Wolf, Oliver T

2014-07-01

Olfactory information seems to play a special role in memory due to the fast and direct processing of olfactory information in limbic areas like the amygdala and the hippocampus. This has led to the assumption that odors can serve as effective retrieval cues for autobiographic memories, especially emotional memories. The current study sought to investigate whether an olfactory cue can serve as an effective retrieval cue for memories of a stressful episode. A total of 95 participants were exposed to a psychosocial stressor or a well matching but not stressful control condition. During both conditions were visual objects present, either bound to the situation (central objects) or not (peripheral objects). Additionally, an ambient odor was present during both conditions. The next day, participants engaged in an unexpected object recognition task either under the influence of the same odor as was present during encoding (congruent odor) or another odor (non-congruent odor). Results show that stressed participants show a better memory for all objects and especially for central visual objects if recognition took place under influence of the congruent odor. An olfactory cue thus indeed seems to be an effective retrieval cue for stressful memories. Copyright © 2013 Elsevier Inc. All rights reserved.

Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory Impairments

PubMed Central

Coronas-Samano, Guillermo; Baker, Keeley L.; Tan, Winston J. T.; Ivanova, Alla V.; Verhagen, Justus V.

2016-01-01

Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4–5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus), in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term), olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie), spatial memory (learning impairments on finding the platform in the Morris water maze) and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation), association memory (passive avoidance) or in species-typical behavior (nest building) and no increased anxiety (open field, light-dark box) or depression/anhedonia (sucrose preference) at this relatively young age. These neurobehavioral deficits of the Fus1 KO mice at this relatively young age are highly relevant to sAD, making them suitable for effective research on pharmacological targets in the context of early intervention of sAD. PMID:27895577

Aversive olfactory associative memory loses odor specificity over time

PubMed Central

König, Christian; Antwi-Adjei, Emmanuel; Ganesan, Mathangi; Kilonzo, Kasyoka; Viswanathan, Vignesh; Durairaja, Archana; Voigt, Anne

2017-01-01

ABSTRACT Avoiding associatively learned predictors of danger is crucial for survival. Aversive memories can, however, become counter-adaptive when they are overly generalized to harmless cues and contexts. In a fruit fly odor–electric shock associative memory paradigm, we found that learned avoidance lost its specificity for the trained odor and became general to novel odors within a day of training. We discuss the possible neural circuit mechanisms of this effect and highlight the parallelism to over-generalization of learned fear behavior after an incubation period in rodents and humans, with due relevance for post-traumatic stress disorder. PMID:28468811

Functional Neuroanatomy of "Drosophila" Olfactory Memory Formation

ERIC Educational Resources Information Center

Guven-Ozkan, Tugba; Davis, Ronald L.

2014-01-01

New approaches, techniques and tools invented over the last decade and a half have revolutionized the functional dissection of neural circuitry underlying "Drosophila" learning. The new methodologies have been used aggressively by researchers attempting to answer three critical questions about olfactory memories formed with appetitive…

Anatomy and behavioral function of serotonin receptors in Drosophila melanogaster larvae.

PubMed

Huser, Annina; Eschment, Melanie; Güllü, Nazli; Collins, Katharina A N; Böpple, Kathrin; Pankevych, Lyubov; Rolsing, Emilia; Thum, Andreas S

2017-01-01

The biogenic amine serotonin (5-HT) is an important neuroactive molecule in the central nervous system of the majority of animal phyla. 5-HT binds to specific G protein-coupled and ligand-gated ion receptors to regulate particular aspects of animal behavior. In Drosophila, as in many other insects this includes the regulation of locomotion and feeding. Due to its genetic amenability and neuronal simplicity the Drosophila larva has turned into a useful model for studying the anatomical and molecular basis of chemosensory behaviors. This is particularly true for the olfactory system, which is mostly described down to the synaptic level over the first three orders of neuronal information processing. Here we focus on the 5-HT receptor system of the Drosophila larva. In a bipartite approach consisting of anatomical and behavioral experiments we describe the distribution and the implications of individual 5-HT receptors on naïve and acquired chemosensory behaviors. Our data suggest that 5-HT1A, 5-HT1B, and 5-HT7 are dispensable for larval naïve olfactory and gustatory choice behaviors as well as for appetitive and aversive associative olfactory learning and memory. In contrast, we show that 5-HT/5-HT2A signaling throughout development, but not as an acute neuronal function, affects associative olfactory learning and memory using high salt concentration as a negative unconditioned stimulus. These findings describe for the first time an involvement of 5-HT signaling in learning and memory in Drosophila larvae. In the longer run these results may uncover developmental, 5-HT dependent principles related to reinforcement processing possibly shared with adult Drosophila and other insects.

Anatomy and behavioral function of serotonin receptors in Drosophila melanogaster larvae

PubMed Central

Huser, Annina; Eschment, Melanie; Güllü, Nazli; Collins, Katharina A. N.; Böpple, Kathrin; Pankevych, Lyubov; Rolsing, Emilia; Thum, Andreas S.

2017-01-01

The biogenic amine serotonin (5-HT) is an important neuroactive molecule in the central nervous system of the majority of animal phyla. 5-HT binds to specific G protein-coupled and ligand-gated ion receptors to regulate particular aspects of animal behavior. In Drosophila, as in many other insects this includes the regulation of locomotion and feeding. Due to its genetic amenability and neuronal simplicity the Drosophila larva has turned into a useful model for studying the anatomical and molecular basis of chemosensory behaviors. This is particularly true for the olfactory system, which is mostly described down to the synaptic level over the first three orders of neuronal information processing. Here we focus on the 5-HT receptor system of the Drosophila larva. In a bipartite approach consisting of anatomical and behavioral experiments we describe the distribution and the implications of individual 5-HT receptors on naïve and acquired chemosensory behaviors. Our data suggest that 5-HT1A, 5-HT1B, and 5-HT7 are dispensable for larval naïve olfactory and gustatory choice behaviors as well as for appetitive and aversive associative olfactory learning and memory. In contrast, we show that 5-HT/5-HT2A signaling throughout development, but not as an acute neuronal function, affects associative olfactory learning and memory using high salt concentration as a negative unconditioned stimulus. These findings describe for the first time an involvement of 5-HT signaling in learning and memory in Drosophila larvae. In the longer run these results may uncover developmental, 5-HT dependent principles related to reinforcement processing possibly shared with adult Drosophila and other insects. PMID:28777821

Effect of circadian phase on memory acquisition and recall: operant conditioning vs. classical conditioning.

PubMed

Garren, Madeleine V; Sexauer, Stephen B; Page, Terry L

2013-01-01

There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning.

Effect of Circadian Phase on Memory Acquisition and Recall: Operant Conditioning vs. Classical Conditioning

PubMed Central

Garren, Madeleine V.; Sexauer, Stephen B.; Page, Terry L.

2013-01-01

There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning. PMID:23533587

Test-retest reliability and validity of the Sniffin' TOM odor memory test.

PubMed

Croy, Ilona; Zehner, Cora; Larsson, Maria; Zucco, Gesualdo M; Hummel, Thomas

2015-03-01

Few attempts have been made to develop an olfactory test that captures episodic retention of olfactory information. Assessment of episodic odor memory is of particular interest in aging and in the cognitively impaired as both episodic memory deficits and olfactory loss have been targeted as reliable hallmarks of cognitive decline and impending dementia. Here, 96 healthy participants (18-92 years) and an additional 19 older people with mild cognitive impairment were tested (73-82 years). Participants were presented with 8 common odors with intentional encoding instructions that were followed by a yes-no recognition test. After recognition completion, participants were asked to identify all odors by means of free or cued identification. A retest of the odor memory test (Sniffin' TOM = test of odor memory) took place 17 days later. The results revealed satisfactory test-retest reliability (0.70) of odor recognition memory. Both recognition and identification performance were negatively affected by age and more pronounced among the cognitively impaired. In conclusion, the present work presents a reliable, valid, and simple test of episodic odor recognition memory that may be used in clinical groups where both episodic memory deficits and olfactory loss are prevalent preclinically such as Alzheimer's disease. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PKA increases in the olfactory bulb act as unconditioned stimuli and provide evidence for parallel memory systems: pairing odor with increased PKA creates intermediate- and long-term, but not short-term, memories.

PubMed

Grimes, Matthew T; Harley, Carolyn W; Darby-King, Andrea; McLean, John H

2012-02-21

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and translation-dependent). Here, we use neonatal odor-preference learning to explore the role of olfactory bulb PKA in these three phases of mammalian memory. PKA activity increased normally in learning animals 10 min after a single training trial. Inhibition of PKA by Rp-cAMPs blocked intermediate-term and long-term memory, with no effect on short-term memory. PKA inhibition also prevented learning-associated CREB phosphorylation, a transcription factor implicated in long-term memory. When long-term memory was rescued through increased β-adrenoceptor activation, CREB phosphorylation was restored. Intermediate-term and long-term, but not short-term odor-preference memories were generated by pairing odor with direct PKA activation using intrabulbar Sp-cAMPs, which bypasses β-adrenoceptor activation. Higher levels of Sp-cAMPs enhanced memory by extending normal 24-h retention to 48-72 h. These results suggest that increased bulbar PKA is necessary and sufficient for the induction of intermediate-term and long-term odor-preference memory, and suggest that PKA activation levels also modulate memory duration. However, short-term memory appears to use molecular mechanisms other than the PKA/CREB pathway. These mechanisms, which are also recruited by β-adrenoceptor activation, must operate in parallel with PKA activation.

The Orexin Component of Fasting Triggers Memory Processes Underlying Conditioned Food Selection in the Rat

ERIC Educational Resources Information Center

Ferry, Barbara; Duchamp-Viret, Patricia

2014-01-01

To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor-malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion…

Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

ERIC Educational Resources Information Center

Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

2004-01-01

The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

Distinct Neural Mechanisms Mediate Olfactory Memory Formation at Different Timescales

ERIC Educational Resources Information Center

McNamara, Ann Marie; Magidson, Phillip D.; Linster, Christiane; Wilson, Donald A.; Cleland, Thomas A.

2008-01-01

Habituation is one of the oldest forms of learning, broadly expressed across sensory systems and taxa. Here, we demonstrate that olfactory habituation induced at different timescales (comprising different odor exposure and intertrial interval durations) is mediated by different neural mechanisms. First, the persistence of habituation memory is…

Sensory memory for odors is encoded in spontaneous correlated activity between olfactory glomeruli.

PubMed

Galán, Roberto F; Weidert, Marcel; Menzel, Randolf; Herz, Andreas V M; Galizia, C Giovanni

2006-01-01

Sensory memory is a short-lived persistence of a sensory stimulus in the nervous system, such as iconic memory in the visual system. However, little is known about the mechanisms underlying olfactory sensory memory. We have therefore analyzed the effect of odor stimuli on the first odor-processing network in the honeybee brain, the antennal lobe, which corresponds to the vertebrate olfactory bulb. We stained output neurons with a calcium-sensitive dye and measured across-glomerular patterns of spontaneous activity before and after a stimulus. Such a single-odor presentation changed the relative timing of spontaneous activity across glomeruli in accordance with Hebb's theory of learning. Moreover, during the first few minutes after odor presentation, correlations between the spontaneous activity fluctuations suffice to reconstruct the stimulus. As spontaneous activity is ubiquitous in the brain, modifiable fluctuations could provide an ideal substrate for Hebbian reverberations and sensory memory in other neural systems.

Cortical Odor Processing in Health and Disease

PubMed Central

Wilson, Donald A.; Xu, Wenjin; Sadrian, Benjamin; Courtiol, Emmanuelle; Cohen, Yaniv; Barnes, Dylan C.

2014-01-01

The olfactory system has a rich cortical representation, including a large archicortical component present in most vertebrates, and in mammals neocortical components including the entorhinal and orbitofrontal cortices. Together, these cortical components contribute to normal odor perception and memory. They help transform the physicochemical features of volatile molecules inhaled or exhaled through the nose into the perception of odor objects with rich associative and hedonic aspects. This chapter focuses on how olfactory cortical areas contribute to odor perception and begins to explore why odor perception is so sensitive to disease and pathology. Odor perception is disrupted by a wide range of disorders including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, autism, and early life exposure to toxins. This olfactory deficit often occurs despite maintained functioning in other sensory systems. Does the unusual network of olfactory cortical structures contribute to this sensitivity? PMID:24767487

Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae

PubMed Central

Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S.

2016-01-01

Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes—besides other forms—a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3’5’-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution. PMID:27768692

Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae.

PubMed

Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Peters, Christina; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S

2016-10-01

Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes-besides other forms-a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3'5'-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution.

From antenna to antenna: lateral shift of olfactory memory recall by honeybees.

PubMed

Rogers, Lesley J; Vallortigara, Giorgio

2008-06-04

Honeybees, Apis mellifera, readily learn to associate odours with sugar rewards and we show here that recall of the olfactory memory, as demonstrated by the bee extending its proboscis when presented with the trained odour, involves first the right and then the left antenna. At 1-2 hour after training using both antennae, recall is possible mainly when the bee uses its right antenna but by 6 hours after training a lateral shift has occurred and the memory can now be recalled mainly when the left antenna is in use. Long-term memory one day after training is also accessed mainly via the left antenna. This time-dependent shift from right to left antenna is also seen as side biases in responding to odour presented to the bee's left or right side. Hence, not only are the cellular events of memory formation similar in bees and vertebrate species but also the lateralized networks involved may be similar. These findings therefore seem to call for remarkable parallel evolution and suggest that the proper functioning of memory formation in a bilateral animal, either vertebrate or invertebrate, requires lateralization of processing.

Paraneoplastic limbic encephalitis associated with mixed olfactory neuroblastoma and craniopharyngioma: A case report and literature review.

PubMed

Nagafuji, Hiroshi; Yokoi, Hidenori; Fujiwara, Masachika; Sato, Dai; Saito, Koichiro

2018-06-01

Paraneoplastic limbic encephalitis (PLE) is a rare disorder of the nervous system associated with malignant disease. It has a subacute onset with the following symptoms: cognitive dysfunction, seizures, irritability, hallucinations, and short-term memory loss. Herein, we report the case of a 35-year-old man with PLE, an olfactory neuroblastoma (ONB) admixed with craniopharyngioma, and serum anti-Hu antibodies. The patient presented with generalized seizures, short-term memory loss, and a polypoid mass located high in the nasal cavity. He underwent surgical resection of the tumor and postoperative chemoradiotherapy with concurrent intra-arterial cisplatin administration. Pathological examination indicated an ONB admixed with craniopharyngioma. The patient's neurological symptoms gradually diminished after surgery. No evidence of recurrence was observed during a 4-year follow-up. We reported a histologically unusual heterogeneous tumor that comprised ONB and craniopharyngioma. This is the first reported case of PLE with anti-Hu antibodies possibly associated with ONB admixed with craniopharyngioma.

Olfactory Stimuli Increase Presence in Virtual Environments

PubMed Central

Munyan, Benson G.; Neer, Sandra M.; Beidel, Deborah C.; Jentsch, Florian

2016-01-01

Background Exposure therapy (EXP) is the most empirically supported treatment for anxiety and trauma-related disorders. EXP consists of repeated exposure to a feared object or situation in the absence of the feared outcome in order to extinguish associated anxiety. Key to the success of EXP is the need to present the feared object/event/situation in as much detail and utilizing as many sensory modalities as possible, in order to augment the sense of presence during exposure sessions. Various technologies used to augment the exposure therapy process by presenting multi-sensory cues (e.g., sights, smells, sounds). Studies have shown that scents can elicit emotionally charged memories, but no prior research has examined the effect of olfactory stimuli upon the patient’s sense of presence during simulated exposure tasks. Methods 60 adult participants navigated a mildly anxiety-producing virtual environment (VE) similar to those used in the treatment of anxiety disorders. Participants had no autobiographical memory associated with the VE. State anxiety, Presence ratings, and electrodermal (EDA) activity were collected throughout the experiment. Results Utilizing a Bonferroni corrected Linear Mixed Model, our results showed statistically significant relationships between olfactory stimuli and presence as assessed by both the Igroup Presence Questionnaire (IPQ: R2 = 0.85, (F(3,52) = 6.625, p = 0.0007) and a single item visual-analogue scale (R2 = 0.85, (F(3,52) = 5.382, p = 0.0027). State anxiety was unaffected by the presence or absence of olfactory cues. EDA was unaffected by experimental condition. Conclusion Olfactory stimuli increase presence in virtual environments that approximate those typical in exposure therapy, but did not increase EDA. Additionally, once administered, the removal of scents resulted in a disproportionate decrease in presence. Implications for incorporating the use of scents to increase the efficacy of exposure therapy is discussed. PMID:27310253

Implicit and Explicit Olfactory Memory in People with and without Down Syndrome

ERIC Educational Resources Information Center

Johns, Adam; Homewood, Judi; Stevenson, Richard; Taylor, Alan

2012-01-01

This study examined differences in implicit and explicit memory performance between people with Down syndrome (DS), their siblings, children matched on mental age, and university undergraduates, using olfactory stimuli. The DS and mental-age matched participants were also compared on two tasks of executive function. The data revealed implicit…

Kinase Activity in the Olfactory Bulb Is Required for Odor Memory Consolidation

ERIC Educational Resources Information Center

Tong, Michelle T.; Kim, Tae-Young P.; Cleland, Thomas A.

2018-01-01

Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)--a process that is closely associated…

c-Fos expression predicts long-term social memory retrieval in mice.

PubMed

Lüscher Dias, Thomaz; Fernandes Golino, Hudson; Moura de Oliveira, Vinícius Elias; Dutra Moraes, Márcio Flávio; Schenatto Pereira, Grace

2016-10-15

The way the rodent brain generally processes socially relevant information is rather well understood. How social information is stored into long-term social memory, however, is still under debate. Here, brain c-Fos expression was measured after adult mice were exposed to familiar or novel juveniles and expression was compared in several memory and socially relevant brain areas. Machine Learning algorithm Random Forest was then used to predict the social interaction category of adult mice based on c-Fos expression in these areas. Interaction with a familiar co-specific altered brain activation in the olfactory bulb, amygdala, hippocampus, lateral septum and medial prefrontal cortex. Remarkably, Random Forest was able to predict interaction with a familiar juvenile with 100% accuracy. Activity in the olfactory bulb, amygdala, hippocampus and the medial prefrontal cortex were crucial to this prediction. From our results, we suggest long-term social memory depends on initial social olfactory processing in the medial amygdala and its output connections synergistically with non-social contextual integration by the hippocampus and medial prefrontal cortex top-down modulation of primary olfactory structures. Copyright © 2016 Elsevier B.V. All rights reserved.

Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats.

PubMed

Guevara-Guzmán, R; Arriaga, V; Kendrick, K M; Bernal, C; Vega, X; Mercado-Gómez, O F; Rivas-Arancibia, S

2009-03-31

There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, alpha and beta estrogen receptors and dopamine beta-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17beta-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for alpha and beta estrogen receptors, and dopamine beta-hydroxylase were reduced as were alpha and beta estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

Interference with olfactory memory by visual and verbal tasks.

PubMed

Annett, J M; Cook, N M; Leslie, J C

1995-06-01

It has been claimed that olfactory memory is distinct from memory in other modalities. This study investigated the effectiveness of visual and verbal tasks in interfering with olfactory memory and included methodological changes from other recent studies. Subjects were allocated to one of four experimental conditions involving interference tasks [no interference task; visual task; verbal task; visual-plus-verbal task] and presented 15 target odours. Either recognition of the odours or free recall of the odour names was tested on one occasion, either within 15 minutes of presentation or one week later. Recognition and recall performance both showed effects of interference of visual and verbal tasks but there was no effect for time of testing. While the results may be accommodated within a dual coding framework, further work is indicated to resolve theoretical issues relating to task complexity.

Overexpression of the NR2A subunit in the forebrain impairs long-term social recognition and non-social olfactory memory.

PubMed

Jacobs, S A; Tsien, J Z

2014-04-01

Animals must recognize and remember conspecifics and potential mates, and distinguish these animals from potential heterospecific competitors and predators. Despite its necessity, aged animals are known to exhibit impaired social recognition memory. As the brain ages, the ratio of NR2A:NR2B in the brain increases over time and has been postulated to underlie the cognitive decline observed during the aging process. Here, we test the hypothesis that an increased NR2A:NR2B subunit ratio underlies long-term social recognition memory. Using transgenic overexpression of NR2A in the forebrain regions, we investigated the ability of these mice to learn and remember male and female conspecifics, mice of another strain and animals of another rodent species, the rat. Furthermore, due to the importance of olfaction in social recognition, we tested the olfactory memory in the NR2A transgenic mice. Our series of behavioral experiments revealed significant impairments in the NR2A transgenic mice in long-term social memory of both male and female conspecifics. Additionally, the NR2A transgenic mice are unable to recognize mice of another strain or rats. The NR2A transgenic mice also exhibited long-term memory impairments in the olfactory recognition task. Taken together, our results provide evidence that an increased NR2A:NR2B ratio in the forebrain leads to reduced long-term memory function, including the ethologically important memories such as social recognition and olfactory memory.

Olfactory Function and Associated Clinical Correlates in Former National Football League Players

PubMed Central

Alosco, Michael L.; Jarnagin, Johnny; Tripodis, Yorghos; Platt, Michael; Martin, Brett; Chaisson, Christine E.; Baugh, Christine M.; Fritts, Nathan G.; Cantu, Robert C.

2017-01-01

Abstract Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40–69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health–funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction. PMID:27430424

Olfactory Function and Associated Clinical Correlates in Former National Football League Players.

PubMed

Alosco, Michael L; Jarnagin, Johnny; Tripodis, Yorghos; Platt, Michael; Martin, Brett; Chaisson, Christine E; Baugh, Christine M; Fritts, Nathan G; Cantu, Robert C; Stern, Robert A

2017-02-15

Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40-69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health-funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction.

Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

PubMed

Brünner, Yvonne F; Rodriguez-Raecke, Rea; Mutic, Smiljana; Benedict, Christian; Freiherr, Jessica

2016-10-01

This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance. Copyright © 2016 Elsevier Inc. All rights reserved.

Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase.

PubMed

Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya

2017-05-31

Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact. SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila , Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Copyright © 2017 the authors 0270-6474/17/375496-•$15.00/0.

An engram found? Evaluating the evidence from fruit flies.

PubMed

Gerber, Bertram; Tanimoto, Hiromu; Heisenberg, Martin

2004-12-01

Is it possible to localize a memory trace to a subset of cells in the brain? If so, it should be possible to show: first, that neuronal plasticity occurs in these cells. Second, that neuronal plasticity in these cells is sufficient for memory. Third, that neuronal plasticity in these cells is necessary for memory. Fourth, that memory is abolished if these cells cannot provide output during testing. And fifth, that memory is abolished if these cells cannot receive input during training. With regard to olfactory learning in flies, we argue that the notion of the olfactory memory trace being localized to the Kenyon cells of the mushroom bodies is a reasonable working hypothesis.

Circuit oscillations in odor perception and memory.

PubMed

Kay, Leslie M

2014-01-01

Olfactory system neural oscillations as seen in the local field potential have been studied for many decades. Recent research has shown that there is a functional role for the most studied gamma oscillations (40-100Hz in rats and mice, and 20Hz in insects), without which fine odor discrimination is poor. When these oscillations are increased artificially, fine discrimination is increased, and when rats learn difficult and highly overlapping odor discriminations, gamma is increased in power. Because of the depth of study on this oscillation, it is possible to point to specific changes in neural firing patterns as represented by the increase in gamma oscillation amplitude. However, we know far less about the mechanisms governing beta oscillations (15-30Hz in rats and mice), which are best associated with associative learning of responses to odor stimuli. These oscillations engage every part of the olfactory system that has so far been tested, plus the hippocampus, and the beta oscillation frequency band is the one that is most reliably coherent with other regions during odor processing. Respiratory oscillations overlapping with the theta frequency band (2-12Hz) are associated with odor sniffing and normal breathing in rats. They also show coupling in some circumstances between olfactory areas and rare coupling between the hippocampus and olfactory bulb. The latter occur in specific learning conditions in which coherence strength is negatively or positively correlated with performance, depending on the task. There is still much to learn about the role of neural oscillations in learning and memory, but techniques that have been brought to bear on gamma oscillations (current source density, computational modeling, slice physiology, behavioral studies) should deliver much needed knowledge of these events. © 2014 Elsevier B.V. All rights reserved.

Context-dependent memory: colour versus odour.

PubMed

Pointer, S C; Bond, N W

1998-06-01

An olfactory stimulus and a visual stimulus were employed in a context-dependent memory study using a prose passage as the to-be-remembered item. Ninety-five university students (aged 17-35 years) learned the passage of prose in the presence of one of the stimuli and were then asked to recall the passage with the original context either reinstated or not reinstated. The results revealed a significant context-dependent memory effect for the olfactory cue but not for the visual cue. They demonstrate support for the effectiveness of odours as context cues and it is suggested that context-dependent memory processes may underlie the formation and retrieval of odour-evoked autobiographical memories.

Drosophila Learn Opposing Components of a Compound Food Stimulus

PubMed Central

Das, Gaurav; Klappenbach, Martín; Vrontou, Eleftheria; Perisse, Emmanuel; Clark, Christopher M.; Burke, Christopher J.; Waddell, Scott

2014-01-01

Summary Dopaminergic neurons provide value signals in mammals and insects [1–3]. During Drosophila olfactory learning, distinct subsets of dopaminergic neurons appear to assign either positive or negative value to odor representations in mushroom body neurons [4–9]. However, it is not known how flies evaluate substances that have mixed valence. Here we show that flies form short-lived aversive olfactory memories when trained with odors and sugars that are contaminated with the common insect repellent DEET. This DEET-aversive learning required the MB-MP1 dopaminergic neurons that are also required for shock learning [7]. Moreover, differential conditioning with DEET versus shock suggests that formation of these distinct aversive olfactory memories relies on a common negatively reinforcing dopaminergic mechanism. Surprisingly, as time passed after training, the behavior of DEET-sugar-trained flies reversed from conditioned odor avoidance into odor approach. In addition, flies that were compromised for reward learning exhibited a more robust and longer-lived aversive-DEET memory. These data demonstrate that flies independently process the DEET and sugar components to form parallel aversive and appetitive olfactory memories, with distinct kinetics, that compete to guide learned behavior. PMID:25042590

The relationship between smell identification and neuropsychological domains: Results from a sample of community-dwelling adults suspected of dementia.

PubMed

Goette, William F; Werry, Amy E; Schmitt, Andrew L

2018-08-01

This study aimed to test the theoretical relationships between smell identification and cognitive tasks based on existing neuroimaging and anatomical findings. Utilizing data collected from a memory assessment clinic, theory-derived mediation and moderation models were tested. The sample used in this study consisted of 103 (39 male, 64 female) individuals referred for memory assessments. The sample's mean education was 12.4 years (SD = 3.2), and the mean age of the sample was 77.2 years (SD = 6.3). The University of Pennsylvania Smell Identification Test (UPSIT) was a significant, partial mediator of the relationship between the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Immediate and Delayed Memory indexes. Olfactory identification did not mediate list learning and retrieval; however, olfactory identification was a significant partial mediator of the relationship between story encoding and later memory retrieval of the story. Olfactory identification also fully mediated the relationship between a visuospatial construction task and its reconstruction from memory after a short delay. The relationship between processing speed and the olfactory identification was significantly mediated by semantic memory. Finally, the UPSIT moderated the relationship between a measure of premorbid ability, the Wechsler Test of Adult Reading, and current global cognitive functioning. Our results support theoretical relationships between olfaction and neuropsychological domains. Additionally, our results suggest that the UPSIT may serve as a proxy for cerebral integrity and is likely related to the duration of neurodegeneration.

Directional coupling from the olfactory bulb to the hippocampus during a go/no-go odor discrimination task.

PubMed

Gourévitch, Boris; Kay, Leslie M; Martin, Claire

2010-05-01

The hippocampus and olfactory regions are anatomically close, and both play a major role in memory formation. However, the way they interact during odor processing is still unclear. In both areas, strong oscillations of the local field potential (LFP) can be recorded, and are modulated by behavior. In particular, in the olfactory system, the beta rhythm (15-35 Hz) is associated with cognitive processing of an olfactory stimulus. Using LFP recordings in the olfactory bulb and dorsal and ventral hippocampus during performance of an olfactory go/no-go task in rats, we previously showed that beta oscillations are also present in the hippocampus, coherent with those in the olfactory bulb, during odor sampling. In this study, we provide further insight into information transfer in the olfacto-hippocampal network by using directional coherence (DCOH estimate), a method based on the temporal relation between two or more signals in the frequency domain. In the theta band (6-12 Hz), coherence between the olfactory bulb (OB) and the hippocampus (HPC) is weak and can be both in the feedback and feedforward directions. However, at this frequency, modulation of the coupling between the dorsal and ventral hippocampus is seen during stimulus expectation versus odor processing. In the beta frequency band (15-35 Hz), analysis showed a strong unidirectional coupling from the OB to dorsal and ventral HPC, indicating that, during odor processing, beta oscillations in the hippocampus are driven by the olfactory bulb.

Reference memory, anxiety and estrous cyclicity in C57BL/6NIA mice are affected by age and sex.

PubMed

Frick, K M; Burlingame, L A; Arters, J A; Berger-Sweeney, J

2000-01-01

Age-related changes in learning and memory are common in rodents. However, direct comparisons of the effects of aging on learning and memory in both males and females are lacking. The present study examined whether memory deteriorates with increasing age in C57BL/6NIA mice, and whether age-related changes in learning and memory are similar in both sexes. Male and female mice (five, 17 and 25 months of age) were tested in a battery of behavioral tasks including the Morris water maze (spatial and non-spatial reference memory), simple odor discrimination (olfactory reference memory), plus maze (anxiety/exploration), locomotor activity, and basic reflexes. Five-month-old mice learned the water maze and odor discrimination tasks rapidly. Relative to five-month-old mice, 25-month-old mice exhibited impaired spatial and olfactory reference memory, but intact non-spatial reference memory. The spatial reference memory of 17-month-old mice was also impaired, but less so than 25-month mice. Seventeen-month-old mice exhibited intact non-spatial (visual and olfactory) reference memory. Five and 25-month-old mice had similar levels of plus maze exploration and locomotor activity, whereas 17-month-old mice were more active than both groups and were slightly less exploratory than five-month-old mice. Although sex differences were not observed in the five- and 25-month groups, 17-month-old females exhibited more impaired spatial reference memory and increased anxiety relative to 17-month-old males. Estrous cycling in females deteriorated significantly with increased age; all 25-month-old females had ceased cycling and 80% of 17-month-old females displayed either irregular or absent estrous cycling. This study is the first to directly compare age-related mnemonic decline in male and female mice. The results suggest that: (i) aged mice exhibit significant deficits in spatial and olfactory reference memory relative to young mice, whereas middle-aged mice exhibit only a moderate spatial memory deficit and; (ii) spatial reference memory decline begins at an earlier age in females than in males, a finding that may be related to the cessation of estrous cycling.

DNA methylation mediates neural processing after odor learning in the honeybee

PubMed Central

Biergans, Stephanie D.; Claudianos, Charles; Reinhard, Judith; Galizia, C. Giovanni

2017-01-01

DNA methyltransferases (Dnmts) - epigenetic writers catalyzing the transfer of methyl-groups to cytosine (DNA methylation) – regulate different aspects of memory formation in many animal species. In honeybees, Dnmt activity is required to adjust the specificity of olfactory reward memories and bees’ relearning capability. The physiological relevance of Dnmt-mediated DNA methylation in neural networks, however, remains unknown. Here, we investigated how Dnmt activity impacts neuroplasticity in the bees’ primary olfactory center, the antennal lobe (AL) an equivalent of the vertebrate olfactory bulb. The AL is crucial for odor discrimination, an indispensable process in forming specific odor memories. Using pharmacological inhibition, we demonstrate that Dnmt activity influences neural network properties during memory formation in vivo. We show that Dnmt activity promotes fast odor pattern separation in trained bees. Furthermore, Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmt activity is necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network. PMID:28240742

Odor-Specific Habituation Arises from Interaction of Afferent Synaptic Adaptation and Intrinsic Synaptic Potentiation in Olfactory Cortex

ERIC Educational Resources Information Center

Linster, Christiane; Menon, Alka V.; Singh, Christopher Y.; Wilson, Donald A.

2009-01-01

Segmentation of target odorants from background odorants is a fundamental computational requirement for the olfactory system and is thought to be behaviorally mediated by olfactory habituation memory. Data from our laboratory have shown that odor-specific adaptation in piriform neurons, mediated at least partially by synaptic adaptation between…

Odour recognition memory and odour identification in patients with mild and severe major depressive disorders.

PubMed

Zucco, Gesualdo M; Bollini, Fabiola

2011-12-30

Olfactory deficits, in detection, recognition and identification of odorants have been documented in ageing and in several neurodegenerative and psychiatric conditions. However, olfactory abilities in Major Depressive Disorder (MDD) have been less investigated, and available studies have provided inconsistent results. The present study assessed odour recognition memory and odour identification in two groups of 12 mild MDD patients (M age 41.3, range 25-57) and 12 severe MDD patients (M age, 41.9, range 23-58) diagnosed according to DSM-IV criteria and matched for age and gender to 12 healthy normal controls. The suitability of olfactory identification and recognition memory tasks as predictors of the progression of MDD was also addressed. Data analyses revealed that Severe MDD patients performed significantly worse than Mild MDD patients and Normal controls on both tasks, with these last groups not differing significantly from one another. The present outcomes are consistent with previous studies in other domains which have shown reliable, although not conclusive, impairments in cognitive function, including memory, in patients with MDD, and highlight the role of olfactory identification and recognition tasks as an important additional tool to discriminate between patients characterised by different levels of severity of MDD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Odor-induced recall of emotional memories in PTSD-Review and new paradigm for research.

PubMed

Daniels, Judith K; Vermetten, Eric

2016-10-01

It is clinically well known that olfactory intrusions in PTSD can be a disabling phenomena due to the involuntary recall of odor memories. Odorants can trigger involuntary recall of emotional memories as well have the potential to help diminishing emotional arousal as grounding stimuli. Despite major advances in our understanding of the function of olfactory system, the study of the relation of olfaction and emotional memory is still relatively scarce. Odor memory is long thought to be different than other types of memories such as verbal or visual memories, being more strongly engraved and more closely related to strong emotions. Brain areas mediating smell memory including orbitofrontal cortex and other parts of medial prefrontal cortex, hippocampus and amygdala, have been implicated in learning and memory and are part of a neural circuitry that is involved in PTSD. The olfactory cortex itself also plays an important role in emotional processing. Clinical observations support the notion that odor-evoked memories can play a role in the symptomatology of PTSD. This paper reviews a re-emerging body of science linking odor processing to emotional processing in PTSD using the calming and grounding effect of odors as well as the use of odors in augmented exposure therapy. This results in converging evidence that olfaction is an excellent model for studying many questions germane to the field of human emotional memory processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Caffeine on Olfactory Learning in Crickets.

PubMed

Sugimachi, Seigo; Matsumoto, Yukihisa; Mizunami, Makoto; Okada, Jiro

2016-10-01

Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS functions in insects, we used an appetitive olfactory learning paradigm for the cricket Gryllus bimaculatus. Crickets can form significant long-term memories (LTMs) after repetitive training sessions, during which they associate a conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward). Administration of hemolymphal injections of caffeine established LTM after only single-trial conditioning over a wide range of caffeine dosages (1.6 µµg/kg to 39 mg/kg). We investigated the physiological mechanisms underlying this enhancement of olfactory learning performance pharmacologically, focusing on three major physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2) agonism of ryanodine receptors, and 3) antagonism of adenosine receptors. Application of drugs relevant to these actions resulted in significant effects on LTM formation. These results suggest that externally applied caffeine enhances LTM formation in insect olfactory learning via multiple cellular mechanisms.

Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb.

PubMed

Tong, Jia; Okutani, Fumino; Murata, Yoshihiro; Taniguchi, Mutsuo; Namba, Toshiharu; Wang, Yu-Jie; Kaba, Hideto

2017-03-06

Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory. Histological analyses revealed that TM infusion upregulated C/EBP homologous protein (CHOP), a marker of ER stress, in the mitral and granule cell layers of MOB. Electrophysiological data indicated that TM inhibited tetanus-induced long-term potentiation (LTP) at the dendrodendritic excitatory synapse from mitral to granule cells. A low dose of TM (250nM) abolished the late phase of LTP, and a high dose (1μM) inhibited the early and late phases of LTP. Further, high-dose, but not low-dose, TM reduced the paired-pulse facilitation ratio, suggesting that the inhibitory effects of TM on LTP are partially mediated through the presynaptic machinery. Thus, our results support the hypothesis that TM-induced ER stress impairs olfactory learning by inhibiting synaptic plasticity via presynaptic and postsynaptic mechanisms in MOB. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

PubMed

Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

2011-07-07

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

SEX DIFFERENCES AND REPRODUCTIVE HORMONE INFLUENCES ON HUMAN ODOR PERCEPTION

PubMed Central

Doty, Richard L.; Cameron, E. Leslie

2009-01-01

The question of whether men and women differ in their ability to smell has been the topic of scientific investigation for over a hundred years. Although conflicting findings abound, most studies suggest that, for at least some odorants, women outperform men on tests of odor detection, identification, discrimination, and memory. Most functional imaging and electrophysiological studies similarly imply that, when sex differences are present, they favor women. In this review we examine what is known about sex-related alterations in human smell function, including influences of the menstrual cycle, pregnancy, gonadectomy, and hormone replacement therapy on a range of olfactory measures. We conclude that the relationship between reproductive hormones and human olfactory function is complex and that simple associations between circulating levels of gonadal hormones and measures of olfactory function are rarely present. PMID:19272398

Apolipoprotein E4 causes early olfactory network abnormalities and short-term olfactory memory impairments.

PubMed

Peng, Katherine Y; Mathews, Paul M; Levy, Efrat; Wilson, Donald A

2017-02-20

While apolipoprotein (Apo) E4 is linked to increased incidence of Alzheimer's disease (AD), there is growing evidence that it plays a role in functional brain irregularities that are independent of AD pathology. However, ApoE4-driven functional differences within olfactory processing regions have yet to be examined. Utilizing knock-in mice humanized to ApoE4 versus the more common ApoE3, we examined a simple olfactory perceptual memory that relies on the transfer of information from the olfactory bulb (OB) to the piriform cortex (PCX), the primary cortical region involved in higher order olfaction. In addition, we have recorded in vivo resting and odor-evoked local field potentials (LPF) from both brain regions and measured corresponding odor response magnitudes in anesthetized young (6-month-old) and middle-aged (12-month-old) ApoE mice. Young ApoE4 compared to ApoE3 mice exhibited a behavioral olfactory deficit coinciding with hyperactive odor-evoked response magnitudes within the OB that were not observed in older ApoE4 mice. Meanwhile, middle-aged ApoE4 compared to ApoE3 mice exhibited heightened response magnitudes in the PCX without a corresponding olfactory deficit, suggesting a shift with aging in ApoE4-driven effects from OB to PCX. Interestingly, the increased ApoE4-specific response in the PCX at middle-age was primarily due to a dampening of baseline spontaneous activity rather than an increase in evoked response power. Our findings indicate that early ApoE4-driven olfactory memory impairments and OB network abnormalities may be a precursor to later network dysfunction in the PCX, a region that not only is targeted early in AD, but may be selectively vulnerable to ApoE4 genotype. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neuropeptide F neurons modulate sugar reward during associative olfactory learning of Drosophila larvae.

PubMed

Rohwedder, Astrid; Selcho, Mareike; Chassot, Bérénice; Thum, Andreas S

2015-12-15

All organisms continuously have to adapt their behavior according to changes in the environment in order to survive. Experience-driven changes in behavior are usually mediated and maintained by modifications in signaling within defined brain circuits. Given the simplicity of the larval brain of Drosophila and its experimental accessibility on the genetic and behavioral level, we analyzed if Drosophila neuropeptide F (dNPF) neurons are involved in classical olfactory conditioning. dNPF is an ortholog of the mammalian neuropeptide Y, a highly conserved neuromodulator that stimulates food-seeking behavior. We provide a comprehensive anatomical analysis of the dNPF neurons on the single-cell level. We demonstrate that artificial activation of dNPF neurons inhibits appetitive olfactory learning by modulating the sugar reward signal during acquisition. No effect is detectable for the retrieval of an established appetitive olfactory memory. The modulatory effect is based on the joint action of three distinct cell types that, if tested on the single-cell level, inhibit and invert the conditioned behavior. Taken together, our work describes anatomically and functionally a new part of the sugar reinforcement signaling pathway for classical olfactory conditioning in Drosophila larvae. © 2015 Wiley Periodicals, Inc.

[Changes in olfaction during ageing and in certain neurodegenerative diseases: up-to-date].

PubMed

Bianchi, A-J; Guépet-Sordet, H; Manckoundia, P

2015-01-01

Olfaction is a complex sensory system, and increasing interest is being shown in the link between olfaction and cognition, notably in the elderly. In this literature review, we revisit the specific neurophysiological features of the olfactory system and odorants that lead to a durable olfactory memory and an emotional memory, for which the implicit component produces subconscious olfactory conditioning. Olfaction is known to affect cognitive abilities and mood. We also consider the impairment of olfactory function due to ageing and to neurodegenerative diseases, in particular Alzheimer's disease and Parkinson's disease, through anatomopathological changes in the peripheral and central olfactory structures. The high frequency of these olfactory disorders as well as their early occurrence in Alzheimer disease and Parkinson disease are in favour of their clinical detection in subjects suffering from these two neurodegenerative diseases. Finally, we analyse the impact of olfactory stimulation on cognitive performance and attention. Current observational data from studies in elderly patients with Alzheimer-type dementia are limited to multiple sensory stimulation methods, such as the Snoezelen method, and aromatherapy. These therapies have shown benefits for dementia-related mood and behaviour disorders in the short term, with few side effects. Since olfactory chemosensory stimulation may be beneficial, it may be proposed in patients with dementia, especially Alzheimer-type dementia, as a complementary or even alternative therapy to existing medical strategies. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Estimating Information Processing in a Memory System: The Utility of Meta-analytic Methods for Genetics.

PubMed

Yildizoglu, Tugce; Weislogel, Jan-Marek; Mohammad, Farhan; Chan, Edwin S-Y; Assam, Pryseley N; Claridge-Chang, Adam

2015-12-01

Genetic studies in Drosophila reveal that olfactory memory relies on a brain structure called the mushroom body. The mainstream view is that each of the three lobes of the mushroom body play specialized roles in short-term aversive olfactory memory, but a number of studies have made divergent conclusions based on their varying experimental findings. Like many fields, neurogenetics uses null hypothesis significance testing for data analysis. Critics of significance testing claim that this method promotes discrepancies by using arbitrary thresholds (α) to apply reject/accept dichotomies to continuous data, which is not reflective of the biological reality of quantitative phenotypes. We explored using estimation statistics, an alternative data analysis framework, to examine published fly short-term memory data. Systematic review was used to identify behavioral experiments examining the physiological basis of olfactory memory and meta-analytic approaches were applied to assess the role of lobular specialization. Multivariate meta-regression models revealed that short-term memory lobular specialization is not supported by the data; it identified the cellular extent of a transgenic driver as the major predictor of its effect on short-term memory. These findings demonstrate that effect sizes, meta-analysis, meta-regression, hierarchical models and estimation methods in general can be successfully harnessed to identify knowledge gaps, synthesize divergent results, accommodate heterogeneous experimental design and quantify genetic mechanisms.

Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees.

PubMed

Williamson, Sally M; Wright, Geraldine A

2013-05-15

Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes.

Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees

PubMed Central

Williamson, Sally M.; Wright, Geraldine A.

2013-01-01

SUMMARY Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes. PMID:23393272

Reorganization of neuronal circuits of the central olfactory system during postprandial sleep

PubMed Central

Yamaguchi, Masahiro; Manabe, Hiroyuki; Murata, Koshi; Mori, Kensaku

2013-01-01

Plastic changes in neuronal circuits often occur in association with specific behavioral states. In this review, we focus on an emerging view that neuronal circuits in the olfactory system are reorganized along the wake-sleep cycle. Olfaction is crucial to sustaining the animals' life, and odor-guided behaviors have to be newly acquired or updated to successfully cope with a changing odor world. It is therefore likely that neuronal circuits in the olfactory system are highly plastic and undergo repeated reorganization in daily life. A remarkably plastic feature of the olfactory system is that newly generated neurons are continually integrated into neuronal circuits of the olfactory bulb (OB) throughout life. New neurons in the OB undergo an extensive selection process, during which many are eliminated by apoptosis for the fine tuning of neuronal circuits. The life and death decision of new neurons occurs extensively during a short time window of sleep after food consumption (postprandial sleep), a typical daily olfactory behavior. We review recent studies that explain how olfactory information is transferred between the OB and the olfactory cortex (OC) along the course of the wake-sleep cycle. Olfactory sensory input is effectively transferred from the OB to the OC during waking, while synchronized top-down inputs from the OC to the OB are promoted during the slow-wave sleep. We discuss possible neuronal circuit mechanisms for the selection of new neurons in the OB, which involves the encoding of olfactory sensory inputs and memory trace formation during waking and internally generated activities in the OC and OB during subsequent sleep. The plastic changes in the OB and OC are well coordinated along the course of olfactory behavior during wakefulness and postbehavioral rest and sleep. We therefore propose that the olfactory system provides an excellent model in which to understand behavioral state-dependent plastic mechanisms of the neuronal circuits in the brain. PMID:23966911

Adult Mammalian Neurogenesis and Motivated Behaviors.

PubMed

Jorgensen, Claudia

2018-05-31

Adult neurogenesis continues to captivate the curiosity of the scientific community; and researchers seem to have a particular interest in identifying the functional implications of such plasticity. While the majority of research focuses on the association between adult neurogenesis and learning and memory (including spatial learning associated with hippocampal neurogenesis and olfactory discrimination associated with neurogenesis in the olfactory system), the following review will explore the link to motivated behaviors. In particular, goal-directed behaviors such as sociosexual, parental, aggressive, as well as depression- and anxiety-like behaviors and their reciprocal association to adult neurogenesis will be evaluated. The review will detail research in humans and other mammalian species. Furthermore, the potential mechanisms underlying these neurogenic alterations will be highlighted. Lastly, the review will conclude with a discussion on the functional significance of these newly generated cells in mediating goal-directed behaviors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Olfaction Is Related to Motor Function in Older Adults.

PubMed

Tian, Qu; Resnick, Susan M; Studenski, Stephanie A

2017-08-01

Among older adults, both olfaction and motor function predict future cognitive decline and dementia, suggesting potential shared causal pathways. However, it is not known whether olfactory and motor function are independently related in late life. We assessed cross-sectional associations of olfaction with motor and cognitive function, using concurrent data on olfactory function, mobility, balance, fine motor function, manual dexterity, and cognition in 163 Baltimore Longitudinal Study of Aging participants aged 60 and older without common neurological diseases (n = 114 with available cognitive data). Using multiple linear regression, we adjusted for age, sex, race, smoking history, height, and weight for mobility and balance, and education for cognition. We used multiple linear regression to test whether olfaction-motor associations were independent of cognition and depressive symptoms. Olfactory scores were significantly associated with mobility (usual gait speed, rapid gait speed, 400-m walk time, and Health ABC Physical Performance Battery score), balance, fine motor function, and manual dexterity (all p < .05). In those with available cognitive data, additional adjustment for depressive symptoms, verbal memory, or visuoperceptual speed demonstrated especially strong independent relationships with challenging motor tasks such as 400-m walk and nondominant hand manual dexterity (p < .005). This study demonstrates for the first time that, in older adults, olfactory function is associated with mobility, balance, fine motor function, and manual dexterity, and independent of cognitive function, with challenging upper and lower extremity motor function tasks. Longitudinal studies are needed to determine if olfactory performance predicts future mobility and functional decline. Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

PubMed Central

2011-01-01

Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

Dynamics of memory-guided choice behavior in Drosophila

PubMed Central

ICHINOSE, Toshiharu; TANIMOTO, Hiromu

2016-01-01

Memory retrieval requires both accuracy and speed. Olfactory learning of the fruit fly Drosophila melanogaster serves as a powerful model system to identify molecular and neuronal substrates of memory and memory-guided behavior. The behavioral expression of olfactory memory has traditionally been tested as a conditioned odor response in a simple T-maze, which measures the result, but not the speed, of odor choice. Here, we developed multiplexed T-mazes that allow video recording of the choice behavior. Automatic fly counting in each arm of the maze visualizes choice dynamics. Using this setup, we show that the transient blockade of serotonergic neurons slows down the choice, while leaving the eventual choice intact. In contrast, activation of the same neurons impairs the eventual performance leaving the choice speed unchanged. Our new apparatus contributes to elucidating how the speed and the accuracy of memory retrieval are implemented in the fly brain. PMID:27725473

Traces of Drosophila Memory

PubMed Central

Davis, Ronald L.

2012-01-01

Summary Studies using functional cellullar imaging of living flies have identified six memory traces that form in the olfactory nervous system after conditioning with odors. These traces occur in distinct nodes of the olfactory nervous system, form and disappear across different windows of time, and are detected in the imaged neurons as increased calcium influx or synaptic release in response to the conditioned odor. Three traces form at, or near acquisition and co-exist with short-term behavioral memory. One trace forms with a delay after learning and co-exists with intermediate-term behavioral memory. Two traces form many hours after acquisition and co-exist with long-term behavioral memory. The transient memory traces may support behavior across the time-windows of their existence. The experimental approaches for dissecting memory formation in the fly, ranging from the molecular to the systems, make it an ideal system for dissecting the logic by which the nervous system organizes and stores different temporal forms of memory. PMID:21482352

Acute ethanol ingestion impairs appetitive olfactory learning and odor discrimination in the honey bee

PubMed Central

Mustard, Julie A; Wright, Geraldine A; Edgar, Elaina A; Mazade, Reece E.; Wu, Chen; Lillvis, Joshua L

2008-01-01

Invertebrates are valuable models for increasing our understanding of the effects of ethanol on the nervous system, but most studies on invertebrates and ethanol have focused on the effects of ethanol on locomotor behavior. In this work we investigate the influence of an acute dose of ethanol on appetitive olfactory learning in the honey bee (Apis mellifera), a model system for learning and memory. Adult worker honey bees were fed a range of doses (2.5, 5, 10 or 25%) of ethanol and then conditioned to associate an odor with a sucrose reward using either a simple or differential conditioning paradigm. Consumption of ethanol before conditioning significantly reduced both the rate of acquisition and the asymptotic strength of the association. Honey bees also exhibited a dose dependent reduction in arousal/attention during conditioning. Consumption of ethanol after conditioning did not affect recall 24 h later. The observed deficits in acquisition were not due to the affect of ethanol on gustatory sensitivity or motor function. However, honey bees given higher doses of ethanol had difficulty discriminating amongst different odors suggesting that ethanol consumption influences olfactory processing. Taken together, these results demonstrate that an acute dose of ethanol affects appetitive learning and olfactory perception in the honey bee. PMID:18723103

The impact of expertise in olfaction

PubMed Central

Royet, Jean-Pierre; Plailly, Jane; Saive, Anne-Lise; Veyrac, Alexandra; Delon-Martin, Chantal

2013-01-01

Olfactory expertise remains poorly understood, most likely because experts in odor, such as perfumers, sommeliers, and oenologists, are much rarer than experts in other modalities, such as musicians or sportsmen. In this review, we address the specificities of odor expertise in both odor experts and in a priori untrained individuals who have undergone specific olfactory training in the frame of an experiment, such as repeated exposure to odors or associative learning. Until the 21st century, only the behavioral effects of olfactory training of untrained control individuals had been reported, revealing an improvement of olfactory performance in terms of sensitivity, discrimination, memory, and identification. Behavioral studies of odor experts have been scarce, with inconsistent or inconclusive results. Recently, the development of cerebral imaging techniques has enabled the identification of brain areas and neural networks involved in odor processing, revealing functional and structural modifications as a function of experience. The behavioral approach to odor expertise has also evolved. Researchers have particularly focused on odor mental imagery, which is characteristic of odor experts, because this ability is absent in the average person but is part of a perfumer’s professional practice. This review summarizes behavioral, functional, and structural findings on odor expertise. These data are compared with those obtained using animals subjected to prolonged olfactory exposure or to olfactory-enriched environments and are discussed in the context of functional and structural plasticity. PMID:24379793

Role of olfactory bulb serotonin in olfactory learning in the greater short-nosed fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae).

PubMed

Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Haupt, Moritz; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2010-09-17

The role of olfactory bulb (OB) serotonin [5-hydroxytryptamine (5-HT)] in olfactory learning and memory was tested in the greater short-nosed fruit bat, Cynopterus sphinx (family Pteropodidae). Graded concentrations (25, 40, and 60microg) of 5,7-dihydroxytryptamine (5,7-DHT) or saline were injected into the OB of bats one day before training to the novel odor. In a behavioral test, 5,7-DHT (60microg) injected bats made significantly fewer feeding attempts and bouts when compared to saline-injected bats during learning and in the memory test. Subsequent biochemical analysis showed that 5-HT level was effectively depleted in the OB of 5,7-DHT injected bats. To test odor-induced 5-HT mediated changes in 5-HT receptors and second messenger cascade in the OB, we examined the expression of 5-HT receptors and mitogen-activated protein kinase (MAPK)/Erk cascade after training to the novel odor. We found that odor stimulation up-regulated the expression of 5-HT(1A) receptor, Erk1 and Creb1 mRNA, and phosphorylation of ERK1 and CREB1. Odor stimulation failed to induce expression in 5-HT-depleted bats, which is similar to control bats and significantly low compared to saline-treated bats. Together these data revealed that the level of 5-HT in the OB may regulate olfactory learning and memory in C. sphinx through Erk and CREB.

ESTROGEN REPLACEMENT THERAPY INDUCES FUNCTIONAL ASYMMETRY ON AN ODOR MEMORY/DISCRIMINATION TEST

PubMed Central

Doty, Richard L.; Kisat, Mehreen; Tourbier, Isabelle

2008-01-01

The secondary afferents of the olfactory system largely project to the ipsilateral cortex without synapsing in the thalamus, making unilateral olfactory testing a useful probe of ipsilateral hemispheric activity. In light of evidence that lateralized performance on some perceptual tasks may be influenced by estrogen, we assessed left:right nostril differences in two measures of olfactory function in 14 post-menopausal women receiving estrogen replacement therapy (ERT) and 48 post-menopausal women receiving no such therapy. Relative to women not taking ERT, those receiving ERT exhibited better performance in the left nostril and poorer performance in the right nostril on an odor memory/discrimination test. Similar laterality effects were not observed for an odor detection threshold test employing phenyl ethyl alcohol. These results suggest that estrogen influences the lateralization of an odor memory/discrimination task and that hormone replacement therapy in the menopause may be an excellent paradigm for understanding lateralizing effects of hormones on some sensory processes. PMID:18466883

Involvement of hormones in olfactory imprinting and homing in chum salmon.

PubMed

Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko

2016-02-16

The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker.

Odor-enriched environment rescues long-term social memory, but does not improve olfaction in social isolated adult mice.

PubMed

Gusmão, Isabela D; Monteiro, Brisa M M; Cornélio, Guilherme O S; Fonseca, Cristina S; Moraes, Márcio F D; Pereira, Grace S

2012-03-17

Prolonged permanence of animals under social isolation (SI) arouses a variety of psychological symptoms like aggression, stress, anxiety and depression. However, short-term SI is commonly used to evaluate social memory. Interestingly, the social memory cannot be accessed with delays higher than 30min in SI mice. Our hypothesis is that SI with intermediate duration, like one week (1w), impairs the long-term storage of new social information (S-LTM), without affecting anxiety or other types of memories, because the SI compromises the olfactory function of the animal. Our results demonstrated that SI impaired S-LTM, without affecting other kinds of memory or anxiety. In addition, the SI increased the latency in the buried-food finding task, but did not affect the habituation or the discrimination of odors. Next, we postulated that if continuous input to the olfactory system is fundamental for the maintenance of the olfactory function and social memory persistence, isolated mice under odor-enriched environment (OEE) should behave like group-housed (GH) animals. In fact, the OEE prevented the S-LTM deficit imposed by the SI. However, OEE did not restore the SI mice olfaction to the GH mice level. Our results suggest that SI modulates olfaction and social memory persistence, probably, by independent mechanisms. We also showed for the first time that OEE rescued S-LTM in SI mice through a mechanism not necessarily involved with olfaction. Copyright © 2011 Elsevier B.V. All rights reserved.

Olfactory discrimination deficits in mice lacking the dopamine transporter or the D2 dopamine receptor.

PubMed

Tillerson, Jennifer L; Caudle, W Michael; Parent, Jack M; Gong, C; Schallert, Timothy; Miller, Gary W

2006-09-15

Previous pharmacological studies have implicated dopamine as a modulator of olfactory bulb processing. Several disorders characterized by altered dopamine homeostasis in olfaction-related brain regions display olfactory deficits. To further characterize the role of dopamine in olfactory processing, we subjected dopamine transporter knockout mice (DAT -/-) and dopamine receptor 2 knockout mice (D2 -/-) to a battery of olfactory tests. In addition to behavioral characterization, several neurochemical markers of olfactory bulb integrity and function were examined. DAT -/- mice displayed an olfactory discrimination deficit, but did not differ detectably from DAT wildtype (DAT +/+) mice in odor habituation, olfactory sensitivity, or odor recognition memory. Neurochemically, DAT -/- mice have decreased D2 receptor staining in the periglomerular layer of the olfactory bulb and increased tyrosine hydroxylase immunoreactivity compared to DAT +/+ controls. D2 -/- mice exhibited the same olfactory deficit as the DAT -/- mice, further supporting the role of dopamine at the D2 synapse in olfactory discrimination processing. The findings presented in this paper reinforce the functional significance of dopamine and more specifically the D2 receptor in olfactory discrimination and may help explain the behavioral phenotype in the DAT and D2 knockout mice.

Proteomics Reveals the Molecular Underpinnings of Stronger Learning and Memory in Eastern Compared to Western Bees*

PubMed Central

Meng, Lifeng; Huo, Xinmei; Feng, Mao; Fang, Yu; Han, Bin; Hu, Han; Wu, Fan; Li, Jianke

2018-01-01

The eastern (Apis cerana cerana, Acc) and western (Apis mellifera ligustica, Aml) honeybee are two major honeybee species. Surprisingly, little is known about the fundamental molecular neurobiology of brain suborgans of Acc and Aml. We characterized and compared the proteomes of mushroom bodies (MBs), antennal lobes (ALs) and optical lobes (OLs) in the brain of both species, and biologically validated the functions related to learning and memory. Acc and Aml have evolved similar proteome signatures in MBs and OLs to drive the domain-specific neural activities. In MBs of both species, commonly enriched and enhanced functional groups related to protein metabolism and Ca2+ transport relative to ALs and OLs, suggests that proteins and Ca2+ are vital for consolidating learning and memory via modulation of synaptic structure and signal transduction. Furthermore, in OLs of both species, the mainly enriched ribonucleoside metabolism suggests its vital role as second messenger in promoting phototransduction. Notably, in ALs of both species, distinct proteome settings have shaped to prime olfactory learning and memory. In ALs of Acc, this is supported by the enriched cytoskeleton organization to sustain olfactory signaling through modulation of plasticity in glomeruli and intracellular transport. In ALs of Aml, however, the enriched functional groups implicated in hydrogen ion transport are indicative of their importance in supporting olfactory processes by regulation of synaptic transmission. The biological confirmation of enhanced activities of protein metabolism and signal transduction in ALs and MBs of Acc relative to in Aml demonstrates that a stronger sense of olfactory learning and memory has evolved in Acc. The reported first in-depth proteome data of honeybee brain suborgans provide a novel insight into the molecular basis of neurobiology, and is potentially useful for further neurological studies in honeybees and other insects. PMID:29187519

Resistance to Interference of Olfactory Perceptual Learning

ERIC Educational Resources Information Center

Stevenson, Richard J.; Case, Trevor I.; Tomiczek, Caroline

2007-01-01

Olfactory memory is especially persistent. The current study explored whether this applies to a form of perceptual learning, in which experience of an odor mixture results in greater judged similarity between its elements. Experiment 1A contrasted 2 forms of interference procedure, "compound" (mixture AW, followed by presentation of new mixtures…

Chronically Increased G[subscript s][alpha] Signaling Disrupts Associative and Spatial Learning

ERIC Educational Resources Information Center

Bourtchouladze, Rusiko; Patterson, Susan L.; Kelly, Michele P.; Kreibich, Arati; Kandel, Eric R.; Abel, Ted

2006-01-01

The cAMP/PKA pathway plays a critical role in learning and memory systems in animals ranging from mice to "Drosophila" to "Aplysia." Studies of olfactory learning in "Drosophila" suggest that altered expression of either positive or negative regulators of the cAMP/PKA signaling pathway beyond a certain optimum range may be deleterious. Here we…

Olfactory stimuli as context cues in human memory.

PubMed

Cann, A; Ross, D A

1989-01-01

Olfactory stimuli were used as context cues in a recognition memory paradigm. Male college students were exposed to 50 slides of the faces of college females while in the presence of a pleasant or an unpleasant odor. During the acquisition phase, ratings of physical attractiveness of the slides were collected. After a 48-hr delay, a recognition test was given using the original 50 slides and 50 new slides. The recognition test was conducted with either the original odor or the alternative odor present. A no-odor control group did not receive olfactory cues. The attractiveness ratings indicated that the odor variations had no effect on these social judgments. Analyses of d' scores, hits, and false alarms for the recognition performance indicated support for the predicted interaction in which presence of the same odor at both sessions led to better overall performance.

Multimodal retrieval of autobiographical memories: sensory information contributes differently to the recollection of events.

PubMed

Willander, Johan; Sikström, Sverker; Karlsson, Kristina

2015-01-01

Previous studies on autobiographical memory have focused on unimodal retrieval cues (i.e., cues pertaining to one modality). However, from an ecological perspective multimodal cues (i.e., cues pertaining to several modalities) are highly important to investigate. In the present study we investigated age distributions and experiential ratings of autobiographical memories retrieved with unimodal and multimodal cues. Sixty-two participants were randomized to one of four cue-conditions: visual, olfactory, auditory, or multimodal. The results showed that the peak of the distributions depends on the modality of the retrieval cue. The results indicated that multimodal retrieval seemed to be driven by visual and auditory information to a larger extent and to a lesser extent by olfactory information. Finally, no differences were observed in the number of retrieved memories or experiential ratings across the four cue-conditions.

Roles of Aminergic Neurons in Formation and Recall of Associative Memory in Crickets

PubMed Central

Mizunami, Makoto; Matsumoto, Yukihisa

2010-01-01

We review recent progress in the study of roles of octopaminergic (OA-ergic) and dopaminergic (DA-ergic) signaling in insect classical conditioning, focusing on our studies on crickets. Studies on olfactory learning in honey bees and fruit-flies have suggested that OA-ergic and DA-ergic neurons convey reinforcing signals of appetitive unconditioned stimulus (US) and aversive US, respectively. Our work suggested that this is applicable to olfactory, visual pattern, and color learning in crickets, indicating that this feature is ubiquitous in learning of various sensory stimuli. We also showed that aversive memory decayed much faster than did appetitive memory, and we proposed that this feature is common in insects and humans. Our study also suggested that activation of OA- or DA-ergic neurons is needed for appetitive or aversive memory recall, respectively. To account for this finding, we proposed a model in which it is assumed that two types of synaptic connections are strengthened by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus (CS) to neurons inducing conditioned response and the other being connections from neurons representing CS to OA- or DA-ergic neurons representing appetitive or aversive US, respectively. The former is called stimulus–response (S–R) connection and the latter is called stimulus–stimulus (S–S) connection by theorists studying classical conditioning in vertebrates. Results of our studies using a second-order conditioning procedure supported our model. We propose that insect classical conditioning involves the formation of S–S connection and its activation for memory recall, which are often called cognitive processes. PMID:21119781

Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of odors.

PubMed

Trellakis, Sokratis; Tagay, Sefik; Fischer, Cornelia; Rydleuskaya, Alena; Scherag, André; Bruderek, Kirsten; Schlegl, Sandra; Greve, Jens; Canbay, Ali E; Lang, Stephan; Brandau, Sven

2011-02-25

Several lines of evidence point to a close relationship between the hormones of energy homeostasis and the olfactory system. Examples are the localization of leptin and adiponectin receptors in the olfactory system or increased activation of brain regions related to the palatability and the hedonic value of food in response to food pictures after application of ghrelin. In this preliminary study, we tested in 31 subjects (17 male and 14 female) if and to what extent the peripheral blood concentrations of "satiety" hormones, such as leptin, adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings of odor pleasantness and with the objective olfactory and gustatory ability. The hedonic values of some odors were found to be differently rated between donors depending on gender and body weight. The concentrations of leptin, adiponectin and total ghrelin were significantly associated with the hedonic value of pepper black oil, but failed to show significant correlations for 5 other odors tested. Except for a significant association between leptin and odor identification, hormone concentrations were not linked to the abilities of smell and taste. Peripheral adipokines and gut hormones may alter the perception and pleasantness of specific odors, presumably either directly through their receptors in the olfactory system or indirectly through central interfaces between the regulation systems of olfaction, appetite control, memory and motivation. Copyright © 2010 Elsevier B.V. All rights reserved.

Neonicotinoid-induced impairment of odour coding in the honeybee

PubMed Central

Andrione, Mara; Vallortigara, Giorgio; Antolini, Renzo; Haase, Albrecht

2016-01-01

Exposure to neonicotinoid pesticides is considered one of the possible causes of honeybee (Apis mellifera) population decline. At sublethal doses, these chemicals have been shown to negatively affect a number of behaviours, including performance of olfactory learning and memory, due to their interference with acetylcholine signalling in the mushroom bodies. Here we provide evidence that neonicotinoids can affect odour coding upstream of the mushroom bodies, in the first odour processing centres of the honeybee brain, i.e. the antennal lobes (ALs). In particular, we investigated the effects of imidacloprid, the most common neonicotinoid, in the AL glomeruli via in vivo two-photon calcium imaging combined with pulsed odour stimulation. Following acute imidacloprid treatment, odour-evoked calcium response amplitude in single glomeruli decreases, and at the network level the representations of different odours are no longer separated. This demonstrates that, under neonicotinoid influence, olfactory information might reach the mushroom bodies in a form that is already incorrect. Thus, some of the impairments in olfactory learning and memory caused by neonicotinoids could, in fact, arise from the disruption in odor coding and olfactory discrimination ability of the honey bees. PMID:27905515

Odour discrimination learning in the Indian greater short-nosed fruit bat (Cynopterus sphinx): differential expression of Egr-1, C-fos and PP-1 in the olfactory bulb, amygdala and hippocampus.

PubMed

Mukilan, Murugan; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2018-06-15

Activity-dependent expression of immediate-early genes (IEGs) is induced by exposure to odour. The present study was designed to investigate whether there is differential expression of IEGs ( Egr-1 , C-fos ) in the brain region mediating olfactory memory in the Indian greater short-nosed fruit bat, Cynopterus sphinx We assumed that differential expression of IEGs in different brain regions may orchestrate a preference odour (PO) and aversive odour (AO) memory in C. sphinx We used preferred (0.8% w/w cinnamon powder) and aversive (0.4% w/v citral) odour substances, with freshly prepared chopped apple, to assess the behavioural response and induction of IEGs in the olfactory bulb, hippocampus and amygdala. After experiencing PO and AO, the bats initially responded to both, later only engaging in feeding bouts in response to the PO food. The expression pattern of EGR-1 and c-Fos in the olfactory bulb, hippocampus and amygdala was similar at different time points (15, 30 and 60 min) following the response to PO, but was different for AO. The response to AO elevated the level of c-Fos expression within 30 min and reduced it at 60 min in both the olfactory bulb and the hippocampus, as opposed to the continuous increase noted in the amygdala. In addition, we tested whether an epigenetic mechanism involving protein phosphatase-1 (PP-1) acts on IEG expression. The observed PP-1 expression and the level of unmethylated/methylated promoter revealed that C-fos expression is possibly controlled by odour-mediated regulation of PP-1. These results in turn imply that the differential expression of C-fos in the hippocampus and amygdala may contribute to olfactory learning and memory in C. sphinx . © 2018. Published by The Company of Biologists Ltd.

Parallel pathways for cross-modal memory retrieval in Drosophila.

PubMed

Zhang, Xiaonan; Ren, Qingzhong; Guo, Aike

2013-05-15

Memory-retrieval processing of cross-modal sensory preconditioning is vital for understanding the plasticity underlying the interactions between modalities. As part of the sensory preconditioning paradigm, it has been hypothesized that the conditioned response to an unreinforced cue depends on the memory of the reinforced cue via a sensory link between the two cues. To test this hypothesis, we studied cross-modal memory-retrieval processing in a genetically tractable model organism, Drosophila melanogaster. By expressing the dominant temperature-sensitive shibire(ts1) (shi(ts1)) transgene, which blocks synaptic vesicle recycling of specific neural subsets with the Gal4/UAS system at the restrictive temperature, we specifically blocked visual and olfactory memory retrieval, either alone or in combination; memory acquisition remained intact for these modalities. Blocking the memory retrieval of the reinforced olfactory cues did not impair the conditioned response to the unreinforced visual cues or vice versa, in contrast to the canonical memory-retrieval processing of sensory preconditioning. In addition, these conditioned responses can be abolished by blocking the memory retrieval of the two modalities simultaneously. In sum, our results indicated that a conditioned response to an unreinforced cue in cross-modal sensory preconditioning can be recalled through parallel pathways.

Internal Representation and Memory Formation of Odor Preference Based on Oscillatory Activities in a Terrestrial Slug

ERIC Educational Resources Information Center

Sekiguchi, Tatsuhiko; Furudate, Hiroyuki; Kimura, Tetsuya

2010-01-01

The terrestrial slug "Limax" exhibits a highly developed ability to learn odors with a small nervous system. When a fluorescent dye, Lucifer Yellow (LY), is injected into the slug's body cavity after odor-taste associative conditioning, a group of neurons in the procerebral (PC) lobe, an olfactory center of the slug, is labeled by LY. We examined…

Anosmia: Differential diagnosis, evaluation, and management.

PubMed

Scangas, George A; Bleier, Benjamin S

2017-01-01

The ability to scrutinize our surroundings remains heavily dependent on the sense of smell. From the ability to detect dangerous situations such as fires to the recollection of a fond memory triggered by an odor, the advantages of an intact olfactory system cannot be overstated. Outcomes studies have highlighted the profound negative impact of anosmia and parosmia on the overall quality of life. The National Institute on Deafness and Other Communication Disorders estimates that ∼1.4% of the United States population experiences chronic olfactory dysfunction and smell loss. Efforts have focused on improving both the diagnosis of olfactory dysfunction through olfactory testing and improved reporting of treatment outcomes of olfactory training. The purpose of this article was to review the differential diagnosis, workup, and current treatment strategies of anosmia and smell disorders.

Molecular mechanisms underlying formation of long-term reward memories and extinction memories in the honeybee (Apis mellifera)

PubMed Central

2014-01-01

The honeybee (Apis mellifera) has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates. PMID:25225299

Rapid learning dynamics in individual honeybees during classical conditioning.

PubMed

Pamir, Evren; Szyszka, Paul; Scheiner, Ricarda; Nawrot, Martin P

2014-01-01

Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3298 animals). We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response (CR) in learners, and the high stability of the CR during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24 h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla-Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled.

Rapid learning dynamics in individual honeybees during classical conditioning

PubMed Central

Pamir, Evren; Szyszka, Paul; Scheiner, Ricarda; Nawrot, Martin P.

2014-01-01

Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3298 animals). We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response (CR) in learners, and the high stability of the CR during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24 h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla–Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled. PMID:25309366

Olfactory function in psychotic disorders: Insights from neuroimaging studies

PubMed Central

Good, Kimberley P; Sullivan, Randii Lynn

2015-01-01

Olfactory deficits on measures of identification, familiarity, and memory are consistently noted in patients with psychotic disorders relative to age-matched controls. Olfactory intensity ratings, however, appear to remain intact while the data on hedonics and detection threshold are inconsistent. Despite the behavioral abnormalities noted, no specific regional brain hypoactivity has been identified in psychosis patients, for any of the olfactory domains. However, an intriguing finding emerged from this review in that the amygdala and pirifom cortices were not noted to be abnormal in hedonic processing (nor was the amygdala identified abnormal in any study) in psychotic disorders. This finding is in contrast to the literature in healthy individuals, in that this brain region is strongly implicated in olfactory processing (particularly for unpleasant odorants). Secondary olfactory cortex (orbitofrontal cortices, thalamus, and insula) was abnormally activated in the studies examined, particularly for hedonic processing. Further research, using consistent methodology, is required for better understanding the neurobiology of olfactory deficits. The authors suggest taking age and sex differences into consideration and further contrasting olfactory subgroups (impaired vs intact) to better our understanding of the heterogeneity of psychotic disorders. PMID:26110122

MiR-132 regulated olfactory bulb proteins linked to olfactory learning in greater short-nosed fruit bat Cynopterus sphinx.

PubMed

Mukilan, Murugan; Rajathei, David Mary; Jeyaraj, Edwin; Kayalvizhi, Nagarajan; Rajan, Koilmani Emmanuvel

2018-05-30

Earlier, we showed that micro RNA-132 (miR-132) regulate the immediate early genes (IEGs) in the olfactory bulb (OB) of fruit bat Cynopterus sphinx during olfactory learning. This study was designed to examine whether the miR-132 regulate other proteins in OB during olfactory learning. To test this, miR-132 anti-sense oligodeoxynucleotide (AS-ODN) was delivered to the OB and then trained to novel odor. The 2-dimensional gel electrophoresis analysis showed that inhibition of miR-132 altered olfactory training induced expression of 321 proteins. Further, liquid chromatography-mass spectrometry (LC-MS/MS) analysis reveals the identity of differently expressed proteins such as phosphoribosyl transferase domain containing protein (PRTFDC 1), Sorting nexin-8 (SNX8), Creatine kinase B-type (CKB) and Annexin A11 (ANX A11). Among them PRTFDC 1 showing 189 matching peptides with highest sequence coverage (67.0%) and protein-protein interaction analysis showed that PRTFDC 1 is a homolog of hypoxanthine phosphoribosyltransferase-1 (HPRT-1). Subsequent immunohistochemical analysis (IHC) showed that inhibition of miR-132 down-regulated HPRT expression in OB of C. sphinx. In addition, western blot analysis depicts that HPRT, serotonin transporter (SERT), N-methyl-d-asparate (NMDA) receptors (2A,B) were down-regulated, but not altered in OB of non-sense oligodeoxynucleotide (NS-ODN) infused groups. These analyses suggest that miR-132 regulates the process of olfactory learning and memory formation through SERT and NMDA receptors signalling, which is possibly associated with the PRTFDC1-HPRT interaction. Copyright © 2017. Published by Elsevier B.V.

Noise facilitation in associative memories of exponential capacity.

PubMed

Karbasi, Amin; Salavati, Amir Hesam; Shokrollahi, Amin; Varshney, Lav R

2014-11-01

Recent advances in associative memory design through structured pattern sets and graph-based inference algorithms have allowed reliable learning and recall of an exponential number of patterns that satisfy certain subspace constraints. Although these designs correct external errors in recall, they assume neurons that compute noiselessly, in contrast to the highly variable neurons in brain regions thought to operate associatively, such as hippocampus and olfactory cortex. Here we consider associative memories with boundedly noisy internal computations and analytically characterize performance. As long as the internal noise level is below a specified threshold, the error probability in the recall phase can be made exceedingly small. More surprising, we show that internal noise improves the performance of the recall phase while the pattern retrieval capacity remains intact: the number of stored patterns does not reduce with noise (up to a threshold). Computational experiments lend additional support to our theoretical analysis. This work suggests a functional benefit to noisy neurons in biological neuronal networks.

The propensity for consuming ethanol in Drosophila requires rutabaga adenylyl cyclase expression within mushroom body neurons

PubMed Central

Xu, Shiyu; Chan, Tammy; Shah, Vruntant; Zhang, Shixing; Pletcher, Scott D.; Roman, Gregg

2012-01-01

Alcohol activates reward systems through an unknown mechanism, in some cases leading to alcohol abuse and dependence. Herein, we utilized a two-choice Capillary Feeding assay to address the neural and molecular basis for ethanol self-administration in Drosophila melanogaster. Wild-type Drosophila demonstrates a significant preference for food containing between 5 and 15% ethanol. Preferred ethanol self-administration does not appear to be due to caloric advantage, nor due to perceptual biases, suggesting a hedonic bias for ethanol exists in Drosophila. Interestingly, rutabaga adenylyl cyclase expression within intrinsic mushroom body neurons is necessary for robust ethanol self-administration. The expression of rutabaga in mushroom bodies is also required for both appetitive and aversive olfactory associative memories, suggesting that reinforced behavior has an important role in the ethanol self-administration in Drosophila. However, rutabaga expression is required more broadly within the mushroom bodies for the preference for ethanol-containing food than for olfactory memories reinforced by sugar reward. Together these data implicate cAMP signaling and behavioral reinforcement for preferred ethanol self-administration in Drosophila melanogaster. PMID:22624869

Olfactory Cued Learning Paradigm.

PubMed

Liu, Gary; McClard, Cynthia K; Tepe, Burak; Swanson, Jessica; Pekarek, Brandon; Panneerselvam, Sugi; Arenkiel, Benjamin R

2017-05-05

Sensory stimulation leads to structural changes within the CNS (Central Nervous System), thus providing the fundamental mechanism for learning and memory. The olfactory circuit offers a unique model for studying experience-dependent plasticity, partly due to a continuous supply of integrating adult born neurons. Our lab has recently implemented an olfactory cued learning paradigm in which specific odor pairs are coupled to either a reward or punishment to study downstream circuit changes. The following protocol outlines the basic set up for our learning paradigm. Here, we describe the equipment setup, programming of software, and method of behavioral training.

Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila.

PubMed

Drago, Ilaria; Davis, Ronald L

2016-09-06

The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn)-a brain region critical for olfactory memory formation-causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

NMDA Receptors Mediate Olfactory Learning and Memory in Drosophila

PubMed Central

Xia, Shouzhen; Miyashita, Tomoyuki; Fu, Tsai-Feng; Lin, Wei-Yong; Wu, Chia-Lin; Pyzocha, Lori; Lin, Inn-Ray; Saitoe, Minoru; Tully, Tim; Chiang, Ann-Shyn

2011-01-01

Summary Background Molecular and electrophysiological properties of NMDARs suggest that they may be the Hebbian “coincidence detectors” hypothesized to underlie associative learning. Because of the nonspecificity of drugs that modulate NMDAR function or the relatively chronic genetic manipulations of various NMDAR subunits from mammalian studies, conclusive evidence for such an acute role for NMDARs in adult behavioral plasticity, however, is lacking. Moreover, a role for NMDARs in memory consolidation remains controversial. Results The Drosophila genome encodes two NMDAR homologs, dNR1 and dNR2. When coexpressed in Xenopus oocytes or Drosophila S2 cells, dNR1 and dNR2 form functional NMDARs with several of the distinguishing molecular properties observed for vertebrate NMDARs, including voltage/Mg2+-dependent activation by glutamate. Both proteins are weakly expressed throughout the entire brain but show preferential expression in several neurons surrounding the dendritic region of the mushroom bodies. Hypomorphic mutations of the essential dNR1 gene disrupt olfactory learning, and this learning defect is rescued with wild-type transgenes. Importantly, we show that Pavlovian learning is disrupted in adults within 15 hr after transient induction of a dNR1 antisense RNA transgene. Extended training is sufficient to overcome this initial learning defect, but long-term memory (LTM) specifically is abolished under these training conditions. Conclusions Our study uses a combination of molecular-genetic tools to (1) generate genomic mutations of the dNR1 gene, (2) rescue the accompanying learning deficit with a dNR1+ transgene, and (3) rapidly and transiently knockdown dNR1+ expression in adults, thereby demonstrating an evolutionarily conserved role for the acute involvement of NMDARs in associative learning and memory. PMID:15823532

NMDA receptors mediate olfactory learning and memory in Drosophila.

PubMed

Xia, Shouzhen; Miyashita, Tomoyuki; Fu, Tsai-Feng; Lin, Wei-Yong; Wu, Chia-Lin; Pyzocha, Lori; Lin, Inn-Ray; Saitoe, Minoru; Tully, Tim; Chiang, Ann-Shyn

2005-04-12

Molecular and electrophysiological properties of NMDARs suggest that they may be the Hebbian "coincidence detectors" hypothesized to underlie associative learning. Because of the nonspecificity of drugs that modulate NMDAR function or the relatively chronic genetic manipulations of various NMDAR subunits from mammalian studies, conclusive evidence for such an acute role for NMDARs in adult behavioral plasticity, however, is lacking. Moreover, a role for NMDARs in memory consolidation remains controversial. The Drosophila genome encodes two NMDAR homologs, dNR1 and dNR2. When coexpressed in Xenopus oocytes or Drosophila S2 cells, dNR1 and dNR2 form functional NMDARs with several of the distinguishing molecular properties observed for vertebrate NMDARs, including voltage/Mg(2+)-dependent activation by glutamate. Both proteins are weakly expressed throughout the entire brain but show preferential expression in several neurons surrounding the dendritic region of the mushroom bodies. Hypomorphic mutations of the essential dNR1 gene disrupt olfactory learning, and this learning defect is rescued with wild-type transgenes. Importantly, we show that Pavlovian learning is disrupted in adults within 15 hr after transient induction of a dNR1 antisense RNA transgene. Extended training is sufficient to overcome this initial learning defect, but long-term memory (LTM) specifically is abolished under these training conditions. Our study uses a combination of molecular-genetic tools to (1) generate genomic mutations of the dNR1 gene, (2) rescue the accompanying learning deficit with a dNR1+ transgene, and (3) rapidly and transiently knockdown dNR1+ expression in adults, thereby demonstrating an evolutionarily conserved role for the acute involvement of NMDARs in associative learning and memory.

Cyclic Nucleotide-Gated Channels, Calmodulin, Adenylyl Cyclase, and Calcium/Calmodulin-Dependent Protein Kinase II Are Required for Late, but Not Early, Long-Term Memory Formation in the Honeybee

ERIC Educational Resources Information Center

Matsumoto, Yukihisa; Sandoz, Jean-Christophe; Devaud, Jean-Marc; Lormant, Flore; Mizunami, Makoto; Giurfa, Martin

2014-01-01

Memory is a dynamic process that allows encoding, storage, and retrieval of information acquired through individual experience. In the honeybee "Apis mellifera," olfactory conditioning of the proboscis extension response (PER) has shown that besides short-term memory (STM) and mid-term memory (MTM), two phases of long-term memory (LTM)…

The interaction of working memory and emotion in persons clinically at risk for psychosis: an fMRI pilot study.

PubMed

Pauly, Katharina; Seiferth, Nina Y; Kellermann, Thilo; Ruhrmann, Stephan; Daumann, Bianca; Backes, Volker; Klosterkötter, Joachim; Shah, N Jon; Schneider, Frank; Kircher, Tilo T; Habel, Ute

2010-07-01

Subtle emotional and cognitive dysfunctions may already be apparent in individuals at risk for psychosis. However, there is a paucity of research on the neural correlates of the interaction of both domains. It remains unclear whether those correlates are already dysfunctional before a transition to psychosis. We used functional magnetic resonance imaging to examine the interaction of working memory and emotion in 12 persons clinically at high risk for psychosis (CHR) and 12 healthy subjects individually matched for age, gender and parental education. Participants performed an n-back task while negative or neutral emotion was induced by olfactory stimulation. Although healthy and psychosis-prone subjects did not differ in their working memory performance or the evaluation of the induced emotion, decreased activations were found in CHR subjects in the superior parietal lobe and the precuneus during working memory and in the insula during emotion induction. Looking at the interaction, CHR subjects, showed decreased activation in the right superior temporal gyrus, which correlated negatively with psychopathological scores. Decreased activation was also found in the thalamus. However, an increase of activation emerged in several cerebellar regions. Dysfunctions in areas associated with controlling whether incoming information is linked to emotional content and in the integration of multimodal information might lead to compensatory activations of cerebellar regions known to be involved in olfactory and working memory processes. Our study underlines that cerebral dysfunctions related to cognitive and emotional processes, as well as their interaction, can emerge in persons with CHR, even in absence of behavioral differences. (c) 2009 Elsevier B.V. All rights reserved.

Both odor identification and ApoE-ε4 contribute to normative cognitive aging.

PubMed

Finkel, Deborah; Reynolds, Chandra A; Larsson, Maria; Gatz, Margaret; Pedersen, Nancy L

2011-12-01

Research indicates that apoliprotein E (ApoE) plays a role in the development of Alzheimer's disease (AD) and possibly in the cognitive decline associated with normative aging. More recently, researchers have shown that ApoE is expressed in olfactory brain structures, and a relationship among ApoE, AD, and olfactory function has been proposed. In the current analyses, we investigated the contribution of ApoE and odor identification in decline trajectories associated with normative cognitive aging in various domains, using longitudinal data on cognitive performance available from the Swedish Adoption/Twin Study of Aging. Data on both ApoE status and olfactory functioning were available from 455 individuals ranging in age from 50 to 88 years at the first measurement occasion. Odor identification was measured via a mailed survey. Cognitive performance was assessed in up to 5 waves of in-person testing covering a period of 16 years. Latent growth curve analyses incorporating odor identification and ApoE status indicated a main effect of odor identification on the performance level in three cognitive domains: verbal, memory, and speed. A main effect of ApoE on rates of decline after age 65 was found for verbal, spatial, and speed factors. The consistency of results across cognitive domains provides support for theories that posit central nervous system-wide origins of the olfaction-cognition-ApoE relationship; however, olfactory errors and APOE ε4 show unique and differential effects on cognitive trajectory features.

[Learning and memory in Drosophila: physiologic and genetic bases].

PubMed

Zhuravlev, A V; Nikitina, E A; Savvateeva-Popova, E V

2015-01-01

Elucidation of molecular mechanisms of cognitive functions is one of the major achievements in neurobiology. At most, this is due to the studies on the simple nervous systems, such as the CNS in Drosophila melanogaster. Many of its functional characteristics are pretty similar to higher vertebrates. Among these are: 1) evolutionary conservation of genes and molecular systems involved in the regulation of learning acquisition and memory formation; 2) presence of highly specialized and differentiated sensory, associative and motor centers; 3) utilization of similar modes of informational coding and analysis; 4) availability of major learning forms including non-associative, as well as associative learning; 5) diversity of different memories, including short-term- and protein synthesis- dependent long-term memory; 6) presence of aminergic reinforcement systems in the brain; 7) feed-back loops of circadian clocks, current organism experience and individual organism characters affecting cognitive process per se. In this review the main attention is paid to the two mostly studied Drosophila learning forms, namely to olfactory Iearning and courtship suppression conditioning (CCS). A separate consideration is given to the impacts of kynurenins and metabolite of actin remodeling signal cascade.

CaMKII knockdown affects both early and late phases of olfactory long-term memory in the honeybee.

PubMed

Scholl, Christina; Kübert, Natalie; Muenz, Thomas S; Rössler, Wolfgang

2015-12-01

Honeybees are able to solve complex learning tasks and memorize learned information for long time periods. The molecular mechanisms mediating long-term memory (LTM) in the honeybee Apis mellifera are, to a large part, still unknown. We approached this question by investigating the potential function of the calcium/calmodulin-dependent protein kinase II (CaMKII), an enzyme known as a 'molecular memory switch' in vertebrates. CaMKII is able to switch to a calcium-independent constitutively active state, providing a mechanism for a molecular memory and has further been shown to play an essential role in structural synaptic plasticity. Using a combination of knockdown by RNA interference and pharmacological manipulation, we disrupted the function of CaMKII during olfactory learning and memory formation. We found that learning, memory acquisition and mid-term memory were not affected, but all manipulations consistently resulted in an impaired LTM. Both early LTM (24 h after learning) and late LTM (72 h after learning) were significantly disrupted, indicating the necessity of CaMKII in two successive stages of LTM formation in the honeybee. © 2015. Published by The Company of Biologists Ltd.

Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

PubMed Central

Brunert, Daniela; Kurtenbach, Stefan; Isik, Sonnur; Benecke, Heike; Gisselmann, Günter; Schuhmann, Wolfgang; Hatt, Hanns; Wetzel, Christian H.

2009-01-01

The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis. PMID:19430528

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release

PubMed Central

Gupta, Varun K.; Pech, Ulrike; Fulterer, Andreas; Ender, Anatoli; Mauermann, Stephan F.; Andlauer, Till F. M.; Beuschel, Christine; Thriene, Kerstin; Quentin, Christine; Schwärzel, Martin; Mielke, Thorsten; Madeo, Frank; Dengjel, Joern; Fiala, André; Sigrist, Stephan J.

2016-01-01

Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse. PMID:27684064

Long-Term Memory Shapes the Primary Olfactory Center of an Insect Brain

ERIC Educational Resources Information Center

Hourcade, Benoit; Perisse, Emmanuel; Devaud, Jean-Marc; Sandoz, Jean-Christophe

2009-01-01

The storage of stable memories is generally considered to rely on changes in the functional properties and/or the synaptic connectivity of neural networks. However, these changes are not easily tractable given the complexity of the learning procedures and brain circuits studied. Such a search can be narrowed down by studying memories of specific…

Side-Specificity of Olfactory Learning in the Honeybee: Generalization between Odors and Sides

PubMed Central

Sandoz, Jean-Christophe; Menzel, Randolf

2001-01-01

Honeybees (Apis mellifera) can be trained to associate an odor stimulus with a sucrose reward. The neural structures involved in the detection and integration of olfactory stimuli are represented bilaterally in the brain. Little is known about the respective roles of the two sides of the brain in olfactory learning. Does each side learn independently of the other, or do they communicate, and if so, to what extent and at what level of neural integration? We addressed these questions using the proboscis extension response (PER) conditioning paradigm applied in a preparation that allows the separation of the two input sides during olfactory stimulations. Bees conditioned to two odorants A and B, one being learned on each side (A+/B+ training), showed in extinction tests rather unspecific responses: They responded to both odorants on both sides. This could be attributable to either a transfer of the learned information between sides, or to a generalization between odorants on each side. By subjecting bees to conditioning on one side only (A+/0 training), we found that the learned information is indeed transferred between sides. However, when bees were trained explicitly to give opposite values to the two odorants on the two sides (A+B−/B+A− training), they showed clear side-specific response patterns to these odorants. These results are used in the elaboration of a functional model of laterality of olfactory learning and memory processing in the honeybee brain. PMID:11584076

It takes two-coincidence coding within the dual olfactory pathway of the honeybee.

PubMed

Brill, Martin F; Meyer, Anneke; Rössler, Wolfgang

2015-01-01

To rapidly process biologically relevant stimuli, sensory systems have developed a broad variety of coding mechanisms like parallel processing and coincidence detection. Parallel processing (e.g., in the visual system), increases both computational capacity and processing speed by simultaneously coding different aspects of the same stimulus. Coincidence detection is an efficient way to integrate information from different sources. Coincidence has been shown to promote associative learning and memory or stimulus feature detection (e.g., in auditory delay lines). Within the dual olfactory pathway of the honeybee both of these mechanisms might be implemented by uniglomerular projection neurons (PNs) that transfer information from the primary olfactory centers, the antennal lobe (AL), to a multimodal integration center, the mushroom body (MB). PNs from anatomically distinct tracts respond to the same stimulus space, but have different physiological properties, characteristics that are prerequisites for parallel processing of different stimulus aspects. However, the PN pathways also display mirror-imaged like anatomical trajectories that resemble neuronal coincidence detectors as known from auditory delay lines. To investigate temporal processing of olfactory information, we recorded PN odor responses simultaneously from both tracts and measured coincident activity of PNs within and between tracts. Our results show that coincidence levels are different within each of the two tracts. Coincidence also occurs between tracts, but to a minor extent compared to coincidence within tracts. Taken together our findings support the relevance of spike timing in coding of olfactory information (temporal code).

Phenomenal and access consciousness in olfaction.

PubMed

Stevenson, Richard J

2009-12-01

Contemporary literature on consciousness, with some exceptions, rarely considers the olfactory system. In this article the characteristics of olfactory consciousness, viewed from the standpoint of the phenomenal (P)/access (A) distinction, are examined relative to the major senses. The review details several qualitative differences in both olfactory P consciousness (shifts in the felt location, universal synesthesia-like and affect-rich experiences, and misperceptions) and A consciousness (recovery from habituation, capacity for conscious processing, access to semantic and episodic memory, learning, attention, and in the serial-unitary nature of olfactory percepts). The basis for these differences is argued to arise from the functions that the olfactory system performs and from the unique neural architecture needed to instantiate them. These data suggest, at a minimum, that P and A consciousness are uniquely configured in olfaction and an argument can be made that the P and A distinction may not hold for this sensory system.

Olfactory Perceptual Learning Requires Action of Noradrenaline in the Olfactory Bulb: Comparison with Olfactory Associative Learning

ERIC Educational Resources Information Center

Vinera, Jennifer; Kermen, Florence; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie; Richard, Marion

2015-01-01

Noradrenaline contributes to olfactory-guided behaviors but its role in olfactory learning during adulthood is poorly documented. We investigated its implication in olfactory associative and perceptual learning using local infusion of mixed a1-ß adrenergic receptor antagonist (labetalol) in the adult mouse olfactory bulb. We reported that…

Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates.

PubMed

Vyhnalek, Martin; Magerova, Hana; Andel, Ross; Nikolai, Tomas; Kadlecova, Alexandra; Laczo, Jan; Hort, Jakub

2015-02-15

Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI. 75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination. Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (p<0.001), albeit also better than patients with mild AD (p<.001). In the aMCI group, higher scores on MMSE, verbal and non-verbal memory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI. Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI. Copyright © 2015. Published by Elsevier B.V.

(-)Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short-term social memory in rats.

PubMed

Tseng, Hsiang-Chien; Wang, Mao-Hsien; Soung, Hung-Sheng; Chang, Yi; Chang, Kuo-Chi

2015-12-01

Reserpine has been confirmed to induce cognitive dysfunction and increase brain neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3-gallate (EGCG), have strong antioxidative properties and can protect against numerous oxidative damages. In this study, we examined the possible protective effects of EGCG on reserpine-induced impairment of short-term memory in rats. Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using the social recognition task method; locomotor activity and the olfactory discrimination ability were not altered as measured by an open-field test and an olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg, intraperitoneal, for 7 days, starting 6 days before the reserpine injection) could improve the worsened social memory of reserpine-treated rats. Also, EGCG treatment reduced reserpine-induced lipid peroxidation and enhanced the antioxidation power in the hippocampi of reserpine-treated rats. These results suggest a protective effect of EGCG in treating reserpine-induced impairment of memory, most probably through its powerful antioxidative activities. Accordingly, EGCG may hold a clinically relevant value in preventing reserpine-induced cognitive dysfunction.

Rapid Consolidation to a radish and Protein Synthesis-Dependent Long-Term Memory after Single-Session Appetitive Olfactory Conditioning in Drosophila

PubMed Central

Krashes, Michael J.; Waddell, Scott

2008-01-01

In Drosophila, formation of aversive olfactory long-term memory (LTM) requires multiple training sessions pairing odor and electric shock punishment with rest intervals. In contrast, here we show that a single 2 min training session pairing odor with a more ethologically relevant sugar reinforcement forms long-term appetitive memory that lasts for days. Appetitive LTM has some mechanistic similarity to aversive LTM in that it can be disrupted by cycloheximide, the dCreb2-b transcriptional repressor, and the crammer and tequila LTM-specific mutations. However, appetitive LTM is completely disrupted by the radish mutation that apparently represents a distinct mechanistic phase of consolidated aversive memory. Furthermore, appetitive LTM requires activity in the dorsal paired medial neuron and mushroom body α′ β′ neuron circuit during the first hour after training and mushroom body αβ neuron output during retrieval, suggesting that appetitive middle-term memory and LTM are mechanistically linked. Last, experiments feeding and/or starving flies after training reveals a critical motivational drive that enables appetitive LTM retrieval. PMID:18354013

Memory-Relevant Mushroom Body Output Synapses Are Cholinergic.

PubMed

Barnstedt, Oliver; Owald, David; Felsenberg, Johannes; Brain, Ruth; Moszynski, John-Paul; Talbot, Clifford B; Perrat, Paola N; Waddell, Scott

2016-03-16

Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olfactory-driven behavior. Local ACh application, or direct Kenyon cell activation, evokes activity in mushroom body output neurons (MBONs). MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh receptor antagonism. Furthermore, reducing nicotinic ACh receptor subunit expression in MBONs compromises odor-evoked activation and redirects odor-driven behavior. Lastly, peptidergic corelease enhances ACh-evoked responses in MBONs, suggesting an interaction between the fast- and slow-acting transmitters. Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

PubMed Central

Shuai, Yichun; Hirokawa, Areekul; Ai, Yulian; Zhang, Min; Li, Wanhe; Zhong, Yi

2015-01-01

Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β′1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts. PMID:26627257

First demonstration of olfactory learning and long term memory in honey bee queens.

PubMed

Gong, Zhiwen; Tan, Ken; Nieh, James C

2018-05-18

As the primary source of colony reproduction, social insect queens play a vital role. However, the cognitive abilities of queens are not well understood, although queen learning and memory are essential in multiple species such as honey bees, in which virgin queens must leave the nest and then successful learn to navigate back over repeated nuptial flights. Honey bee queen learning has never been previously demonstrated. We therefore tested olfactory learning in queens and workers and examined the role of DNA methylation, which plays a key role in long term memory formation. We provide the first evidence that honey bee queens have excellent learning and memory. The proportion of honey bee queens that exhibited learning was 5-fold higher than workers at every tested age and, for memory, 4-fold higher than workers at a very young age. DNA methylation may play a key role in this queen memory because queens exhibiting remote memory had a more consistent elevation in Dnmt3 gene expression as compared to workers. Both castes also showed excellent remote memory (7 day memory), which was reduced by 14-20% by the DNA methylation inhibitor, zebularine. Given that queens live about 10-fold longer than workers, these results suggest that queens can serve as an excellently long-term reservoir of colony memory. © 2018. Published by The Company of Biologists Ltd.

Short-term memory in olfactory network dynamics

NASA Astrophysics Data System (ADS)

Stopfer, Mark; Laurent, Gilles

1999-12-01

Neural assemblies in a number of animal species display self-organized, synchronized oscillations in response to sensory stimuli in a variety of brain areas.. In the olfactory system of insects, odour-evoked oscillatory synchronization of antennal lobe projection neurons (PNs) is superimposed on slower and stimulus-specific temporal activity patterns. Hence, each odour activates a specific and dynamic projection neuron assembly whose evolution during a stimulus is locked to the oscillation clock. Here we examine, using locusts, the changes in population dynamics of projection-neuron assemblies over repeated odour stimulations, as would occur when an animal first encounters and then repeatedly samples an odour for identification or localization. We find that the responses of these assemblies rapidly decrease in intensity, while they show a marked increase in spike time precision and inter-neuronal oscillatory coherence. Once established, this enhanced precision in the representation endures for several minutes. This change is stimulus-specific, and depends on events within the antennal lobe circuits, independent of olfactory receptor adaptation: it may thus constitute a form of sensory memory. Our results suggest that this progressive change in olfactory network dynamics serves to converge, over repeated odour samplings, on a more precise and readily classifiable odour representation, using relational information contained across neural assemblies.

Odor preference and olfactory memory are impaired in Olfaxin-deficient mice.

PubMed

Islam, Saiful; Ueda, Masashi; Nishida, Emika; Wang, Miao-Xing; Osawa, Masatake; Lee, Dongsoo; Itoh, Masanori; Nakagawa, Kiyomi; Tana; Nakagawa, Toshiyuki

2018-06-01

Olfaxin, which is a BNIP2 and Cdc42GAP homology (BCH) domain-containing protein, is predominantly expressed in mitral and tufted (M/T) cells in the olfactory bulb (OB). Olfaxin and Caytaxin, which share 56.3% amino acid identity, are similar in their glutamatergic terminal localization, kidney-type glutaminase (KGA) interaction, and caspase-3 substrate. Although the deletion of Caytaxin protein causes human Cayman ataxia and ataxia in the mutant mouse, the function of Olfaxin is largely unknown. In this study, we generated Prune2 gene mutant mice (Prune2 Ex16-/- ; knock out [KO] mice) using the CRISPR/Cas9 system, during which the exon 16 containing start codon of Olfaxin mRNA was deleted. Exon 16 has 80 nucleotides and is contained in four of five Prune2 isoforms, including PRUNE2, BMCC1, BNIPXL, and Olfaxin/BMCC1s. The levels of Olfaxin mRNA and Olfaxin protein in the OB and piriform cortex of KO mice significantly decreased. Although Prune2 mRNA also significantly decreased in the spinal cord, the gross anatomy of the spinal cord and dorsal root ganglion (DRG) was intact. Further, disturbance of the sensory and motor system was not observed in KO mice. Therefore, in the current study, we examined the role of Olfaxin in the olfactory system where PRUNE2, BMCC1, and BNIPXL are scarcely expressed. Odor preference was impaired in KO mice using opposite-sex urinary scents as well as a non-social odor stimulus (almond). Results of the odor-aversion test demonstrated that odor-associative learning was disrupted in KO mice. Moreover, the NMDAR2A/NMDAR2B subunits switch in the piriform cortex was not observed in KO mice. These results indicated that Olfaxin may play a critical role in odor preference and olfactory memory. Copyright © 2018 Elsevier B.V. All rights reserved.

Serotonin–mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila

PubMed Central

Lee, Pei-Tseng; Lin, Hsuan-Wen; Chang, Yu-Hsuan; Fu, Tsai-Feng; Dubnau, Josh; Hirsh, Jay; Lee, Tzumin; Chiang, Ann-Shyn

2011-01-01

Pavlovian olfactory learning in Drosophila produces two genetically distinct forms of intermediate-term memories: anesthesia-sensitive memory, which requires the amnesiac gene, and anesthesia-resistant memory (ARM), which requires the radish gene. Here, we report that ARM is specifically enhanced or inhibited in flies with elevated or reduced serotonin (5HT) levels, respectively. The requirement for 5HT was additive with the memory defect of the amnesiac mutation but was occluded by the radish mutation. This result suggests that 5HT and Radish protein act on the same pathway for ARM formation. Three supporting lines of evidence indicate that ARM formation requires 5HT released from only two dorsal paired medial (DPM) neurons onto the mushroom bodies (MBs), the olfactory learning and memory center in Drosophila: (i) DPM neurons were 5HT-antibody immunopositive; (ii) temporal inhibition of 5HT synthesis or release from DPM neurons, but not from other serotonergic neurons, impaired ARM formation; (iii) knocking down the expression of d5HT1A serotonin receptors in α/β MB neurons, which are innervated by DPM neurons, inhibited ARM formation. Thus, in addition to the Amnesiac peptide required for anesthesia-sensitive memory formation, the two DPM neurons also release 5HT acting on MB neurons for ARM formation. PMID:21808003

Anosmia and Ageusia in Parkinson's Disease.

PubMed

Tarakad, Arjun; Jankovic, Joseph

2017-01-01

Anosmia, the loss of sense of smell, is a common nonmotor feature of Parkinson's disease (PD). Ageusia, the loss of sense of taste, is additionally an underappreciated nonmotor feature of PD. The olfactory tract is involved early in PD as indicated by frequent occurrence of hyposmia or anosmia years or decades before motor symptoms and by autopsy studies showing early synuclein pathology in the olfactory tract and anterior olfactory nucleus even in the early stages of PD. Testing for olfaction consists of evaluation of olfactory thresholds, smell identification and discrimination, and olfactory memory. Testing for gustation involves evaluating thresholds and discrimination of five basic tastes (salty, sweet, bitter, sour, and umami). The presence of a specific pattern of loss in both olfaction and gustation in PD has been proposed, but this has not yet been confirmed. Within PD, olfactory loss is strongly tied with cognitive status though links to other features of PD or a particular PD phenotype is debated. Hyposmia is more often present and typically more severe in PD patients than other parkinsonian syndromes, making it a potentially useful biomarker for the disease. © 2017 Elsevier Inc. All rights reserved.

Cognitive impairment and olfactory panic from occupational exposure to VOCs.

PubMed

Reinhartz, Abe

2006-10-01

A Canadian government clerical worker in her early thirties developed frontal lobe dysfunction from inhalation of volatile organic compounds off-gassed during an office renovation. Pulmonary function, bronchial provocation, allergy testing, and a brain (SPECT) scan were performed. SPECT scanning showed frontotemporal hypoperfusion and neuropsychologic testing revealed deficits in verbal learning and poor organizational memory. A significant component of this worker's impairment was the development of "olfactory panic," a debilitating aversion to odor accompanied by symptoms of panic. The Ontario Workplace Safety and Insurance Appeals Tribunal granted entitlement for her cognitive difficulties and olfactory panic as a result of her toxic exposure.

Biological complexity and adaptability of simple mammalian olfactory memory systems.

PubMed

Brennan, P; Keverne, E B

2015-03-01

Chemosensory systems play vital roles in the lives of most mammals, including the detection and identification of predators, as well as sex and reproductive status and the identification of individual conspecifics. All of these capabilities require a process of recognition involving a combination of innate (kairomonal/pheromonal) and learned responses. Across very different phylogenies, the mechanisms for pheromonal and odour learning have much in common. They are frequently associated with plasticity of GABA-ergic feedback at the initial level of processing the chemosensory information, which enhances its pattern separation capability. Association of odourant features into an odour object primarily involves anterior piriform cortex for non-social odours. However, the medial amygdala appears to be involved in both the recognition of social odours and their association with chemosensory information sensed by the vomeronasal system. Unusually not only the sensory neurons themselves, but also the GABA-ergic interneurons in the olfactory bulb are continually being replaced, with implications for the induction and maintenance of learned chemosensory responses. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Density of mushroom body synaptic complexes limits intraspecies brain miniaturization in highly polymorphic leaf-cutting ant workers

PubMed Central

Groh, Claudia; Kelber, Christina; Grübel, Kornelia; Rössler, Wolfgang

2014-01-01

Hymenoptera possess voluminous mushroom bodies (MBs), brain centres associated with sensory integration, learning and memory. The mushroom body input region (calyx) is organized in distinct synaptic complexes (microglomeruli, MG) that can be quantified to analyse body size-related phenotypic plasticity of synaptic microcircuits in these small brains. Leaf-cutting ant workers (Atta vollenweideri) exhibit an enormous size polymorphism, which makes them outstanding to investigate neuronal adaptations underlying division of labour and brain miniaturization. We particularly asked how size-related division of labour in polymorphic workers is reflected in volume and total numbers of MG in olfactory calyx subregions. Whole brains of mini, media and large workers were immunolabelled with anti-synapsin antibodies, and mushroom body volumes as well as densities and absolute numbers of MG were determined by confocal imaging and three-dimensional analyses. The total brain volume and absolute volumes of olfactory mushroom body subdivisions were positively correlated with head widths, but mini workers had significantly larger MB to total brain ratios. Interestingly, the density of olfactory MG was remarkably independent from worker size. Consequently, absolute numbers of olfactory MG still were approximately three times higher in large compared with mini workers. The results show that the maximum packing density of synaptic microcircuits may represent a species-specific limit to brain miniaturization. PMID:24807257

Age- and sex-related disturbance in a battery of sensorimotor and cognitive tasks in Kunming mice.

PubMed

Chen, Gui-Hai; Wang, Yue-Ju; Zhang, Li-Qun; Zhou, Jiang-Ning

2004-12-15

A battery of tasks, i.e. beam walking, open field, tightrope, radial six-arm water maze (RAWM), novel-object recognition and olfactory discrimination, was used to determine whether there was age- and sex-related memory deterioration in Kunming (KM) mice, and whether these tasks are independent or correlated with each other. Two age groups of KM mice were used: a younger group (7-8 months old, 12 males and 11 females) and an older group (17-18 months old, 12 males and 12 females). The results showed that the spatial learning ability and memory in the RAWM were lower in older female KM mice relative to younger female mice and older male mice. Consistent with this, in the novel-object recognition task, a non-spatial cognitive task, older female mice but not older male mice had impairment of short-term memory. In olfactory discrimination, another non-spatial task, the older mice retained this ability. Interestingly, female mice performed better than males, especially in the younger group. The older females exhibited sensorimotor impairment in the tightrope task and low locomotor activity in the open-field task. Moreover, older mice spent a longer time in the peripheral squares of the open-field than younger ones. The non-spatial cognitive performance in the novel-object recognition and olfactory discrimination tasks was related to performance in the open-field, whereas the spatial cognitive performance in the RAWM was not related to performance in any of the three sensorimotor tasks. These results suggest that disturbance of spatial learning and memory, as well as selective impairment of non-spatial learning and memory, existed in older female KM mice.

High-throughput olfactory conditioning and memory retention test show variation in Nasonia parasitic wasps

PubMed Central

Hoedjes, K M; Steidle, J L M; Werren, J H; Vet, L E M; Smid, H M

2012-01-01

Most of our knowledge on learning and memory formation results from extensive studies on a small number of animal species. Although features and cellular pathways of learning and memory are highly similar in this diverse group of species, there are also subtle differences. Closely related species of parasitic wasps display substantial variation in memory dynamics and can be instrumental to understanding both the adaptive benefit of and mechanisms underlying this variation. Parasitic wasps of the genus Nasonia offer excellent opportunities for multidisciplinary research on this topic. Genetic and genomic resources available for Nasonia are unrivaled among parasitic wasps, providing tools for genetic dissection of mechanisms that cause differences in learning. This study presents a robust, high-throughput method for olfactory conditioning of Nasonia using a host encounter as reward. A T-maze olfactometer facilitates high-throughput memory retention testing and employs standardized odors of equal detectability, as quantified by electroantennogram recordings. Using this setup, differences in memory retention between Nasonia species were shown. In both Nasonia vitripennis and Nasonia longicornis, memory was observed up to at least 5 days after a single conditioning trial, whereas Nasonia giraulti lost its memory after 2 days. This difference in learning may be an adaptation to species-specific differences in ecological factors, for example, host preference. The high-throughput methods for conditioning and memory retention testing are essential tools to study both ultimate and proximate factors that cause variation in learning and memory formation in Nasonia and other parasitic wasp species. PMID:22804968

Tc1 mouse model of trisomy-21 dissociates properties of short- and long-term recognition memory.

PubMed

Hall, Jessica H; Wiseman, Frances K; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Harwood, John L; Good, Mark A

2016-04-01

The present study examined memory function in Tc1 mice, a transchromosomic model of Down syndrome (DS). Tc1 mice demonstrated an unusual delay-dependent deficit in recognition memory. More specifically, Tc1 mice showed intact immediate (30sec), impaired short-term (10-min) and intact long-term (24-h) memory for objects. A similar pattern was observed for olfactory stimuli, confirming the generality of the pattern across sensory modalities. The specificity of the behavioural deficits in Tc1 mice was confirmed using APP overexpressing mice that showed the opposite pattern of object memory deficits. In contrast to object memory, Tc1 mice showed no deficit in either immediate or long-term memory for object-in-place information. Similarly, Tc1 mice showed no deficit in short-term memory for object-location information. The latter result indicates that Tc1 mice were able to detect and react to spatial novelty at the same delay interval that was sensitive to an object novelty recognition impairment. These results demonstrate (1) that novelty detection per se and (2) the encoding of visuo-spatial information was not disrupted in adult Tc1 mice. The authors conclude that the task specific nature of the short-term recognition memory deficit suggests that the trisomy of genes on human chromosome 21 in Tc1 mice impacts on (perirhinal) cortical systems supporting short-term object and olfactory recognition memory. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

PubMed Central

Naimark, Ari; Barkai, Edi; Matar, Michael A.; Kaplan, Zeev; Kozlovsky, Nitzan; Cohen, Hagit

2007-01-01

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks. PMID:17710248

Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes.

PubMed

Zhang, Zhou; Zhang, Bing; Wang, Xin; Zhang, Xin; Yang, Qing X; Qing, Zhao; Lu, Jiaming; Bi, Yan; Zhu, Dalong

2018-05-01

Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. © 2018 by the American Diabetes Association.

Olfactory ability and object memory in three mouse models of varying body weight, metabolic hormones, and adiposity

PubMed Central

Tucker, Kristal R.; Godbey, Steven J.; Thiebaud, Nicolas; Fadool, Debra Ann

2012-01-01

Physiological and nutritional state can modify sensory ability and perception through hormone signaling. Obesity and related metabolic disorders present a chronic imbalance in hormonal signaling that could impact sensory systems. In the olfactory system, external chemical cues are transduced into electrical signals to encode information. It is becoming evident that this system can also detect internal chemical cues in the form of molecules of energy homeostasis and endocrine hormones, whereby neurons of the olfactory system are modulated to change animal behavior towards olfactory cues. We hypothesized that chronic imbalance in hormonal signaling and energy homeostasis due to obesity would thereby disrupt olfactory behaviors in mice. To test this idea, we utilized three mouse models of varying body weight, metabolic hormones, and visceral adiposity – 1) C57BL6/J mice maintained on a condensed-milk based, moderately high-fat diet (MHF) of 32% fat for 6 months as the diet-induced obesity model, 2) an obesity-resistant, lean line of mice due to a gene-targeted deletion of a voltage-dependent potassium channel (Kv1.3-null), and 3) a genetic model of obesity as a result of a gene-targeted deletion of the melanocortin 4 receptor (MC4R-null). Diet-induced obese (DIO) mice failed to find fatty-scented hidden peanut butter cracker, based solely on olfactory cues, any faster than an unscented hidden marble, initially suggesting general anosmia. However, when these DIO mice were challenged to find a sweet-scented hidden chocolate candy, they had no difficulty. Furthermore, DIO mice were able to discriminate between fatty acids that differ by a single double bond and are components of the MHF diet (linoleic and oleic acid) in a habituation-dishabituation paradigm. Obesity-resistant, Kv1.3-null mice exhibited no change in scented object retrieval when placed on the MHF-diet, nor did they perform differently than wild-type mice in parallel habituation-dishabituation paradigms of fatty food-related odor components. Genetically obese, MC4R-null mice successfully found hidden scented objects, but did so more slowly than lean, wild-type mice, in an object-dependent fashion. In habituation-dishabituation trials of general odorants, MC4R-null mice failed to discriminate a novel odor, but were able to distinguish two fatty acids. Object memory recognition tests for short- and long-term memory retention demonstrated that maintenance on the MHF diet did not modify ability to perform these tasks independent of whether mice became obese or were resistant to weight gain (Kv1.3-null), however, the genetically predisposed obese mice (MC4R-null) failed the long-term object memory recognition performed at 24 hours. These results demonstrate that even though both the DIO mice and genetically predisposed obese mice are obese, they vary in the degree to which they exhibit behavioral deficits in odor detection, odor discrimination, and long-term memory. PMID:22995978

The CC chemokine receptor 5 regulates olfactory and social recognition in mice.

PubMed

Kalkonde, Y V; Shelton, R; Villarreal, M; Sigala, J; Mishra, P K; Ahuja, S S; Barea-Rodriguez, E; Moretti, P; Ahuja, S K

2011-12-01

Chemokines are chemotactic cytokines that regulate cell migration and are thought to play an important role in a broad range of inflammatory diseases. The availability of chemokine receptor blockers makes them an important therapeutic target. In vitro, chemokines are shown to modulate neurotransmission. However, it is not very clear if chemokines play a role in behavior and cognition. Here we evaluated the role of CC chemokine receptor 5 (CCR5) in various behavioral tasks in mice using Wt (Ccr5⁺/⁺) and Ccr5-null (Ccr5⁻/⁻)mice. Ccr5⁻/⁻ mice showed enhanced social recognition. Administration of CC chemokine ligand 3 (CCL3), one of the CCR5-ligands, impaired social recognition. Since the social recognition task is dependent on the sense of olfaction, we tested olfactory recognition for social and non-social scents in these mice. Ccr5⁻/⁻ mice had enhanced olfactory recognition for both these scents indicating that enhanced performance in social recognition task could be due to enhanced olfactory recognition in these mice. Spatial memory and aversive memory were comparable in Wt and Ccr5⁻/⁻ mice. Collectively, these results suggest that chemokines/chemokine receptors might play an important role in olfactory recognition tasks in mice and to our knowledge represents the first direct demonstration of an in vivo role of CCR5 in modulating social behavior in mice. These studies are important as CCR5 blockers are undergoing clinical trials and can potentially modulate behavior. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Sensory Preconditioning in Newborn Rabbits: From Common to Distinct Odor Memories

ERIC Educational Resources Information Center

Coureaud, Gerard; Tourat, Audrey; Ferreira, Guillaume

2013-01-01

This study evaluated whether olfactory preconditioning is functional in newborn rabbits and based on joined or independent memory of odorants. First, after exposure to odorants A+B, the conditioning of A led to high responsiveness to odorant B. Second, responsiveness to B persisted after amnesia of A. Third, preconditioning was also functional…

A processing architecture for associative short-term memory in electronic noses

NASA Astrophysics Data System (ADS)

Pioggia, G.; Ferro, M.; Di Francesco, F.; DeRossi, D.

2006-11-01

Electronic nose (e-nose) architectures usually consist of several modules that process various tasks such as control, data acquisition, data filtering, feature selection and pattern analysis. Heterogeneous techniques derived from chemometrics, neural networks, and fuzzy rules used to implement such tasks may lead to issues concerning module interconnection and cooperation. Moreover, a new learning phase is mandatory once new measurements have been added to the dataset, thus causing changes in the previously derived model. Consequently, if a loss in the previous learning occurs (catastrophic interference), real-time applications of e-noses are limited. To overcome these problems this paper presents an architecture for dynamic and efficient management of multi-transducer data processing techniques and for saving an associative short-term memory of the previously learned model. The architecture implements an artificial model of a hippocampus-based working memory, enabling the system to be ready for real-time applications. Starting from the base models available in the architecture core, dedicated models for neurons, maps and connections were tailored to an artificial olfactory system devoted to analysing olive oil. In order to verify the ability of the processing architecture in associative and short-term memory, a paired-associate learning test was applied. The avoidance of catastrophic interference was observed.

Parametric and genetic analysis of Drosophila appetitive long-term memory and sugar motivation.

PubMed

Colomb, J; Kaiser, L; Chabaud, M-A; Preat, T

2009-06-01

Distinct forms of memory can be highlighted using different training protocols. In Drosophila olfactory aversive learning, one conditioning session triggers memory formation independently of protein synthesis, while five spaced conditioning sessions lead to the formation of long-term memory (LTM), a long-lasting memory dependent on de novo protein synthesis. In contrast, one session of odour-sugar association appeared sufficient for the fly to form LTM. We designed and tuned an apparatus that facilitates repeated discriminative conditioning by alternate presentations of two odours, one being associated with sugar, as well as a new paradigm to test sugar responsiveness (SR). Our results show that both SR and short-term memory (STM) scores increase with starvation length before conditioning. The protein dependency of appetitive LTM is independent of the repetition and the spacing of training sessions, on the starvation duration and on the strength of the unconditioned stimulus. In contrast to a recent report, our test measures an abnormal SR of radish mutant flies, which might initiate their STM and LTM phenotypes. In addition, our work shows that crammer and tequila mutants, which are deficient for aversive LTM, present both an SR and an appetitive STM defect. Using the MB247-P[switch] system, we further show that tequila is required in the adult mushroom bodies for normal sugar motivation.

Pattern separation: a common function for new neurons in hippocampus and olfactory bulb.

PubMed

Sahay, Amar; Wilson, Donald A; Hen, René

2011-05-26

While adult-born neurons in the olfactory bulb (OB) and the dentate gyrus (DG) subregion of the hippocampus have fundamentally different properties, they may have more in common than meets the eye. Here, we propose that new granule cells in the OB and DG may function as modulators of principal neurons to influence pattern separation and that adult neurogenesis constitutes an adaptive mechanism to optimally encode contextual or olfactory information. See the related Perspective from Aimone, Deng, and Gage, "Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern Separation," in this issue of Neuron. Copyright © 2011 Elsevier Inc. All rights reserved.

Bilateral Olfactory Mucosa Damage Induces the Disappearance of Olfactory Glomerulus and Reduces the Expression of Extrasynaptic α5GABAARs in the Hippocampus in Early Postnatal Sprague Dawley Rats.

PubMed

Zheng, Xiaomin; Liang, Liang; Hei, Changchun; Yang, Wenjuan; Zhang, Tingyuan; Wu, Kai; Qin, Yi; Chang, Qing

2018-04-17

Chloroform-induced olfactory mucosal degeneration has been reported in adult rats following gavage. We used fixed-point chloroform infusions on different postnatal days (PNDs) to investigate the effects of early olfactory bilateral deprivation on the main olfactory bulbs in Sprague Dawley rats. The experimental groups included rats infused with chloroform (5 μl) or saline (sham, 5 μl) on PNDs 3 and 8, and rats not receiving infusions (control) (n = 6 in all groups). Rats receiving chloroform on PND 3 showed significant hypoevolutism when compared to those in other groups (P < 0.05). There was a complete disappearance and a significant reduction in the size of olfactory glomeruli in the PND 3 and 8 groups, respectively, when compared to the respective sham groups. Rats receiving chloroform on PND 3 had significant memory impairment (P < 0.01) and increased levels of learned helplessness (P < 0.05), as measured using the Morris water maze and tail suspension tests, respectively. GABA A receptor alpha5 subunit (α5GABA A R) expression in hippocampal neurons was significantly lower in rats receiving chloroform on PND 3 than in rats in other groups (P < 0.01), as measured using immunohistochemistry and polymerase chain reaction. There was thus a critical period for the preservation of regenerative ability in olfactory receptor neurons, during which damage and olfactory deprivation led to altered rhinencephalon structure and disappearance of olfactory glomeruli, which induced hypoevolutism. Olfactory deprivation after the critical period had no significant effect on olfactory receptor neuron regeneration, leading to reduced developmental and behavioral effects in Sprague Dawley rats.

Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice.

PubMed

Moriguchi, Shigeki; Tanaka, Tomoya; Tagashira, Hideaki; Narahashi, Toshio; Fukunaga, Kohji

2013-04-01

Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKIIα (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKCα (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of visual and verbal interference tasks on olfactory memory: the role of task complexity.

PubMed

Annett, J M; Leslie, J C

1996-08-01

Recent studies have demonstrated that visual and verbal suppression tasks interfere with olfactory memory in a manner which is partially consistent with a dual coding interpretation. However, it has been suggested that total task complexity rather than modality specificity of the suppression tasks might account for the observed pattern of results. This study addressed the issue of whether or not the level of difficulty and complexity of suppression tasks could explain the apparent modality effects noted in earlier experiments. A total of 608 participants were each allocated to one of 19 experimental conditions involving interference tasks which varied suppression type (visual or verbal), nature of complexity (single, double or mixed) and level of difficulty (easy, optimal or difficult) and presented with 13 target odours. Either recognition of the odours or free recall of the odour names was tested on one occasion, either within 15 minutes of presentation or one week later. Both recognition and recall performance showed an overall effect for suppression nature, suppression level and time of testing with no effect for suppression type. The results lend only limited support to Paivio's (1986) dual coding theory, but have a number of characteristics which suggest that an adequate account of olfactory memory may be broadly similar to current theories of face and object recognition. All of these phenomena might be dealt with by an appropriately modified version of dual coding theory.

Behavioral and neural plasticity caused by early social experiences: the case of the honeybee

PubMed Central

Arenas, Andrés; Ramírez, Gabriela P.; Balbuena, María Sol; Farina, Walter M.

2013-01-01

Cognitive experiences during the early stages of life play an important role in shaping future behavior. Behavioral and neural long-term changes after early sensory and associative experiences have been recently reported in the honeybee. This invertebrate is an excellent model for assessing the role of precocious experiences on later behavior due to its extraordinarily tuned division of labor based on age polyethism. These studies are mainly focused on the role and importance of experiences occurred during the first days of the adult lifespan, their impact on foraging decisions, and their contribution to coordinate food gathering. Odor-rewarded experiences during the first days of honeybee adulthood alter the responsiveness to sucrose, making young hive bees more sensitive to assess gustatory features about the nectar brought back to the hive and affecting the dynamic of the food transfers and the propagation of food-related information within the colony. Early olfactory experiences lead to stable and long-term associative memories that can be successfully recalled after many days, even at foraging ages. Also they improve memorizing of new associative learning events later in life. The establishment of early memories promotes stable reorganization of the olfactory circuits inducing structural and functional changes in the antennal lobe (AL). Early rewarded experiences have relevant consequences at the social level too, biasing dance and trophallaxis partner choice and affecting recruitment. Here, we revised recent results in bees' physiology, behavior, and sociobiology to depict how the early experiences affect their cognition abilities and neural-related circuits. PMID:23986708

Sleep for cognitive enhancement.

PubMed

Diekelmann, Susanne

2014-01-01

Sleep is essential for effective cognitive functioning. Loosing even a few hours of sleep can have detrimental effects on a wide variety of cognitive processes such as attention, language, reasoning, decision making, learning and memory. While sleep is necessary to ensure normal healthy cognitive functioning, it can also enhance performance beyond the boundaries of the normal condition. This article discusses the enhancing potential of sleep, mainly focusing on the domain of learning and memory. Sleep is known to facilitate the consolidation of memories learned before sleep as well as the acquisition of new memories to be learned after sleep. According to a widely held model this beneficial effect of sleep relies on the neuronal reactivation of memories during sleep that is associated with sleep-specific brain oscillations (slow oscillations, spindles, ripples) as well as a characteristic neurotransmitter milieu. Recent research indicates that memory processing during sleep can be boosted by (i) cueing memory reactivation during sleep; (ii) stimulating sleep-specific brain oscillations; and (iii) targeting specific neurotransmitter systems pharmacologically. Olfactory and auditory cues can be used, for example, to increase reactivation of associated memories during post-learning sleep. Intensifying neocortical slow oscillations (the hallmark of slow wave sleep (SWS)) by electrical or auditory stimulation and modulating specific neurotransmitters such as noradrenaline and glutamate likewise facilitates memory processing during sleep. With this evidence in mind, this article concludes by discussing different methodological caveats and ethical issues that should be considered when thinking about using sleep for cognitive enhancement in everyday applications.

Sleep for cognitive enhancement

PubMed Central

Diekelmann, Susanne

2014-01-01

Sleep is essential for effective cognitive functioning. Loosing even a few hours of sleep can have detrimental effects on a wide variety of cognitive processes such as attention, language, reasoning, decision making, learning and memory. While sleep is necessary to ensure normal healthy cognitive functioning, it can also enhance performance beyond the boundaries of the normal condition. This article discusses the enhancing potential of sleep, mainly focusing on the domain of learning and memory. Sleep is known to facilitate the consolidation of memories learned before sleep as well as the acquisition of new memories to be learned after sleep. According to a widely held model this beneficial effect of sleep relies on the neuronal reactivation of memories during sleep that is associated with sleep-specific brain oscillations (slow oscillations, spindles, ripples) as well as a characteristic neurotransmitter milieu. Recent research indicates that memory processing during sleep can be boosted by (i) cueing memory reactivation during sleep; (ii) stimulating sleep-specific brain oscillations; and (iii) targeting specific neurotransmitter systems pharmacologically. Olfactory and auditory cues can be used, for example, to increase reactivation of associated memories during post-learning sleep. Intensifying neocortical slow oscillations (the hallmark of slow wave sleep (SWS)) by electrical or auditory stimulation and modulating specific neurotransmitters such as noradrenaline and glutamate likewise facilitates memory processing during sleep. With this evidence in mind, this article concludes by discussing different methodological caveats and ethical issues that should be considered when thinking about using sleep for cognitive enhancement in everyday applications. PMID:24765066

A program for undergraduate research into the mechanisms of sensory coding and memory decay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calin-Jageman, R J

This is the final technical report for this DOE project, entitltled "A program for undergraduate research into the mechanisms of sensory coding and memory decay". The report summarizes progress on the three research aims: 1) to identify phyisological and genetic correlates of long-term habituation, 2) to understand mechanisms of olfactory coding, and 3) to foster a world-class undergraduate neuroscience program. Progress on the first aim has enabled comparison of learning-regulated transcripts across closely related learning paradigms and species, and results suggest that only a small core of transcripts serve truly general roles in long-term memory. Progress on the second aimmore » has enabled testing of several mutant phenotypes for olfactory behaviors, and results show that responses are not fully consistent with the combinitoral coding hypothesis. Finally, 14 undergraduate students participated in this research, the neuroscience program attracted extramural funding, and we completed a successful summer program to enhance transitions for community-college students into 4-year colleges to persue STEM fields.« less

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure

PubMed Central

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-01-01

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N = 33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 µg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL × sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. PMID:25936521

Distinct amyloid precursor protein processing machineries of the olfactory system.

PubMed

Kim, Jae Yeon; Rasheed, Ameer; Yoo, Seung-Jun; Kim, So Yeun; Cho, Bongki; Son, Gowoon; Yu, Seong-Woon; Chang, Keun-A; Suh, Yoo-Hun; Moon, Cheil

2018-01-01

Processing of amyloid precursor protein (APP) occurs through sequential cleavages first by β-secretase and then by the γ-secretase complex. However, abnormal processing of APP leads to excessive production of β-amyloid (Aβ) in the central nervous system (CNS), an event which is regarded as a primary cause of Alzheimer's disease (AD). In particular, gene mutations of the γ-secretase complex-which contains presenilin 1 or 2 as the catalytic core-could trigger marked Aβ accumulation. Olfactory dysfunction usually occurs before the onset of typical AD-related symptoms (eg, memory loss or muscle retardation), suggesting that the olfactory system may be one of the most vulnerable regions to AD. To date however, little is known about why the olfactory system is affected so early by AD prior to other regions. Thus, we examined the distribution of secretases and levels of APP processing in the olfactory system under either healthy or pathological conditions. Here, we show that the olfactory system has distinct APP processing machineries. In particular, we identified higher expressions levels and activity of γ-secretase in the olfactory epithelium (OE) than other regions of the brain. Moreover, APP c-terminal fragments (CTF) are markedly detected. During AD progression, we note increased expression of presenilin2 of γ-secretases in the OE, not in the OB, and show that neurotoxic Aβ*56 accumulates more quickly in the OE. Taken together, these results suggest that the olfactory system has distinct APP processing machineries under healthy and pathological conditions. This finding may provide a crucial understanding of the unique APP-processing mechanisms in the olfactory system, and further highlights the correlation between olfactory deficits and AD symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

Exercise Is Associated with Lower Long-Term Risk of Olfactory Impairment in Older Adults

PubMed Central

Schubert, Carla R.; Cruickshanks, Karen J.; Nondahl, David M.; Klein, Barbara EK; Klein, Ronald; Fischer, Mary E.

2013-01-01

Importance The prevalence of olfactory impairment is high in older adults and this decline in olfactory ability may pose health and safety risks, affect nutrition and decrease quality of life. It is important to identify modifiable risk factors to reduce the burden of olfactory impairment in aging populations. Objectives To determine if exercise is associated with the 10-year cumulative incidence of olfactory impairment. Design, Setting and Participants Observational longitudinal population-based Epidemiology of Hearing Loss Study. Participants without olfactory impairment (n=1611) were ages 53-97 years at baseline and were followed for up to ten years (1998-2010). Interventions None Main Outcome and Measures Olfaction was measured with the San Diego Odor Identification Test at three examinations (1998-2000, 2003-2005, 2009-2010) of the Epidemiology of Hearing Loss Study. The main outcome was the incidence of olfactory impairment five (2003-2005) or ten (2009-2010) years later and the association of baseline exercise with the long-term risk of developing olfactory impairment. Results The 10-year cumulative incidence of olfactory impairment was 27.6% (95% confidence interval =25.3, 29.9) and rates varied by age and sex; those who were older (Hazard Ratio =1.88, 95% Confidence Interval=1.74, 2.03, for every 5 years) or male (Hazard Ratio=1.27, 95% Confidence Interval=1.00, 1.61) had an increased risk of olfactory impairment. Participants who reported exercising at least once a week long enough to work up a sweat had a decreased risk of olfactory impairment (age and sex adjusted Hazard Ratio= 0.76, 95% CI= 0.60, 0.97). Increasing frequency of exercise was associated with decreasing risk of developing olfactory impairment (p for trend = 0.02). Conclusion and Relevance Regular exercise was associated with lower 10-year cumulative incidence of olfactory impairment. Older adults who exercise may be able to retain olfactory function with age. PMID:24135745

Cross-modal interaction between visual and olfactory learning in Apis cerana.

PubMed

Zhang, Li-Zhen; Zhang, Shao-Wu; Wang, Zi-Long; Yan, Wei-Yu; Zeng, Zhi-Jiang

2014-10-01

The power of the small honeybee brain carrying out behavioral and cognitive tasks has been shown repeatedly to be highly impressive. The present study investigates, for the first time, the cross-modal interaction between visual and olfactory learning in Apis cerana. To explore the role and molecular mechanisms of cross-modal learning in A. cerana, the honeybees were trained and tested in a modified Y-maze with seven visual and five olfactory stimulus, where a robust visual threshold for black/white grating (period of 2.8°-3.8°) and relatively olfactory threshold (concentration of 50-25%) was obtained. Meanwhile, the expression levels of five genes (AcCREB, Acdop1, Acdop2, Acdop3, Actyr1) related to learning and memory were analyzed under different training conditions by real-time RT-PCR. The experimental results indicate that A. cerana could exhibit cross-modal interactions between visual and olfactory learning by reducing the threshold level of the conditioning stimuli, and that these genes may play important roles in the learning process of honeybees.

Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice

PubMed Central

Bell, Genevieve A.; Fadool, Debra Ann

2017-01-01

Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5 μg/μl of insulin twice daily for 30 and 60 days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice performed no different from controls regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3X increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR Kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors – as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se. PMID:28259806

Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.

PubMed

Bell, Genevieve A; Fadool, Debra Ann

2017-05-15

Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se. Copyright © 2017 Elsevier Inc. All rights reserved.

Olfactory function and neurocognitive outcomes in old age: The Atherosclerosis Risk in Communities Neurocognitive Study.

PubMed

Palta, Priya; Chen, Honglei; Deal, Jennifer A; Sharrett, A Richey; Gross, Alden; Knopman, David; Griswold, Michael; Heiss, Gerardo; Mosley, Thomas H

2018-03-30

We tested the hypothesis that poor sense of smell is associated with lower cognitive function and higher mild cognitive impairment (MCI) prevalence. Olfaction, measured by the Sniffin' Sticks test, was categorized as olfactory impairment (OI) (score ≤6) or no OI (score >6). MCI was adjudicated based on review of a neuropsychological examination. Linear regression estimated the mean difference in cognitive factor scores, and log-binomial regression quantified MCI prevalence among participants with versus without OI. Participants with OI had lower mean factor scores (memory: -0.27 standard deviation [SD], 95% confidence interval [CI]: -0.35 to -0.19; language: -0.24 SD, 95% CI: -0.30 to -0.17; executive function/processing speed: -0.09 SD, 95% CI: -0.12 to -0.06; and general cognitive performance: -0.25 SD, 95% CI: -0.30 to -0.20). OI was also associated with MCI (n = 204; prevalence ratio = 1.56, 95% CI: 1.37, 1.78). An impaired sense of smell may serve as a readily accessible early marker of neurodegeneration and improve upon the prevailing delayed diagnoses and underascertainment of MCI/dementia. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Odor Preference Learning and Memory Modify GluA1 Phosphorylation and GluA1 Distribution in the Neonate Rat Olfactory Bulb: Testing the AMPA Receptor Hypothesis in an Appetitive Learning Model

ERIC Educational Resources Information Center

Cui, Wen; Darby-King, Andrea; Grimes, Matthew T.; Howland, John G.; Wang, Yu Tian; McLean, John H.; Harley, Carolyn W.

2011-01-01

An increase in synaptic AMPA receptors is hypothesized to mediate learning and memory. AMPA receptor increases have been reported in aversive learning models, although it is not clear if they are seen with memory maintenance. Here we examine AMPA receptor changes in a cAMP/PKA/CREB-dependent appetitive learning model: odor preference learning in…

Amyloid-β Peptide Exacerbates the Memory Deficit Caused by Amyloid Precursor Protein Loss-of-Function in Drosophila

PubMed Central

Bourdet, Isabelle; Lampin-Saint-Amaux, Aurélie; Preat, Thomas; Goguel, Valérie

2015-01-01

The amyloid precursor protein (APP) plays a central role in Alzheimer’s disease (AD). APP can undergo two exclusive proteolytic pathways: cleavage by the α-secretase initiates the non-amyloidogenic pathway while cleavage by the β-secretase initiates the amyloidogenic pathway that leads, after a second cleavage by the γ-secretase, to amyloid-β (Aβ) peptides that can form toxic extracellular deposits, a hallmark of AD. The initial events leading to AD are still unknown. Importantly, aside from Aβ toxicity whose molecular mechanisms remain elusive, several studies have shown that APP plays a positive role in memory, raising the possibility that APP loss-of-function may participate to AD. We previously showed that APPL, the Drosophila APP ortholog, is required for associative memory in young flies. In the present report, we provide the first analysis of the amyloidogenic pathway’s influence on memory in the adult. We show that transient overexpression of the β-secretase in the mushroom bodies, the center for olfactory memory, did not alter memory. In sharp contrast, β-secretase overexpression affected memory when associated with APPL partial loss-of-function. Interestingly, similar results were observed with Drosophila Aβ peptide. Because Aβ overexpression impaired memory only when combined to APPL partial loss-of-function, the data suggest that Aβ affects memory through the APPL pathway. Thus, memory is altered by two connected mechanisms—APPL loss-of-function and amyloid peptide toxicity—revealing in Drosophila a functional interaction between APPL and amyloid peptide. PMID:26274614

Opioid Modulation of Fos Protein Expression and Olfactory Circuitry Plays a Pivotal Role in What Neonates Remember

ERIC Educational Resources Information Center

Roth, Tania L.; Moriceau, Stephanie; Sullivan, Regina M.

2006-01-01

Paradoxically, fear conditioning (odor-0.5 mA shock) yields a learned odor preference in the neonate, presumably due to a unique learning and memory circuit that does not include apparent amygdala participation. Post-training opioid antagonism with naltrexone (NTX) blocks consolidation of this odor preference and instead yields memory of a learned…

The Magic Number 70 (Plus or Minus 20): Variables Determining Performance in the Rodent Odor Span Task

ERIC Educational Resources Information Center

April, L. Brooke; Bruce, Katherine; Galizio, Mark

2013-01-01

The olfactory span task (OST) uses an incrementing non-matching to sample procedure such that the number of stimuli to remember increases during the session. The number of consecutive correct responses (span length) and percent correct as a function of the memory load have been viewed as defining rodent working memory capacity limitations in…

Proteomic Analysis of the Human Olfactory Bulb.

PubMed

Dammalli, Manjunath; Dey, Gourav; Madugundu, Anil K; Kumar, Manish; Rodrigues, Benvil; Gowda, Harsha; Siddaiah, Bychapur Gowrishankar; Mahadevan, Anita; Shankar, Susarla Krishna; Prasad, Thottethodi Subrahmanya Keshava

2017-08-01

The importance of olfaction to human health and disease is often underappreciated. Olfactory dysfunction has been reported in association with a host of common complex diseases, including neurological diseases such as Alzheimer's disease and Parkinson's disease. For health, olfaction or the sense of smell is also important for most mammals, for optimal engagement with their environment. Indeed, animals have developed sophisticated olfactory systems to detect and interpret the rich information presented to them to assist in day-to-day activities such as locating food sources, differentiating food from poisons, identifying mates, promoting reproduction, avoiding predators, and averting death. In this context, the olfactory bulb is a vital component of the olfactory system receiving sensory information from the axons of the olfactory receptor neurons located in the nasal cavity and the first place that processes the olfactory information. We report in this study original observations on the human olfactory bulb proteome in healthy subjects, using a high-resolution mass spectrometry-based proteomic approach. We identified 7750 nonredundant proteins from human olfactory bulbs. Bioinformatics analysis of these proteins showed their involvement in biological processes associated with signal transduction, metabolism, transport, and olfaction. These new observations provide a crucial baseline molecular profile of the human olfactory bulb proteome, and should assist the future discovery of biomarker proteins and novel diagnostics associated with diseases characterized by olfactory dysfunction.

Role of olfaction in the foraging behavior and trial-and-error learning in short-nosed fruit bat, Cynopterus sphinx.

PubMed

Zhang, Wei; Zhu, Guangjian; Tan, Liangjing; Yang, Jian; Chen, Yi; Liu, Qi; Shen, Qiqi; Chen, Jinping; Zhang, Libiao

2014-03-01

We observed the foraging behavior of short-nosed fruit bats, Cynopterus sphinx, in captivity. The role of olfaction in their foraging behavior was examined using real fruit, mimetic fruit, and mimetic fruit soaked in the juice of real fruit. The results showed that C. sphinx visited the real fruit more often than the mimetic fruit, but they had no preference between real fruit and treated mimetic fruit. Our experiment indicates that this bat has the ability to find and identify fruit by olfaction. We also tested for behavior of trial-and-error learning. Our observations revealed that the bats could form a sensory memory of the olfactory cue (cedar wood oil) after five days of training because they responded to the olfactory cues. Our results provide the evidence that C. sphinx can establish the connection between the fruit and a non-natural odor through learning and memory with the assistance of olfaction, and can thus recognize a variety of odors by trial-and-error learning. This behavioral flexibility based on olfactory cues will be beneficial for the short-nosed fruit bat in foraging. Copyright © 2013 Elsevier B.V. All rights reserved.

Modulation of dendrodendritic interactions and mitral cell excitability in the mouse accessory olfactory bulb by vaginocervical stimulation.

PubMed

Otsuka, T; Ishii, K; Osako, Y; Okutani, F; Taniguchi, M; Oka, T; Kaba, H

2001-05-01

When female mice are mated, they form a memory to the pheromonal signal of their male partner. The neural changes underlying this memory occur in the accessory olfactory bulb, depend upon vaginocervical stimulation at mating and involve changes at the reciprocal synapses between mitral and granule cells. However, the action of vaginocervical stimulation on the reciprocal interactions between mitral and granule cells remains to be elucidated. We have examined the effects of vaginocervical stimulation on paired-pulse depression of amygdala-evoked field potentials recorded in the external plexiform layer of the accessory olfactory bulb (AOB) and the single-unit activity of mitral cells antidromically stimulated from the amygdala in urethane-anaesthetized female mice. Artificial vaginocervical stimulation reduced paired-pulse depression (considered to be due to feedback inhibition of the mitral cell dendrites from the granule cells via reciprocal dendrodendritic synapses) recorded in the AOB external plexiform layer. As would be expected from this result, vaginocervical stimulation also enhanced the spontaneous activity of a proportion of the mitral cells tested. These results suggest that vaginocervical stimulation reduces dendrodendritic feedback inhibition to mitral cells and enhances their activity.

Gender differences in the cognitive control of emotion: An fMRI study.

PubMed

Koch, Kathrin; Pauly, Katharina; Kellermann, Thilo; Seiferth, Nina Y; Reske, Martina; Backes, Volker; Stöcker, Tony; Shah, N Jon; Amunts, Katrin; Kircher, Tilo; Schneider, Frank; Habel, Ute

2007-09-20

The interaction of emotion and cognition has become a topic of major interest. However, the influence of gender on the interplay between the two processes, along with its neural correlates have not been fully analysed so far. In this functional magnetic resonance imaging (fMRI) study we induced negative emotion using negative olfactory stimulation while male (n=21) and female (n=19) participants performed an n-back verbal working memory task. Based on findings indicating increased emotional reactivity in women, we expected the female participants to exhibit stronger activation in characteristically emotion-associated areas during the interaction of emotional and cognitive processing in comparison to the male participants. Both groups were found to be significantly impaired in their working memory performance by negative emotion induction. However, fMRI analysis revealed distinct differences in neuronal activation between groups. In men, cognitive performance under negative emotion induction was associated with extended activation patterns in mainly prefrontal and superior parietal regions. In women, the interaction between emotion and working memory yielded a significantly stronger response in the amygdala and the orbitofrontal cortex (OFC) compared to their male counterparts. Our data suggest that in women the interaction of verbal working memory and negative emotion is associated with relative hyperactivation in more emotion-associated areas whereas in men regions commonly regarded as important for cognition and cognitive control are activated. These results provide new insights in gender-specific cerebral mechanisms.

Olfactory Dysfunction Is Associated with the Intake of Macronutrients in Korean Adults

PubMed Central

Kong, Il Gyu; Kim, So Young; Kim, Min-Su; Park, Bumjung; Kim, Jin-Hwan

2016-01-01

Background Olfactory function can impact food selection. However, few large population-based studies have investigated this effect across different age groups. The objective of this study was to assess the association between subjective olfactory dysfunction (anosmia or hyposmia) and macronutrient intake. Methods A total of 24,990 participants aged 20 to 98 years were evaluated based on data collected through the Korea National Health and Nutrition Examination Survey from 2008 through 2012. Olfactory dysfunction was surveyed using a self-reported questionnaire, and the nutritional status was assessed through a validated 24-hour recall method. Simple and multiple linear regression analyses with complex sampling were performed to evaluate the relationships between olfactory dysfunction and protein intake (daily protein intake/recommended protein intake [%]), carbohydrate intake (daily carbohydrate intake/total calories [%]), and fat intake (daily fat intake/total calories [%]) after adjusting for age, sex, body mass index, income, smoking history, alcohol consumption, and stress level. Results Olfactory dysfunction was reported by 5.4% of Korean adults and was found to be associated with decreased fat consumption (estimated value [EV] of fat intake [%] = -0.57, 95% confidence interval [CI] = -1.13 to -0.13, P = 0.045). A subgroup analysis according to age and sex revealed that among young females, olfactory dysfunction was associated with reduced fat consumption (EV = -2.30, 95% CI = -4.16 to -0.43, P = 0.016) and increased carbohydrate intake (EV = 2.80, 95% CI = 0.55 to 5.05, P = 0.015), and that among middle-aged females, olfactory dysfunction was also associated with reduced fat intake (EV = -1.26, 95% CI = -2.37 to -0.16, P = 0.025). In contrast, among young males, olfactory dysfunction was associated with reduced protein intake (EV = -26.41 95% CI = -45.14 to -7.69, P = 0.006). Conclusion Olfactory dysfunction was associated with reduced fat intake. Moreover, olfactory dysfunction exerted differential effects on eating behavior depending on age and sex. PMID:27723843

Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types.

PubMed

Blum, Allison L; Li, Wanhe; Cressy, Mike; Dubnau, Josh

2009-08-25

A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons.

Distinct molecular underpinnings of Drosophila olfactory trace conditioning

PubMed Central

Shuai, Yichun; Hu, Ying; Qin, Hongtao; Campbell, Robert A. A.; Zhong, Yi

2011-01-01

Trace conditioning is valued as a simple experimental model to assess how the brain associates events that are discrete in time. Here, we adapted an olfactory trace conditioning procedure in Drosophila melanogaster by training fruit flies to avoid an odor that is followed by foot shock many seconds later. The molecular underpinnings of the learning are distinct from the well-characterized simultaneous conditioning, where odor and punishment temporally overlap. First, Rutabaga adenylyl cyclase (Rut-AC), a putative molecular coincidence detector vital for simultaneous conditioning, is dispensable in trace conditioning. Second, dominant-negative Rac expression, thought to sustain early labile memory, significantly enhances learning of trace conditioning, but leaves simultaneous conditioning unaffected. We further show that targeting Rac inhibition to the mushroom body (MB) but not the antennal lobe (AL) suffices to achieve the enhancement effect. Moreover, the absence of trace conditioning learning in D1 dopamine receptor mutants is rescued by restoration of expression specifically in the adult MB. These results suggest the MB as a crucial neuroanatomical locus for trace conditioning, which may harbor a Rac activity-sensitive olfactory “sensory buffer” that later converges with the punishment signal carried by dopamine signaling. The distinct molecular signature of trace conditioning revealed here shall contribute to the understanding of how the brain overcomes a temporal gap in potentially related events. PMID:22123966

Association of Amine-Receptor DNA Sequence Variants with Associative Learning in the Honeybee.

PubMed

Lagisz, Malgorzata; Mercer, Alison R; de Mouzon, Charlotte; Santos, Luana L S; Nakagawa, Shinichi

2016-03-01

Octopamine- and dopamine-based neuromodulatory systems play a critical role in learning and learning-related behaviour in insects. To further our understanding of these systems and resulting phenotypes, we quantified DNA sequence variations at six loci coding octopamine-and dopamine-receptors and their association with aversive and appetitive learning traits in a population of honeybees. We identified 79 polymorphic sequence markers (mostly SNPs and a few insertions/deletions) located within or close to six candidate genes. Intriguingly, we found that levels of sequence variation in the protein-coding regions studied were low, indicating that sequence variation in the coding regions of receptor genes critical to learning and memory is strongly selected against. Non-coding and upstream regions of the same genes, however, were less conserved and sequence variations in these regions were weakly associated with between-individual differences in learning-related traits. While these associations do not directly imply a specific molecular mechanism, they suggest that the cross-talk between dopamine and octopamine signalling pathways may influence olfactory learning and memory in the honeybee.

Upgrading the sleeping brain with targeted memory reactivation.

PubMed

Oudiette, Delphine; Paller, Ken A

2013-03-01

A fundamental feature of human memory is the propensity for beneficial changes in information storage after initial encoding. Recent research findings favor the possibility that memory consolidation during sleep is instrumental for actively maintaining the storehouse of memories that individuals carry through their lives. The information that ultimately remains available for retrieval may tend to be that which is reactivated during sleep. A novel source of support for this idea comes from demonstrations that neurocognitive processing during sleep can benefit memory storage when memories are covertly cued via auditory or olfactory stimulation. Investigations of these subtle manipulations of memory processing during sleep can help elucidate the mechanisms of memory preservation in the human brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

The functional significance of newly born neurons integrated into olfactory bulb circuits.

PubMed

Sakamoto, Masayuki; Kageyama, Ryoichiro; Imayoshi, Itaru

2014-01-01

The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons.

The functional significance of newly born neurons integrated into olfactory bulb circuits

PubMed Central

Sakamoto, Masayuki; Kageyama, Ryoichiro; Imayoshi, Itaru

2014-01-01

The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons. PMID:24904263

Olfactory discrimination ability and brain expression of c-fos, Gir and Glut1 mRNA are altered in n-3 fatty acid-depleted rats.

PubMed

Hichami, Aziz; Datiche, Frédérique; Ullah, Sana; Liénard, Fabienne; Chardigny, Jean-Michel; Cattarelli, Martine; Khan, Naim Akhtar

2007-11-22

The long-chain polyunsaturated n-3 fatty acids (n-3 PUFA), particularly docosahexaenoic acid (DHA), are abundantly present in the central nervous system and play an important role in cognitive functions such as learning and memory. We, therefore, investigated the effects of n-3 PUFA-depletion in rats (F2 generation) on the learning of an olfactory discrimination task, progressively acquired within a four-arm maze, and on the mRNA expression of some candidate genes, i.e., c-fos, Gir and glucose transporter (Glut1), which could reflect the level of cerebral activity. We observed that DHA contents were dramatically decreased in the olfactory bulb, the piriform cortex and the neocortex of n-3-depleted rats. Furthermore, the n-3 deficiency resulted in a mild olfactory learning impairment as these rats required more days to master the olfactory task compared to control rats. Real-time RT-PCR experiments revealed that the training induced the expression of c-fos mRNA in all the three regions of the brain whereas Gir and Glut1 mRNA were induced only in olfactory bulb and neocortex. However, such an increase was less marked in the n-3-deficient rats. Taken together, these results allow us to assume that the behavioural impairment in n-3-deficient rats is linked to the depletion of n-3 fatty acids in brain regions processing olfactory cues. Data are discussed in view of the possible role of some of these genes in learning-induced neuronal olfactory plasticity.

Predictors of Olfactory Dysfunction in Rhinosinusitis Using the Brief Smell Identification Test

PubMed Central

Alt, Jeremiah A.; Mace, Jess C.; Buniel, Maria C. F.; Soler, Zachary M.; Smith, Timothy L.

2014-01-01

Objective Associations between olfactory function to quality-of-life (QOL) and disease severity in patients with rhinosinusitis is poorly understood. We sought to evaluate and compare olfactory function between subgroups of patients with rhinosinusitis using the Brief Smell Identification Test (BSIT). Study Design Cross-sectional evaluation of a multi-center cohort. Methods Patients with recurrent acute sinusitis (RARS) and chronic rhinosinusitis (CRS) with and without nasal polyposis were prospectively enrolled from three academic tertiary care sites. Each subject completed the BSIT, in addition to measures of disease-specific QOL. Patient demographics, comorbidities, and clinical measures of disease severity were compared between patients with normal (BSIT; ≥9) and abnormal (BSIT; <9) olfaction scores. Regression modeling was used to identify potential risk factors associated with olfactory impairment. Results Patients with rhinosinusitis (n=445) were found to suffer olfactory dysfunction as measured by the BSIT (28.3%). Subgroups of rhinosinusitis differed in the degree of olfactory dysfunction reported. Worse disease severity, measured by computed tomography and nasal endoscopy, correlated to worse olfaction. Olfactory scores did not consistently correlate with Rhinosinusitis Disability Index or Sinonasal Outcome Test scores. Regression models demonstrated nasal polyposis was the strongest predictor of olfactory dysfunction. Recalcitrant disease and aspirin intolerance were strongly predictive of worse olfactory function. Conclusion Olfactory dysfunction is a complex, multi-factorial process found to be differentially expressed within subgroups of rhinosinusitis. Olfaction was associated with disease severity as measured by imaging and endoscopy, with only weak associations to disease-specific QOL measures. PMID:24402746

Anisomycin administered in the olfactory bulb and dorsal hippocampus impaired social recognition memory consolidation in different time-points.

PubMed

Pena, R R; Pereira-Caixeta, A R; Moraes, M F D; Pereira, G S

2014-10-01

To identify an individual as familiar, rodents form a specific type of memory named social recognition memory. The olfactory bulb (OB) is an important structure for social recognition memory, while the hippocampus recruitment is still controversial. The present study was designed to elucidate the OB and the dorsal hippocampus contribution to the consolidation of social memory. For that purpose, we tested the effect of anisomycin (ANI), which one of the effects is the inhibition of protein synthesis, on the consolidation of social recognition memory. Swiss adult mice with cannulae implanted into the CA1 region of the dorsal hippocampus or into the OB were exposed to a juvenile during 5 min (training session; TR), and once again 1.5 h or 24 h later to test social short-term memory (S-STM) or social long-term memory (S-LTM), respectively. To study S-LTM consolidation, mice received intra-OB or intra-CA1 infusion of saline or ANI immediately, 3, 6 or 18 h after TR. ANI impaired S-LTM consolidation in the OB, when administered immediately or 6h after TR. In the dorsal hippocampus, ANI was amnesic only if administered 3 h after TR. Furthermore, the infusion of ANI in either OB or CA1, immediately after training, did not affect S-STM. Moreover, ANI administered into the OB did not alter the animal's performance in the buried food-finding task. Altogether, our results suggest the consolidation of S-LTM requires both OB and hippocampus participation, although in different time points. This study may help shedding light on the specific roles of the OB and dorsal hippocampus in social recognition memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of a thymol application on olfactory memory and gene expression levels in the brain of the honeybee Apis mellifera.

PubMed

Bonnafé, Elsa; Drouard, Florian; Hotier, Lucie; Carayon, Jean-Luc; Marty, Pierre; Treilhou, Michel; Armengaud, Catherine

2015-06-01

Essential oils are used by beekeepers to control the Varroa mites that infest honeybee colonies. So, bees can be exposed to thymol formulations in the hive. The effects of the monoterpenoid thymol were explored on olfactory memory and gene expression in the brain of the honeybee. In bees previously exposed to thymol (10 or 100 ng/bee), the specificity of the response to the conditioned stimulus (CS) was lost 24 h after learning. Besides, the octopamine receptor OA1 gene Amoa1 showed a significant decrease of expression 3 h after exposure with 10 or 100 ng/bee of thymol. With the same doses, expression of Rdl gene, coding for a GABA receptor subunit, was not significantly modified but the trpl gene was upregulated 1 and 24 h after exposure to thymol. These data indicated that the genes coding for the cellular targets of thymol could be rapidly regulated after exposure to this molecule. Memory and sensory processes should be investigated in bees after chronic exposure in the hive to thymol-based preparations.

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

PubMed

Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

2016-01-01

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a non-disease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more "error-prone" than other sensory systems.

Olfactory Function is Associated with Cognitive Performance: Results of the Heinz Nixdorf Recall Study.

PubMed

Tebrügge, Sarah; Winkler, Angela; Gerards, Diana; Weimar, Christian; Moebus, Susanne; Jöckel, Karl-Heinz; Erbel, Raimund; Jokisch, Martha

2018-01-01

There is strong evidence for an association of olfactory dysfunction and neurodegenerative diseases. Studies on the association of olfaction and cognition in the general population are rare. To evaluate gender- and age-specific associations of olfactory function and cognitive performance in a well characterized population-based study sample. At the third examination of the Heinz Nixdorf Recall study (n = 3,087), 2,640 participants (48% men; 68.2±7.2 years) underwent Sniffin' Sticks Screening Test measuring olfactory function on a scale of 0-12 points. Olfactory function was rated as anosmic, hyposmic, or normosmic (≤6, 7-10 or ≥11 points, respectively). All participants performed eight validated cognitive subtests. Age- (55-64 years, 65-74 years, 75-86 years) and gender-stratified multivariate analysis of covariance was used to evaluate group differences in cognitive performance. Women showed better olfactory function than men (p < 0.001). For middle-aged participants, olfactory groups differed in almost all cognitive subtests. The analyses revealed no gender effects, although associations were slightly greater for women than for men. Anosmics showed the worst cognitive performance and normosmics showed the best cognitive performance. In the young- and old-aged groups, a quantitative association was found for anosmics in all subtests and for normosmics and hyposmics in almost all subtests. This is the first study reporting on age-specific associations of olfactory function and cognitive performance in the general population. The association found in middle-aged participants (65-74 years) may serve as a marker to improve identification of persons at high risk for cognitive decline and dementia.

Effects of MDMA on olfactory memory and reversal learning in rats

PubMed Central

Hawkey, Andrew; April, L. Brooke; Galizio, Mark

2014-01-01

The effects of acute and sub-chronic MDMA were assessed using a procedure designed to test rodent working memory capacity: the odor span task (OST). Rats were trained to select an odor that they had not previously encountered within the current session, and the number of odors to remember was incremented up to 24 during the course of each session. In order to separate drug effects on the OST from more general performance impairment, a simple olfactory discrimination was also assessed in each session. In Experiment 1, acute doses of MDMA were administered prior to select sessions. MDMA impaired memory span in a dose-dependent fashion, but impairment was seen only at doses (1.8 and 3.0 mg/kg) that also increased response omissions on both the simple discrimination and the OST. In Experiment 2, a sub-chronic regimen of MDMA (10.0 mg/kg, twice daily over four days) was administered after OST training. There was no evidence of reduced memory span following sub-chronic MDMA, but a temporary increase in omission errors on the OST was observed. In addition, rats exposed to sub-chronic MDMA showed delayed learning when the simple discrimination was reversed. Overall, the disruptive effects of both acute and sub-chronic MDMA appeared to be due to non-mnemonic processes, rather than effects on specific memory functions. PMID:25017644

Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function

PubMed Central

Jiang, Heidi; Zhou, Guangyu; Arora, Nikita; Schuele, Stephan; Rosenow, Joshua; Gottfried, Jay A.

2016-01-01

The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2–12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16–0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior. SIGNIFICANCE STATEMENT Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment of local field potential activity in human piriform cortex, amygdala, and hippocampus. These effects diminished when breathing was diverted to the mouth, highlighting the importance of nasal airflow for generating respiratory oscillations. Finally, behavioral data in healthy subjects suggest that breathing phase systematically influences cognitive tasks related to amygdala and hippocampal functions. PMID:27927961

Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function.

PubMed

Zelano, Christina; Jiang, Heidi; Zhou, Guangyu; Arora, Nikita; Schuele, Stephan; Rosenow, Joshua; Gottfried, Jay A

2016-12-07

The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2-12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16-0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior. Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment of local field potential activity in human piriform cortex, amygdala, and hippocampus. These effects diminished when breathing was diverted to the mouth, highlighting the importance of nasal airflow for generating respiratory oscillations. Finally, behavioral data in healthy subjects suggest that breathing phase systematically influences cognitive tasks related to amygdala and hippocampal functions. Copyright © 2016 the authors 0270-6474/16/3612448-20$15.00/0.

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure.

PubMed

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-07-02

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N=33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 μg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL×sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Delta-9-Tetrahydrocannabinol Potentiates Fear Memory Salience Through Functional Modulation of Mesolimbic Dopaminergic Activity States.

PubMed

Fitoussi, Aurelie; Zunder, Jordan; Tan, Huibing; Laviolette, Steven R

2018-05-18

Chronic or acute exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and pre-clinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine (DA) activity states in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood. Using an olfactory associative fear memory procedure combined with in vivo neuronal electrophysiology, we examined the effects of direct THC microinfusions targeting the shell region of the NAc (NASh) and examined how THC may modulate the processing of fear-related emotional memory and concomitant activity states of the mesolimbic DA system. We report that intra-NASh THC dose-dependently potentiates the emotional salience of normally sub-threshold fear-conditioning cues. These effects were dependent upon intra-VTA transmission through GABAergic receptor mechanisms and intra-NASh DAergic transmission. Furthermore, doses of intra-NASh THC that potentiated fear memory salience were found to modulate intra-VTA neuronal network activity by increasing the spontaneous firing and bursting frequency of DAergic neurons whilst decreasing the activity levels of a subpopulation of putative GABAergic VTA neurons. These findings demonstrate that THC can act directly in the NASh to modulate mesolimbic activity states and induce disturbances in emotional salience and memory formation through modulation of VTA DAergic transmission. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Olfactory-triggered panic attacks among Khmer refugees: a contextual approach.

PubMed

Hinton, Devon; Pich, Vuth; Chhean, Dara; Pollack, Mark

2004-06-01

One hundred Khmer refugees attending a psychiatric clinic were surveyed to determine the prevalence of olfactory-triggered panic attacks as well as certain characteristics of the episodes, including trigger (i.e. type of odor), frequency, length, somatic symptoms, and the rate of associated flashbacks and catastrophic cognitions. Forty-five of the 100 patients had experienced an olfactory-triggered panic attack in the last month. Trauma associations and catastrophic cognitions (e.g. fears of a 'wind attack', 'weakness', and 'weak heart') were common during events of olfactory panic. Several case examples are presented. A multifactorial model of the generation of olfactory panic is adduced. The therapeutic implications of this model for the treatment of olfactory panic are discussed.

Nutritional value and taste play different roles in learning and memory in the honey bee (Apis mellifera).

PubMed

Mustard, Julie A; Alvarez, Valerie; Barocio, Sofy; Mathews, Jamie; Stoker, Alexander; Malik, Kashif

Honey bees will learn to respond to an odor when their antennae are stimulated with sucrose, even if they are not fed during the conditioning phase. However, if they are not fed, the memory of this association is significantly reduced 24 h after conditioning. These results suggest that stimulation of proboscis with sucrose and/or the nutritional quality of the reward plays an important role in establishing a long lasting memory. Three sugars, xylose, sorbitol and mannitol, are used to investigate the relationship among learning, sensory perception and nutritional value. The proboscis extension reflex is used to show that honey bees cannot taste these sugars, whereas mortality data suggest that bees can metabolize all three sugars. Feeding with sorbitol or xylose during olfactory associative conditioning restores robust 24 h memories. However, when given a free choice between consuming sucrose alone or sucrose supplemented with these nutritional sugars, bees did not show a preference for food containing the higher nutritional content. Furthermore, bees did not ingest solutions containing only the tasteless sugar even when it was the only food source. Together, these results suggest that nutritional content and not just sensory information is important for establishing long term memories, but that bees may not be able to assess nutritional content when it is disassociated from taste. Copyright © 2018 Elsevier Ltd. All rights reserved.

The reluctant visitor: an alkaloid in toxic nectar can reduce olfactory learning and memory in Asian honey bees.

PubMed

Zhang, Junjun; Wang, Zhengwei; Wen, Ping; Qu, Yufeng; Tan, Ken; Nieh, James C

2018-03-01

The nectar of the thunder god vine, Tripterygium hypoglaucum , contains a terpenoid, triptolide (TRP), that may be toxic to the sympatric Asian honey bee, Apis cerana , because honey produced from this nectar is toxic to bees. However, these bees will forage on, recruit for, and pollinate this plant during a seasonal dearth of preferred food sources. Olfactory learning plays a key role in forager constancy and pollination, and we therefore tested the effects of acute and chronic TRP feeding on forager olfactory learning, using proboscis extension reflex conditioning. At concentrations of 0.5-10 µg TRP ml -1 , there were no learning effects of acute exposure. However, memory retention (1 h after the last learning trial) significantly decreased by 56% following acute consumption of 0.5 µg TRP ml -1 Chronic exposure did not alter learning or memory, except at high concentrations (5 and 10 µg TRP ml -1 ). TRP concentrations in nectar may therefore not significantly harm plant pollination. Surprisingly, TRP slightly increased bee survival, and thus other components in T. hypoglaucum honey may be toxic. Long-term exposure to TRP could have colony effects but these may be ameliorated by the bees' aversion to T. hypoglaucum nectar when other food sources are available and, perhaps, by detoxification mechanisms. The co-evolution of this plant and its reluctant visitor may therefore likely illustrate a classic compromise between the interests of both actors. © 2018. Published by The Company of Biologists Ltd.

Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lu; Gallagher, Evan P., E-mail: evang3@uw.edu

2013-01-15

Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidativemore » stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The olfactory antioxidant response is blocked by Nrf2 knockdown. ► Disruption of olfactory neurobehaviors is associated with Nrf2 knockdown. ► Nrf2 morphants show increased cell death and olfactory sensory neuron loss.« less

Olfactory-Triggered Panic Attacks Among Khmer Refugees: A Contextual Approach

PubMed Central

Hinton, Devon; Pich, Vuth; Chhean, Dara; Pollack, Mark

2009-01-01

One hundred Khmer refugees attending a psychiatric clinic were surveyed to determine the prevalence of olfactory-triggered panic attacks as well as certain characteristics of the episodes, including trigger (i.e. type of odor), frequency, length, somatic symptoms, and the rate of associated flashbacks and catastrophic cognitions. Forty-five of the 100 patients had experienced an olfactory-triggered panic attack in the last month. Trauma associations and catastrophic cognitions (e.g. fears of a ‘wind attack,’ ‘weakness,’ and ‘weak heart’) were common during events of olfactory panic. Several case examples are presented. A multifactorial model of the generation of olfactory panic is adduced. The therapeutic implications of this model for the treatment of olfactory panic are discussed. PMID:15446720

Involvement of DNA methylation in memory processing in the honey bee.

PubMed

Lockett, Gabrielle A; Helliwell, Paul; Maleszka, Ryszard

2010-08-23

DNA methylation, an important and evolutionarily conserved epigenetic mechanism, is implicated in learning and memory processes in vertebrates, but its role in behaviour in invertebrates is unknown. We examined the role of DNA methylation in memory in the honey bee using an appetitive Pavlovian olfactory discrimination task, and by assessing the expression of DNA methyltransferase3, a key driver of epigenetic reprogramming. Here we report that DNA methyltransferase inhibition reduces acquisition retention and alters the extinction depending on treatment time, and DNA methyltransferase3 is upregulated after training. Our findings add to the understanding of epigenetic mechanisms in learning and memory, extending known roles of DNA methylation to appetitive and extinction memory, and for the first time implicate DNA methylation in memory in invertebrates.

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

PubMed Central

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-01-01

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962

Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

PubMed

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-05-22

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

Olfactory epithelium changes in germfree mice

PubMed Central

François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

2016-01-01

Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

Octopamine and Dopamine differentially modulate the nicotine-induced calcium response in Drosophila Mushroom Body Kenyon Cells.

PubMed

Leyton, V; Goles, N I; Fuenzalida-Uribe, N; Campusano, J M

2014-02-07

In Drosophila associative olfactory learning, an odor, the conditioned stimulus (CS), is paired to an unconditioned stimulus (US). The CS and US information arrive at the Mushroom Bodies (MB), a Drosophila brain region that processes the information to generate new memories. It has been shown that olfactory information is conveyed through cholinergic inputs that activate nicotinic acetylcholine receptors (nAChRs) in the MB, while the US is coded by biogenic amine (BA) systems that innervate the MB. In this regard, the MB acts as a coincidence detector. A better understanding of the properties of the responses gated by nicotinic and BA receptors is required to get insights on the cellular and molecular mechanisms responsible for memory formation. In recent years, information has become available on the properties of the responses induced by nAChR activation in Kenyon Cells (KCs), the main neuronal MB population. However, very little information exists on the responses induced by aminergic systems in fly MB. Here we have evaluated some of the properties of the calcium responses gated by Dopamine (DA) and Octopamine (Oct) in identified KCs in culture. We report that exposure to BAs induces a fast but rather modest increase in intracellular calcium levels in cultured KCs. The responses to Oct and DA are fully blocked by a VGCC blocker, while they are differentially modulated by cAMP. Moreover, co-application of BAs and nicotine has different effects on intracellular calcium levels: while DA and nicotine effects are additive, Oct and nicotine induce a synergistic increase in calcium levels. These results suggest that a differential modulation of nicotine-induced calcium increase by DA and Oct could contribute to the events leading to learning and memory in flies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Sex differences in catechol contents in the olfactory bulb of control and unilaterally deprived rats.

PubMed

Gómez, C; Briñón, J G; Valero, J; Recio, J S; Murias, A R; Curto, G G; Orio, L; Colado, M I; Alonso, J R

2007-03-01

The dopaminergic system plays important roles in the modulation of olfactory transmission. The present study examines the distribution of dopaminergic cells and the content of dopamine (DA) and its metabolites in control and deprived olfactory bulbs (OB), focusing on the differences between sexes. The content of DA and of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by HPLC. The morphology and distribution of dopaminergic neurons were studied using tyrosine hydroxylase (TH) immunohistochemistry. Cells were typified with TH-parvalbumin, TH-cholecystokinin or TH-neurocalcin double-immunofluorescence assays. Biochemical analyses revealed sex differences in the content of DA and of its metabolites. In normal conditions, the OBs of male rats had higher concentrations of DA, DOPAC and HVA than the OBs of females. The immunohistochemical data pointed to sex differences in the number of TH-immunopositive cells (higher in male than in female rats). Colocalization analyses revealed that dopaminergic cells constitute a different cell subpopulation from those labelled after parvalbumin, cholecystokinin or neurocalcin immunostaining. Unilateral olfactory deprivation caused dramatic alterations in the dopaminergic system. The DA content and the density of dopaminergic cells decreased, the contents of DA and DOPAC as well as TH immunoreactivity were similar in deprived males and females and, finally, the metabolite/neurotransmitter ratio increased. Our results show that the dopaminergic modulation of olfactory transmission seems to differ between males and females and that it is regulated by peripheral olfactory activity. A possible role of the dopaminergic system in the sexually different olfactory sensitivity, discrimination and memory is discussed.

Neural Correlates of Odor Learning in the Presynaptic Microglomerular Circuitry in the Honeybee Mushroom Body Calyx.

PubMed

Haenicke, Joachim; Yamagata, Nobuhiro; Zwaka, Hanna; Nawrot, Martin; Menzel, Randolf

2018-01-01

The mushroom body (MB) in insects is known as a major center for associative learning and memory, although exact locations for the correlating memory traces remain to be elucidated. Here, we asked whether presynaptic boutons of olfactory projection neurons (PNs) in the main input site of the MB undergo neuronal plasticity during classical odor-reward conditioning and correlate with the conditioned behavior. We simultaneously measured Ca 2+ responses in the boutons and conditioned behavioral responses to learned odors in honeybees. We found that the absolute amount of the neural change for the rewarded but not for the unrewarded odor was correlated with the behavioral learning rate across individuals. The temporal profile of the induced changes matched with odor response dynamics of the MB-associated inhibitory neurons, suggestive of activity modulation of boutons by this neural class. We hypothesize the circuit-specific neural plasticity relates to the learned value of the stimulus and underlies the conditioned behavior of the bees.

Olfactory Functioning in First-Episode Psychosis.

PubMed

Kamath, Vidyulata; Lasutschinkow, Patricia; Ishizuka, Koko; Sawa, Akira

2018-04-06

Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.

Nitrogen dioxide pollution exposure is associated with olfactory dysfunction in older US adults

PubMed Central

Adams, Dara R.; Ajmani, Gaurav S.; Pun, Vivian C.; Wroblewski, Kristen E.; Kern, David W.; Schumm, L. Philip; McClintock, Martha K.; Suh, Helen H.; Pinto, Jayant M.

2017-01-01

Background Olfactory dysfunction has profound effects on quality of life, physical and social function, and mortality itself. Nitrogen dioxide (NO2) is a pervasive air pollutant that is associated with respiratory diseases. Given the olfactory nerve’s anatomic exposure to airborne pollutants, we investigated the relationship between NO2 exposure and olfactory dysfunction. Methods The ability to identify odors was evaluated using a validated test in respondents from the National Social Life, Health, and Aging Project (NSHAP), a representative probability sample of home-dwelling, older US adults ages 57–85. Exposure to NO2 pollution was assessed using measurements obtained from the US EPA AIRS ambient monitoring site closest to each respondent’s home. We tested the association between NO2 exposure and olfactory dysfunction using multivariate logistic regression. Results Among older adults in the US, 22.6% had impaired olfactory function, defined as ≤ 3 correct (out of 5) on the odor identification test. Median NO2 exposure during the 365 days prior to the interview date was 14.7 ppb (interquartile range [IQR] 10.8–19.7 ppb). An IQR increase in NO2 exposure was associated with increased odds of olfactory dysfunction (OR 1.35, 95% CI: 1.07–1.72), adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and season of the home interview (n=1,823). Conclusion We show for the first time that NO2 exposure is associated with olfactory dysfunction in older US adults. These results suggest an important role for NO2 exposure on olfactory dysfunction, and, potentially, nasal disease more broadly. PMID:27620703

The brain structural and cognitive basis of odor identification deficits in mild cognitive impairment and Alzheimer’s disease

PubMed Central

2014-01-01

Background The objectives of this study were to explore the relationship between olfactory impairment, cognitive measures, and brain structure volumes in healthy elderly individuals, compared to patients with amnestic mild cognitive impairment (aMCI) or early Alzheimer’s disease (AD). The primary aim was to elucidate possible differences in cognitive scores and brain structure volumes between aMCI/AD patients with relatively intact odor identification (OI) ability and those with reduced ability. Methods Twelve patients with aMCI, six with early AD, and 30 control subjects were included. OI abilities were assessed with the Brief Smell Identification Test (B-SIT) and Sniffin Sticks Identification Test (SSIT). Neuropsychological tests of executive functions and memory were performed. Brain structural volumes were obtained from T1 weighted 3D MRI at 3 Tesla. Statistical comparisons between the patients with aMCI and AD indicated no significant differences in performance on most tests. Since the groups were small and AD patients were in an early phase of disease, all patients were subsequently considered together as a single group for studying OI. Patients were subdivided into relatively intact (scores >50%) and reduced OI (≤ 50% score) on the olfactory tests. Results The aMCI/AD group with reduced OI ability, as measured by both B-SIT and SSIT, had significantly smaller hippocampal volume as compared to the patient group with OI scores > 50%. There was a significant association between OI scores and hippocampal volume in the patient (not the control) group. Similar changes with tests of executive function and memory were not found. Low OI scores on B-SIT were associated with conversion from aMCI to AD in patients. The reduced OI patient group was significantly faster on Rey complex figure copying than the fairly intact OI group. Conclusion The results from this pilot study suggest that the reduction in the size of hippocampus in connection with early AD is associated more with loss of OI ability rather than loss of memory, thus demonstrating that impaired OI is an early marker of medial temporal lobe degeneration. PMID:25154749

Mammalian social odours: attraction and individual recognition

PubMed Central

Brennan, Peter A; Kendrick, Keith M

2006-01-01

Mammalian social systems rely on signals passed between individuals conveying information including sex, reproductive status, individual identity, ownership, competitive ability and health status. Many of these signals take the form of complex mixtures of molecules sensed by chemosensory systems and have important influences on a variety of behaviours that are vital for reproductive success, such as parent–offspring attachment, mate choice and territorial marking. This article aims to review the nature of these chemosensory cues and the neural pathways mediating their physiological and behavioural effects. Despite the complexities of mammalian societies, there are instances where single molecules can act as classical pheromones attracting interest and approach behaviour. Chemosignals with relatively high volatility can be used to signal at a distance and are sensed by the main olfactory system. Most mammals also possess a vomeronasal system, which is specialized to detect relatively non-volatile chemosensory cues following direct contact. Single attractant molecules are sensed by highly specific receptors using a labelled line pathway. These act alongside more complex mixtures of signals that are required to signal individual identity. There are multiple sources of such individuality chemosignals, based on the highly polymorphic genes of the major histocompatibility complex (MHC) or lipocalins such as the mouse major urinary proteins. The individual profile of volatile components that make up an individual odour signature can be sensed by the main olfactory system, as the pattern of activity across an array of broadly tuned receptor types. In addition, the vomeronasal system can respond highly selectively to non-volatile peptide ligands associated with the MHC, acting at the V2r class of vomeronasal receptor. The ability to recognize individuals or their genetic relatedness plays an important role in mammalian social behaviour. Thus robust systems for olfactory learning and recognition of chemosensory individuality have evolved, often associated with major life events, such as mating, parturition or neonatal development. These forms of learning share common features, such as increased noradrenaline evoked by somatosensory stimulation, which results in neural changes at the level of the olfactory bulb. In the main olfactory bulb, these changes are likely to refine the pattern of activity in response to the learned odour, enhancing its discrimination from those of similar odours. In the accessory olfactory bulb, memory formation is hypothesized to involve a selective inhibition, which disrupts the transmission of the learned chemosignal from the mating male. Information from the main olfactory and vomeronasal systems is integrated at the level of the corticomedial amygdala, which forms the most important pathway by which social odours mediate their behavioural and physiological effects. Recent evidence suggests that this region may also play an important role in the learning and recognition of social chemosignals. PMID:17118924

Multimodal Floral Signals and Moth Foraging Decisions

PubMed Central

Riffell, Jeffrey A.; Alarcón, Ruben

2013-01-01

Background Combinations of floral traits – which operate as attractive signals to pollinators – act on multiple sensory modalities. For Manduca sexta hawkmoths, how learning modifies foraging decisions in response to those traits remains untested, and the contribution of visual and olfactory floral displays on behavior remains unclear. Methodology/Principal Findings Using M. sexta and the floral traits of two important nectar resources in southwestern USA, Datura wrightii and Agave palmeri, we examined the relative importance of olfactory and visual signals. Natural visual and olfactory cues from D. wrightii and A. palmeri flowers permits testing the cues at their native intensities and composition – a contrast to many studies that have used artificial stimuli (essential oils, single odorants) that are less ecologically relevant. Results from a series of two-choice assays where the olfactory and visual floral displays were manipulated showed that naïve hawkmoths preferred flowers displaying both olfactory and visual cues. Furthermore, experiments using A. palmeri flowers – a species that is not very attractive to hawkmoths – showed that the visual and olfactory displays did not have synergistic effects. The combination of olfactory and visual display of D. wrightii, however – a flower that is highly attractive to naïve hawkmoths – did influence the time moths spent feeding from the flowers. The importance of the olfactory and visual signals were further demonstrated in learning experiments in which experienced moths, when exposed to uncoupled floral displays, ultimately chose flowers based on the previously experienced olfactory, and not visual, signals. These moths, however, had significantly longer decision times than moths exposed to coupled floral displays. Conclusions/Significance These results highlight the importance of specific sensory modalities for foraging hawkmoths while also suggesting that they learn the floral displays as combinatorial signals and use the integrated floral traits from their memory traces to mediate future foraging decisions. PMID:23991154

Intrinsic and Extrinsic Neuromodulation of Olfactory Processing.

PubMed

Lizbinski, Kristyn M; Dacks, Andrew M

2017-01-01

Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a "memory" by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform.

Successful acquisition of an olfactory discrimination test by Asian elephants, Elephas maximus.

PubMed

Arvidsson, Josefin; Amundin, Mats; Laska, Matthias

2012-02-01

The present study demonstrates that Asian elephants, Elephas maximus, can successfully be trained to cooperate in an olfactory discrimination test based on a food-rewarded two-alternative instrumental conditioning procedure. The animals learned the basic principle of the test within only 60 trials and readily mastered intramodal stimulus transfer tasks. Further, they were capable of distinguishing between structurally related odor stimuli and remembered the reward value of previously learned odor stimuli after 2, 4, 8, and 16 weeks of recess without any signs of forgetting. The precision and consistency of the elephants' performance in tests of odor discrimination ability and long-term odor memory demonstrate the suitability of this method for assessing olfactory function in this proboscid species. An across-species comparison of several measures of olfactory learning capabilities such as speed of initial task acquisition and ability to master intramodal stimulus transfer tasks shows that Asian elephants are at least as good in their performance as mice, rats, and dogs, and clearly superior to nonhuman primates and fur seals. The results support the notion that Asian elephants may use olfactory cues for social communication and food selection and that the sense of smell may play an important role in the control of their behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

Olfactory systems and neural circuits that modulate predator odor fear

PubMed Central

Takahashi, Lorey K.

2014-01-01

When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator odors activate fear. PMID:24653685

Olfactory systems and neural circuits that modulate predator odor fear.

PubMed

Takahashi, Lorey K

2014-01-01

When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator odors activate fear.

Monoterpenoid-based preparations in beehives affect learning, memory, and gene expression in the bee brain.

PubMed

Bonnafé, Elsa; Alayrangues, Julie; Hotier, Lucie; Massou, Isabelle; Renom, Allan; Souesme, Guillaume; Marty, Pierre; Allaoua, Marion; Treilhou, Michel; Armengaud, Catherine

2017-02-01

Bees are exposed in their environment to contaminants that can weaken the colony and contribute to bee declines. Monoterpenoid-based preparations can be introduced into hives to control the parasitic mite Varroa destructor. The long-term effects of monoterpenoids are poorly investigated. Olfactory conditioning of the proboscis extension reflex (PER) has been used to evaluate the impact of stressors on cognitive functions of the honeybee such as learning and memory. The authors tested the PER to odorants on bees after exposure to monoterpenoids in hives. Octopamine receptors, transient receptor potential-like (TRPL), and γ-aminobutyric acid channels are thought to play a critical role in the memory of food experience. Gene expression levels of Amoa1, Rdl, and trpl were evaluated in parallel in the bee brain because these genes code for the cellular targets of monoterpenoids and some pesticides and neural circuits of memory require their expression. The miticide impaired the PER to odors in the 3 wk following treatment. Short-term and long-term olfactory memories were improved months after introduction of the monoterpenoids into the beehives. Chronic exposure to the miticide had significant effects on Amoa1, Rdl, and trpl gene expressions and modified seasonal changes in the expression of these genes in the brain. The decrease of expression of these genes in winter could partly explain the improvement of memory. The present study has led to new insights into alternative treatments, especially on their effects on memory and expression of selected genes involved in this cognitive function. Environ Toxicol Chem 2017;36:337-345. © 2016 SETAC. © 2016 SETAC.

The effects of partial sleep restriction and altered sleep timing on olfactory performance.

PubMed

McNeil, J; Forest, G; Hintze, L J; Brunet, J-F; Doucet, É

2017-12-01

Olfaction can increase the drive to eat and may partially explain the consistent increases in energy intake (EI) following sleep restriction. We investigated the effects of 50% sleep restriction with altered sleep timing on olfactory performance. We also evaluated whether changes (Δ) in olfactory performance were associated with Δ24 h EI. Twelve men and six women (age: 23±4 years; BMI: 23±3 kg/m 2 ) completed three randomized cross-over conditions: habitual sleep duration, 50% sleep restriction with advanced wake-time, and 50% sleep restriction with delayed bedtime. Sleep was measured in-laboratory (polysomnography). Olfactory performance ('sniffin sticks') and 24 h EI (food menu) were evaluated the next day. A trend for a significant condition*sex interaction was noted for threshold-discrimination-identification (TDI) scores (P=0.09); TDI scores were lowest in women and highest in men, following sleep restriction with advanced wake-time. Δolfactory performance were not associated with Δ24 h EI. The impact of sleep restriction on olfactory performance may differ between sexes. Changes in olfactory performance were not associated with changes in 24 h EI. Studies investigating prolonged effects of sleep loss on the relationship between olfactory performance with EI are needed.

Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

PubMed

Gur, Rotem; Tendler, Alex; Wagner, Shlomo

2014-09-01

Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis.

PubMed

Apter, A J; Gent, J F; Frank, M E

1999-09-01

To characterize the relationship between allergic rhinitis, the severity and duration of nasal disease, olfactory function, and self-reported olfactory symptoms, including fluctuations or distortions in odor perception. Assessment of olfactory function and symptoms of 90 patients with allergic rhinitis. A clinic of a university teaching hospital and research facility. Sixty patients who presented to the Taste and Smell Clinic who had positive allergy test results and 30 patients who presented to the Allergy-Immunology Clinic. The Taste and Smell Clinic patients were grouped by nasal-sinus disease status (30 without chronic rhinosinusitis or nasal polyps, 14 with chronic rhinosinusitis but without polyps, and 16 with nasal polyps). Subjective olfactory symptom questionnaire and objective olfactory function tests. The Allergy-Immunology Clinic patients were diagnosed as being normosmic and the Taste and Smell Clinic patients as being hyposmic or anosmic with olfactory loss that increased significantly with nasal-sinus disease severity. Comparisons with normative data confirm that olfactory scores observed in all groups were significantly lower than expected because of the aging process alone. The self-reported duration of olfactory loss increased significantly with nasal-sinus disease severity. The Taste and Smell Clinic patients without chronic rhinosinusitis or nasal polyps reported the greatest incidence of olfactory distortions and olfactory loss associated with upper respiratory tract infections. There appears to be a continuum of duration and severity of olfactory loss in allergic rhinitis that parallels increasing severity of nasal-sinus disease. As a result of the increased frequency of respiratory infection associated with allergic rhinitis, these patients are at risk for damage to the olfactory epithelium.

Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function.

PubMed

Landis, Basile N; Scheibe, Mandy; Weber, Cornelia; Berger, Robert; Brämerson, Annika; Bende, Mats; Nordin, Steven; Hummel, Thomas

2010-08-01

Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 +/- 0.6 points and 22.9 +/- 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi(2), F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r (210) = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory-gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.

A potential link among biogenic amines-based pesticides, learning and memory, and colony collapse disorder: a unique hypothesis.

PubMed

Farooqui, Tahira

2013-01-01

Pesticides are substances that have been widely used throughout the world to kill, repel, or control organisms such as certain forms of plants or animals considered as pests. Depending on their type, dose, and persistence in the environment, they can have impact even on non-target species such as beneficial insects (honeybees) in different ways, including reduction in their survival rate and interference with their reproduction process. Honeybee Apis mellifera is a major pollinator and has substantial economical and ecological values. Colony collapse disorder (CCD) is a mysterious phenomenon in which adult honeybee workers suddenly abandon from their hives, leaving behind food, brood, and queen. It is lately drawing a lot of attention due to pollination crisis as well as global agriculture and medical demands. If the problem of CCD is not resolved soon enough, this could have a major impact on food industry affecting world's economy a big time. Causes of CCD are not known. In this overview, I discuss CCD, biogenic amines-based-pesticides (neonicotinoids and formamidines), and their disruptive effects on biogenic amine signaling causing olfactory dysfunction in honeybees. According to my hypothesis, chronic exposure of biogenic amines-based-pesticides to honeybee foragers in hives and agricultural fields can disrupt neural cholinergic and octopaminergic signaling. Abnormality in biogenic amines-mediated neuronal signaling impairs their olfactory learning and memory, therefore foragers do not return to their hive - a possible cause of CCD. This overview is an attempt to discuss a hypothetical link among biogenic amines-based pesticides, olfactory learning and memory, and CCD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cognitive Load Alters Neuronal Processing of Food Odors.

PubMed

Hoffmann-Hensel, Sonja Maria; Sijben, Rik; Rodriguez-Raecke, Rea; Freiherr, Jessica

2017-10-31

Obesity is a major health concern in modern societies. Although decreased physical activity and enhanced intake of high-caloric foods are important risk factors for developing obesity, human behavior during eating also plays a role. Previous studies have shown that distraction while eating increases food intake and leads to impaired processing of food stimuli. As olfaction is the most important sense involved in flavor perception, we used functional magnetic resonance imaging techniques to investigate the influence of cognitive memory load on olfactory perception and processing. Low- and high-caloric food odors were presented in combination with either low or high cognitive loads utilizing a memory task. The efficacy of the memory task was verified by a decrease in participant recall accuracy and an increase in skin conductance response during high cognitive load. Our behavioral data reveal a diminished perceived intensity for low- but not high-caloric food odors during high cognitive load. For low-caloric food odors, bilateral orbitofrontal (OFC) and piriform cortices (pirC) showed significantly lower activity during high compared with low cognitive load. For high-caloric food odors, a similar effect was established in pirC, but not in OFC. Insula activity correlates with higher intensity ratings found during the low cognitive load condition. We conclude lower activity in pirC and OFC to be responsible for diminished intensity perception, comparable to results in olfactory impaired patients and elderly. Further studies should investigate the influence of olfactory/gustatory intensities on food choices under distraction with special regards to low-caloric food. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of Ambient Air Pollution Exposure on Olfaction: A Review.

PubMed

Ajmani, Gaurav S; Suh, Helen H; Pinto, Jayant M

2016-11-01

Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution-related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. Citation: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683-1693; http://dx.doi.org/10.1289/EHP136.

The vanadium (IV) compound rescues septo-hippocampal cholinergic neurons from neurodegeneration in olfactory bulbectomized mice.

PubMed

Han, F; Shioda, N; Moriguchi, S; Qin, Z-H; Fukunaga, K

2008-02-06

The bilateral olfactory bulbectomy (OBX) mouse exhibits neurodegeneration of cholinergic neurons in the medial septum with concomitant cognitive deficits. Consistent with our previous observations, choline acetyltransferase (ChAT) protein levels in the medial septum decreased by 43.5% 2 weeks after OBX without changes in glutamic acid decarboxylase-65 (GAD65) levels. Interestingly, levels of the vesicular acetylcholine transporter (VAChT), which is localized at cholinergic neuron terminals, decreased both in hippocampal CA1 and CA3 regions following OBX. Confocal microscopy showed that VAChT expression was more severely reduced in CA3 14 days after OBX compared with CA1. Intriguingly, chronic treatment with a vanadium (IV) compound, VO(OPT) [bis(1-N-oxide-pyridine-2-thiolato)oxovanadium(IV)] (0.5-1 mg as vanadium (V)/kg/day, i.p.), significantly rescued cholinergic neurons in the medial septum in a dose-dependent manner. VO(OPT) treatment also prevented decreased VAChT immunoreactivity both in CA1 and CA3 regions in the hippocampus. Consistent with these findings, an impaired hippocampal long-term potentiation (LTP) and memory deficits seen in OBX mice were significantly prevented by VO(OPT) treatment. Taken together, OBX induces neurodegeneration of septo-hippocampal cholinergic neurons and impairment of memory-related behaviors. The neuroprotective effect of VO(OPT) could lead to novel therapeutic strategies to ameliorate cognitive deficits associated with cholinergic neuron degeneration in Alzheimer's disease and other neurodegenerative disorders.

Evolution, Discovery, and Interpretations of Arthropod Mushroom Bodies

PubMed Central

Strausfeld, Nicholas J.; Hansen, Lars; Li, Yongsheng; Gomez, Robert S.; Ito, Kei

1998-01-01

Mushroom bodies are prominent neuropils found in annelids and in all arthropod groups except crustaceans. First explicitly identified in 1850, the mushroom bodies differ in size and complexity between taxa, as well as between different castes of a single species of social insect. These differences led some early biologists to suggest that the mushroom bodies endow an arthropod with intelligence or the ability to execute voluntary actions, as opposed to innate behaviors. Recent physiological studies and mutant analyses have led to divergent interpretations. One interpretation is that the mushroom bodies conditionally relay to higher protocerebral centers information about sensory stimuli and the context in which they occur. Another interpretation is that they play a central role in learning and memory. Anatomical studies suggest that arthropod mushroom bodies are predominately associated with olfactory pathways except in phylogenetically basal insects. The prominent olfactory input to the mushroom body calyces in more recent insect orders is an acquired character. An overview of the history of research on the mushroom bodies, as well as comparative and evolutionary considerations, provides a conceptual framework for discussing the roles of these neuropils. PMID:10454370

Circuit Analysis of a Drosophila Dopamine Type 2 Receptor That Supports Anesthesia-Resistant Memory.

PubMed

Scholz-Kornehl, Sabrina; Schwärzel, Martin

2016-07-27

Dopamine is central to reinforcement processing and exerts this function in species ranging from humans to fruit flies. It can do so via two different types of receptors (i.e., D1 or D2) that mediate either augmentation or abatement of cellular cAMP levels. Whereas D1 receptors are known to contribute to Drosophila aversive odor learning per se, we here show that D2 receptors are specific for support of a consolidated form of odor memory known as anesthesia-resistant memory. By means of genetic mosaicism, we localize this function to Kenyon cells, the mushroom body intrinsic neurons, as well as GABAergic APL neurons and local interneurons of the antennal lobes, suggesting that consolidated anesthesia-resistant memory requires widespread dopaminergic modulation within the olfactory circuit. Additionally, dopaminergic neurons themselves require D2R, suggesting a critical role in dopamine release via its recognized autoreceptor function. Considering the dual role of dopamine in balancing memory acquisition (proactive function of dopamine) and its "forgetting" (retroactive function of dopamine), our analysis suggests D2R as central player of either process. Dopamine provides different information; while it mediates reinforcement during the learning act (proactive function), it balances memory performance between two antithetic processes thereafter (retroactive function) (i.e., forgetting and augmentation). Such bidirectional design can also be found at level of dopamine receptors, where augmenting D1 and abating D2 receptors are engaged to balance cellular cAMP levels. Here, we report that consolidated anesthesia-resistant memory (ARM), but not other concomitant memory phases, are sensitive to bidirectional dopaminergic signals. By means of genetic mosaicism, we identified widespread dopaminergic modulation within the olfactory circuit that suggests nonredundant and reiterating functions of D2R in support of ARM. Our results oppose ARM to its concomitant memory phases that localize to mushroom bodies and propose a decentralized organization of consolidated ARM. Copyright © 2016 the authors 0270-6474/16/367936-10$15.00/0.

Genealogical correspondence of a forebrain centre implies an executive brain in the protostome–deuterostome bilaterian ancestor

PubMed Central

2016-01-01

Orthologous genes involved in the formation of proteins associated with memory acquisition are similarly expressed in forebrain centres that exhibit similar cognitive properties. These proteins include cAMP-dependent protein kinase A catalytic subunit (PKA-Cα) and phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKII), both required for long-term memory formation which is enriched in rodent hippocampus and insect mushroom bodies, both implicated in allocentric memory and both possessing corresponding neuronal architectures. Antibodies against these proteins resolve forebrain centres, or their equivalents, having the same ground pattern of neuronal organization in species across five phyla. The ground pattern is defined by olfactory or chemosensory afferents supplying systems of parallel fibres of intrinsic neurons intersected by orthogonal domains of afferent and efferent arborizations with local interneurons providing feedback loops. The totality of shared characters implies a deep origin in the protostome–deuterostome bilaterian ancestor of elements of a learning and memory circuit. Proxies for such an ancestral taxon are simple extant bilaterians, particularly acoels that express PKA-Cα and pCaMKII in discrete anterior domains that can be properly referred to as brains. PMID:26598732

Drosophila Neprilysins Are Involved in Middle-Term and Long-Term Memory.

PubMed

Turrel, Oriane; Lampin-Saint-Amaux, Aurélie; Préat, Thomas; Goguel, Valérie

2016-09-14

Neprilysins are type II metalloproteinases known to degrade and inactivate a number of small peptides. Neprilysins in particular are the major amyloid-β peptide-degrading enzymes. In mouse models of Alzheimer's disease, neprilysin overexpression improves learning and memory deficits, whereas neprilysin deficiency aggravates the behavioral phenotypes. However, whether these enzymes are involved in memory in nonpathological conditions is an open question. Drosophila melanogaster is a well suited model system with which to address this issue. Several memory phases have been characterized in this organism and the neuronal circuits involved are well described. The fly genome contains five neprilysin-encoding genes, four of which are expressed in the adult. Using conditional RNA interference, we show here that all four neprilysins are involved in middle-term and long-term memory. Strikingly, all four are required in a single pair of neurons, the dorsal paired medial (DPM) neurons that broadly innervate the mushroom bodies (MBs), the center of olfactory memory. Neprilysins are also required in the MB, reflecting the functional relationship between the DPM neurons and the MB, a circuit believed to stabilize memories. Together, our data establish a role for neprilysins in two specific memory phases and further show that DPM neurons play a critical role in the proper targeting of neuropeptides involved in these processes. Neprilysins are endopeptidases known to degrade a number of small peptides. Neprilysin research has essentially focused on their role in Alzheimer's disease and heart failure. Here, we use Drosophila melanogaster to study whether neprilysins are involved in memory. Drosophila can form several types of olfactory memory and the neuronal structures involved are well described. Four neprilysin genes are expressed in adult Drosophila Using conditional RNA interference, we show that all four are specifically involved in middle-term memory (MTM) and long-term memory (LTM) and that their expression is required in the mushroom bodies and also in a single pair of closely connected neurons. The data show that these two neurons play a critical role in targeting neuropeptides essential for MTM and LTM. Copyright © 2016 the authors 0270-6474/16/369535-12$15.00/0.

Olfaction: New Understandings, Diagnostic Applications.

PubMed

Ruggiero, Gabrielle F; Wick, Jeannette Y

2016-11-01

Estimates indicate that 14 million Americans have olfactory dysfunction. As with other senses, such as sight and hearing, olfaction frequently declines with age. Impaired olfaction can be a warning sign of Parkinson's disease, sometimes occurring before motor symptoms develop. It's also an initial symptom of Alzheimer's dementia (AD); the amyloid plaques and tangles characterizing AD invade the olfactory bulb and hippocampus early in its course, hampering odor identification. Olfactory dysfunction is associated with some serious problems, including inability to smell warning odors (fire, gas) and impaired ability to taste food. Standardized, validated methods are available to measure several different dimensions of olfactory function, including odor identification, discrimination, and threshold levels. Researchers are currently studying the unique olfactory deficits associated with different conditions in hopes of identifying new, noninvasive tools for early diagnosis and treatment. Drugs may cause or contribute to olfactory dysfunction, but it can be difficult to pinpoint offending medications.

Antennal tactile learning in the honeybee: effect of nicotinic antagonists on memory dynamics.

PubMed

Dacher, M; Lagarrigue, A; Gauthier, M

2005-01-01

Restrained worker honeybees (Apis mellifera L.) are able to learn to associate antennal-scanning of a metal plate with a sucrose reinforcement delivered to the mouthparts. Learning occurs reliably in a single association of the two sensory stimuli. The involvement of nicotinic pathways in memory formation and retrieval processes was tested by injecting, into the whole brain through the median ocellus, either mecamylamine (0.6 microg per bee) or alpha-bungarotoxin (2.4 ng per bee). Saline served as a control. Mecamylamine injected 10 min before the retrieval test impairs the retention level tested 3 h and 24 h after single- or multi-trial learning. Retrieval tests performed at various times after the injection show that the blocking effect of mecamylamine lasts about 1 h. The drug has no effect on the reconsolidation or extinction processes. Mecamylamine injected 10 min before conditioning impairs single-trial learning but has no effect on five-trial learning and on the consolidation process. By contrast, alpha-bungarotoxin only impairs the formation of long-term memory (24 h) induced by the five-trial learning and has no effect on medium-term memory (3 h), on single-trial learning or on the retrieval process. Hence, owing to previous data, at least two kinds of nicotinic receptors seem to be involved in honeybee memory, an alpha-bungarotoxin-sensitive and an alpha-bungarotoxin-insensitive receptor. Our results extend to antennal mechanosensory conditioning the role of the cholinergic system that we had previously described for olfactory conditioning in the honeybee. Moreover, we describe here in this insect a pharmacological dissociation between alpha-bungarotoxin sensitive long-term memory and alpha-bungarotoxin insensitive medium-term memory, the last one being affected by mecamylamine.

The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.

PubMed

Bourdet, Isabelle; Preat, Thomas; Goguel, Valérie

2015-01-21

The APP plays a central role in AD, a pathology that first manifests as a memory decline. Understanding the role of APP in normal cognition is fundamental in understanding the progression of AD, and mammalian studies have pointed to a role of secreted APPα in memory. In Drosophila, we recently showed that APPL, the fly APP ortholog, is required for associative memory. In the present study, we aimed to characterize which form of APPL is involved in this process. We show that expression of a secreted-APPL form in the mushroom bodies, the center for olfactory memory, is able to rescue the memory deficit caused by APPL partial loss of function. We next assessed the impact on memory of the Drosophila α-secretase kuzbanian (KUZ), the enzyme initiating the nonamyloidogenic pathway that produces secreted APPLα. Strikingly, KUZ overexpression not only failed to rescue the memory deficit caused by APPL loss of function, it exacerbated this deficit. We further show that in addition to an increase in secreted-APPL forms, KUZ overexpression caused a decrease of membrane-bound full-length species that could explain the memory deficit. Indeed, we observed that transient expression of a constitutive membrane-bound mutant APPL form is sufficient to rescue the memory deficit caused by APPL reduction, revealing for the first time a role of full-length APPL in memory formation. Our data demonstrate that, in addition to secreted APPL, the noncleaved form is involved in memory, raising the possibility that secreted and full-length APPL act together in memory processes. Copyright © 2015 the authors 0270-6474/15/351043-09$15.00/0.

Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: possible involvement of glutamatergic and cholinergic systems.

PubMed

Le, Xoan Thi; Pham, Hang Thi Nguyet; Do, Phuong Thi; Fujiwara, Hironori; Tanaka, Ken; Li, Feng; Van Nguyen, Tai; Nguyen, Khoi Minh; Matsumoto, Kinzo

2013-10-01

This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

PubMed

Woodward, Matthew R; Hafeez, Muhammad Ubaid; Qi, Qianya; Riaz, Ahmed; Benedict, Ralph H B; Yan, Li; Szigeti, Kinga

2018-04-19

To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. Prospective multicenter cross-sectional study with a longitudinal arm. Outpatient memory diagnostic clinics in New York and Texas. Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Ethmoid Histopathology Does Not Predict Olfactory Outcomes after Endoscopic Sinus Surgery

PubMed Central

Soler, Zachary M.; Sauer, David A.; Mace, Jess C.; Smith, Timothy L.

2010-01-01

BACKGROUND Histologic inflammation correlates with the degree of baseline olfactory dysfunction in patients with chronic rhinosinusitis (CRS), however factors associated with improvement in olfactory status after endoscopic sinus surgery (ESS) remain elusive. OBJECTIVE Our purpose was to compare histopathologic findings in CRS patients with olfactory loss and evaluate whether inflammatory markers can predict long-term olfactory improvement after ESS. METHODS Adult (≥18 years) patients with CRS were prospectively enrolled after electing ESS due to failed medical management. Mucosal tissue specimens were collected at the time of surgery and underwent pathlogic review in a blinded fashion. Subjects completed the 40-item Smell Identification Test (SIT) preoperatively and at least 6 months postoperatively. Multivariate logistic regression was used to identify histologic factors associated with postoperative improvement in SIT score. RESULTS The final cohort was comprised of 101 patients with a mean follow-up of 16.7 ± 6.0 months. Mean mucosal eosinophil count was higher in patients with hyposmia and anosmia (p<0.001). Patients with preoperative anosmia were more likely to have greater severity of BM thickening compared to subjects with hyposmia or normosmia (p=0.021). In patients with olfactory dysfunction, 54.7% reported olfactory improvement of at least 4 points on postoperative SIT scores. After controlling for nasal polyposis, histologic variables were not associated with postoperative improvement in olfaction. CONCLUSIONS Patients with severe olfactory dysfunction were more likely to have mucosal eosinophilia and basement membrane thickening on ethmoid histopathologic examination compared to normosmics. The presence of specific histologic inflammatory findings did not however predict olfactory improvement after surgery. PMID:20819467

A view of Kanerva's sparse distributed memory

NASA Technical Reports Server (NTRS)

Denning, P. J.

1986-01-01

Pentti Kanerva is working on a new class of computers, which are called pattern computers. Pattern computers may close the gap between capabilities of biological organisms to recognize and act on patterns (visual, auditory, tactile, or olfactory) and capabilities of modern computers. Combinations of numeric, symbolic, and pattern computers may one day be capable of sustaining robots. The overview of the requirements for a pattern computer, a summary of Kanerva's Sparse Distributed Memory (SDM), and examples of tasks this computer can be expected to perform well are given.

Histone deacetylase inhibitor treatment restores memory-related gene expression and learning ability in neonicotinoid-treated Apis mellifera.

PubMed

Hu, Y-T; Tang, C-K; Wu, C-P; Wu, P-C; Yang, E-C; Tai, C-C; Wu, Y-L

2018-04-25

Apis mellifera plays crucial roles in maintaining the balance of global ecosystems and stability of agricultural systems by helping pollination of flowering plants, including many crops. In recent years, this balance has been disrupted greatly by some pesticides, which results in great losses of honeybees worldwide. Previous studies have found that pesticide-caused memory loss might be one of the major reasons for colony loss. Histone deacetylase inhibitors (HDACis) are chemical compounds that inhibit the activity of histone deacetylases and are known to cause hyperacetylation of histone cores and influence gene expression. In our study, the HDACi sodium butyrate was applied to honeybees as a dietary supplement. The effect of sodium butyrate on the expression profiles of memory-related genes was analysed by quantitative reverse transcription PCR. The results revealed that this HDACi had up-regulation effects on most of the memory-related genes in bees, even in bees treated with imidacloprid. In addition, using the proboscis extension reflex to evaluate olfactory learning in bees, we found that this HDACi boosted the memory formation of bees after impairment owing to imidacloprid exposure. This study investigated the association between gene expression and memory formation from an epigenetic perspective. Additionally, we further demonstrate the possibility of enhancing bee learning using HDACis and provide initial data for future research. © 2018 The Royal Entomological Society.

Odour discrimination and identification are improved in early blindness.

PubMed

Cuevas, Isabel; Plaza, Paula; Rombaux, Philippe; De Volder, Anne G; Renier, Laurent

2009-12-01

Previous studies showed that early blind humans develop superior abilities in the use of their remaining senses, hypothetically due to a functional reorganization of the deprived visual brain areas. While auditory and tactile functions have been investigated for long, little is known about the effects of early visual deprivation on olfactory processing. However, blind humans make an extensive use of olfactory information in their daily life. Here we investigated olfactory discrimination and identification abilities in early blind subjects and age-matched sighted controls. Three levels of cuing were used in the identification task, i.e., free-identification (no cue), categorization (semantic cues) and multiple choice (semantic and phonological cues). Early blind subjects significantly outperformed the controls in odour discrimination, free-identification and categorization. In addition, the larger group difference was observed in the free-identification as compared to the categorization and the multiple choice conditions. This indicated that a better access to the semantic information from odour perception accounted for part of the improved olfactory performances in odour identification in the blind. We concluded that early blind subjects have both improved perceptual abilities and a better access to the information stored in semantic memory than sighted subjects.

From Perception to Metacognition: Auditory and Olfactory Functions in Early Blind, Late Blind, and Sighted Individuals

PubMed Central

Cornell Kärnekull, Stina; Arshamian, Artin; Nilsson, Mats E.; Larsson, Maria

2016-01-01

Although evidence is mixed, studies have shown that blind individuals perform better than sighted at specific auditory, tactile, and chemosensory tasks. However, few studies have assessed blind and sighted individuals across different sensory modalities in the same study. We tested early blind (n = 15), late blind (n = 15), and sighted (n = 30) participants with analogous olfactory and auditory tests in absolute threshold, discrimination, identification, episodic recognition, and metacognitive ability. Although the multivariate analysis of variance (MANOVA) showed no overall effect of blindness and no interaction with modality, follow-up between-group contrasts indicated a blind-over-sighted advantage in auditory episodic recognition, that was most pronounced in early blind individuals. In contrast to the auditory modality, there was no empirical support for compensatory effects in any of the olfactory tasks. There was no conclusive evidence for group differences in metacognitive ability to predict episodic recognition performance. Taken together, the results showed no evidence of an overall superior performance in blind relative sighted individuals across olfactory and auditory functions, although early blind individuals exceled in episodic auditory recognition memory. This observation may be related to an experience-induced increase in auditory attentional capacity. PMID:27729884

Sniffing shapes the dynamics of olfactory bulb gamma oscillations in awake behaving rats.

PubMed

Rosero, Mario A; Aylwin, María L

2011-09-01

Mammals actively sample the environment for relevant olfactory objects. This active sampling is revealed by rapid changes in respiratory rate that influence the olfactory input. Yet the role of sniffing in shaping the neural responses to odorants has not been elucidated. In the olfactory bulb (OB), odorant-evoked gamma oscillations reflect the synchronous activity of mitral/tufted cells, a proposed mechanism for odorant representation. Here we examined the effect of sniffing frequency on the odorant-evoked gamma oscillations in the OB. We simultaneously recorded the respiratory rate and the local field potential while rats performed a lick/no-lick olfactory discrimination task with low odorant concentrations. High-frequency sniffing (HFS) augmented the power of gamma oscillations, suggesting an increase in the sensitivity to odorants. By contrast, coupling of the gamma oscillations to the sniff cycle and the amplitude of individual bursts were not modified by the respiratory rate. However, HFS prolonged the overall response to odorants and increased the frequency of the gamma oscillations, indicating that HFS reduces the adaptation to continuous odorant stimulation. Therefore, the increase in gamma power during HFS is the result of more frequent gamma bursts and the extended response to odorants. As odorant discrimination can be performed in a single sniff, a reduction in the adaptation mediated by HFS of novel odorants may facilitate odorant memory formation for subsequent odorant identification. Finally, these results corroborate that olfactory sampling should be integrated to the study of odorant coding in behaving animals. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task.

PubMed

MacQueen, David A; Dalrymple, Savannah R; Drobes, David J; Diamond, David M

2016-06-01

Developed as a tool to assess working memory capacity in rodents, the odor span task (OST) has significant potential to advance drug discovery in animal models of psychiatric disorders. Prior investigations indicate OST performance is impaired by systemic administration of N-methyl-d-aspartate receptor (NMDA-r) antagonists and is sensitive to cholinergic manipulations. The present study sought to determine whether an impairment in OST performance can be produced by systemic administration of the competitive NMDA-r antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 3, 10, 17 mg/kg i.p.) in a unique dual-component variant of the OST, and whether this impairment is ameliorated by nicotine (0.75 mg/kg i.p.). Male Sprague-Dawley rats were trained to asymptotic level of performance on a 24-trial two-comparison incrementing nonmatching to sample OST. In addition, rats were administered a two-comparison olfactory reference memory (RM) task, which was integrated into the OST. The RM task provided an assessment of the effects of drug administration on global behavioral measures, long-term memory and motivation. Several measures of working memory (span, longest run, and accuracy) were dose dependently impaired by CPP without adversely affecting RM. Analysis of drug effects across trial blocks demonstrated a significant impairment of performance even at low memory loads, suggesting a CPP-induced deficit of olfactory short-term memory that is not load-dependent. Although nicotine did not ameliorate CPP-induced impairments in span or accuracy, it did block the impairment in longest run produced by the 10 mg/kg dose of CPP. Overall, our results indicate that performance in our 24 odor two-comparison OST is capacity dependent and that CPP impaired OST working, but not reference, memory. © 2016 MacQueen et al.; Published by Cold Spring Harbor Laboratory Press.

The adaptive significance of adult neurogenesis: an integrative approach

PubMed Central

Konefal, Sarah; Elliot, Mick; Crespi, Bernard

2013-01-01

Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts. PMID:23882188

Effects of Ambient Air Pollution Exposure on Olfaction: A Review

PubMed Central

Ajmani, Gaurav S.; Suh, Helen H.; Pinto, Jayant M.

2016-01-01

Background: Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. Objectives: To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. Methods: We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. Results: We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Conclusions: Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution–related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. Citation: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683–1693; http://dx.doi.org/10.1289/EHP136 PMID:27285588

Single olfactory organ associated with prosencephalic malformation and cyclopia in a Xenopus laevis tadpole.

PubMed

Magrassi, L; Graziadei, P P

1987-06-02

A cyclops Xenopus laevis tadpole with a single olfactory organ is described. At a stage comparable to 48, the telencephalon was severely atrophic and only the region where the olfactory fibres terminated appeared to have the cytoarchitecture of the olfactory bulb. In this animal the central nervous system (CNS) appeared normally developed only posterior to the preoptic area. The hypothesis of a diencephalic origin of the region where the olfactory fibres terminated is discussed in the light of our previous results of olfactory placode transplantation. By analogy between this case and other malformations (cyclopia, holoprosencephaly) in higher vertebrates and humans, the need is emphasized for a more precise anatomical description of the olfactory input in related malformations.

Learning at different satiation levels reveals parallel functions for the cAMP-protein kinase A cascade in formation of long-term memory.

PubMed

Friedrich, Anke; Thomas, Ulf; Müller, Uli

2004-05-05

Learning and memory formation in intact animals is generally studied under defined parameters, including the control of feeding. We used associative olfactory conditioning of the proboscis extension response in honeybees to address effects of feeding status on processes of learning and memory formation. Comparing groups of animals with different but defined feeding status at the time of conditioning reveals new and characteristic features in memory formation. In animals fed 18 hr earlier, three-trial conditioning induces a stable memory that consists of different phases: a mid-term memory (MTM), translation-dependent early long-term memory (eLTM; 1-2 d), and a transcription-dependent late LTM (lLTM; > or =3 d). Additional feeding of a small amount of sucrose 4 hr before conditioning leads to a loss of all of these memory phases. Interestingly, the basal activity of the cAMP-dependent protein kinase A (PKA), a key player in LTM formation, differs in animals with different satiation levels. Pharmacological rescue of the low basal PKA activity in animals fed 4 hr before conditioning points to a specific function of cAMP-PKA cascade in mediating satiation-dependent memory formation. An increase in PKA activity during conditioning rescues only transcription-dependent lLTM; acquisition, MTM, and eLTM are still impaired. Thus, during conditioning, the cAMP-PKA cascade mediates the induction of the transcription-dependent lLTM, depending on the satiation level. This result provides the first evidence for a central and distinct function of the cAMP-PKA cascade connecting satiation level with learning.

Olfactory Cleft Endoscopy Scale correlates with olfactory metrics in patients with chronic rhinosinusitis

PubMed Central

Soler, Zachary M.; Hyer, J. Madison; Karnezis, Tom T.; Schlosser, Rodney J.

2015-01-01

Introduction Olfactory loss affects a majority of patients with chronic rhinosinusitis (CRS). Traditional objective measures of disease severity, including endoscopy scales, focus upon the paranasal sinuses and often have weak correlation to olfaction. Methods Adults with CRS were prospectively evaluated by blinded reviewers with a novel Olfactory Cleft Endoscopy Scale (OCES) that evaluated discharge, polyps, edema, crusting and scarring of the olfactory cleft. Objective olfactory function was assessed using “Sniffin’ Sticks testing, including composite threshold-discrimination-identification (TDI) scores. Olfactory-specific quality-of-life was evaluated using the short modified version of the Questionnaire of Olfactory Disorders (QOD-NS). Inter- and intra-rater reliability was assessed among 3 reviewers for OCES grading. Multivariate linear regression was then used to test associations between OCES scores and measures of olfaction, controlling for potential confounding factors. Results The OCES score was evaluated in 38 patients and had a high overall reliability (ICC=0.92; 95% CI: 0.91–0.96). The OCES significantly correlated with objective olfaction as measured by TDI score (p<0.001), with TDI score falling by 1.13 points for every 1 point increase in OCES score. Similar significant associations were found for threshold, discrimination, and identification scores (p<0.003 for all) after controlling for age, gender, race, and reviewer/review. The OCES was also highly associated with patient-reported QOD-NS scores (p=0.009). Conclusion A novel olfactory cleft endoscopy scale shows high reliability and correlates with both objective and patient-reported olfaction in patients with CRS. Further studies to determine prognostic value and responsiveness to change are warranted. PMID:26718315

Insulin signaling is acutely required for long-term memory in Drosophila.

PubMed

Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

2015-01-01

Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

Item-specific proactive interference in olfactory working memory.

PubMed

Moss, Andrew; Miles, Christopher; Elsley, Jane; Johnson, Andrew

2018-04-01

We examine item-specific olfactory proactive interference (PI) effects and undertake comparisons with verbal and non-verbal visual stimuli. Using a sequential recent-probes task, we show no evidence for PI with hard-to-name odours (Experiment 1). However, verbalisable odours do exhibit PI effects (Experiment 2). These findings occur despite above chance performance and similar serial position functions across both tasks. Experiments 3 and 4 apply words and faces, respectively, to our modified procedure, and show that methodological differences cannot explain the null finding in Experiment 1. The extent to which odours exhibit analogous PI effects to that of other modalities is, we argue, contingent on the characteristics of the odours employed.

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

2016-01-01

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

Brain composition and olfactory learning in honey bees

PubMed Central

Gronenberg, Wulfila; Couvillon, Margaret J.

2015-01-01

Correlations between brain or brain component size and behavioral measures are frequently studied by comparing different animal species, which sometimes introduces variables that complicate interpretation in terms of brain function. Here, we have analyzed the brain composition of honey bees (Apis mellifera) that have been individually tested in an olfactory learning paradigm. We found that the total brain size correlated with the bees’ learning performance. Among different brain components, only the mushroom body, a structure known to be involved in learning and memory, showed a positive correlation with learning performance. In contrast, visual neuropils were relatively smaller in bees that performed better in the olfactory learning task, suggesting modality-specific behavioral specialization of individual bees. This idea is also supported by inter-individual differences in brain composition. Some slight yet statistically significant differences in the brain composition of European and Africanized honey bees are reported. Larger bees had larger brains, and by comparing brains of different sizes, we report isometric correlations for all brain components except for a small structure, the central body. PMID:20060918

The Evaluation of Olfactory Function in Patients With Schizophrenia.

PubMed

Robabeh, Soleimani; Mohammad, Jalali Mir; Reza, Ahmadi; Mahan, Badri

2015-04-23

The aim of this study was to compare olfactory threshold, smell identification, intensity and pleasantness ratings between patients with schizophrenia and healthy controls, and (2) to evaluate correlations between ratings of olfactory probes and illness characteristics. Thirty one patients with schizophrenia and 31 control subjects were assessed with the olfactory n-butanol threshold test, the Iran smell identification test (Ir-SIT), and the suprathreshold amyl acetate odor intensity and odor pleasantness rating test. All olfactory tasks were performed unirhinally. Patients with schizophrenia showed disrupted olfaction in all four measures. Longer duration of schizophrenia was associated with a larger impairment of olfactory threshold or microsmic range on the Ir-SIT (P=0.04, P=0.05, respectively). In patients with schizophrenia, female subjects' ratings of pleasantness followed the same trend as control subjects, whereas male patients' ratings showed an opposite trend. Patients exhibiting high positive score on the positive and negative syndrome scale (PANSS) performed better on the olfactory threshold test (r=0.37, P=0.04). The higher odor pleasantness ratings of patients were associated with presence of positive symptoms. The results suggest that both male and female patients with schizophrenia had difficulties on the olfactory threshold and smell identification tests, but appraisal of odor pleasantness was more disrupted in male patients.

Searching for anatomical correlates of olfactory lateralization in the honeybee antennal lobes: A morphological and behavioural study

PubMed Central

Frasnelli, Elisa; Vinegoni, Claudio; Antolini, Renzo; Anfora, Gianfranco; Vallortigara, Giorgio; Haase, Albrecht

2011-01-01

The honeybee, Apis mellifera L. (Hymenoptera: Apidae), has recently become a model for studying brain asymmetry among invertebrates. A strong lateralization favouring the right antenna was discovered in odour learning and short-term memory recall experiments, and a lateral shift favouring the left antenna for long-term memory recall. Corresponding morphological asymmetries have been found in the distribution of olfactory sensilla between the antennae and confirmed by electrophysiological odour response measurements in isolated right and left antennae. The aim of this study was to investigate whether a morphological asymmetry can be observed in the volume of the primary olfactory centres of the central nervous system, the antennal lobes (ALs). Precise volume measurements of a subset of their functional units, the glomeruli, were performed in both sides of the brain, exploiting the advantages of two-photon microscopy. This novel method allowed minimal invasive acquisition of volume images of the ALs, avoiding artefacts from brain extraction and dehydration. The study was completed by a series of behavioural experiments in which response asymmetry in odour recall following proboscis extension reflex conditioning was assessed for odours, chosen to stimulate strong activity in the same glomeruli as in the morphological study. The volumetric measurements found no evidence of lateralization in the investigated glomeruli within the experimental limits. Instead, in the behavioural experiments, a striking odour dependence of the lateralization was observed. The results are discussed on the basis of recent neurophysiological and ethological experiments in A. mellifera. PMID:21402106

Changes in olfactory bulb volume following lateralized olfactory training.

PubMed

Negoias, S; Pietsch, K; Hummel, T

2017-08-01

Repeated exposure to odors modifies olfactory function. Consequently, "olfactory training" plays a significant role in hyposmia treatment. In addition, numerous studies show that the olfactory bulb (OB) volume changes in disorders associated with olfactory dysfunction. Aim of this study was to investigate whether and how olfactory bulb volume changes in relation to lateralized olfactory training in healthy people. Over a period of 4 months, 97 healthy participants (63 females and 34 males, mean age: 23.74 ± 4.16 years, age range: 19-43 years) performed olfactory training by exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other nostril. Before and after olfactory training, magnetic resonance imaging (MRI) scans were performed to measure OB volume. Furthermore, participants underwent lateralized odor threshold and odor identification testing using the "Sniffin' Sticks" test battery.OB volume increased significantly after olfactory training (11.3 % and 13.1 % respectively) for both trained and untrained nostril. No significant effects of sex, duration and frequency of training or age of the subjects were seen. Interestingly, PEA odor thresholds worsened after training, while olfactory identification remained unchanged.These data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in olfactory bulb volume.

Involving the cerebellum in cocaine-induced memory: pattern of cFos expression in mice trained to acquire conditioned preference for cocaine.

PubMed

Carbo-Gas, María; Vazquez-Sanroman, Dolores; Aguirre-Manzo, Luisa; Coria-Avila, Genaro A; Manzo, Jorge; Sanchis-Segura, Carla; Miquel, Marta

2014-01-01

Because of its primary role in drug-seeking, consumption and addictive behaviour, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-related memories. Human studies, which focused on neuronal systems that store and control drug-conditioned memories, have found cerebellar activations during the retrieval of drug-associated cue memory. However, at the pre-clinical level, almost no attention has been paid to a possible role of the cerebellum in drug-related memories. In the present study, we ought to fill this gap by aiming to investigate the pattern of neuronal activation (as revealed by cFos expression) in different regions of the prefrontal cortex and cerebellum of mice trained to develop conditioned preference for an olfactory stimulus (CS+) paired with cocaine. Our results indicate that CS+ preference was directly associated with cFos expression in cells at the apical region of the granule cell layer of the cerebellar vermis; this relationship being more prominent in some specific lobules. Conversely, cFos+ immunostaining in other cerebellar regions seems to be unrelated to CS+ preference but to other aspects of the conditioning procedure. At the prefrontal cortex, cFos expression seemed to be related to cocaine administration rather than to its ability to establish conditioned preference. The present results suggest that as it has been observed in some clinical studies, the cerebellum might be an important and largely overlooked part of the neural circuits involved in generating, maintaining and/or retrieving drug memories. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

Interhemispheric EEG differences in olfactory bulbectomized rats with different cognitive abilities and brain beta-amyloid levels.

PubMed

Bobkova, Natalia; Vorobyov, Vasily; Medvinskaya, Natalia; Aleksandrova, Irina; Nesterova, Inna

2008-09-26

Alterations in electroencephalogram (EEG) asymmetry and deficits in interhemispheric integration of information have been shown in patients with Alzheimer's disease (AD). However, no direct evidence of an association between EEG asymmetry, morphological markers in the brain, and cognition was found either in AD patients or in AD models. In this study we used rats with bilateral olfactory bulbectomy (OBX) as one of the AD models and measured their learning/memory abilities, brain beta-amyloid levels and EEG spectra in symmetrical frontal and occipital cortices. One year after OBX or sham-surgery, the rats were tested with the Morris water paradigm and assigned to three groups: sham-operated rats, SO, and OBX rats with virtually normal, OBX(+), or abnormal, OBX(-), learning (memory) abilities. In OBX vs. SO, the theta EEG activity was enhanced to a higher extent in the right frontal cortex and in the left occipital cortex. This produced significant interhemispheric differences in the frontal cortex of the OBX(-) rats and in the occipital cortex of both OBX groups. The beta1 EEG asymmetry in SO was attenuated in OBX(+) and completely eliminated in OBX(-). OBX produced highly significant beta2 EEG decline in the right frontal cortex, with OBX(-)>OBX(+) rank order of strength. The beta-amyloid level, examined by post-mortem immunological DOT-analysis in the cortex-hippocampus samples, was about six-fold higher in OBX(-) than in SO, but significantly less (enhanced by 82% vs. SO) in OBX(+) than in OBX(-). The involvement of the brain mediatory systems in the observed EEG asymmetry differences is discussed.

Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.

PubMed

Charbel Issa, Peter; Reuter, Peggy; Kühlewein, Laura; Birtel, Johannes; Gliem, Martin; Tropitzsch, Anke; Whitcroft, Katherine L; Bolz, Hanno J; Ishihara, Kenji; MacLaren, Robert E; Downes, Susan M; Oishi, Akio; Zrenner, Eberhart; Kohl, Susanne; Hummel, Thomas

2018-05-24

Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause. To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons. This case series was conducted from August 2015 through July 2017. The setting was a multicenter study involving 4 tertiary referral centers for inherited retinal dystrophies. Participants were 9 patients with CNGB1-associated RP. Results of olfactory testing, ocular phenotyping, and molecular genetic testing using targeted next-generation sequencing. Nine patients were included in the study, 3 of whom were female. Their ages ranged between 34 and 79 years. All patients had an early onset of night blindness but were usually not diagnosed as having RP before the fourth decade because of slow retinal degeneration. Retinal features were characteristic of a rod-cone dystrophy. Olfactory testing revealed reduced or absent olfactory function, with all except one patient scoring in the lowest quartile in relation to age-related norms. Brain magnetic resonance imaging and electroencephalography measurements in response to olfactory stimulation were available for 1 patient and revealed no visible olfactory bulbs and reduced responses to odor, respectively. Molecular genetic testing identified 5 novel (c.1312C>T, c.2210G>A, c.2492+1G>A, c.2763C>G, and c.3044_3050delGGAAATC) and 5 previously reported mutations in CNGB1. Mutations in CNGB1 may cause an autosomal recessive RP-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia.

Drosophila SLC22A transporter is a memory suppressor gene that influences cholinergic neurotransmission to the mushroom bodies

PubMed Central

Gai, Yunchao; Liu, Ze; Cervantes-Sandoval, Isaac; Davis, Ronald L.

2016-01-01

SUMMARY The mechanisms that constrain memory formation are of special interest because they provide insights into the brain’s memory management systems and potential avenues for correcting cognitive disorders. RNAi knockdown in the Drosophila mushroom body neurons (MBn) of a newly discovered memory suppressor gene, Solute Carrier DmSLC22A, a member of the organic cation transporter family, enhances olfactory memory expression, while overexpression inhibits it. The protein localizes to the dendrites of the MBn, surrounding the presynaptic terminals of cholinergic afferent fibers from projection neurons (Pn). Cell-based expression assays show that this plasma membrane protein transports cholinergic compounds with the highest affinity among several in vitro substrates. Feeding flies choline or inhibiting acetylcholinesterase in Pn enhances memory; an effect blocked by overexpression of the transporter in the MBn. The data argue that DmSLC22A is a memory suppressor protein that limits memory formation by helping to terminate cholinergic neurotransmission at the Pn:MBn synapse. PMID:27146270

Two pairs of mushroom body efferent neurons are required for appetitive long-term memory retrieval in Drosophila.

PubMed

Plaçais, Pierre-Yves; Trannoy, Séverine; Friedrich, Anja B; Tanimoto, Hiromu; Preat, Thomas

2013-11-14

One of the challenges facing memory research is to combine network- and cellular-level descriptions of memory encoding. In this context, Drosophila offers the opportunity to decipher, down to single-cell resolution, memory-relevant circuits in connection with the mushroom bodies (MBs), prominent structures for olfactory learning and memory. Although the MB-afferent circuits involved in appetitive learning were recently described, the circuits underlying appetitive memory retrieval remain unknown. We identified two pairs of cholinergic neurons efferent from the MB α vertical lobes, named MB-V3, that are necessary for the retrieval of appetitive long-term memory (LTM). Furthermore, LTM retrieval was correlated to an enhanced response to the rewarded odor in these neurons. Strikingly, though, silencing the MB-V3 neurons did not affect short-term memory (STM) retrieval. This finding supports a scheme of parallel appetitive STM and LTM processing. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Nosema parasitism in honey bees (Apis mellifera) impacts olfactory learning and memory and neurochemistry

USDA-ARS?s Scientific Manuscript database

Nosema sp. is an internal parasite of the honey bee, Apis mellifera, and one of the leading contributors to colony losses worldwide. This parasite is found in the honey bee midgut, and has profound consequences on the host’s physiology. There are reports that Nosema sp. impairs foraging performance ...

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome

PubMed Central

Simoes de Souza, Fabio M.; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N.; Restrepo, Diego

2011-01-01

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities. PMID:22355654

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome.

PubMed

de Souza, Fabio M Simoes; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N; Restrepo, Diego

2011-01-01

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities.

Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice.

PubMed

Nakajima, Akira; Yamakuni, Tohru; Haraguchi, Mitsuya; Omae, Naoki; Song, Si-Young; Kato, Chieko; Nakagawasai, Osamu; Tadano, Takeshi; Yokosuka, Akihito; Mimaki, Yoshihiro; Sashida, Yutaka; Ohizumi, Yasushi

2007-09-01

We have recently reported that nobiletin, a citrus flavonoid, improves impaired memory in olfactory-bulbectomized (OBX) mice, which have been widely utilized as a useful paradigm that shares some major clinical features of Alzheimer's disease. Here, we examined the effects of nobiletin on OBX-induced cholinergic neurodegeneration in mice. OBX mice showed reduced acetylcholinesterase (AChE) staining and choline acetyltransferase (ChAT) expression in the hippocampus. An 11-day administration of nobiletin rescued OBX-induced decrease in the density of AChE-staining and ChAT expression in the hippocampus. These results suggest that nobiletin rescues OBX-induced cholinergic neurodegeneration, accompanied by improvement of impaired memory in OBX mice.

Caffeine in floral nectar enhances a pollinator's memory of reward.

PubMed

Wright, G A; Baker, D D; Palmer, M J; Stabler, D; Mustard, J A; Power, E F; Borland, A M; Stevenson, P C

2013-03-08

Plant defense compounds occur in floral nectar, but their ecological role is not well understood. We provide evidence that plant compounds pharmacologically alter pollinator behavior by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times as likely to remember a learned floral scent as were honeybees rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar did not exceed the bees' bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success.

Caffeine in floral nectar enhances a pollinator’s memory of reward

PubMed Central

Wright, G. A.; Baker, D. D.; Palmer, M. J.; Stabler, D.; Mustard, J. A.; Power, E. F.; Borland, A. M.; Stevenson, P. C.

2015-01-01

Plant defence compounds occur in floral nectar, but their ecological role is not well-understood. We provide the first evidence that plant compounds pharmacologically alter pollinator behaviour by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times more likely to remember a learned floral scent than those rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar never exceeded the bees’ bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success. PMID:23471406

Interglomerular Connectivity within the Canonical and GC-D/Necklace Olfactory Subsystems

PubMed Central

Puche, Adam C.; Munger, Steven D.

2016-01-01

The mammalian main olfactory system contains several subsystems that differ not only in the receptors they express and the glomerular targets they innervate within the main olfactory bulb (MOB), but also in the strategies they use to process odor information. The canonical main olfactory system employs a combinatorial coding strategy that represents odorant identity as a pattern of glomerular activity. By contrast, the "GC-D/necklace" olfactory subsystem—formed by olfactory sensory neurons expressing the receptor guanylyl cyclase GC-D and their target necklace glomeruli (NGs) encircling the caudal MOB—is critical for the detection of a small number of semiochemicals that promote the acquisition of food preferences. The formation of these socially-transmitted food preferences requires the animal to integrate information about two types of olfactory stimuli: these specialized social chemosignals and the food odors themselves. However, the neural mechanisms with which the GC-D/necklace subsystem processes this information are unclear. We used stimulus-induced increases in intrinsic fluorescence signals to map functional circuitry associated with NGs and canonical glomeruli (CGs) in the MOB. As expected, CG-associated activity spread laterally through both the glomerular and external plexiform layers associated with activated glomeruli. Activation of CGs or NGs resulted in activity spread between the two types of glomeruli; there was no evidence of preferential connectivity between individual necklace glomeruli. These results support previous anatomical findings that suggest the canonical and GC-D/necklace subsystems are functionally connected and may integrate general odor and semiochemical information in the MOB. PMID:27902696

The olfactory gonadotropin-releasing hormone immunoreactive system in mouse.

PubMed

Jennes, L

1986-10-29

The olfactory gonadotropin-releasing hormone (GnRH) system in mice was studied with immunofluorescence in combination with lesions of the olfactory bulb and retrograde transport of horseradish peroxidase (HRP) which was administered intravascularly, intranasally or into the subarachnoid space. GnRH-positive neurons were located in the two major branches forming the septal roots of the nervus terminalis, in the ganglion terminale, within the fascicles of the nervus terminalis throughout its extent, in a conspicuous band which connects the ventral neck of the caudal olfactory bulb with the accessory olfactory bulb and in the nasal mucosa. GnRH-positive fibers were seen in all areas in which neurons were found, i.e. in the rostral septum, the ganglion and nervus terminalis and in the nasal subepithelium. In addition, a broad bundle of fibers was observed to surround the entire caudal olfactory bulb, connecting the rostral sulcus rhinalis with the ventrocaudal olfactory bulb. Fibers were seen in close association with the main and accessory olfactory bulb, with the fila olfactoria and with the nasal mucosa. Throughout the olfactory bulb and the nasal epithelium, an association of GnRH fibers with blood vessels was apparent. Intravascular and intranasal injection of HRP resulted in labeling of certain GnRH neurons in the septal roots of the nervus terminalis, the ganglion terminale, the nervus terminalis, the caudal ventrodorsal connection and in the accessory olfactory bulb. After placement of HRP into the subarachnoid space dorsal to the accessory olfactory bulb, about 50% of the GnRH neurons in the accessory olfactory bulb and in the ventrodorsal connection were labeled with HRP. Also, a few GnRH neurons in the rostral septum, the ganglion terminale and in the fascicles of the nervus terminalis had taken up the enzyme. Lesions of the nervus terminalis caudal to the ganglion terminale resulted in sprouting of GnRH fibers at both sites of the knife cut. Lesions rostral to the ganglion terminale induced sprouting mostly at the distal site of the knife cut while most but not all GnRH fibers proximal to the lesion had disappeared. The results of the present study indicate that the olfactory GnRH system is mostly associated with the nervus terminalis. This cranial nerve apparently projects to the central nervous system as well as the periphery. The results of the HRP uptake studies suggest that the GnRH neurons in the nervus terminalis have access to fenestrated capillaries in the subepithelial connective tissue of the nasal mucosa, to the nasal epithelium proper, and to the subarachnoid space.(ABSTRACT TRUNCATED AT 400 WORDS)

Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study.

PubMed

Kiparizoska, Sara; Ikuta, Toshikazu

2017-09-01

Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of CINP.

The Olfactory Mosaic: Bringing an Olfactory Network Together for Odor Perception.

PubMed

Courtiol, Emmanuelle; Wilson, Donald A

2017-01-01

Olfactory perception and its underlying neural mechanisms are not fixed, but rather vary over time, dependent on various parameters such as state, task, or learning experience. In olfaction, one of the primary sensory areas beyond the olfactory bulb is the piriform cortex. Due to an increasing number of functions attributed to the piriform cortex, it has been argued to be an associative cortex rather than a simple primary sensory cortex. In fact, the piriform cortex plays a key role in creating olfactory percepts, helping to form configural odor objects from the molecular features extracted in the nose. Moreover, its dynamic interactions with other olfactory and nonolfactory areas are also critical in shaping the olfactory percept and resulting behavioral responses. In this brief review, we will describe the key role of the piriform cortex in the larger olfactory perceptual network, some of the many actors of this network, and the importance of the dynamic interactions among the piriform-trans-thalamic and limbic pathways.

Olfactory function and malnutrition in geriatric patients.

PubMed

Smoliner, Christine; Fischedick, Andrea; Sieber, Cornel C; Wirth, Rainer

2013-12-01

Impaired olfaction is considered to be a risk factor for malnutrition in older adults; however, there is little research on this association. The aim of this study was to investigate whether olfactory deficits are associated with an impaired nutritional status in older patients. Study participants were recruited from a geriatric day hospital. Nutritional status was assessed with body mass index and Mini-Nutritional Assessment. Olfactory function was evaluated with the Sniffin' Sticks test (SST) and subjectively rated by the patient. Self-caring capacity was rated with the Barthel Index and cognitive status with the Mini-Mental State Examination. One hundred ninety-one patients, 71.7% female, were included with a mean age of 79.6 ± 6.3 years. Prevalence of hyposmia was 39.3%, and 31.9% of patients were functionally anosmic. Malnourished patients did not have a significantly lower Sniffin' Sticks test score than patients at nutritional risk or malnourished patients. In linear regression analysis, nutritional status was only influenced by Barthel Index, age, and number of drugs but not by olfactory function. In this sample, olfactory function was not associated with nutritional status.

Unlocking the secrets of Lake Clark sockeye salmon

USGS Publications Warehouse

Woody, Carol Ann

2003-01-01

Sockeye salmon are a cornerstone species in many Alaska watersheds. Each summer, adults lay eggs in rocky nests called “redds,” and they die soon after. In spring, their fry emerge from gravels and then rear in a nearby freshwater lake for one year or more before migrating as smolt to the sea. During this smolt phase, an olfactory map of their route is imprinted on their memories. Sockeye salmon spend one to four years in the ocean feeding and growing. Then, some innate cue sends them back in a mass migration to their natal lake systems, which they find using the olfactory map made years before. They complete their life cycle by spawning, then dying in habitats of their birth.

Multimodal cuing of autobiographical memory in semantic dementia.

PubMed

Greenberg, Daniel L; Ogar, Jennifer M; Viskontas, Indre V; Gorno Tempini, Maria Luisa; Miller, Bruce; Knowlton, Barbara J

2011-01-01

Individuals with semantic dementia (SD) have impaired autobiographical memory (AM), but the extent of the impairment has been controversial. According to one report (Westmacott, Leach, Freedman, & Moscovitch, 2001), patient performance was better when visual cues were used instead of verbal cues; however, the visual cues used in that study (family photographs) provided more retrieval support than do the word cues that are typically used in AM studies. In the present study, we sought to disentangle the effects of retrieval support and cue modality. We cued AMs of 5 patients with SD and 5 controls with words, simple pictures, and odors. Memories were elicited from childhood, early adulthood, and recent adulthood; they were scored for level of detail and episodic specificity. The patients were impaired across all time periods and stimulus modalities. Within the patient group, words and pictures were equally effective as cues (Friedman test; χ² = 0.25, p = .61), whereas odors were less effective than both words and pictures (for words vs. odors, χ² = 7.83, p = .005; for pictures vs. odors, χ² = 6.18, p = .01). There was no evidence of a temporal gradient in either group (for patients with SD, χ² = 0.24, p = .89; for controls, χ² < 2.07, p = .35). Once the effect of retrieval support is equated across stimulus modalities, there is no evidence for an advantage of visual cues over verbal cues. The greater impairment for olfactory cues presumably reflects degeneration of anterior temporal regions that support olfactory memory. (c) 2010 APA, all rights reserved.

Is there a correlation between hippocampus and amygdala volume and olfactory function in healthy subjects?

PubMed

Smitka, M; Puschmann, S; Buschhueter, D; Gerber, J C; Witt, M; Honeycutt, N; Abolmaali, N; Hummel, T

2012-01-16

Both amygdala (AG) and hippocampus (HC) are integral parts of the olfactory system. The present study, including a large number of healthy subjects, was performed to compare HC and AG volumes, measured by manual tracing, in relation to specific olfactory functions, including odor threshold, discrimination, identification, and odor memory tasks. It also aimed to provide age-related normative data about the volume of the HC and AG. A total of 117 healthy volunteers participated (age range 19-77 years, mean age 37 years; 62 women, 55 men). Using the "Sniffin' Sticks", subjects received lateralized tests for odor threshold, and odor discrimination. In addition, an odor memory and an odor identification task were performed bilaterally. A Mini-Mental-State test excluded dementia. MR scans were performed using a 1.5 T scanner for later manual volumetric measurements. Volumetric measurements exhibited a good reproducibility. The average volume for the right HC was 3.29 cm(3) (SD 0.47), for the left HC it was 3.15 cm(3) (SD 0.47). The average right AG had a volume of 1.60 cm(3) (SD 0.31), left 1.59 cm(3) (SD 0.3). Increasing age was accompanied by a decrease of HC and AG volumes, which were much more pronounced for the right compared to the left side. Only the volume of the right HC showed a small but significant correlation with odor threshold (r(117)=0.21; p=0.02). Importantly, this correlation was not mediated by age as indicated by the significant partial correlation when controlling for age (r(114)=0.18; p=0.049). In conclusion, the present data obtained in a relatively large group of subjects demonstrates a small correlation between the volume of the HC, as an integral part of the olfactory system, and smell function. In addition, these data can be used as the basis for normative values of HC and AG volumes, separately for men, women and different age groups. This is of potential interest in diseases with acute or chronic impairment of olfactory function, in metabolic or neurodegenerative diseases or in disorders with damage of areas involved in adult neurogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes

PubMed Central

Petit, Emilie I; Michalak, Zuzanna; Cox, Rachel; O'Tuathaigh, Colm M P; Clarke, Niamh; Tighe, Orna; Talbot, Konrad; Blake, Derek; Joel, Josephine; Shaw, Alexander; Sheardown, Steven A; Morrison, Alastair D; Wilson, Stephen; Shapland, Ellen M; Henshall, David C; Kew, James N; Kirby, Brian P; Waddington, John L

2017-01-01

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A−/−, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A−/− showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A−/− provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects. PMID:27986973

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes.

PubMed

Petit, Emilie I; Michalak, Zuzanna; Cox, Rachel; O'Tuathaigh, Colm M P; Clarke, Niamh; Tighe, Orna; Talbot, Konrad; Blake, Derek; Joel, Josephine; Shaw, Alexander; Sheardown, Steven A; Morrison, Alastair D; Wilson, Stephen; Shapland, Ellen M; Henshall, David C; Kew, James N; Kirby, Brian P; Waddington, John L

2017-05-01

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/- , with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/- showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/- provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects.

C. elegans positive butanone learning, short-term, and long-term associative memory assays.

PubMed

Kauffman, Amanda; Parsons, Lance; Stein, Geneva; Wills, Airon; Kaletsky, Rachel; Murphy, Coleen

2011-03-11

The memory of experiences and learned information is critical for organisms to make choices that aid their survival. C. elegans navigates its environment through neuron-specific detection of food and chemical odors, and can associate nutritive states with chemical odors, temperature, and the pathogenicity of a food source. Here, we describe assays of C. elegans associative learning and short- and long-term associative memory. We modified an aversive olfactory learning paradigm to instead produce a positive response; the assay involves starving ~400 worms, then feeding the worms in the presence of the AWC neuron-sensed volatile chemoattractant butanone at a concentration that elicits a low chemotactic index (similar to Toroyama et al.). A standard population chemotaxis assay1 tests the worms' attraction to the odorant immediately or minutes to hours after conditioning. After conditioning, wild-type animals' chemotaxis to butanone increases ~0.6 Chemotaxis Index units, its "Learning Index". Associative learning is dependent on the presence of both food and butanone during training. Pairing food and butanone for a single conditioning period ("massed training") produces short-term associative memory that lasts ~2 hours. Multiple conditioning periods with rest periods between ("spaced training") yields long-term associative memory (<40 hours), and is dependent on the cAMP Response Element Binding protein (CREB), a transcription factor required for long-term memory across species. Our protocol also includes image analysis methods for quick and accurate determination of chemotaxis indices. High-contrast images of animals on chemotaxis assay plates are captured and analyzed by worm counting software in MatLab. The software corrects for uneven background using a morphological tophat transformation. Otsu's method is then used to determine a threshold to separate worms from the background. Very small particles are removed automatically and larger non-worm regions (plate edges or agar punches) are removed by manual selection. The software then estimates the size of single worm by ignoring regions that are above a specified maximum size and taking the median size of the remaining regions. The number of worms is then estimated by dividing the total area identified as occupied by worms by the estimated size of a single worm. We have found that learning and short- and long-term memory can be distinguished, and that these processes share similar key molecules with higher organisms. Our assays can quickly test novel candidate genes or molecules that affect learning and short- or long-term memory in C. elegans that are relevant across species.

Loss of olfactory function and nutritional status in vital older adults and geriatric patients.

PubMed

Toussaint, Nicole; de Roon, Margot; van Campen, Jos P C M; Kremer, Stefanie; Boesveldt, Sanne

2015-03-01

The aim of this cross-sectional study was to assess the association of olfactory function and nutritional status in vital older adults and geriatric patients. Three hundred forty-five vital (mean age 67.1 years) and 138 geriatric older adults (mean age 80.9 years) were included. Nutritional status was assessed using the mini nutritional assessment-short form. The Sniffin' Sticks was used to measure olfactory function. Eleven percentage of the vital older adults were at risk of malnutrition, whereas 60% of the geriatric participants were malnourished or at risk. Only 2% of the vital older adults were anosmic, compared with 46% of the geriatric participants. Linear regression demonstrated a significant association (P = 0.015) between olfactory function and nutritional status in the geriatric subjects. However, this association became insignificant after adjustment for confounders. Both crude and adjusted analysis in the vital older adults did not show a significant association. The results indicate that, in both groups of elderly, there is no direct relation between olfactory function and nutritional status. We suggest that a decline in olfactory function may still be considered as one of the risk-factors for malnutrition in geriatric patients-once co-occurring with other mental and/or physical problems that are more likely to occur in those patients experience. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neural correlates of social odor recognition and the representation of individual distinctive social odors within entorhinal cortex and ventral subiculum.

PubMed

Petrulis, A; Alvarez, P; Eichenbaum, H

2005-01-01

Recognition of individual conspecifics is important for social behavior and requires the formation of memories for individually distinctive social signals. Individual recognition is often mediated by olfactory cues in mammals, especially nocturnal rodents such as golden hamsters. In hamsters, this form of recognition requires main olfactory system input to the lateral entorhinal cortex (LEnt). Here, we tested whether neurons in LEnt and the nearby ventral subiculum (VS) would show cellular correlates of this natural form of recognition memory. Two hundred ninety single neurons were recorded from both superficial (SE) and deep layers of LEnt (DE) and VS while male hamsters investigated volatile odorants from female vaginal secretions. Many neurons encoded differences between female's odors with many discriminating between odors from different individual females but not between different odor samples from the same female. Other neurons discriminated between odor samples from one female and generalized across collections from other females. LEnt and VS neurons showed enhanced or suppressed cellular activity during investigation of previously presented odors and in response to novel odors. A majority of SE neurons decreased firing to odor repetition and increased activity to novel odors. In contrast, DE neurons often showed suppressed activity in response to novel odors. Thus, neurons in LEnt and VS of male hamsters encode information that is critical for the identification and recognition of individual females by odor cues. This study reveals cellular mechanisms in LEnt and VS that may mediate a natural form of recognition memory in hamsters. These neuronal responses were similar to those observed in rats and monkeys during performance in standard recognition memory tasks. Consequently, the present data extend our understanding of the cellular basis for recognition memory and suggest that individual recognition requires similar neural mechanisms as those employed in laboratory tests of recognition memory.

Olfactory acuity in theropods: palaeobiological and evolutionary implications.

PubMed

Zelenitsky, Darla K; Therrien, François; Kobayashi, Yoshitsugu

2009-02-22

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds.

Olfactory acuity in theropods: palaeobiological and evolutionary implications

PubMed Central

Zelenitsky, Darla K.; Therrien, François; Kobayashi, Yoshitsugu

2008-01-01

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds. PMID:18957367

History of smoking and olfaction in Parkinson's disease.

PubMed

Lucassen, Elisabeth B; Sterling, Nicholas W; Lee, Eun-Young; Chen, Honglei; Lewis, Mechelle M; Kong, Lan; Huang, Xuemei

2014-07-01

Olfactory dysfunction is the most common pre-motor symptom in Parkinson's disease (PD), and smoking is known to be associated with lower risk of PD. This study tested the hypothesis that smoking is associated with better olfaction in PD. Smoking history was obtained from 76 PD subjects (22 with a history of smoking [smokers], 54 who never smoked [nonsmokers]), and 70 controls (17 smokers, 53 nonsmokers). Olfaction was assessed using the 40-item University of Pennsylvania Smell Identification Test (UPSIT). The olfactory scores between groups and subgroups were compared using analysis of covariance with adjustment for age, gender, and monoamine oxidase B (MAO-B) inhibitor usage. Overall the olfactory score was lower in PD compared with controls (olfactory scores: 21.5 vs. 33.5, P < 0.0001). Among controls, there was no significant difference in olfaction between smokers and nonsmokers (olfactory scores, 33.2 vs. 34.2; P = 0.95). Among PD subjects, however, smokers scored significantly better regarding olfaction compared with nonsmokers (olfactory scores: 24.4 vs. 19.9, P = 0.02). These data suggest that a history of smoking is associated with better olfaction among PD patients. The finding may be related to why smoking may be protective against PD. Further studies are needed to confirm this finding and investigate the underlying mechanisms. © 2014 International Parkinson and Movement Disorder Society.

Nasal neuron PET imaging quantifies neuron generation and degeneration

PubMed Central

Van de Bittner, Genevieve C.; Riley, Misha M.; Cao, Luxiang; Herrick, Scott P.; Ricq, Emily L.; O’Neill, Michael J.; Ahmed, Zeshan; Murray, Tracey K.; Smith, Jaclyn E.; Wang, Changning; Schroeder, Frederick A.; Albers, Mark W.; Hooker, Jacob M.

2017-01-01

Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics. PMID:28112682

Circadian modulation of consolidated memory retrieval following sleep deprivation in Drosophila.

PubMed

Le Glou, Eric; Seugnet, Laurent; Shaw, Paul J; Preat, Thomas; Goguel, Valérie

2012-10-01

Several lines of evidence indicate that sleep plays a critical role in learning and memory. The aim of this study was to evaluate anesthesia resistant memory following sleep deprivation in Drosophila. Four to 16 h after aversive olfactory training, flies were sleep deprived for 4 h. Memory was assessed 24 h after training. Training, sleep deprivation, and memory tests were performed at different times during the day to evaluate the importance of the time of day for memory formation. The role of circadian rhythms was further evaluated using circadian clock mutants. Memory was disrupted when flies were exposed to 4 h of sleep deprivation during the consolidation phase. Interestingly, normal memory was observed following sleep deprivation when the memory test was performed during the 2 h preceding lights-off, a period characterized by maximum wake in flies. We also show that anesthesia resistant memory was less sensitive to sleep deprivation in flies with disrupted circadian rhythms. Our results indicate that anesthesia resistant memory, a consolidated memory less costly than long-term memory, is sensitive to sleep deprivation. In addition, we provide evidence that circadian factors influence memory vulnerability to sleep deprivation and memory retrieval. Taken together, the data show that memories weakened by sleep deprivation can be retrieved if the animals are tested at the optimal circadian time.

Learning Modifies Odor Mixture Processing to Improve Detection of Relevant Components

PubMed Central

Chen, Jen-Yung; Marachlian, Emiliano; Assisi, Collins; Huerta, Ramon; Smith, Brian H.

2015-01-01

Honey bees have a rich repertoire of olfactory learning behaviors, and they therefore are an excellent model to study plasticity in olfactory circuits. Recent behavioral, physiological, and molecular evidence suggested that the antennal lobe, the first relay of the olfactory system in insects and analog to the olfactory bulb in vertebrates, is involved in associative and nonassociative olfactory learning. Here we use calcium imaging to reveal how responses across antennal lobe projection neurons change after association of an input odor with appetitive reinforcement. After appetitive conditioning to 1-hexanol, the representation of an odor mixture containing 1-hexanol becomes more similar to this odor and less similar to the background odor acetophenone. We then apply computational modeling to investigate how changes in synaptic connectivity can account for the observed plasticity. Our study suggests that experience-dependent modulation of inhibitory interactions in the antennal lobe aids perception of salient odor components mixed with behaviorally irrelevant background odors. PMID:25568113

Dietary intakes of fats, fish and nuts and olfactory impairment in older adults.

PubMed

Gopinath, Bamini; Sue, Carolyn M; Flood, Victoria M; Burlutsky, George; Mitchell, Paul

2015-07-01

It is unclear whether lifestyle modifications, such as dietary changes, should be advocated to prevent olfactory dysfunction. We investigated the association between dietary intakes of fats (saturated, mono-unsaturated and polyunsaturated fats, and cholesterol) and related food groups (nuts, fish, butter, margarine) with olfactory impairment. There were 1331 and 667 participants (older than 60 years) at baseline and 5-year follow-up, respectively, with complete olfaction and dietary data. Dietary data were collected using a validated semi-quantitative FFQ. Olfaction was measured using the San Diego Odor Identification Test. In a cross-sectional analysis of baseline data, those in the highest v. lowest quartile of n-6 PUFA intake had reduced odds of having any olfactory impairment, multivariable-adjusted OR 0.66 (95% CI 0.44, 0.97), P for trend = 0.06. Participants in the highest v. lowest quartile of margarine consumption had a 65% reduced odds of having moderate/severe olfactory impairment (P for trend = 0.02). Participants in the highest quartile compared to the lowest quartile (reference) of nut consumption had a 46% (P for trend = 0.01) and 58% (P for trend = 0.001) reduced odds of having any or mild olfactory impairment, respectively. Older adults in the highest v. lowest quartile of fish consumption had 35% (P for trend = 0.03) and 50% (P for trend = 0.01) reduced likelihood of having any or mild olfactory impairment, respectively. In longitudinal analyses, a marginally significant association was observed between nut consumption and incidence of any olfactory impairment, highest v. lowest quartile of nut consumption: OR 0.61 (95% CI 0.37, 1.00). Older adults with the highest consumption of nuts and fish had reduced odds of olfactory impairment, independent of potential confounding variables.

Sadness might isolate you in a non-smelling world: olfactory perception and depression

PubMed Central

Schablitzky, Sylvia; Pause, Bettina M.

2014-01-01

Major depressive disorder (MDD) occurs with a high prevalence among mental illnesses. MDD patients experience sadness and hopelessness, with blunted affective reactivity. However, such depressive episodes are also key symptoms in other depressive disorders, like Bipolar Disorder (BPD) or Seasonal Affective Disorder (SAD). Moreover, depressive symptoms can also be found in healthy individuals, but are experienced as less severe or for a shorter duration than in patients. Here, it is aimed to summarize studies investigating odor perception in depression, including depressive states in healthy individuals and patient populations. Odor perception in depression has been assessed with psychophysical methods (olfactory sensitivity, odor identification, and discrimination), and odor ratings (intensity, emotional valence, familiarity). In addition, some studies investigated affective reactions to odors, and physiological and anatomical correlates of odor perception in depression. The summary reveals that MDD is associated with reduced olfactory sensitivity. However, odor identification and discrimination scores seem to be unaffected by depression. The reduced olfactory sensitivity might be associated with a reduced ability to encode olfactory information and a reduced volume of the olfactory bulb. While similar processes seem to occur in healthy individuals experiencing depressive states, they have not been observed in BPD or SAD patients. However, in order to conclude that the reduced olfactory sensitivity is directly linked to depression, it is suggested that studies should implement control measures of cognitive performances or perceptual abilities in other stimulus modalities. It is concluded that the reduced olfactory performance in MDD patients seems to be disorder-, modality-, and test-specific, and that the application of an appropriate olfactory and cognitive test-battery might be highly useful in the differential diagnosis of MDD. PMID:24570666

Presence of neuropathic pain may explain poor performances on olfactory testing in diabetes mellitus patients.

PubMed

Brady, Shauna; Lalli, Paul; Midha, Nisha; Chan, Ayechen; Garven, Alexandra; Chan, Cynthia; Toth, Cory

2013-07-01

Olfactory dysfunction in neurodegenerative conditions such as Parkinson's syndrome and Alzheimer's disease can hallmark disease onset. We hypothesized that patients with diabetes mellitus, a condition featuring peripheral and central neurodegeneration, would have decreased olfaction abilities. We examined participants with diabetic peripheral neuropathy, participants with diabetes without diabetic peripheral neuropathy, and control participants in blinded fashion using standardized Sniffin' Sticks. Diabetic peripheral neuropathy severity was quantified using the Utah Early Neuropathy Scale. Further subcategorization of diabetic peripheral neuropathy based on presence of neuropathic pain was performed with Douleur Neuropathique 4 Questionnaires. Participants with diabetes had decreased olfactory sensitivity, impaired olfactory discrimination abilities, and reduced odor identification skills when compared with controls. However, loss of olfaction ability was, at least partially, attributed to presence of neuropathic pain on subcategory assessment, although pain severity was not associated with dysfunction. Those participants with diabetes without diabetic peripheral neuropathy and those with diabetic peripheral neuropathy without neuropathic pain had similar olfactory function as controls in general. The presence of neuropathic pain, associated with limited attention and concentration, may explain at least a portion of the olfactory dysfunction witnessed in the diabetic patient population.

Distinct circuits for the formation and retrieval of an imprinted olfactory memory

PubMed Central

Jin, Xin; Pokala, Navin; Bargmann, Cornelia I.

2016-01-01

Summary Memories formed early in life are particularly stable and influential, representing privileged experiences that shape enduring behaviors. Here we show that exposing newly-hatched C. elegans to pathogenic bacteria results in persistent aversion to those bacterial odors, whereas adult exposure generates only transient aversive memory. Long-lasting imprinted aversion has a critical period in the first larval stage, and is specific to the experienced pathogen. Distinct groups of neurons are required during formation (AIB, RIM) and retrieval (AIY, RIA) of the imprinted memory. RIM synthesizes the neuromodulator tyramine, which is required in the L1 stage for learning. AIY memory retrieval neurons sense tyramine via the SER-2 receptor, which is essential for imprinted but not for adult-learned aversion. Odor responses in several neurons, most notably RIA, are altered in imprinted animals. These findings provide insight into neuronal substrates of different forms of memory, and lay a foundation for further understanding of early learning. PMID:26871629

Odor Memory and Discrimination Covary as a Function of Delay between Encoding and Recall in Rats.

PubMed

Hackett, Chelsea; Choi, Christina; O'Brien, Brenna; Shin, Philip; Linster, Christiane

2015-06-01

Nonassociative odor learning paradigms are often used to assess memory, social recognition and neuromodulation of olfactory pathways. We here use a modified object recognition paradigm to investigate how an important task parameter, delay between encoding and recall trials, affects the properties of this memory. We show that both memory for a previously investigated odorant and discrimination of a novel odorant decay with delay time and that rats can remember an odorant for up to 45min after a single trial encoding event. The number of odorants that can be encoded, as well as the specificity of the encoded memory, decrease with increased delay and also depend on stimulus concentration. Memory for an odorant and discrimination of a novel odorant decay at approximately the same rate, whereas the specificity of the formed memory decays faster than the memory itself. These results have important implications for the interpretation of behavioral data obtained with this paradigm. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Method for training honeybees to respond to olfactory stimuli and enhancement of memory retention therein

DOEpatents

McCade, Kirsten J.; Wingo, Robert M.; Haarmann, Timothy K.; Sutherland, Andrew; Gubler, Walter D.

2015-12-15

A specialized conditioning protocol for honeybees that is designed for use within a complex agricultural ecosystem. This method ensures that the conditioned bees will be less likely to exhibit a conditioned response to uninfected plants, a false positive response that would render such a biological sensor unreliable for agricultural decision support. Also described is a superboosting training regime that allows training without the aid of expensive equipment and protocols for training in out in the field. Also described is a memory enhancing cocktail that aids in long term memory retention of a vapor signature. This allows the bees to be used in the field for longer durations and with fewer bees trained overall.

Evaluation of olfactory and auditory system effects of the antihyperthyroid drug carbimazole in the Long-Evans rat.

PubMed

Genter, M B

1998-01-01

Carbimazole (2-carbethoxythio-1-methylimidazole) is a thiocarbamide drug used in the treatment of hyperthyroidism in humans. Side effects associated with carbimazole treatment are reported to include impaired taste, impaired olfaction, and hearing loss. The structurally similar antihyperthyroid drug methimazole (1-methyl-2-mercaptoimidazole), also reportedly associated with impaired taste and olfaction in humans, has recently been demonstrated by this laboratory to be an olfactory toxicant by both the oral and intraperitoneal routes of exposure in rodents. A systematic evaluation of sensory system effects of these compounds, either in rodents or humans, is not available in the literature. Male Long-Evans rats were used to evaluate the auditory and olfactory toxicity of carbimazole by two routes of exposure. Histopathological evaluation of nasal cavities from rats administered carbimazole via i.p. and oral routes revealed olfactory mucosal damage and early evidence of repair; a no-observed effect level (NOEL) of 100 mg/kg was observed for orally administered carbimazole. Further, these studies demonstrate evidence for the generation of the olfactory toxic metabolites of carbimazole by the olfactory mucosa itself, as incubation of carbimazole with an olfactory S9 preparation resulted in NADPH-dependent degradation of carbimazole. Evaluation of the auditory startle response in carbimazole-treated rats revealed no deficits, demonstrating that carbimazole does not cause a global loss of hearing in rats.

Appetitive but Not Aversive Olfactory Conditioning Modifies Antennal Movements in Honeybees

ERIC Educational Resources Information Center

Cholé, Hanna; Junca, Pierre; Sandoz, Jean-Christophe

2015-01-01

In honeybees, two olfactory conditioning protocols allow the study of appetitive and aversive Pavlovian associations. Appetitive conditioning of the proboscis extension response (PER) involves associating an odor, the conditioned stimulus (CS) with a sucrose solution, the unconditioned stimulus (US). Conversely, aversive conditioning of the sting…

Olfactory modulation by dopamine in the context of aversive learning

PubMed Central

Riffell, Jeffrey A.; Martin, Joshua P.; Gage, Stephanie L.; Nighorn, Alan J.

2012-01-01

The need to detect and process sensory cues varies in different behavioral contexts. Plasticity in sensory coding can be achieved by the context-specific release of neuromodulators in restricted brain areas. The context of aversion triggers the release of dopamine in the insect brain, yet the effects of dopamine on sensory coding are unknown. In this study, we characterize the morphology of dopaminergic neurons that innervate each of the antennal lobes (ALs; the first synaptic neuropils of the olfactory system) of the moth Manduca sexta and demonstrate with electrophysiology that dopamine enhances odor-evoked responses of the majority of AL neurons while reducing the responses of a small minority. Because dopamine release in higher brain areas mediates aversive learning we developed a naturalistic, ecologically inspired aversive learning paradigm in which an innately appetitive host plant floral odor is paired with a mimic of the aversive nectar of herbivorized host plants. This pairing resulted in a decrease in feeding behavior that was blocked when dopamine receptor antagonists were injected directly into the ALs. These results suggest that a transient dopaminergic enhancement of sensory output from the AL contributes to the formation of aversive memories. We propose a model of olfactory modulation in which specific contexts trigger the release of different neuromodulators in the AL to increase olfactory output to downstream areas of processing. PMID:22552185

The role of social relationships in the link between olfactory dysfunction and mortality.

PubMed

Leschak, Carrianne J; Eisenberger, Naomi I

2018-01-01

Recent work suggests that olfactory dysfunction is a strong predictor of five-year mortality in older adults. Based on past work showing: 1) that olfactory dysfunction impairs social functioning and 2) that social ties are linked with mortality, the current work explored whether impairments in social life mediated the relationship between olfactory dysfunction and mortality. Additionally, based on work showing gender differences in the social consequences of olfactory dysfunction, gender was assessed as a potential moderator of this association. Social network size mediated the olfactory-mortality link for females. To probe what feature of social networks was driving this effect, we investigated two subcomponents of social life: emotional closeness (e.g., perceived social support, loneliness) and physical closeness (e.g., physical contact, in-person socializing with others). Physical closeness significantly mediated the olfactory-mortality link for females, even after controlling for social network size. Emotional closeness did not mediate this link. Possible mechanisms underlying this relationship are discussed.

Evolution of olfactory receptors.

PubMed

Hoover, Kara C

2013-01-01

Olfactory receptors are a specialized set of receptor cells responsible for the detection of odors. These cells are G protein-coupled receptors and expressed in the cell membranes of olfactory sensory neurons. Once a cell is activated by a ligand, it initiates a signal transduction cascade that produces a nerve impulse to the brain where odor perception is processed. Vertebrate olfactory evolution is characterized by birth-and-death events, a special case of the stochastic continuous time Markov process. Vertebrate fish have three general types of receptor cells (two dedicated to pheromones). Terrestrial animals have different epithelial biology due to the specialized adaptation to detecting airborne odors. Two general classes of olfactory receptor gene reflect the vertebrate marine heritage (Class I) and the derived amphibian, reptile, and mammal terrestrial heritage (Class II). While we know much about olfactory receptor cells, there are still areas where our knowledge is insufficient, such as intra-individual diversity throughout the life time, epigenetic processes acting on olfactory receptors, and association of ligands to specific cells.

Nosema ceranae parasitism impacts olfactory learning and memory and neurochemistry in honey bees (Apis mellifera).

PubMed

Gage, Stephanie L; Kramer, Catherine; Calle, Samantha; Carroll, Mark; Heien, Michael; DeGrandi-Hoffman, Gloria

2018-02-19

Nosema sp. is an internal parasite of the honey bee, Apis mellifera , and one of the leading contributors to colony losses worldwide. This parasite is found in the honey bee midgut and has profound consequences for the host's physiology. Nosema sp. impairs foraging performance in honey bees, yet, it is unclear whether this parasite affects the bee's neurobiology. In this study, we examined whether Nosema sp. affects odor learning and memory and whether the brains of parasitized bees show differences in amino acids and biogenic amines. We took newly emerged bees and fed them with Nosema ceranae At approximate nurse and forager ages, we employed an odor-associative conditioning assay using the proboscis extension reflex and two bioanalytical techniques to measure changes in brain chemistry. We found that nurse-aged bees infected with N. ceranae significantly outperformed controls in odor learning and memory, suggestive of precocious foraging, but by forager age, infected bees showed deficits in learning and memory. We also detected significant differences in amino acid concentrations, some of which were age specific, as well as altered serotonin, octopamine, dopamine and l-dopa concentrations in the brains of parasitized bees. These findings suggest that N. ceranae infection affects honey bee neurobiology and may compromise behavioral tasks. These results yield new insight into the host-parasite dynamic of honey bees and N. ceranae , as well as the neurochemistry of odor learning and memory under normal and parasitic conditions. © 2018. Published by The Company of Biologists Ltd.

Multisensory integration processing during olfactory-visual stimulation-An fMRI graph theoretical network analysis.

PubMed

Ripp, Isabelle; Zur Nieden, Anna-Nora; Blankenagel, Sonja; Franzmeier, Nicolai; Lundström, Johan N; Freiherr, Jessica

2018-05-07

In this study, we aimed to understand how whole-brain neural networks compute sensory information integration based on the olfactory and visual system. Task-related functional magnetic resonance imaging (fMRI) data was obtained during unimodal and bimodal sensory stimulation. Based on the identification of multisensory integration processing (MIP) specific hub-like network nodes analyzed with network-based statistics using region-of-interest based connectivity matrices, we conclude the following brain areas to be important for processing the presented bimodal sensory information: right precuneus connected contralaterally to the supramarginal gyrus for memory-related imagery and phonology retrieval, and the left middle occipital gyrus connected ipsilaterally to the inferior frontal gyrus via the inferior fronto-occipital fasciculus including functional aspects of working memory. Applied graph theory for quantification of the resulting complex network topologies indicates a significantly increased global efficiency and clustering coefficient in networks including aspects of MIP reflecting a simultaneous better integration and segregation. Graph theoretical analysis of positive and negative network correlations allowing for inferences about excitatory and inhibitory network architectures revealed-not significant, but very consistent-that MIP-specific neural networks are dominated by inhibitory relationships between brain regions involved in stimulus processing. © 2018 Wiley Periodicals, Inc.

A computational model of conditioning inspired by Drosophila olfactory system.

PubMed

Faghihi, Faramarz; Moustafa, Ahmed A; Heinrich, Ralf; Wörgötter, Florentin

2017-03-01

Recent studies have demonstrated that Drosophila melanogaster (briefly Drosophila) can successfully perform higher cognitive processes including second order olfactory conditioning. Understanding the neural mechanism of this behavior can help neuroscientists to unravel the principles of information processing in complex neural systems (e.g. the human brain) and to create efficient and robust robotic systems. In this work, we have developed a biologically-inspired spiking neural network which is able to execute both first and second order conditioning. Experimental studies demonstrated that volume signaling (e.g. by the gaseous transmitter nitric oxide) contributes to memory formation in vertebrates and invertebrates including insects. Based on the existing knowledge of odor encoding in Drosophila, the role of retrograde signaling in memory function, and the integration of synaptic and non-synaptic neural signaling, a neural system is implemented as Simulated fly. Simulated fly navigates in a two-dimensional environment in which it receives odors and electric shocks as sensory stimuli. The model suggests some experimental research on retrograde signaling to investigate neural mechanisms of conditioning in insects and other animals. Moreover, it illustrates a simple strategy to implement higher cognitive capabilities in machines including robots. Copyright © 2016 Elsevier Ltd. All rights reserved.

Re-presentation of Olfactory Exposure Therapy Success Cues during Non-Rapid Eye Movement Sleep did not Increase Therapy Outcome but Increased Sleep Spindles

PubMed Central

Rihm, Julia S.; Sollberger, Silja B.; Soravia, Leila M.; Rasch, Björn

2016-01-01

Exposure therapy induces extinction learning and is an effective treatment for specific phobias. Sleep after learning promotes extinction memory and benefits therapy success. As sleep-dependent memory-enhancing effects are based on memory reactivations during sleep, here we aimed at applying the beneficial effect of sleep on therapy success by cueing memories of subjective therapy success during non-rapid eye movement sleep after in vivo exposure-based group therapy for spider phobia. In addition, oscillatory correlates of re-presentation during sleep (i.e., sleep spindles and slow oscillations) were investigated. After exposure therapy, spider-phobic patients verbalized their subjectively experienced therapy success under presence of a contextual odor. Then, patients napped for 90 min recorded by polysomnography. Half of the sleep group received the odor during sleep while the other half was presented an odorless vehicle as control. A third group served as a wake control group without odor presentation. While exposure therapy significantly reduced spider-phobic symptoms in all subjects, these symptoms could not be further reduced by re-presenting the odor associated with therapy success, probably due to a ceiling effect of the highly effective exposure therapy. However, odor re-exposure during sleep increased left-lateralized frontal slow spindle (11.0–13.0 Hz) and right-lateralized parietal fast spindle (13.0–15.0 Hz) activity, suggesting the possibility of a successful re-presentation of therapy-related memories during sleep. Future studies need to further examine the possibility to enhance therapy success by targeted memory reactivation (TMR) during sleep. PMID:27445775

Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

PubMed Central

Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

2015-01-01

Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

Measurement and Analysis of Olfactory Responses with the Aim of Establishing an Objective Diagnostic Method for Central Olfactory Disorders

NASA Astrophysics Data System (ADS)

Uno, Tominori; Wang, Li-Qun; Miwakeichi, Fumikazu; Tonoike, Mitsuo; Kaneda, Teruo

In order to establish a new diagnostic method for central olfactory disorders and to identify objective indicators, we measured and analyzed brain activities in the parahippocampal gyrus and uncus, region of responsibility for central olfactory disorders. The relationship between olfactory stimulation and brain response at region of responsibility can be examined in terms of fitted responses (FR). FR in these regions may be individual indicators of changes in brain olfactory responses. In the present study, in order to non-invasively and objectively measure olfactory responses, an odor oddball task was conducted on four healthy volunteers using functional magnetic resonance imaging (fMRI) and a odorant stimulator with blast-method. The results showed favorable FR and activation in the parahippocampal gyrus or uncus in all subjects. In some subjects, both the parahippocampal gyrus and uncus were activated. Furthermore, activation was also confirmed in the cingulate gyrus, middle frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus and insula. The hippocampus and uncus are known to be involved in the olfactory disorders associated with early-stage Alzheimer's disease and other olfactory disorders. In the future, it will be necessary to further develop the present measurement and analysis method to clarify the relationship between central olfactory disorders and brain activities and establish objective indicators that are useful for diagnosis.

Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice

PubMed Central

Dong, Frederick N.

2017-01-01

Animals detect odorous chemicals through specialized olfactory sensory neurons (OSNs) that transduce odorants into neural electrical signals. We identified a novel and evolutionarily conserved protein, cilia- and flagella-associated protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory transduction occurs. Bioinformatic analysis suggests that a large portion of CFAP69 can form Armadillo-type α-helical repeats, which may mediate protein–protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics in both the on and off phases of electrophysiological responses at both the neuronal ensemble level as observed by electroolfactogram and the single-cell level as observed by single-cell suction pipette recordings. In single-cell analysis, OSNs lacking CFAP69 showed faster response integration and were able to fire APs more faithfully to repeated odor stimuli. Furthermore, both male and female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated performance in a buried food pellet test when a background of the same odor to the food pellet was present even though they should have better temporal resolution of coding olfactory stimulation at the peripheral. Therefore, the role of CFAP69 in the olfactory system seems to be to allow the olfactory transduction machinery to work at a precisely regulated range of response kinetics for robust olfactory behavior. SIGNIFICANCE STATEMENT Sensory receptor cells are generally thought to evolve to respond to sensory cues as fast as they can. This idea is consistent with mutational analyses in various sensory systems, where mutations of sensory receptor cells often resulted in reduced response size and slowed response kinetics. Contrary to this idea, we have found that there is a kinetic “damper” present in the olfactory transduction cascade of the mouse that slows down the response kinetics and, by doing so, it reduces the peripheral temporal resolution in coding odor stimuli and allows for robust olfactory behavior. This study should trigger a rethinking of the significance of the intrinsic speed of sensory transduction and the pattern of the peripheral coding of sensory stimuli. PMID:28495971

Effects of field-realistic doses of glyphosate on honeybee appetitive behaviour.

PubMed

Herbert, Lucila T; Vázquez, Diego E; Arenas, Andrés; Farina, Walter M

2014-10-01

Glyphosate (GLY) is a broad-spectrum herbicide used for weed control. The sub-lethal impact of GLY on non-target organisms such as insect pollinators has not yet been evaluated. Apis mellifera is the main pollinator in agricultural environments and is a well-known model for behavioural research. Honeybees are also accurate biosensors of environmental pollutants and their appetitive behavioural response is a suitable tool with which to test sub-lethal effects of agrochemicals. We studied the effects of field-realistic doses of GLY on honeybees exposed chronically or acutely to the herbicide. We focused on sucrose sensitivity, elemental and non-elemental associative olfactory conditioning of the proboscis extension response (PER), and foraging-related behaviour. We found a reduced sensitivity to sucrose and learning performance for the groups chronically exposed to GLY concentrations within the range of recommended doses. When olfactory PER conditioning was performed with sucrose reward with the same GLY concentrations (acute exposure), elemental learning and short-term memory retention decreased significantly compared with controls. Non-elemental associative learning was also impaired by an acute exposure to GLY traces. Altogether, these results imply that GLY at concentrations found in agro-ecosystems as a result of standard spraying can reduce sensitivity to nectar reward and impair associative learning in honeybees. However, no effect on foraging-related behaviour was found. Therefore, we speculate that successful forager bees could become a source of constant inflow of nectar with GLY traces that could then be distributed among nestmates, stored in the hive and have long-term negative consequences on colony performance. © 2014. Published by The Company of Biologists Ltd.

Ultrastructural characterisation of the olfactory mucosa of the armadillo Dasypus hybridus (Dasypodidae, Xenarthra)

PubMed Central

FERRARI, C. C.; CARMANCHAHI, P. D.; ALDANA MARCOS, H. J.; AFFANNI, J. M.

2000-01-01

The ultrastructure of the olfactory mucosa of the armadillo Dasypus hybridus was studied. A comparison with the olfactory mucosa of another armadillo (Chaetophractus villosus) was made. The olfactory mucosa of D. hybridus shows many features which are similar to those of other mammals. Interestingly, it differs from the olfactory mucosa of the armadillo C. villosus. A suggestion is made that these differences may be due to differences in the digging habits of these species. In Dasypus, the supporting cells (SCs) showed dense vacuoles, multivesicular bodies and lysosome-like bodies probably related with the endocytotic system. The SCs show a dense network of SER presumably associated with xenobiotic mechanisms. The olfactory receptor neurons exhibit lysosome-like bodies and multivesicular bodies in their perikarya. These organelles suggest the presence of an endocytotic system. Duct cells of Bowman's glands exhibit secretory activities. Bowman's glands are compound-branched tubulo-acinar mixed glands with merocrine secretory mechanisms. PMID:10739023

[Clinical and MRI Findings in Patients with Congenital Anosmia].

PubMed

Ogawa, Takao; Kato, Tomohisa; Ono, Mayu; Shimizu, Takeshi

2015-08-01

The clinical characteristics of 16 patients with congenital anosmia were examined retrospectively. MRI (magnetic resonance imaging) was used to assess the morphological changes in the olfactory bulbs and olfactory sulci according to the method of P. Rombaux (2009). Congenital anosmia was divided into two forms: syndromic forms in association with a syndrome, and isolated forms without evidence of other defects. Only three patients (19%) in our series had syndromic forms of congenital anosmia, such as the Kallmann syndrome. Most cases (13 patients, 81%) had isolated congenital anosmia. Psychophysical testing of the olfactory function included T&T olfactometry and the intravenous Alinamin test, which are widely used in Japan. In T&T olfactometry, detection and recognition thresholds for the five odorants are used to assign a diagnostic category representing the level of olfactory function. Most cases (14 patients, 88%) showed off-scale results on T&T olfactometry, and the Alinamin test resulted in no response in all 11 patients who underwent the test. Abnormal MRI findings of the olfactory bulbs and sulci were detected in 15 of 16 patients (94%). Olfactory bulbs were bilaterally absent in nine patients (56%), and two patients (13%) had unilateral olfactory bulbs. Four patients (25%) had bilateral hypoplastic olfactory bulbs, and only one patient had normal olfactory bulbs (6%). The olfactory sulcus was unilaterally absent in one patient (6%), and nine patients (56%) had bilaterally hypoplastic olfactory sulci. Two patients (13%) had a unilateral normal olfactory sulcus and hypoplastic olfactory sulcus. Three patients (19%) had normal olfactory sulci. Quantitative analysis showed that the volume of olfactory bulbs varied from 0 mm3 to 63.5 mm3, with a mean volume of 10.20 ± 18 mm3, and the mean depth of the olfactory sulcus varied from 0 mm to 12.22 mm, with a mean length of 4.85 ± 4.1 mm. Currently, there is no effective treatment for congenital anosmia. However, diagnosis of congenital anosmia is important, as its presence can lead to dangerous situations. Careful examination for hypogonadism is also required in people with anosmia. MRI examinations of the olfactory bulbs and sulci were useful for the diagnosis of congenital anosmia.

A Subtype of Olfactory Bulb Interneurons Is Required for Odor Detection and Discrimination Behaviors.

PubMed

Takahashi, Hiroo; Ogawa, Yoichi; Yoshihara, Sei-Ichi; Asahina, Ryo; Kinoshita, Masahito; Kitano, Tatsuro; Kitsuki, Michiko; Tatsumi, Kana; Okuda, Mamiko; Tatsumi, Kouko; Wanaka, Akio; Hirai, Hirokazu; Stern, Peter L; Tsuboi, Akio

2016-08-03

Neural circuits that undergo reorganization by newborn interneurons in the olfactory bulb (OB) are necessary for odor detection and discrimination, olfactory memory, and innate olfactory responses, including predator avoidance and sexual behaviors. The OB possesses many interneurons, including various types of granule cells (GCs); however, the contribution that each type of interneuron makes to olfactory behavioral control remains unknown. Here, we investigated the in vivo functional role of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic arborization of 5T4-expressing GCs (5T4 GCs), the level of which is reduced in the OB of 5T4 knock-out (KO) mice. Electrophysiological recordings with acute OB slices indicated that external tufted cells (ETCs) can be divided into two types, bursting and nonbursting. Optogenetic stimulation of 5T4 GCs revealed their connection to both bursting and nonbursting ETCs, as well as to mitral cells (MCs). Interestingly, nonbursting ETCs received fewer inhibitory inputs from GCs in 5T4 KO mice than from those in wild-type (WT) mice, whereas bursting ETCs and MCs received similar inputs in both mice. Furthermore, 5T4 GCs received significantly fewer excitatory inputs in 5T4 KO mice. Remarkably, in olfactory behavior tests, 5T4 KO mice had higher odor detection thresholds than the WT, as well as defects in odor discrimination learning. Therefore, the loss of 5T4 attenuates inhibitory inputs from 5T4 GCs to nonbursting ETCs and excitatory inputs to 5T4 GCs, contributing to disturbances in olfactory behavior. Our novel findings suggest that, among the various types of OB interneurons, the 5T4 GC subtype is required for odor detection and discrimination behaviors. Neuronal circuits in the brain include glutamatergic principal neurons and GABAergic interneurons. Although the latter is a minority cell type, they are vital for normal brain function because they regulate the activity of principal neurons. If interneuron function is impaired, brain function may be damaged, leading to behavior disorder. The olfactory bulb (OB) possesses various types of interneurons, including granule cells (GCs); however, the contribution that each type of interneuron makes to the control of olfactory behavior remains unknown. Here, we analyzed electrophysiologically and behaviorally the function of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic branching in OB GCs. We found that, among the various types of OB interneuron, the 5T4 GC subtype is required for odor detection and odor discrimination behaviors. Copyright © 2016 the authors 0270-6474/16/368211-18$15.00/0.

Olfactory Impairment in Chronic Rhinosinusitis Using Threshold, Discrimination, and Identification Scores

PubMed Central

Kohli, Preeti; Storck, Kristina A.; Schlosser, Rodney J.

2016-01-01

Differences in testing modalities and cut-points used to define olfactory dysfunction contribute to the wide variability in estimating the prevalence of olfactory dysfunction in chronic rhinosinusitis (CRS). The aim of this study is to report the prevalence of olfactory impairment using each component of the Sniffin’ Sticks test (threshold, discrimination, identification, and total score) with age-adjusted and ideal cut-points from normative populations. Patients meeting diagnostic criteria for CRS were enrolled from rhinology clinics at a tertiary academic center. Olfaction was assessed using the Sniffin’ Sticks test. The study population consisted of 110 patients. The prevalence of normosmia, hyposmia, and anosmia using total Sniffin’ Sticks score was 41.8%, 20.0%, and 38.2% using age-appropriate cut-points and 20.9%, 40.9%, and 38.2% using ideal cut-points. Olfactory impairment estimates for each dimension mirrored these findings, with threshold yielding the highest values. Threshold, discrimination, and identification were also found to be significantly correlated to each other (P < 0.001). In addition, computed tomography scores, asthma, allergy, and diabetes were found to be associated with olfactory dysfunction. In conclusion, the prevalence of olfactory dysfunction is dependent upon olfactory dimension and if age-adjusted cut-points are used. The method of olfactory testing should be chosen based upon specific clinical and research goals. PMID:27469973

Causality Assessment of Olfactory and Gustatory Dysfunction Associated with Intranasal Fluticasone Propionate: Application of the Bradford Hill Criteria.

PubMed

Muganurmath, Chandrashekhar S; Curry, Amy L; Schindzielorz, Andrew H

2018-02-01

Causality assessment is crucial to post-marketing pharmacovigilance and helps optimize safe and appropriate use of medicines by patients in the real world. Self-reported olfactory and gustatory dysfunction are common in the general population as well as in patients with allergic rhinitis and nasal polyposis. Intranasal corticosteroids, including intranasal fluticasone propionate (INFP), are amongst the most effective drugs indicated in the treatment of allergic rhinitis and nasal polyposis. While intranasal corticosteroids are associated with olfactory and gustatory dysfunction and are currently labeled for these adverse events, causality assessment has not been performed to date. Although there is no single widely accepted method to assess causality in pharmacovigilance, the Bradford Hill criteria offer a robust and comprehensive approach because nine distinct aspects of an observed potential drug-event association are assessed. In this literature-based narrative review, Hill's criteria were applied to determine causal inference between INFP and olfactory and gustatory dysfunction.

Odor information transfer in the stingless bee Melipona quadrifasciata: effect of in-hive experiences on classical conditioning of proboscis extension.

PubMed

Mc Cabe, Sofía I; Farina, Walter M

2009-02-01

A recent study showed that the stingless bee Melipona quadrifasciata could learn to discriminate odors in a classical conditioning of proboscis extension response (PER). Here we used this protocol to investigate the ability of these bees to use olfactory information obtained within the colony in an experimental context: the PER paradigm. We compared their success in solving a classical differential conditioning depending on the previous olfactory experiences received inside the nest. We found that M. quadrifasciata bees are capable of transferring the food-odor information acquired in the colony to a differential conditioning in the PER paradigm. Bees attained higher discrimination levels when they had previously encountered the rewarded odor associated to food inside the hive. The increase in the discrimination levels, however, was in some cases unspecific to the odor used indicating a certain degree of generalization. The influence of the food scent offered at a field feeder 24 h before the classical conditioning could also be seen in the discrimination attained by the foragers in the PER setup, detecting the presence of long-term memory. Moreover, the improved performance of recruited bees in the PER paradigm suggests the occurrence of social learning of nectar scents inside the stingless bees' hives.

Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

PubMed

Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

2016-01-15

Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Associations of olfactory bulb and depth of olfactory sulcus with basal ganglia and hippocampus in patients with Parkinson's disease.

PubMed

Tanik, Nermin; Serin, Halil Ibrahim; Celikbilek, Asuman; Inan, Levent Ertugrul; Gundogdu, Fatma

2016-05-04

Parkinson's disease (PD) is a neurodegenerative disorder characterized by hyposmia in the preclinical stages. We investigated the relationships of olfactory bulb (OB) volume and olfactory sulcus (OS) depth with basal ganglia and hippocampal volumes. The study included 25 patients with PD and 40 age- and sex-matched control subjects. Idiopathic PD was diagnosed according to published diagnostic criteria. The Hoehn and Yahr (HY) scale, the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS III), and the Mini-Mental State Examination (MMSE) were administered to participants. Volumetric measurements of olfactory structures, the basal ganglia, and hippocampus were performed using magnetic resonance imaging (MRI). OB volume and OS depth were significantly reduced in PD patients compared to healthy control subjects (p<0.001 and p<0.001, respectively). The OB and left putamen volumes were significantly correlated (p=0.048), and the depth of the right OS was significantly correlated with right hippocampal volume (p=0.018). We found significant correlations between OB and putamen volumes and OS depth and hippocampal volume. Our study is the first to demonstrate associations of olfactory structures with the putamen and hippocampus using MRI volumetric measurements. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats.

PubMed

Yamazaki, Mayako; Okabe, Mayuko; Yamamoto, Noriyuki; Yarimizu, Junko; Harada, Katsuya

2015-03-01

Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%-50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Regulation of inflammation-associated olfactory neuronal death and regeneration by the type II tumor necrosis factor receptor.

PubMed

Pozharskaya, Tatyana; Liang, Jonathan; Lane, Andrew P

2013-09-01

Olfactory loss is a debilitating symptom of chronic rhinosinusitis. To study the impact of inflammation on the olfactory system, the inducible olfactory inflammation (IOI) transgenic mouse was created in which inflammation can be turned on and off within the olfactory epithelium. In this study, the type II tumor necrosis factor (TNF) receptor (TNFR2) was knocked out, and the effect on the olfactory loss phenotype was assessed. IOI mice were bred to TNFR2 knockout mice to yield progeny IOI mice lacking the TNFR2 receptor (TNFR2(-/-) ). TNF-α expression was induced within the olfactory epithelium for 6 weeks to generate chronic inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Compared to IOI mice with wild-type TNFR2, IOI mice lacking the TNFR2 demonstrated similar levels of inflammatory infiltration and enlargement of the subepithelial layer. However, IOI-TNFR2(-/-) mice differed markedly in that the neuronal layer was largely preserved and active progenitor cell proliferation was present. Odorant responses were maintained in the IOI-TNFR2(-/-) mice, in contrast to IOI mice. TNFR2 is the minor receptor for TNF-α, but appears to play an important role in mediating TNF-induced disruption of the olfactory system. This finding suggests that neuronal death and inhibition of proliferation in CRS may be mediated by TNFR2 on olfactory neurons and progenitor cells. Further studies are needed to elucidate the subcellular pathways involved and develop novel therapies for treating olfactory loss in the setting of CRS. © 2013 ARS-AAOA, LLC.

Unirhinal Olfactory Testing for the Diagnostic Workup of Mild Cognitive Impairment.

PubMed

Huart, Caroline; Rombaux, Philippe; Gérard, Thomas; Hanseeuw, Bernard; Lhommel, Renaud; Quenon, Lisa; Ivanoiu, Adrian; Mouraux, André

2015-01-01

Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage. Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI). Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls. As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups. MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.

Long-Term Memory for Odors: Influences of Familiarity and Identification Across 64 Days

PubMed Central

Jönsson, Fredrik U.; Willander, Johan; Sikström, Sverker; Larsson, Maria

2015-01-01

Few studies have investigated long-term odor recognition memory, although some early observations suggested that the forgetting rate of olfactory representations is slower than for other sensory modalities. This study investigated recognition memory across 64 days for high and low familiar odors and faces. Memory was assessed in 83 young participants at 4 occasions; immediate, 4, 16, and 64 days after encoding. The results indicated significant forgetting for odors and faces across the 64 days. The forgetting functions for the 2 modalities were not fundamentally different. Moreover, high familiar odors and faces were better remembered than low familiar ones, indicating an important role of semantic knowledge on recognition proficiency for both modalities. Although odor recognition was significantly better than chance at the 64 days testing, memory for the low familiar odors was relatively poor. Also, the results indicated that odor identification consistency across sessions, irrespective of accuracy, was positively related to successful recognition. PMID:25740304

Associative Learning during Early Adulthood Enhances Later Memory Retention in Honeybees

PubMed Central

Arenas, Andrés; Fernández, Vanesa M.; Farina, Walter M.

2009-01-01

Background Cognitive experiences during the early stages of life play an important role in shaping the future behavior in mammals but also in insects, in which precocious learning can directly modify behaviors later in life depending on both the timing and the rearing environment. However, whether olfactory associative learning acquired early in the adult stage of insects affect memorizing of new learning events has not been studied yet. Methodology Groups of adult honeybee workers that experienced an odor paired with a sucrose solution 5 to 8 days or 9 to 12 days after emergence were previously exposed to (i) a rewarded experience through the offering of scented food, or (ii) a non-rewarded experience with a pure volatile compound in the rearing environment. Principal Findings Early rewarded experiences (either at 1–4 or 5–8 days of adult age) enhanced retention performance in 9–12-day-conditioned bees when they were tested at 17 days of age. The highest retention levels at this age, which could not be improved with prior rewarded experiences, were found for memories established at 5–8 days of adult age. Associative memories acquired at 9–12 days of age showed a weak effect on retention for some pure pre-exposed volatile compounds; whereas the sole exposure of an odor at any younger age did not promote long-term effects on learning performance. Conclusions The associative learning events that occurred a few days after adult emergence improved memorizing in middle-aged bees. In addition, both the timing and the nature of early sensory inputs interact to enhance retention of new learning events acquired later in life, an important matter in the social life of honeybees. PMID:19956575

Evolutionary Genomics of Genes Involved in Olfactory Behavior in the Drosophila melanogaster Species Group

PubMed Central

Lavagnino, Nicolás; Serra, François; Arbiza, Leonardo; Dopazo, Hernán; Hasson, Esteban

2012-01-01

Previous comparative genomic studies of genes involved in olfactory behavior in Drosophila focused only on particular gene families such as odorant receptor and/or odorant binding proteins. However, olfactory behavior has a complex genetic architecture that is orchestrated by many interacting genes. In this paper, we present a comparative genomic study of olfactory behavior in Drosophila including an extended set of genes known to affect olfactory behavior. We took advantage of the recent burst of whole genome sequences and the development of powerful statistical tools to analyze genomic data and test evolutionary and functional hypotheses of olfactory genes in the six species of the Drosophila melanogaster species group for which whole genome sequences are available. Our study reveals widespread purifying selection and limited incidence of positive selection on olfactory genes. We show that the pace of evolution of olfactory genes is mostly independent of the life cycle stage, and of the number of life cycle stages, in which they participate in olfaction. However, we detected a relationship between evolutionary rates and the position that the gene products occupy in the olfactory system, genes occupying central positions tend to be more constrained than peripheral genes. Finally, we demonstrate that specialization to one host does not seem to be associated with bursts of adaptive evolution in olfactory genes in D. sechellia and D. erecta, the two specialists species analyzed, but rather different lineages have idiosyncratic evolutionary histories in which both historical and ecological factors have been involved. PMID:22346339

Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.

PubMed

Mizera, L; Gossrau, G; Hummel, T; Haehner, A

2017-01-01

There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without intake of analgesics. Non-opioid and opioid drugs did not differ in their effects on chemosensory function. © 2016 European Pain Federation - EFIC®.

Learning performance and brain structure of artificially-reared honey bees fed with different quantities of food

PubMed Central

Spaethe, Johannes; Steffan-Dewenter, Ingolf; Härtel, Stephan

2017-01-01

Background Artificial rearing of honey bee larvae is an established method which enables to fully standardize the rearing environment and to manipulate the supplied diet to the brood. However, there are no studies which compare learning performance or neuroanatomic differences of artificially-reared (in-lab) bees in comparison with their in-hive reared counterparts. Methods Here we tested how different quantities of food during larval development affect body size, brain morphology and learning ability of adult honey bees. We used in-lab rearing to be able to manipulate the total quantity of food consumed during larval development. After hatching, a subset of the bees was taken for which we made 3D reconstructions of the brains using confocal laser-scanning microscopy. Learning ability and memory formation of the remaining bees was tested in a differential olfactory conditioning experiment. Finally, we evaluated how bees reared with different quantities of artificial diet compared to in-hive reared bees. Results Thorax and head size of in-lab reared honey bees, when fed the standard diet of 160 µl or less, were slightly smaller than hive bees. The brain structure analyses showed that artificially reared bees had smaller mushroom body (MB) lateral calyces than their in-hive counterparts, independently of the quantity of food they received. However, they showed the same total brain size and the same associative learning ability as in-hive reared bees. In terms of mid-term memory, but not early long-term memory, they performed even better than the in-hive control. Discussion We have demonstrated that bees that are reared artificially (according to the Aupinel protocol) and kept in lab-conditions perform the same or even better than their in-hive sisters in an olfactory conditioning experiment even though their lateral calyces were consistently smaller at emergence. The applied combination of experimental manipulation during the larval phase plus subsequent behavioral and neuro-anatomic analyses is a powerful tool for basic and applied honey bee research. PMID:29085743

Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship.

PubMed

Yoshimura, Natsue; Horiuchi, Daisuke; Shibata, Masao; Saitoe, Minoru; Qi, Mei-Ling; Okazawa, Hitoshi

2006-04-17

Frame shift mutations of the polyglutamine binding protein-1 (PQBP1) gene lead to total or partial truncation of the C-terminal domain (CTD) and cause mental retardation in human patients. Interestingly, normal Drosophila homologue of PQBP-1 lacks CTD. As a model to analyze the molecular network of PQBP-1 affecting intelligence, we generated transgenic flies expressing human PQBP-1 with CTD. Pavlovian olfactory conditioning revealed that the transgenic flies showed disturbance of long-term memory. In addition, they showed abnormal courtship that male flies follow male flies. Abnormal functions of PQBP-1 or its binding partner might be linked to these symptoms.

Effect of Flumethrin on Survival and Olfactory Learning in Honeybees

PubMed Central

Tan, Ken; Yang, Shuang; Wang, Zhengwei; Menzel, Randolf

2013-01-01

Flumethrin has been widely used as an acaricide for the control of Varroa mites in commercial honeybee keeping throughout the world for many years. Here we test the mortality of the Asian honeybee Apis cerana cerana after treatment with flumethrin. We also ask (1) how bees react to the odor of flumethrin, (2) whether its odor induces an innate avoidance response, (3) whether its taste transmits an aversive reinforcing component in olfactory learning, and (4) whether its odor or taste can be associated with reward in classical conditioning. Our results show that flumethrin has a negative effect on Apis ceranàs lifespan, induces an innate avoidance response, acts as a punishing reinforcer in olfactory learning, and interferes with the association of an appetitive conditioned stimulus. Furthermore flumethrin uptake within the colony reduces olfactory learning over an extended period of time. PMID:23785490

Genetic disruptions of Drosophila Pavlovian learning leave extinction learning intact.

PubMed

Qin, H; Dubnau, J

2010-03-01

Individuals who experience traumatic events may develop persistent posttraumatic stress disorder. Patients with this disorder are commonly treated with exposure therapy, which has had limited long-term success. In experimental neurobiology, fear extinction is a model for exposure therapy. In this behavioral paradigm, animals are repeatedly exposed in a safe environment to the fearful stimulus, which leads to greatly reduced fear. Studying animal models of extinction already has lead to better therapeutic strategies and development of new candidate drugs. Lack of a powerful genetic model of extinction, however, has limited progress in identifying underlying molecular and genetic factors. In this study, we established a robust behavioral paradigm to study the short-term effect (acquisition) of extinction in Drosophila melanogaster. We focused on the extinction of olfactory aversive 1-day memory with a task that has been the main workhorse for genetics of memory in flies. Using this paradigm, we show that extinction can inhibit each of two genetically distinct forms of consolidated memory. We then used a series of single-gene mutants with known impact on associative learning to examine the effects on extinction. We find that extinction is intact in each of these mutants, suggesting that extinction learning relies on different molecular mechanisms than does Pavlovian learning.

Expression of calmodulin mRNA in rat olfactory neuroepithelium.

PubMed

Biffo, S; Goren, T; Khew-Goodall, Y S; Miara, J; Margolis, F L

1991-04-01

A calmodulin (CaM) cDNA was isolated by differential hybridization screening of a lambda gt10 library prepared from rat olfactory mucosa. This cDNA fragment, containing most of the open reading frame of the rat CaMI gene, was subcloned and used to characterize steady-state expression of CaM mRNA in rat olfactory neuroepithelium and bulb. Within the bulb mitral cells are the primary neuronal population expressing CaM mRNA. The major CaM mRNA expressed in the olfactory mucosa is 1.7 kb with smaller contributions from mRNAs of 4.0 and 1.4 kb. CaM mRNA was primarily associated with the olfactory neurons and, despite the cellular complexity of the tissue and the known involvement of CaM in diverse cellular processes, was only minimally evident in sustentacular cells, gland cells or respiratory epithelium. Following bulbectomy CaM mRNA declines in the olfactory neuroepithelium as does olfactory marker protein (OMP) mRNA. In contrast to the latter, CaM mRNA makes a partial recovery by one month after surgery. These results, coupled with those from in situ hybridization, indicate that CaM mRNA is expressed in both mature and immature olfactory neurons. The program regulating CaM gene expression in olfactory neurons is distinct from those controlling expression of B50/GAP43 in immature, or OMP in mature, neurons respectively.

The Habituation/Cross-Habituation Test Revisited: Guidance from Sniffing and Video Tracking

PubMed Central

Coronas-Samano, G.; Ivanova, A. V.

2016-01-01

The habituation/cross-habituation test (HaXha) is a spontaneous odor discrimination task that has been used for many decades to evaluate olfactory function in animals. Animals are presented repeatedly with the same odorant after which a new odorant is introduced. The time the animal explores the odor object is measured. An animal is considered to cross-habituate during the novel stimulus trial when the exploration time is higher than the prior trial and indicates the degree of olfactory patency. On the other hand, habituation across the repeated trials involves decreased exploration time and is related to memory patency, especially at long intervals. Classically exploration is timed using a stopwatch when the animal is within 2 cm of the object and aimed toward it. These criteria are intuitive, but it is unclear how they relate to olfactory exploration, that is, sniffing. We used video tracking combined with plethysmography to improve accuracy, avoid observer bias, and propose more robust criteria for exploratory scoring when sniff measures are not available. We also demonstrate that sniff rate combined with proximity is the most direct measure of odorant exploration and provide a robust and sensitive criterion. PMID:27516910

Olfactory threshold increase in trigeminal neuralgia after balloon compression.

PubMed

Siqueira, S R D T; Nóbrega, J C M; Teixeira, M J; Siqueira, J T T

2006-12-01

Idiopathic trigeminal neuralgia (ITN) is a well-known disease often treated with neurosurgical procedures, which may produce sensorial abnormalities, such as numbness, dysesthesia and taste complaints. We studied 12 patients that underwent this technique, in order to verify pain, gustative and olfactory thresholds abnormalities, with a follow-up of 120 days. We compared the patients with a matched control group of 12 patients. Our results found a significant difference in the olfactory threshold at the immediate post-operative period (p=0.048). We concluded that injured trigeminal fibers are probably associated with the increase in the olfactory threshold after the surgery, supporting the sensorial interaction theory.

The neuronal architecture of the mushroom body provides a logic for associative learning

PubMed Central

Aso, Yoshinori; Hattori, Daisuke; Yu, Yang; Johnston, Rebecca M; Iyer, Nirmala A; Ngo, Teri-TB; Dionne, Heather; Abbott, LF; Axel, Richard; Tanimoto, Hiromu; Rubin, Gerald M

2014-01-01

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell–MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory. DOI: http://dx.doi.org/10.7554/eLife.04577.001 PMID:25535793

Age-associated loss of selectivity in human olfactory sensory neurons

PubMed Central

Rawson, Nancy E.; Gomez, George; Cowart, Beverly J.; Kriete, Andres; Pribitkin, Edmund; Restrepo, Diego

2011-01-01

We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in two age groups of younger ( 45 years) and older (≥60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to two odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects’ absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in peripheral cellular specificity may impact odor discrimination and olfactory adaptation in the elderly. It is also possible that chronic adaptation as a result of reduced specificity contributes to observed declines in absolute sensitivity. PMID:22074806

Annual life-history dependent seasonal differences in neural activity of the olfactory system between non-migratory and migratory songbirds.

PubMed

Rastogi, Ashutosh; Surbhi; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

2016-01-01

Present study investigated seasonal plasticity in neural activity of the olfactory system, and assessed whether this was influenced by differences in seasonal life-history states (LHSs) between the non-migratory and migratory birds. Brains of non-migratory Indian weaver birds and migratory redheaded buntings were processed for ZENK immunohistochemistry, a marker of neuronal activation, at the times of equinoxes (March, September) and solstices (June, December), which correspond with the periods of different seasonal LHSs during the year. Immunoreactivity was quantified in brain regions comprising the olfactory system viz. olfactory bulb (OB), anterior olfactory nucleus (AON), prepiriform cortex (CPP), lateral olfactory tract (LOT) and olfactory cortex (piriform cortex, CPI; lateral olfactory cortex, LOC). In weaver birds, ZENK-like immunoreactive (ZENK-lir) cells were significantly higher in all the brain areas during post-breeding season (September) than during the other seasons; OBs had higher neuronal activity in the breeding season (June), however. A similar neural activity pattern but at enhanced levels was found in migratory buntings almost all the year. These results for the first time show LHS-associated differences in the seasonal plasticity of a sensory system between the non-migratory and migratory songbirds. Copyright © 2015 Elsevier B.V. All rights reserved.

[Clinical assessment of olfactory performance - why patient interviews are not enough : A report on lessons learned in planning studies with anosmic patients].

PubMed

Schöpf, V; Kollndorfer, K

2015-07-01

Olfactory dysfunction and loss of smell are mostly associated with an immense decrease in the quality of life. The aim of the presented study was to report on particularities in the acquisition of patients with olfactory dysfunction. During July 2011 and May 2014 we were contacted by 300 potential patients with self-reported loss of smell, 95 (54 female, 41 male, mean age 53) of which were invited for clinical testing after phone interviews. Clinical smell testing revealed 46 patients with anosmia, 38 with hyposmia, and 11 with normosmia. Self-assessment of olfactory function only correlated with clinical scores if patients had nearly no olfactory function left. The ability of self-assessment of olfactory function was independent of age or sex. Further, most patients were not able to report on the reason for or the duration of their olfactory dysfunction. Our report shows that patients with olfactory dysfunction are hardly ever ably to assess their grade of performance reduction. Awareness among patients with a reduced sense of smell is of great general importance, since it can be an indicator of neurodegenerative diseases. This should especially be noted for patients older than 50 who are not able to indicate a reason for their loss of smell.

A kinase-dependent feedforward loop affects CREBB stability and long term memory formation.

PubMed

Lee, Pei-Tseng; Lin, Guang; Lin, Wen-Wen; Diao, Fengqiu; White, Benjamin H; Bellen, Hugo J

2018-02-23

In Drosophila , long-term memory (LTM) requires the cAMP-dependent transcription factor CREBB, expressed in the mushroom bodies (MB) and phosphorylated by PKA. To identify other kinases required for memory formation, we integrated Trojan exons encoding T2A-GAL4 into genes encoding putative kinases and selected for genes expressed in MB. These lines were screened for learning/memory deficits using UAS-RNAi knockdown based on an olfactory aversive conditioning assay. We identified a novel, conserved kinase, Meng-Po ( MP , CG11221 , SBK1 in human), the loss of which severely affects 3 hr memory and 24 hr LTM, but not learning. Remarkably, memory is lost upon removal of the MP protein in adult MB but restored upon its reintroduction. Overexpression of MP in MB significantly increases LTM in wild-type flies showing that MP is a limiting factor for LTM. We show that PKA phosphorylates MP and that both proteins synergize in a feedforward loop to control CREBB levels and LTM. key words: Drosophila, Mushroom bodies, SBK1, deGradFP, T2A-GAL4, MiMIC.

Acute exposure to selenium disrupts associative conditioning and long-term memory recall in honey bees (Apis mellifera).

PubMed

Burden, Christina M; Elmore, Christopher; Hladun, Kristen R; Trumble, John T; Smith, Brian H

2016-05-01

A plethora of toxic compounds - including pesticides, heavy metals, and metalloids - have been detected in honey bees (Apis mellifera) and their colonies. One such compound is selenium, which bees are exposed to by consuming nectar and pollen from flowers grown in contaminated areas. Though selenium is lethal at high concentrations, sublethal exposure may also impair honey bees' ability to function normally. Examining the effect of selenium exposure on learning and memory provides a sensitive assay with which to identify sublethal effects on honey bee health and behavior. To determine whether sublethal selenium exposure causes learning and memory deficits, we used proboscis extension reflex conditioning coupled with recall tests 30min and 24h post-conditioning. We exposed forager honey bees to a single sublethal dose of selenium, and 3h later we used an olfactory conditioning assay to train the bees to discriminate between one odor associated with sucrose-reinforcement and a second unreinforced odor. Following conditioning we tested short- and long-term recall of the task. Acute exposure to as little as 1.8ng of an inorganic form of selenium (sodium selenate) before conditioning caused a reduction in behavioral performance during conditioning. And, exposure to 18ng of either an inorganic form (sodium selenate) or an organic form (methylseleno-l-cysteine) of selenium caused a reduction in the bees' performance during the long-term recall test. These concentrations of selenium are lower than those found in the nectar of plants grown in selenium-contaminated soil, indicating that even low-grade selenium toxicity produces significant learning and memory impairments. This may reduce foragers' ability to effectively gather resources for the colony or nurse bees' ability to care for and maintain a healthy colony. Copyright © 2016. Published by Elsevier Inc.

Preservation of olfaction in surgery of olfactory groove meningiomas.

PubMed

Jang, Woo-Youl; Jung, Shin; Jung, Tae-Young; Moon, Kyung-Sub; Kim, In-Young

2013-08-01

Olfaction is commonly considered as secondary among the sensory functions, perhaps reflecting a lack of interest in sparing olfaction after surgery for the olfactory groove meningiomas (OGM). However, considering the repercussions of olfaction for the quality of life, the assessment of post-operative olfaction should be necessary. We retrospectively reviewed the olfactory outcome in patients with OGM and investigated the factors associated with sparing the post-operative olfaction. Between 1993 and 2012, 40 patients with OGM underwent surgical resection and estimated the olfactory function using the Korean version of "Sniffin'Sticks" test (KVSS). Variable factors, such as tumor size, degree of preoperative edema, tumor consistency, preoperative olfactory function, surgical approaches, patient's age, and gender were analyzed with attention to the post-operative olfactory function. Anatomical and functional preservation of olfactory structures were achieved in 26 patients (65%) and 22 patients (55%), respectively. Among the variable factors, size of tumor was significant related to the preservation of post-operative olfaction. (78.6% in size<4 cm and 42.3% in size>4 cm, p=0.035). Sparing the olfaction was significantly better in patients without preoperative olfactory dysfunction (84.6%) compared with ones with preoperative olfactory dysfunction (40.7%, p=0.016). The frontolateral approach achieved much more excellent post-operative olfactory function (71.4%) than the bifrontal approach (36.8%, p=0.032). If the tumor was smaller than 4 cm and the patients did not present olfactory dysfunction preoperatively, the possibility of sparing the post-operative olfaction was high. Among the variable surgical approaches, frontolateral route may be preferable sparing the post-operative olfaction. Copyright © 2012 Elsevier B.V. All rights reserved.

Differential Olfactory Identification in Children with Autism and Asperger's Disorder: A Comparative and Longitudinal Study

ERIC Educational Resources Information Center

May, Tamara; Brewer, Warrick J.; Rinehart, Nicole J.; Enticott, Peter G.; Brereton, Avril V.; Tonge, Bruce J.

2011-01-01

Key theories of autism implicate orbitofrontal cortex (OFC) compromise, while olfactory identification (OI) deficits are associated with OFC dysfunction. This study aimed to complete a 5-year follow-up of children with high-functioning autism (HFA) who previously lacked the normal age-OI association; and compare unirhinal-OI in children with HFA,…

Development and Validation of a Food-Associated Olfactory Test (FAOT).

PubMed

Denzer-Lippmann, Melanie Yvonne; Beauchamp, Jonathan; Freiherr, Jessica; Thuerauf, Norbert; Kornhuber, Johannes; Buettner, Andrea

2017-01-01

Olfactory tests are an important tool in human nutritional research for studying food preferences, yet comprehensive tests dedicated solely to food odors are currently lacking. Therefore, within this study, an innovative food-associated olfactory test (FAOT) system was developed. The FAOT comprises 16 odorant pens that contain representative food odors relating to different macronutrient classes. The test underwent a sensory validation based on identification rate, intensity, hedonic value, and food association scores. The accuracy of the test was further compared to the accuracy of the established Sniffin' Sticks identification test. The identification rates and intensities of this new FAOT were found to be comparable to the Sniffin' Sticks olfactory identification test. The odorant pens were also assessed chemo-analytically and were found to be chemically stable for at least 24 weeks. Overall, this new identification test for use in assessing olfaction in a food-associated context is valid both in terms of its use in sensory perception studies and its chemical stability. The FOAT is particularly suited to examinations of the sense of smell regarding food odors. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.

PubMed

Ostrovskaya, Rita U; Gruden, Marina A; Bobkova, Natalya A; Sewell, Robert D E; Gudasheva, Tatyana A; Samokhin, Alexander N; Seredinin, Sergey B; Noppe, Wim; Sherstnev, Vladimir V; Morozova-Roche, Ludmilla A

2007-08-01

The effects of the novel proline-containing nootropic and neuroprotective dipeptide, noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were investigated in NMRI mice following olfactory bulbectomy. We have shown previously that these animals developed Alzheimer's disease (AD)-like behaviour, morphology and biochemistry including impairment of spatial memory, regional neuronal degeneration and elevated Abeta peptide brain levels. In the current investigation, spatial memory was assessed using the Morris water maze and serum antibodies to in vitro morphologically characterized amyloid structures of both Abeta((25-35)) peptide and equine lysozyme, as well as to neurotrophic glial factor S100b, were analyzed by enzyme-linked immunosorbent assay (ELISA). Noopept (administered at a dose of 0.01 mg/kg for a period of 21 days and during a further 5 days training) restored spatial memory and increased serum antibody levels to oligomers of Abeta((25-35)) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Abeta((25-35)) peptide prefibrillar aggregates was more marked in sham-operated compared to the bulbectomized subjects which were characterized by an overall suppression of immunoreactivity. Enhancement of the immune response to Abeta((25-35)) peptide prefibrils caused by noopept may attenuate the neurotoxic consequences of amyloid fibrillization and also be associated with an improvement in spatial memory in bulbectomized mice. These actions of noopept, combined with its previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.

Prevalence of olfactory impairment in older adults.

PubMed

Murphy, Claire; Schubert, Carla R; Cruickshanks, Karen J; Klein, Barbara E K; Klein, Ronald; Nondahl, David M

2002-11-13

Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. To determine the prevalence of olfactory impairment in older adults. A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.

The Association Between Olfaction and Depression: A Systematic Review.

PubMed

Kohli, Preeti; Soler, Zachary M; Nguyen, Shaun A; Muus, John S; Schlosser, Rodney J

2016-07-01

Previous studies on the relationship between olfaction and depression have revealed mixed results. In addition, few have focused on the reciprocity of this association. The aim of this study is to combine depression and olfactory data in two separate patient populations to further understand their association. A systematic literature review was conducted using 3 online databases to identify studies correlating olfaction and depression in patients presenting with either primary depression or primary olfactory dysfunction. For the depressed population, weighted means and standard deviations for the Sniffin' Sticks Test and the 40-item Smell Identification Test were combined using 10 studies. For the olfactory dysfunction population, weighted means of Beck's Depression Inventory were combined using 3 studies. Independent t-tests were used to compare differences between groups. Comparing primary depressed patients with controls, depressed patients showed decreased scores in olfactory threshold (6.31±1.38 vs. 6.78±0.88, P = 0.0005), discrimination (12.05±1.44 vs. 12.66±1.36, P = 0.0073), identification (12.57±0.74 vs. 12.98±0.90, P < 0.0001), and 40-Item Smell Identification Test (35.31±1.91 vs. 37.41±1.45, P < 0.0001). In patients with primary olfactory dysfunction, Beck's Depression Inventory scores were significantly different between patients classified as normosmics, hyposmics and anosmics (5.21±4.73 vs. 10.93±9.25 vs. 14.15±5.39, P ≤ 0.0274 for all 3 comparisons). In conclusion, patients with depression have reduced olfactory performance when compared with the healthy controls and conversely, patients with olfactory dysfunction, have symptoms of depression that worsen with severity of smell loss. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain structure is changed in congenital anosmia.

PubMed

Frasnelli, Johannes; Fark, Therese; Lehmann, Jacqueline; Gerber, Johannes; Hummel, Thomas

2013-12-01

Olfactory function in healthy people correlates with structural features of both the olfactory bulb and higher order olfactory processing areas, but we do not yet know how congenital anosmia affects these latter structures. In order to examine this question closer, we acquired T1 weighted magnetic resonance images from 17 subjects with congenital anosmia and from 17 age- and sex-matched controls. We compared white and gray matter volumes as well as cortical thickness between both groups. We found subjects with congenital anosmia to exhibit larger gray matter volumes in the left entorhinal and piriform cortices. Further, they had thicker orbitofrontal cortices bilaterally. Their left piriform cortex was also thicker than that of controls. These findings are in contrast to those observed in acquired anosmia, where reduced olfactory function is associated with reduced volumes and thickness. However, they fit well with observations from other sensory systems, e.g., vision, where congenital sensory loss is associated with a thicker primary cortex. This finding has been attributed to reduced or absent synaptic pruning as a result of missing peripheral sensory input. Our findings suggest that similar mechanisms take place in the olfactory system. © 2013.

Olfactory Performance in a Large Sample of Early-Blind and Late-Blind Individuals.

PubMed

Sorokowska, Agnieszka

2016-10-01

Previous examinations of olfactory sensitivity in blind people have produced contradictory findings. Thus, whether visual impairment is associated with increased olfactory abilities is unclear. In the present investigation, I aimed to resolve the existing questions via a relatively large-scale study comprising early-blind (N = 43), and late-blind (N = 41) and sighted (N = 84) individuals matched in terms of gender and age. To compare the results with those of previous studies, I combined data from a free odor identification test, extensive psychophysical testing (Sniffin' Sticks test), and self-assessed olfactory performance. The analyses revealed no significant effects of sight on olfactory threshold, odor discrimination, cued identification, or free identification scores; neither was the performance of the early-blind and late-blind participants significantly different. Additionally, the self-assessed olfactory abilities of the blind people were no different than those of the sighted people. These results suggest that sensory compensation in visually impaired is not pronounced with regards to olfactory abilities as measured by standardized smell tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology

PubMed Central

McShane, R; Nagy, Z; Esiri, M; King, E; Joachim, C; Sullivan, N; Smith, A

2001-01-01

OBJECTIVES—To assess olfactory function of patients with dementia. Odour detection ability is impaired in clinical Parkinson's disease. Evidence of impaired detection in patients with clinically diagnosed Alzheimer's disease is inconsistent. No studies of olfaction have been neuropathologically validated.
METHODS—The olfactory function of 92 patients with dementia and 94 controls was assessed using a simple bedside test as part of the Oxford Project To Investigate Memory and Ageing (OPTIMA). Neuropathological assessment was made of cortical Lewy bodies and substantia nigra (SN) cell counts and of Alzheimer's disease in all 92 patients, 22 of whom had SN Lewy bodies and 43 of whom had only Alzheimer's disease.
RESULTS—Patients with Lewy bodies were more likely to be anosmic than those with Alzheimer's disease or controls. Patients with Alzheimer's disease were not more likely to be anosmic than controls. Nor was anosmia associated with degree of neurofibrillary tangles, as assessed by Braak stage. Among subjects with Lewy bodies, overall cortical Lewy body scores and Lewy body density in the cingulate were higher in those who were anosmic. Consensus clinical criteria for dementia with Lewy bodies had a sensitivity of 64% and specificity of 89%. In the absence of definite Alzheimer's disease, the criteria had sensitivity of 100%. In patients with definite Alzheimer's disease, anosmia was slightly more sensitive (55%) than the consensus criteria (33%). However, the addition of anosmia to the consensus criteria did not improve their overall performance.
CONCLUSION—Dementia with Lewy bodies is associated with impaired odour detection. Misdiagnosis may have accounted for some previous reports of impaired odour detection in Alzheimer's disease. Simple but more sensitive tests of anosmia are required if they are to be clinically useful in identifying patients with dementia with Lewy bodies.

 PMID:11385006

Transient uptake of serotonin by newborn olfactory projection neurons

PubMed Central

Beltz, Barbara S.; Benton, Jeanne L.; Sullivan, Jeremy M.

2001-01-01

A life-long turnover of sensory and interneuronal populations has been documented in the olfactory pathways of both vertebrates and invertebrates, creating a situation where the axons of new afferent and interneuronal populations must insert into a highly specialized glomerular neuropil. A dense serotonergic innervation of the primary olfactory processing areas where these neurons synapse also is a consistent feature across species. Prior studies in lobsters have shown that serotonin promotes the branching of olfactory projection neurons. This paper presents evidence that serotonin also regulates the proliferation and survival of projection neurons in lobsters, and that the serotonergic effects are associated with a transient uptake of serotonin into newborn neurons. PMID:11675504

[Radiological findings in congenital anosmia: a case report].

PubMed

Sánchez-Pérez, María; Recio-Rodríguez, Manuel; Jiménez-De la Peña, Mar; Carrascoso-Arranz, Javier; Martínez-De Vega, Vicente

2011-07-16

Hypoplasia of the olfactory tracts and bulbs is a rare cause of anosmia in the paediatric population. In most cases it is usually due to an acquired cause and in only a few is it associated to chromosomal disorders (Kallman's syndrome, among others). A 10-year-old boy with no chromosomal disorders and a family history of anosmia, who visited because of isolated anosmia; a magnetic resonance scan revealed bilateral hypoplasia of the olfactory tracts and bulbs. Magnetic resonance imaging allows the anatomy of the olfactory tract to be studied in detail and this makes it a valuable tool in the diagnosis of structural abnormalities in cases of olfactory disorders and also in the planning of treatment.

Interaction of inhibitory and facilitatory effects of conditioning trials on long-term memory formation

PubMed Central

Hosono, Shouhei; Matsumoto, Yukihisa

2016-01-01

Animals learn through experience and consolidate the memories into long-time storage. Conditioning parameters to induce protein synthesis-dependent long-term memory (LTM) have been the subject of extensive studies in many animals. Here we found a case in which a conditioning trial inhibits or facilitates LTM formation depending on the intervals from preceding trials. We studied the effects of conditioning parameters on LTM formation in olfactory conditioning of maxillary-palpi extension response with sucrose reward in the cockroach Periplaneta americana. We found, at first, that translation- and transcription-dependent LTM forms 1 h after training, the fastest so far reported in insects. Second, we observed that multiple-trial training with an intertrial interval (ITI) of 20 or 30 sec, often called massed training, is more effective than spaced training for LTM formation, an observation that differs from the results of most studies in other animals. Third, we found that a conditioning trial inhibits LTM formation when the intervals from preceding trials were in the range of 10–16 min. This inhibitory effect is pairing-specific and is not due to decreased motivation for learning (overtraining effect). To our knowledge, no similar inhibition of LTM formation by a conditioning trial has been reported in any animals. We propose a model to account for the effects of trial number and ITIs on LTM formation. Olfactory conditioning in cockroaches should provide pertinent materials in which to study neuronal and molecular mechanisms underlying the inhibitory and facilitatory processes for LTM formation. PMID:27918270

Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

PubMed

Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

2016-01-01

Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth. Copyright © 2015 Elsevier B.V. All rights reserved.

Smelling directions: Olfaction modulates ambiguous visual motion perception

PubMed Central

Kuang, Shenbing; Zhang, Tao

2014-01-01

Senses of smells are often accompanied by simultaneous visual sensations. Previous studies have documented enhanced olfactory performance with concurrent presence of congruent color- or shape- related visual cues, and facilitated visual object perception when congruent smells are simultaneously present. These visual object-olfaction interactions suggest the existences of couplings between the olfactory pathway and the visual ventral processing stream. However, it is not known if olfaction can modulate visual motion perception, a function that is related to the visual dorsal stream. We tested this possibility by examining the influence of olfactory cues on the perceptions of ambiguous visual motion signals. We showed that, after introducing an association between motion directions and olfactory cues, olfaction could indeed bias ambiguous visual motion perceptions. Our result that olfaction modulates visual motion processing adds to the current knowledge of cross-modal interactions and implies a possible functional linkage between the olfactory system and the visual dorsal pathway. PMID:25052162

Long-term control of olfactory neuroblastoma in a dog treated with surgery and radiation therapy.

PubMed

Gumpel, E; Moore, A S; Simpson, D J; Hoffmann, K L; Taylor, D P

2017-07-01

Olfactory neuroblastoma is a rare malignancy of the nasal cavity in dogs that is thought to arise from specialised sensory neuroendocrine olfactory cells derived from the neural crest. An 8-year-old dog was presented for reclusiveness and pacing. On CT and MRI, a contract-enhancing mass was disclosed within the rostral fossa, extending caudally from the cribriform plate into the left nasal sinus. Surgical excision was performed and the diagnosis was histological grade III (Hyams grading scheme) olfactory neuroblastoma. Based on human CT criteria this was high stage (modified Kadish stage C). Surgical excision was incomplete and was followed by curative-intent radiation therapy using a linear accelerator to a total dose of 48 Gy. The dog survived 20 months after diagnosis. Although olfactory neuroblastoma is a rare tumour in dogs, aggressive local therapy may allow for prolonged survival, even when the tumour is advanced. © 2017 Australian Veterinary Association.

Causal Interrogation of Neuronal Networks and Behavior through Virally Transduced Ivermectin Receptors.

PubMed

Obenhaus, Horst A; Rozov, Andrei; Bertocchi, Ilaria; Tang, Wannan; Kirsch, Joachim; Betz, Heinrich; Sprengel, Rolf

2016-01-01

The causal interrogation of neuronal networks involved in specific behaviors requires the spatially and temporally controlled modulation of neuronal activity. For long-term manipulation of neuronal activity, chemogenetic tools provide a reasonable alternative to short-term optogenetic approaches. Here we show that virus mediated gene transfer of the ivermectin (IVM) activated glycine receptor mutant GlyRα1 (AG) can be used for the selective and reversible silencing of specific neuronal networks in mice. In the striatum, dorsal hippocampus, and olfactory bulb, GlyRα1 (AG) promoted IVM dependent effects in representative behavioral assays. Moreover, GlyRα1 (AG) mediated silencing had a strong and reversible impact on neuronal ensemble activity and c-Fos activation in the olfactory bulb. Together our results demonstrate that long-term, reversible and re-inducible neuronal silencing via GlyRα1 (AG) is a promising tool for the interrogation of network mechanisms underlying the control of behavior and memory formation.

Default Mode Network (DMN) Deactivation during Odor-Visual Association

PubMed Central

Karunanayaka, Prasanna R.; Wilson, Donald A.; Tobia, Michael J.; Martinez, Brittany; Meadowcroft, Mark; Eslinger, Paul J.; Yang, Qing X.

2017-01-01

Default mode network (DMN) deactivation has been shown to be functionally relevant for goal-directed cognition. In this study, we investigated the DMN’s role during olfactory processing using two complementary functional magnetic resonance imaging (fMRI) paradigms with identical timing, visual-cue stimulation and response monitoring protocols. Twenty-nine healthy, non-smoking, right-handed adults (mean age = 26±4 yrs., 16 females) completed an odor-visual association fMRI paradigm that had two alternating odor+visual and visual-only trial conditions. During odor+visual trials, a visual cue was presented simultaneously with an odor, while during visual-only trial conditions the same visual cue was presented alone. Eighteen of the 29 participants (mean age = 27.0 ± 6.0 yrs.,11 females) also took part in a control no-odor fMRI paradigm that consisted of visual-only trial conditions which were identical to the visual-only trials in the odor-visual association paradigm. We used Independent Component Analysis (ICA), extended unified structural equation modeling (euSEM), and psychophysiological interaction (PPI) to investigate the interplay between the DMN and olfactory network. In the odor-visual association paradigm, DMN deactivation was evoked by both the odor+visual and visual-only trial conditions. In contrast, the visual-only trials in the no-odor paradigm did not evoke consistent DMN deactivation. In the odor-visual association paradigm, the euSEM and PPI analyses identified a directed connectivity between the DMN and olfactory network which was significantly different between odor+visual and visual-only trial conditions. The results support a strong interaction between the DMN and olfactory network and highlights DMN’s role in task-evoked brain activity and behavioral responses during olfactory processing. PMID:27785847

In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

2012-08-01

Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P < 0.05). Dopamine (DA) receptor D1 was upregulated in the hippocampus of Fe+DHA/EPA rats (fold-change = 1.25; P < 0.05) and there were significant Fe x DHA/EPA interactions on serotonin (5-HT) in the OB and on the DA metabolite dihydroxyphenylacetic acid in the FC and striatum. Working memory performance was impaired in ID+DHA/EPA rats compared with controls (P < 0.05). In the reference memory task, Fe+DHA/EPA improved learning behavior, but Fe or DHA/EPA alone did not. These findings suggest that feeding either Fe or DHA/EPA alone to adult rats with both ID and (n-3)FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.

Sexual odor preference and dopamine release in the nucleus accumbens by estrous olfactory cues in sexually naïve and experienced male rats.

PubMed

Fujiwara, Masaya; Chiba, Atsuhiko

2018-03-01

Sexual behavior is a natural reward that activates mesolimbic dopaminergic system. Microdialysis studies have shown that extracellular level of dopamine (DA) in the nucleus accumbens (NAcc) significantly increases during copulation in male rats. The NAcc DA level is also known to be increased during the presentation of a sexually receptive female before mating. This rise in DA was probably associated with sexual motivation elicited by incentive stimuli from the receptive female. These microdialysis studies, however, did not thoroughly investigated if olfactory stimuli from estrous females could significantly increase the extracellular DA in the NAcc of male rats. The present study was designed to examine systematically the relationship between the expression of preference for the olfactory stimuli from estrous females and the effects of these stimuli on the extracellular DA levels in the NAcc measured by in vivo microdialysis in male Long-Evans (LE) rats. We used two types of olfactory stimuli, either airborne odors (volatile stimuli) or soiled bedding (volatile plus nonvolatile stimuli). The sexually experienced male rats, which experienced six ejaculations, significantly preferred both of these olfactory stimuli from estrous females as opposed to males. Exposure to these female olfactory stimuli gradually increased extracellular DA in the NAcc, which reached significantly higher level above baseline during the period following the removal of the stimuli although not during the 15-min stimulus presentation period. The sexually naïve male rats, on the other hand, showed neither preference for olfactory stimuli from estrous females nor increase in the NAcc DA after exposure to these stimuli. These data suggest that in male LE rats olfactory stimuli from estrous females in and of themselves can be conditional cues that induce both incentive motivation and a significant increase in the NAcc DA probably as a result of being associated with sexual reward through copulatory experience. Copyright © 2017. Published by Elsevier Inc.

Possible link between Toxoplasma gondii and the anosmia associated with neurodegenerative diseases.

PubMed

Prandota, Joseph

2014-05-01

Toxoplasma gondii is an intracellular protozoan infecting 30% to 50% of global human population. Recently, it was suggested that chronic latent neuroinflammation caused by the parasite may be responsible for the development of several neurodegenerative diseases manifesting with the loss of smell. Studies in animals inoculated with the parasite revealed cysts in various regions of the brain, including olfactory bulb. Development of behavioral changes was paralleled by the preferential persistence of cysts in defined anatomic structures of the brain, depending on the host, strain of the parasite, its virulence, and route of inoculation. Olfactory dysfunction reported in Alzheimer's disease, multiple sclerosis, and schizophrenia was frequently associated with the significantly increased serum anti-T gondii immunoglobulin G antibody levels. Damage of the olfactory system may be also at least in part responsible for the development of depression because T gondii infection worsened mood in such patients, and the olfactory bulbectomized rat serves as a model of depression.

Hyperlipidemic Diet Causes Loss of Olfactory Sensory Neurons, Reduces Olfactory Discrimination, and Disrupts Odor-Reversal Learning

PubMed Central

Thiebaud, Nicolas; Johnson, Melissa C.; Butler, Jessica L.; Bell, Genevieve A.; Ferguson, Kassandra L.; Fadool, Andrew R.; Fadool, James C.; Gale, Alana M.; Gale, David S.

2014-01-01

Currently, 65% of Americans are overweight, which leads to well-supported cardiovascular and cognitive declines. Little, however, is known concerning obesity's impact on sensory systems. Because olfaction is linked with ingestive behavior to guide food choice, its potential dysfunction during obesity could evoke a positive feedback loop to perpetuate poor ingestive behaviors. To determine the effect of chronic energy imbalance and reveal any structural or functional changes associated with obesity, we induced long-term, diet-induced obesity by challenging mice to high-fat diets: (1) in an obesity-prone (C57BL/6J) and obesity-resistant (Kv1.3−/−) line of mice, and compared this with (2) late-onset, genetic-induced obesity in MC4R−/− mice in which diabetes secondarily precipitates after disruption of the hypothalamic axis. We report marked loss of olfactory sensory neurons and their axonal projections after exposure to a fatty diet, with a concomitant reduction in electro-olfactogram amplitude. Loss of olfactory neurons and associated circuitry is linked to changes in neuronal proliferation and normal apoptotic cycles. Using a computer-controlled, liquid-based olfactometer, mice maintained on fatty diets learn reward-reinforced behaviors more slowly, have deficits in reversal learning demonstrating behavioral inflexibility, and exhibit reduced olfactory discrimination. When obese mice are removed from their high-fat diet to regain normal body weight and fasting glucose, olfactory dysfunctions are retained. We conclude that chronic energy imbalance therefore presents long-lasting structural and functional changes in the operation of the sensory system designed to encode external and internal chemical information and leads to altered olfactory- and reward-driven behaviors. PMID:24828650

Low plasma tryptophan is associated with olfactory function in healthy elderly community dwellers in Japan.

PubMed

Adachi, Yusuke; Shimodaira, Yoshiki; Nakamura, Hidehiro; Imaizumi, Akira; Mori, Maiko; Kageyama, Yoko; Noguchi, Yasushi; Seki, Asuka; Okabe, Yuki; Miyake, Yuko; Ono, Kaori; Kumagai, Shu

2017-10-16

Decreased circulating tryptophan (Trp) levels are frequently observed in elderly patients with neurodegenerative disease including Alzheimer's disease. Trp may serve as a potential biomarker for monitoring disease risk in elderly people. We aimed to investigate the association between low plasma Trp levels and olfactory function, which is known to predict age-related diseases including dementia in elderly people. A total of 144 healthy elderly Japanese community (≥ 65 years old) dwellers from the Health, Aging and Nutritional Improvement study (HANI study) were the subjects of our analysis. Low Trp levels were classified using the lower limit values of the reference interval according to a previous report. Olfactory function was assessed using a card-type test called Open Essence, which includes 12 odour items that are familiar to Japanese people. The elderly subjects with low circulating Trp levels were compared to a control group with normal plasma Trp levels. We conducted the analyses using 144 people aged 65 years or older (mean age 73.7 ± 5.5 years; 36.1% men). The subjects showed normal serum albumin levels (4.4 ± 0.2 g/dL) and no daily living disabilities. Low plasma Trp levels (low Trp group) were found in 11.1% of the study population. The low Trp group showed a significantly lower correct-answer rate for the items india ink, perfume, curry and sweaty smelling socks than control group (P < 0.05). There was also a significant association between low Trp levels and low olfactory ability, after adjusting for age and sex. Lower plasma Trp levels were associated with a decrease in olfactory function in functionally competent older individuals. Because olfactory dysfunction predicts age-related diseases, low plasma Trp levels may represent a clinical sign of disease risk in elderly people.

Respiratory and olfactory turbinal size in canid and arctoid carnivorans.

PubMed

Green, Patrick A; Van Valkenburgh, Blaire; Pang, Benison; Bird, Deborah; Rowe, Timothy; Curtis, Abigail

2012-12-01

Within the nasal cavity of mammals is a complex scaffold of paper-thin bones that function in respiration and olfaction. Known as turbinals, the bones greatly enlarge the surface area available for conditioning inspired air, reducing water loss, and improving olfaction. Given their functional significance, the relative development of turbinal bones might be expected to differ among species with distinct olfactory, thermoregulatory and/or water conservation requirements. Here we explore the surface area of olfactory and respiratory turbinals relative to latitude and diet in terrestrial Caniformia, a group that includes the canid and arctoid carnivorans (mustelids, ursids, procyonids, mephitids, ailurids). Using high-resolution computed tomography x-ray scans, we estimated respiratory and olfactory turbinal surface area and nasal chamber volume from three-dimensional virtual models of skulls. Across the Caniformia, respiratory surface area scaled isometrically with estimates of body size and there was no significant association with climate, as estimated by latitude. Nevertheless, one-on-one comparisons of sister taxa suggest that arctic species may have expanded respiratory turbinals. Olfactory surface area scaled isometrically among arctoids, but showed positive allometry in canids, reflecting the fact that larger canids, all of which are carnivorous, had relatively greater olfactory surface areas. In addition, among the arctoids, large carnivorous species such as the polar bear (Ursus maritimus) and wolverine (Gulo gulo) also displayed enlarged olfactory turbinals. More omnivorous caniform species that feed on substantial quantities of non-vertebrate foods had less expansive olfactory turbinals. Because large carnivorous species hunt widely dispersed prey, an expanded olfactory turbinal surface area may improve a carnivore's ability to detect prey over great distances using olfactory cues. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Respiratory and olfactory turbinal size in canid and arctoid carnivorans

PubMed Central

Green, Patrick A; Valkenburgh, Blaire; Pang, Benison; Bird, Deborah; Rowe, Timothy; Curtis, Abigail

2012-01-01

Within the nasal cavity of mammals is a complex scaffold of paper-thin bones that function in respiration and olfaction. Known as turbinals, the bones greatly enlarge the surface area available for conditioning inspired air, reducing water loss, and improving olfaction. Given their functional significance, the relative development of turbinal bones might be expected to differ among species with distinct olfactory, thermoregulatory and/or water conservation requirements. Here we explore the surface area of olfactory and respiratory turbinals relative to latitude and diet in terrestrial Caniformia, a group that includes the canid and arctoid carnivorans (mustelids, ursids, procyonids, mephitids, ailurids). Using high-resolution computed tomography x-ray scans, we estimated respiratory and olfactory turbinal surface area and nasal chamber volume from three-dimensional virtual models of skulls. Across the Caniformia, respiratory surface area scaled isometrically with estimates of body size and there was no significant association with climate, as estimated by latitude. Nevertheless, one-on-one comparisons of sister taxa suggest that arctic species may have expanded respiratory turbinals. Olfactory surface area scaled isometrically among arctoids, but showed positive allometry in canids, reflecting the fact that larger canids, all of which are carnivorous, had relatively greater olfactory surface areas. In addition, among the arctoids, large carnivorous species such as the polar bear (Ursus maritimus) and wolverine (Gulo gulo) also displayed enlarged olfactory turbinals. More omnivorous caniform species that feed on substantial quantities of non-vertebrate foods had less expansive olfactory turbinals. Because large carnivorous species hunt widely dispersed prey, an expanded olfactory turbinal surface area may improve a carnivore's ability to detect prey over great distances using olfactory cues. PMID:23035637

FoxP2 and olfaction: divergence of FoxP2 expression in olfactory tubercle between different feeding habit bats.

PubMed

Chen, Qi; Wang, Lina; Jones, G; Metzner, W; Xuan, F J; Yin, Jiangxia; Sun, Y

2013-12-01

FoxP2 is a member of the winged helix/forkhead class of transcription factors. Despite FoxP2 is found to have particular relevance to speech and language, the role of this gene is broader and not yet fully elucidated. In this study, we investigated the expression of FoxP2 in the brains of bats with different feeding habits (two frugivorous species and three insectivorous species). We found FoxP2 expression in the olfactory tubercle of frugivorous species is significantly higher than that in insectivorous species. Difference of FoxP2 expression was not observed within each of the frugivorous or insectivorous group. The diverse expression patterns in olfactory tubercle between two kinds of bats indicate FoxP2 has a close relation with olfactory tubercle associated functions, suggesting its important role in sensory integration within the olfactory tubercle and such a discrepancy of FoxP2 expression in olfactory tubercle may take responsibility for the different feeding behaviors of frugivorous and insectivorous bats.

Stable olfactory sensory neuron in vivo physiology during normal aging.

PubMed

Kass, Marley D; Czarnecki, Lindsey A; McGann, John P

2018-05-08

Normal aging is associated with a number of smell impairments that are paralleled by age-dependent changes in the peripheral olfactory system, including decreases in olfactory sensory neurons (OSNs) and in the regenerative capacity of the epithelium. Thus, an age-dependent degradation of sensory input to the brain is one proposed mechanism for the loss of olfactory function in older populations. Here, we tested this hypothesis by performing in vivo optical neurophysiology in 6-, 12-, 18-, and 24-month-old mice. We visualized odor-evoked neurotransmitter release from populations of OSNs into olfactory bulb glomeruli, and found that these sensory inputs are actually quite stable during normal aging. Specifically, the magnitude and number of odor-evoked glomerular responses were comparable across all ages, and there was no effect of age on the sensitivity of OSN responses to odors or on the neural discriminability of different sensory maps. These results suggest that the brain's olfactory bulbs do not receive deteriorated input during aging and that local bulbar circuitry might adapt to maintain stable nerve input. Copyright © 2018 Elsevier Inc. All rights reserved.

The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

PubMed

Roybon, Laurent; Mastracci, Teresa L; Li, Joyce; Stott, Simon R W; Leiter, Andrew B; Sussel, Lori; Brundin, Patrik; Li, Jia-Yi

2015-01-01

Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1) is commonly associated with glutamatergic neuron development. In this study, we utilized ND1 to identify the different subpopulations of olfactory bulb glutamategic neurons and their progenitors, both in the embryo and postnatally. Using knock-in mice, transgenic mice and retroviral transgene delivery, we demonstrate the existence of several different populations of glutamatergic olfactory bulb neurons, the progenitors of which are ND1+ and ND1- lineage-restricted, and are temporally and regionally separated. We show that the first olfactory bulb glutamatergic neurons produced - the mitral cells - can be divided into molecularly diverse subpopulations. Our findings illustrate the complexity of neuronal diversity in the olfactory bulb and that seemingly homogenous neuronal populations can consist of multiple subpopulations with unique molecular signatures of transcription factors and expressing neuronal subtype-specific markers.

Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors.

PubMed

Grundwald, N J; Benítez, D P; Brunton, P J

2016-04-01

Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans. © 2015 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

Role of sensory cues on food searching behavior of a captive Manta birostris (Chondrichtyes, Mobulidae).

PubMed

Ari, Csilla; Correia, João P

2008-07-01

This study reports on the first experimental research designed specifically for Manta birostris behavior. The authors attempted to learn about the feeding behavior and environmental cues influencing this behavior, as well as general cognitive ability. The preconditioned Manta's ability to identify food, on the basis of a fraction of the ordinary food signal complex, was tested. The opening of cephalic fins was considered a good indicator of feeding motivation level. The study subject animal used its biological clock to predict time and also associated a specific location with food, suggesting an ability to build up a cognitive map of its environment. Both underwater visual stimuli and olfactory stimuli had a very intense effect on food searching behavior over a 30 m distance, in contrast to visual signs from above the water surface. In addition, although an underwater visual signal resulted in a more intense response than from an olfactory signal, the specimen did not discriminate between different objects tested on the basis of visual sensation. It could therefore be suggested that food searching behavior of Mantas are governed by triggering stimuli, including smell or visual recognition, and modulated by the cognitive spatial map stored in their long-term memory. These findings will hopefully prove useful while devising protecting policies in the natural environment and/or while keeping these animals in captivity. Zoo Biol 27:294-304, 2008. (c) 2008 Wiley-Liss, Inc.

Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice.

PubMed

Ueha, Rumi; Ueha, Satoshi; Sakamoto, Takashi; Kanaya, Kaori; Suzukawa, Keigo; Nishijima, Hironobu; Kikuta, Shu; Kondo, Kenji; Matsushima, Kouji; Yamasoba, Tatsuya

2016-08-01

The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa.

Differential Dynamics of Amino Acid Release in the Amygdala and Olfactory Cortex during Odor Fear Acquisition as Revealed with Simultaneous High Temporal Resolution Microdialysis

ERIC Educational Resources Information Center

Hegoburu, Chloe; Sevelinges, Yannick; Thevenet, Marc; Gervais, Remi; Parrot, Sandrine; Mouly, Anne-Marie

2009-01-01

Although the amygdala seems to be essential to the formation and storage of fear memories, it might store only some aspects of the aversive event and facilitate the storage of more specific sensory aspects in cortical areas. We addressed the time course of amygdala and cortical activation in the context of odor fear conditioning in rats. Using…

Cellular registration without behavioral recall of olfactory sensory input under general anesthesia.

PubMed

Samuelsson, Andrew R; Brandon, Nicole R; Tang, Pei; Xu, Yan

2014-04-01

Previous studies suggest that sensory information is "received" but not "perceived" under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. One hundred seven rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. The olfactory sensory processing centers could distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Reexposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity, which was similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the "cellular memory," however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Histologically distinguishable registration of sensory processing continues to occur at the cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications.

Cellular Registration Without Behavioral Recall Of Olfactory Sensory Input Under General Anesthesia

PubMed Central

Samuelsson, Andrew R.; Brandon, Nicole R.; Tang, Pei; Xu, Yan

2014-01-01

Background Previous studies suggest that sensory information is “received” but not “perceived” under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. Methods 107 rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. Results The olfactory sensory processing centers can distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Re-exposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the “cellular memory,” however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Conclusions Histologically distinguishable registration of sensory process continues to occur at cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications. PMID:24694846

Reward signal in a recurrent circuit drives appetitive long-term memory formation.

PubMed

Ichinose, Toshiharu; Aso, Yoshinori; Yamagata, Nobuhiro; Abe, Ayako; Rubin, Gerald M; Tanimoto, Hiromu

2015-11-17

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

Odor-Induced Neuronal Rhythms in the Olfactory Bulb Are Profoundly Modified in ob/ob Obese Mice

PubMed Central

Chelminski, Yan; Magnan, Christophe; Luquet, Serge H.; Everard, Amandine; Meunier, Nicolas; Gurden, Hirac; Martin, Claire

2017-01-01

Leptin, the product of the Ob(Lep) gene, is a peptide hormone that plays a major role in maintaining the balance between food intake and energy expenditure. In the brain, leptin receptors are expressed by hypothalamic cells but also in the olfactory bulb, the first central structure coding for odors, suggesting a precise function of this hormone in odor-evoked activities. Although olfaction plays a key role in feeding behavior, the ability of the olfactory bulb to integrate the energy-related signal leptin is still missing. Therefore, we studied the fate of odor-induced activity in the olfactory bulb in the genetic context of leptin deficiency using the obese ob/ob mice. By means of an odor discrimination task with concomitant local field potential recordings, we showed that ob/ob mice perform better than wild-type (WT) mice in the early stage of the task. This behavioral gain of function was associated in parallel with profound changes in neuronal oscillations in the olfactory bulb. The distribution of the peaks in the gamma frequency range was shifted toward higher frequencies in ob/ob mice compared to WT mice before learning. More notably, beta oscillatory activity, which has been shown previously to be correlated with olfactory discrimination learning, was longer and stronger in expert ob/ob mice after learning. Since oscillations in the olfactory bulb emerge from mitral to granule cell interactions, our results suggest that cellular dynamics in the olfactory bulb are deeply modified in ob/ob mice in the context of olfactory learning. PMID:28154537

On the olfactory anatomy in an archaic whale (Protocetidae, Cetacea) and the minke whale Balaenoptera acutorostrata (Balaenopteridae, Cetacea).

PubMed

Godfrey, Stephen J; Geisler, Jonathan; Fitzgerald, Erich M G

2013-02-01

The structure of the olfactory apparatus is not well known in both archaic and extant whales; the result of poor preservation in most fossils and locational isolation deep within the skulls in both fossil and Recent taxa. Several specimens now shed additional light on the subject. A partial skull of an archaic cetacean is reported from the Pamunkey River, Virginia, USA. The specimen probably derives from the upper middle Eocene (Piney Point Formation) and is tentatively assigned to the Protocetidae. Uncrushed cranial cavities associated with the olfactory apparatus were devoid of sediment. CT scans clearly reveal the dorsal nasal meatus, ethmoturbinates within the olfactory recess, the cribriform plate, the area occupied by the olfactory bulbs, and the olfactory nerve tract. Several sectioned skulls of the minke whale (Balaenoptera acutorostrata) were also examined, and olfactory structures are remarkably similar to those observed in the fossil skull from the Pamunkey River. One important difference between the two is that the fossil specimen has an elongate olfactory nerve tract. The more forward position of the external nares in extant balaenopterids when compared with those of extant odontocetes is interpreted to be the result of the need to retain a functional olfactory apparatus and the forward position of the supraoccipital/cranial vertex. An increase in the distance between the occipital condyles and the vertex in balaenopterids enhances the mechanical advantage of the epaxial musculature that inserts on the occiput, a specialization that likely stabilizes the head of these enormous mammals during lunge feeding. Copyright © 2012 Wiley Periodicals, Inc.

Parallel processing via a dual olfactory pathway in the honeybee.

PubMed

Brill, Martin F; Rosenbaum, Tobias; Reus, Isabelle; Kleineidam, Christoph J; Nawrot, Martin P; Rössler, Wolfgang

2013-02-06

In their natural environment, animals face complex and highly dynamic olfactory input. Thus vertebrates as well as invertebrates require fast and reliable processing of olfactory information. Parallel processing has been shown to improve processing speed and power in other sensory systems and is characterized by extraction of different stimulus parameters along parallel sensory information streams. Honeybees possess an elaborate olfactory system with unique neuronal architecture: a dual olfactory pathway comprising a medial projection-neuron (PN) antennal lobe (AL) protocerebral output tract (m-APT) and a lateral PN AL output tract (l-APT) connecting the olfactory lobes with higher-order brain centers. We asked whether this neuronal architecture serves parallel processing and employed a novel technique for simultaneous multiunit recordings from both tracts. The results revealed response profiles from a high number of PNs of both tracts to floral, pheromonal, and biologically relevant odor mixtures tested over multiple trials. PNs from both tracts responded to all tested odors, but with different characteristics indicating parallel processing of similar odors. Both PN tracts were activated by widely overlapping response profiles, which is a requirement for parallel processing. The l-APT PNs had broad response profiles suggesting generalized coding properties, whereas the responses of m-APT PNs were comparatively weaker and less frequent, indicating higher odor specificity. Comparison of response latencies within and across tracts revealed odor-dependent latencies. We suggest that parallel processing via the honeybee dual olfactory pathway provides enhanced odor processing capabilities serving sophisticated odor perception and olfactory demands associated with a complex olfactory world of this social insect.

Spermidine-triggered autophagy ameliorates memory during aging.

PubMed

Sigrist, Stephan J; Carmona-Gutierrez, Didac; Gupta, Varun K; Bhukel, Anuradha; Mertel, Sara; Eisenberg, Tobias; Madeo, Frank

2014-01-01

The aging process drives the progressive deterioration of an organism and is thus subject to a complex interplay of regulatory and executing mechanisms. Our understanding of this process eventually aims at the delay and/or prevention of age-related pathologies, among them the age-dependent decrease in cognitive performance (e.g., learning and memory). Using the fruit fly Drosophila melanogaster, which combines a generally high mechanistic conservation with an efficient experimental access regarding aging and memory studies, we have recently unveiled a protective function of polyamines (including spermidine) against age-induced memory impairment (AMI). The flies' age-dependent decline of aversive olfactory memory, an established model for AMI, can be rescued by both pharmacological treatment with spermidine and genetic modulation that increases endogenous polyamine levels. Notably, we find that this effect strictly depends on autophagy, which is remarkable in light of the fact that autophagy is considered a key regulator of aging in other contexts. Given that polyamines in general and spermidine in particular are endogenous metabolites, our findings place them as candidate target substances for AMI treatment.

Morphological study on the olfactory systems of the snapping turtle, Chelydra serpentina.

PubMed

Nakamuta, Nobuaki; Nakamuta, Shoko; Kato, Hideaki; Yamamoto, Yoshio

2016-06-01

In this study, the olfactory system of a semi-aquatic turtle, the snapping turtle, has been morphologically investigated by electron microscopy, immunohistochemistry, and lectin histochemistry. The nasal cavity of snapping turtle was divided into the upper and lower chambers, lined by the sensory epithelium containing ciliated and non-ciliated olfactory receptor neurons, respectively. Each neuron expressed both Gαolf, the α-subunit of G-proteins coupling to the odorant receptors, and Gαo, the α-subunit of G-proteins coupling to the type 2 vomeronasal receptors. The axons originating from the upper chamber epithelium projected to the ventral part of the olfactory bulb, while those from the lower chamber epithelium to the dorsal part of the olfactory bulb. Despite the identical expression of G-protein α-subunits in the olfactory receptor neurons, these two projections were clearly distinguished from each other by the differential expression of glycoconjugates. In conclusion, these data indicate the presence of two types of olfactory systems in the snapping turtle. Topographic arrangement of the upper and lower chambers and lack of the associated glands in the lower chamber epithelium suggest their possible involvement in the detection of odorants: upper chamber epithelium in the air and the lower chamber epithelium in the water. Copyright © 2016 Elsevier Ltd. All rights reserved.

From Nose to Memory: The Involuntary Nature of Odor-evoked Autobiographical Memories in Alzheimer's Disease.

PubMed

El Haj, Mohamad; Gandolphe, Marie Charlotte; Gallouj, Karim; Kapogiannis, Dimitrios; Antoine, Pascal

2017-12-25

Research suggests that odors may serve as a potent cue for autobiographical retrieval. We tested this hypothesis in Alzheimer's disease (AD) and investigated whether odor-evoked autobiographical memory is an involuntary process that shares similarities with music-evoked autobiographical memory. Participants with mild AD and controls were asked to retrieve 2 personal memories after odor exposure, after music exposure, and in an odor-and music-free condition. AD participants showed better specificity, emotional experience, mental time travel, and retrieval time after odor and music exposure than in the control condition. Similar beneficial effects of odor and music exposure were observed for autobiographical characteristics (i.e., specificity, emotional experience, and mental time travel), except for retrieval time which was more improved after odor than after music exposure. Interestingly, regression analyses suggested executive involvement in memories evoked in the control condition but not in those evoked after music or odor exposure. These findings suggest the involuntary nature of odor-evoked autobiographical memory in AD. They also suggest that olfactory cuing could serve as a useful and ecologically valid tool to stimulate autobiographical memory, at least in the mild stage of the disease. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Parasites and a host's sense of smell: reduced chemosensory performance of fathead minnows (Pimephales promelas) infected with a monogenean parasite.

PubMed

Lari, Ebrahim; Goater, Cameron P; Cone, David K; Pyle, Greg G

2017-05-01

Parasites residing within the central nervous system of their hosts have the potential to reduce various components of host performance, but such effects are rarely evaluated. We assessed the olfactory acuity of fathead minnows (Pimephales promelas) infected experimentally with the monogenean Dactylogyrus olfactorius, the adults of which live within the host's olfactory chambers. Olfactory acuity was compared between infected and uninfected hosts by assessing electro-olfactography (EOG) neural responses to chemical stimuli that indicate the presence of food (L-alanine) or the presence of conspecifics (taurocholic acid). We also compared differences in gross morphology of the olfactory epithelium in infected and uninfected minnows. Differences in EOG responses between infected and uninfected minnows to both cue types were non-significant at 30 days post-exposure. By days 60 and 90, coincident with a two times increase in parasite intensity in the olfactory chambers, the EOG responses of infected minnows were 70-90% lower than controls. When infected fish were treated with a parasiticide (Prazipro), olfactory acuity returned to control levels by day 7 post-treatment. The observed reduction in olfactory acuity is best explained by the reduced density of cilia covering the olfactory chambers of infected fish, or by the concomitant increase in the density of mucous cells that cover the olfactory chambers. These morphological changes are likely due to the direct effects of attachment and feeding by individual worms or by indirect effects associated with host responses. Our results show that infection of a commonly occurring monogenean in fathead minnows reduces olfactory acuity. Parasite-induced interference with olfactory performance may reduce a fish's ability to detect, or respond to, chemical cues originating from food, predators, competitors or mates. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

An olfactory demography of a diverse metropolitan population.

PubMed

Keller, Andreas; Hempstead, Margaret; Gomez, Iran A; Gilbert, Avery N; Vosshall, Leslie B

2012-10-10

Human perception of the odour environment is highly variable. People vary both in their general olfactory acuity as well as in if and how they perceive specific odours. In recent years, it has been shown that genetic differences contribute to variability in both general olfactory acuity and the perception of specific odours. Odour perception also depends on other factors such as age and gender. Here we investigate the influence of these factors on both general olfactory acuity and on the perception of 66 structurally and perceptually different odours in a diverse subject population. We carried out a large human olfactory psychophysics study of 391 adult subjects in metropolitan New York City, an ethnically and culturally diverse North American metropolis. 210 of the subjects were women and the median age was 34.6 years (range 19-75). We recorded ~2,300 data points per subject to obtain a comprehensive perceptual phenotype, comprising multiple perceptual measures of 66 diverse odours. We show that general olfactory acuity correlates with gender, age, race, smoking habits, and body type. Young, female, non-smoking subjects had the highest average olfactory acuity. Deviations from normal body type in either direction were associated with decreased olfactory acuity. Beyond these factors we also show that, surprisingly, there are many odour-specific influences of race, age, and gender on olfactory perception. We show over 100 instances in which the intensity or pleasantness perception of an odour is significantly different between two demographic groups. These data provide a comprehensive snapshot of the olfactory sense of a diverse population. Olfactory acuity in the population is most strongly influenced by age, followed by gender. We also show a large number of diverse correlations between demographic factors and the perception of individual odours that may reflect genetic differences as well as different prior experiences with these odours between demographic groups.

An olfactory demography of a diverse metropolitan population

PubMed Central

2012-01-01

Background Human perception of the odour environment is highly variable. People vary both in their general olfactory acuity as well as in if and how they perceive specific odours. In recent years, it has been shown that genetic differences contribute to variability in both general olfactory acuity and the perception of specific odours. Odour perception also depends on other factors such as age and gender. Here we investigate the influence of these factors on both general olfactory acuity and on the perception of 66 structurally and perceptually different odours in a diverse subject population. Results We carried out a large human olfactory psychophysics study of 391 adult subjects in metropolitan New York City, an ethnically and culturally diverse North American metropolis. 210 of the subjects were women and the median age was 34.6 years (range 19–75). We recorded ~2,300 data points per subject to obtain a comprehensive perceptual phenotype, comprising multiple perceptual measures of 66 diverse odours. We show that general olfactory acuity correlates with gender, age, race, smoking habits, and body type. Young, female, non-smoking subjects had the highest average olfactory acuity. Deviations from normal body type in either direction were associated with decreased olfactory acuity. Beyond these factors we also show that, surprisingly, there are many odour-specific influences of race, age, and gender on olfactory perception. We show over 100 instances in which the intensity or pleasantness perception of an odour is significantly different between two demographic groups. Conclusions These data provide a comprehensive snapshot of the olfactory sense of a diverse population. Olfactory acuity in the population is most strongly influenced by age, followed by gender. We also show a large number of diverse correlations between demographic factors and the perception of individual odours that may reflect genetic differences as well as different prior experiences with these odours between demographic groups. PMID:23046643

Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery

PubMed Central

Kumar, Niyanta N.; Gautam, Mohan; Lochhead, Jeffrey J.; Wolak, Daniel J.; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G.

2016-01-01

Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID:27558973

Olfactory-visual integration facilitates perception of subthreshold negative emotion.

PubMed

Novak, Lucas R; Gitelman, Darren R; Schuyler, Brianna; Li, Wen

2015-10-01

A fast growing literature of multisensory emotion integration notwithstanding, the chemical senses, intimately associated with emotion, have been largely overlooked. Moreover, an ecologically highly relevant principle of "inverse effectiveness", rendering maximal integration efficacy with impoverished sensory input, remains to be assessed in emotion integration. Presenting minute, subthreshold negative (vs. neutral) cues in faces and odors, we demonstrated olfactory-visual emotion integration in improved emotion detection (especially among individuals with weaker perception of unimodal negative cues) and response enhancement in the amygdala. Moreover, while perceptual gain for visual negative emotion involved the posterior superior temporal sulcus/pSTS, perceptual gain for olfactory negative emotion engaged both the associative olfactory (orbitofrontal) cortex and amygdala. Dynamic causal modeling (DCM) analysis of fMRI timeseries further revealed connectivity strengthening among these areas during crossmodal emotion integration. That multisensory (but not low-level unisensory) areas exhibited both enhanced response and region-to-region coupling favors a top-down (vs. bottom-up) account for olfactory-visual emotion integration. Current findings thus confirm the involvement of multisensory convergence areas, while highlighting unique characteristics of olfaction-related integration. Furthermore, successful crossmodal binding of subthreshold aversive cues not only supports the principle of "inverse effectiveness" in emotion integration but also accentuates the automatic, unconscious quality of crossmodal emotion synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gad67 haploinsufficiency reduces amyloid pathology and rescues olfactory memory deficits in a mouse model of Alzheimer's disease.

PubMed

Wang, Yue; Wu, Zheng; Bai, Yu-Ting; Wu, Gang-Yi; Chen, Gong

2017-10-10

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glutamatergic and GABAergic systems has been associated with AD progression the underlying mechanisms remain elusive. We and others have recently found that GABA content is elevated in AD brains and linked to cognitive deficits in AD mouse models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting glutamate into GABA and has been implied in a number of neurological disorders such as epilepsy and schizophrenia. However, whether Gad67 is involved in AD pathology has not been well studied. Here, we investigate the functional role of GAD67 in an AD mouse model with Gad67 haploinsufficiency that is caused by replacing one allele of Gad67 with green fluorescent protein (GFP) gene during generation of GAD67-GFP mice. To genetically reduce GAD67 in AD mouse brains, we crossed the Gad67 haploinsufficient mice (GAD67-GFP +/- ) with 5xFAD mice (harboring 5 human familial AD mutations in APP and PS1 genes) to generate a new line of bigenic mice. Immunostaining, ELISA, electrophysiology and behavior test were applied to compare the difference between groups. We found that reduction of GAD67 resulted in a significant decrease of amyloid β production in 5xFAD mice. Concurrently, the abnormal astrocytic GABA and tonic GABA currents, as well as the microglial reactivity were significantly reduced in the 5xFAD mice with Gad67 haploinsufficiency. Importantly, the olfactory memory deficit of 5xFAD mice was rescued by Gad67 haploinsufficiency. Our results demonstrate that GAD67 plays an important role in AD pathology, suggesting that GAD67 may be a potential drug target for modulating the progress of AD.

Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

PubMed

Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

2018-06-20

Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

Circadian Modulation of Consolidated Memory Retrieval Following Sleep Deprivation in Drosophila

PubMed Central

Glou, Eric Le; Seugnet, Laurent; Shaw, Paul J.; Preat, Thomas; Goguel, Valérie

2012-01-01

Objectives: Several lines of evidence indicate that sleep plays a critical role in learning and memory. The aim of this study was to evaluate anesthesia resistant memory following sleep deprivation in Drosophila. Design: Four to 16 h after aversive olfactory training, flies were sleep deprived for 4 h. Memory was assessed 24 h after training. Training, sleep deprivation, and memory tests were performed at different times during the day to evaluate the importance of the time of day for memory formation. The role of circadian rhythms was further evaluated using circadian clock mutants. Results Memory was disrupted when flies were exposed to 4 h of sleep deprivation during the consolidation phase. Interestingly, normal memory was observed following sleep deprivation when the memory test was performed during the 2 h preceding lights-off, a period characterized by maximum wake in flies. We also show that anesthesia resistant memory was less sensitive to sleep deprivation in flies with disrupted circadian rhythms. Conclusions Our results indicate that anesthesia resistant memory, a consolidated memory less costly than long-term memory, is sensitive to sleep deprivation. In addition, we provide evidence that circadian factors influence memory vulnerability to sleep deprivation and memory retrieval. Taken together, the data show that memories weakened by sleep deprivation can be retrieved if the animals are tested at the optimal circadian time. Citation: Le Glou E; Seugnet L; Shaw PJ; Preat T; Goguel V. Circadian modulation of consolidated memory retrieval following sleep deprivation in Drosophila. SLEEP 2012;35(10):1377-1384. PMID:23024436

Social Modulation of Associative Fear Learning by Pheromone Communication

ERIC Educational Resources Information Center

Bredy, Timothy W.; Barad, Mark

2009-01-01

Mice communicate through visual, vocal, and olfactory cues that influence innate, nonassociative behavior. We here report that exposure to a recently fear-conditioned familiar mouse impairs acquisition of conditioned fear and facilitates fear extinction, effects mimicked by both an olfactory chemosignal emitted by a recently fear-conditioned…

Identification of olfactory receptor genes in the Japanese grenadier anchovy Coilia nasus.

PubMed

Zhu, Guoli; Wang, Liangjiang; Tang, Wenqiao; Wang, Xiaomei; Wang, Cong

2017-01-01

Olfaction is essential for fish to detect odorant elements in the environment and plays a critical role in navigating, locating food and detecting predators. Olfactory function is produced by the olfactory transduction pathway and is activated by olfactory receptors (ORs) through the binding of odorant elements. Recently, four types of olfactory receptors have been identified in vertebrate olfactory epithelium, including main odorant receptors (MORs), vomeronasal type receptors (VRs), trace-amine associated receptors (TAARs) and formyl peptide receptors (FPRs). It has been hypothesized that migratory fish, which have the ability to perform spawning migration, use olfactory cues to return to natal rivers. Therefore, obtaining OR genes from migratory fish will provide a resource for the study of molecular mechanisms that underlie fish spawning migration behaviors. Previous studies of OR genes have mainly focused on genomic data, however little information has been gained at the transcript level. In this study, we identified the OR genes of an economically important commercial fish Coilia nasus through searching for olfactory epithelium transcriptomes. A total of 142 candidate MOR, 52 V2R/OlfC, 32 TAAR and two FPR putative genes were identified. In addition, through genomic analysis we identified several MOR genes containing introns, which is unusual for vertebrate MOR genes. The transcriptome-scale mining strategy proved to be fruitful in identifying large sets of OR genes from species whose genome information is unavailable. Our findings lay the foundation for further research into the possible molecular mechanisms underlying the spawning migration behavior in C. nasus .

Scents and Nonsense: Olfactory Dysfunction in Schizophrenia

PubMed Central

Turetsky, Bruce I.; Hahn, Chang-Gyu; Borgmann-Winter, Karin; Moberg, Paul J.

2009-01-01

Among the sensory modalities, olfaction is most closely associated with the frontal and temporal brain regions that are implicated in schizophrenia and most intimately related to the affective and mnemonic functions that these regions subserve. Olfactory probes may therefore be ideal tools through which to assess the structural and functional integrity of the neural substrates that underlie disease-related cognitive and emotional disturbances. Perhaps more importantly, to the extent that early sensory afferents are also disrupted in schizophrenia, the olfactory system—owing to its strategic anatomic location—may be especially vulnerable to such disruption. Olfactory dysfunction may therefore be a sensitive indicator of schizophrenia pathology and may even serve as an “early warning” sign of disease vulnerability or onset. In this article, we review the evidence supporting a primary olfactory sensory disturbance in schizophrenia. Convergent data indicate that structural and functional abnormalities extend from the cortex to the most peripheral elements of the olfactory system. These reflect, in part, a genetically mediated neurodevelopmental etiology. Gross structural and functional anomalies are mirrored by cellular and molecular abnormalities that suggest decreased or faulty innervation and/or dysregulation of intracellular signaling. A unifying mechanistic hypothesis may be the epigenetic regulation of gene expression. With the opportunity to obtain olfactory neural tissue from live patients through nasal epithelial biopsy, the peripheral olfactory system offers a uniquely accessible window through which the pathophysiological antecedents and sequelae of schizophrenia may be observed. This could help to clarify underlying brain mechanisms and facilitate identification of clinically relevant biomarkers. PMID:19793796

Sleep deprivation affects extinction but not acquisition memory in honeybees.

PubMed

Hussaini, Syed Abid; Bogusch, Lisa; Landgraf, Tim; Menzel, Randolf

2009-11-01

Sleep-like behavior has been studied in honeybees before, but the relationship between sleep and memory formation has not been explored. Here we describe a new approach to address the question if sleep in bees, like in other animals, improves memory consolidation. Restrained bees were observed by a web camera, and their antennal activities were used as indicators of sleep. We found that the bees sleep more during the dark phase of the day compared with the light phase. Sleep phases were characterized by two distinct patterns of antennal activities: symmetrical activity, more prominent during the dark phase; and asymmetrical activity, more common during the light phase. Sleep-deprived bees showed rebound the following day, confirming effective deprivation of sleep. After appetitive conditioning of the bees to various olfactory stimuli, we observed their sleep. Bees conditioned to odor with sugar reward showed lesser sleep compared with bees that were exposed to either reward alone or air alone. Next, we asked whether sleep deprivation affects memory consolidation. While sleep deprivation had no effect on retention scores after odor acquisition, retention for extinction learning was significantly reduced, indicating that consolidation of extinction memory but not acquisition memory was affected by sleep deprivation.

Context generalization in Drosophila visual learning requires the mushroom bodies

NASA Astrophysics Data System (ADS)

Liu, Li; Wolf, Reinhard; Ernst, Roman; Heisenberg, Martin

1999-08-01

The world is permanently changing. Laboratory experiments on learning and memory normally minimize this feature of reality, keeping all conditions except the conditioned and unconditioned stimuli as constant as possible. In the real world, however, animals need to extract from the universe of sensory signals the actual predictors of salient events by separating them from non-predictive stimuli (context). In principle, this can be achieved ifonly those sensory inputs that resemble the reinforcer in theirtemporal structure are taken as predictors. Here we study visual learning in the fly Drosophila melanogaster, using a flight simulator,, and show that memory retrieval is, indeed, partially context-independent. Moreover, we show that the mushroom bodies, which are required for olfactory but not visual or tactile learning, effectively support context generalization. In visual learning in Drosophila, it appears that a facilitating effect of context cues for memory retrieval is the default state, whereas making recall context-independent requires additional processing.

Olfactory bulb size, odor discrimination and magnetic insensitivity in hummingbirds.

PubMed

Ioalé, P; Papi, F

1989-05-01

Relative olfactory bulb size with respect to telencephalic hemispheres (olfactory ratio) was measured in five species of hummingbirds. Trochiliformes were found to be next to last among 25 avian orders with respect to olfactory bulb development. One hummingbird species, the White-vented Violetear (Colibri serrirostris), was trained in a successive go/no-go discrimination task, and learned to feed or not to feed from a container dependent on the olfactory stimuli associated with it. Test birds learned to discriminate amyl acetate vs. turpentine essence, jasmine essence vs. lavender essence, eucalyptus essence vs. no odor, beta-ionone vs. no odor, carvone vs. eucalyptol. In contrast, 1-phenylethanol vs. beta-ionone discrimination, two odorants which appear similar to humans, was unsuccessful. Using a similar procedure, attempts were made to condition a White-vented Violetear and a Versicolored Emerald (Amazilia versicolor) to magnetic stimuli. The birds were unable to discriminate between a normal field and an oscillating field (square wave, 1 Hz, amplitude +/- 0.40 G).

Non-redundant coding of aversive odours in the main olfactory pathway

PubMed Central

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-01-01

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons which express a large repertoire of canonical odorant receptors (ORs) and a much smaller repertoire of Trace Amine-Associated Receptors (TAARs)1–4. Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a different receptor5–7. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory TAAR gene family, or even a single TAAR gene, eliminates aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute significantly to odour perception. PMID:23624375

Olfactory function in chemical workers exposed to acrylate and methacrylate vapors.

PubMed Central

Schwartz, B S; Doty, R L; Monroe, C; Frye, R; Barker, S

1989-01-01

An investigation of the olfactory function of 731 workers at a chemical facility which manufacturers acrylates and methacrylates was undertaken using a standardized quantitative test. In a cross-sectional analysis of the data, no associations of chemical exposure with olfactory test scores were observed. A nested case-control study designed to evaluate the cumulative effects of exposure on olfactory function, however, revealed elevated crude exposure odds ratios (95% confidence interval) of 2.0 (1.1, 3.8) for all workers and 6.0 (1.7, 21.5) for workers who never smoked cigarettes. Logistic regression analysis, adjusting for multiple confounders, revealed exposure odds ratios of 2.8 (1.1, 7.0) and 13.5 (2.1, 87.6) in these same groups, respectively, and a dose-response relationship between olfactory dysfunction and cumulative exposure scores--semi-quantitative indices of lifetime exposure to the acrylates. The data also revealed decreasing exposure odds ratios with increasing duration since last exposure to these chemicals, suggesting that the effects may be reversible. PMID:2784947

Non-redundant coding of aversive odours in the main olfactory pathway.

PubMed

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-05-23

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

Windscapes and olfactory foraging in a large carnivore

PubMed Central

Togunov, Ron R.; Derocher, Andrew E.; Lunn, Nicholas J.

2017-01-01

The theoretical optimal olfactory search strategy is to move cross-wind. Empirical evidence supporting wind-associated directionality among carnivores, however, is sparse. We examined satellite-linked telemetry movement data of adult female polar bears (Ursus maritimus) from Hudson Bay, Canada, in relation to modelled winds, in an effort to understand olfactory search for prey. In our results, the predicted cross-wind movement occurred most frequently at night during winter, the time when most hunting occurs, while downwind movement dominated during fast winds, which impede olfaction. Migration during sea ice freeze-up and break-up was also correlated with wind. A lack of orientation during summer, a period with few food resources, likely reflected reduced cross-wind search. Our findings represent the first quantitative description of anemotaxis, orientation to wind, for cross-wind search in a large carnivore. The methods are widely applicable to olfactory predators and their prey. We suggest windscapes be included as a habitat feature in habitat selection models for olfactory animals when evaluating what is considered available habitat. PMID:28402340

Ontogenetic changes in responses to settlement cues by Anemonefish

NASA Astrophysics Data System (ADS)

Dixson, D. L.; Munday, P. L.; Pratchett, M.; Jones, G. P.

2011-12-01

Population connectivity for most marine species is dictated by dispersal during the pelagic larval stage. Although reef fish larvae are known to display behavioral adaptations that influence settlement site selection, little is known about the development of behavioral preferences throughout the larval phase. Whether larvae are attracted to the same sensory cues throughout their larval phase, or exhibit distinct ontogenetic shifts in sensory preference is unknown. Here, we demonstrate an ontogenetic shift in olfactory cue preferences for two species of anemonefish, a process that could aid in understanding both patterns of dispersal and settlement. Aquarium-bred naïve Amphiprion percula and A. melanopus larvae were tested for olfactory preference of relevant reef-associated chemical cues throughout the 11-day pelagic larval stage. Age posthatching had a significant effect on the preference for olfactory cues from host anemones and live corals for both species. Preferences of olfactory cues from tropical plants of A. percula, increased by approximately ninefold between hatching and settlement, with A. percula larvae showing a fivefold increase in preference for the olfactory cue produced by the grass species. Larval age had no effect on the olfactory preference for untreated seawater over the swamp-based tree Melaleuca nervosa, which was always avoided compared with blank seawater. These results indicate that reef fish larvae are capable of utilizing olfactory cues early in the larval stage and may be predisposed to disperse away from reefs, with innate olfactory preferences drawing newly hatched larvae into the pelagic environment. Toward the end of the larval phase, larvae become attracted to the olfactory cues of appropriate habitats, which may assist them in identification of and navigation toward suitable settlement sites.

Aquatic adaptations in the nose of carnivorans: evidence from the turbinates

PubMed Central

Van Valkenburgh, Blaire; Curtis, Abigail; Samuels, Joshua X; Bird, Deborah; Fulkerson, Brian; Meachen-Samuels, Julie; Slater, Graham J

2011-01-01

Inside the mammalian nose lies a labyrinth of bony plates covered in epithelium collectively known as turbinates. Respiratory turbinates lie anteriorly and aid in heat and water conservation, while more posterior olfactory turbinates function in olfaction. Previous observations on a few carnivorans revealed that aquatic species have relatively large, complex respiratory turbinates and greatly reduced olfactory turbinates compared with terrestrial species. Body heat is lost more quickly in water than air and increased respiratory surface area likely evolved to minimize heat loss. At the same time, olfactory surface area probably diminished due to a decreased reliance on olfaction when foraging under water. To explore how widespread these adaptations are, we documented scaling of respiratory and olfactory turbinate surface area with body size in a variety of terrestrial, freshwater, and marine carnivorans, including pinnipeds, mustelids, ursids, and procyonids. Surface areas were estimated from high-resolution CT scans of dry skulls, a novel approach that enabled a greater sampling of taxa than is practical with fresh heads. Total turbinate, respiratory, and olfactory surface areas correlate well with body size (r2 ≥ 0.7), and are relatively smaller in larger species. Relative to body mass or skull length, aquatic species have significantly less olfactory surface area than terrestrial species. Furthermore, the ratio of olfactory to respiratory surface area is associated with habitat. Using phylogenetic comparative methods, we found strong support for convergence on 1 : 3 proportions in aquatic taxa and near the inverse in terrestrial taxa, indicating that aquatic mustelids and pinnipeds independently acquired similar proportions of olfactory to respiratory turbinates. Constraints on turbinate surface area in the nasal chamber may result in a trade-off between respiratory and olfactory function in aquatic mammals. PMID:21198587

NADPH-diaphorase activity and NO synthase expression in the olfactory epithelium of the bovine.

PubMed

Wenisch, S; Arnhold, S

2010-06-01

NADPH-diaphorase (NADPH-d) staining of the bovine olfactory epithelium was compared with the immunohistochemical localization of nitric oxide synthase (NOS), soluble guanylyl cyclase, and cGMP (cyclic guanosine 3',5'-monophosphate). Out of the three isoforms, only the inducible NOS (NOS-II) was found at the epithelial surface correlating with the strong labelling for NADPH-d. In contrast, light diaphorase staining associated with deeper epithelial regions did not coincide with any NOS immunoreactivity. As there is overlapping expression of NOS-II, soluble guanylyl cyclase and cGMP at the luminal surface morphologically occupied by dendritic knobs of olfactory receptor neurons and microvillar endings of supporting cells, the nitric oxide (NO)/cGMP pathway is likely to be involved in modulating the odour signals during olfactory transduction.

Dopamine- and Tyrosine Hydroxylase-Immunoreactive Neurons in the Brain of the American Cockroach, Periplaneta americana

PubMed Central

Hamanaka, Yoshitaka; Minoura, Run; Nishino, Hiroshi; Miura, Toru; Mizunami, Makoto

2016-01-01

The catecholamine dopamine plays several vital roles in the central nervous system of many species, but its neural mechanisms remain elusive. Detailed neuroanatomical characterization of dopamine neurons is a prerequisite for elucidating dopamine’s actions in the brain. In the present study, we investigated the distribution of dopaminergic neurons in the brain of the American cockroach, Periplaneta americana, using two antisera: 1) an antiserum against dopamine, and 2) an antiserum against tyrosine hydroxylase (TH, an enzyme required for dopamine synthesis), and identified about 250 putatively dopaminergic neurons. The patterns of dopamine- and TH-immunoreactive neurons were strikingly similar, suggesting that both antisera recognize the same sets of “dopaminergic” neurons. The dopamine and TH antibodies intensively or moderately immunolabeled prominent brain neuropils, e.g. the mushroom body (memory center), antennal lobe (first-order olfactory center) and central complex (motor coordination center). All subdivisions of the mushroom body exhibit both dopamine and TH immunoreactivity. Comparison of immunolabeled neurons with those filled by dye injection revealed that a group of immunolabeled neurons with cell bodies near the calyx projects into a distal region of the vertical lobe, which is a plausible site for olfactory memory formation in insects. In the antennal lobe, ordinary glomeruli as well as macroglomeruli exhibit both dopamine and TH immunoreactivity. It is noteworthy that the dopamine antiserum labeled tiny granular structures inside the glomeruli whereas the TH antiserum labeled processes in the marginal regions of the glomeruli, suggesting a different origin. In the central complex, all subdivisions excluding part of the noduli and protocerebral bridge exhibit both dopamine and TH immunoreactivity. These anatomical findings will accelerate our understanding of dopaminergic systems, specifically in neural circuits underlying aversive memory formation and arousal, in insects. PMID:27494326

Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia

PubMed Central

Roberts, Rosebud O.; Christianson, Teresa J. H.; Kremers, Walter K.; Mielke, Michelle M.; Machulda, Mary M.; Vassilaki, Maria; Alhurani, Rabe E.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.

2015-01-01

IMPORTANCE To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD), markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. OBJECTIVE To examine associations of impaired olfaction with incident MCI subtypes, and progression from MCI subtypes to AD dementia. DESIGN, SETTING, AND PARTICIPANTS Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging were clinically evaluated at baseline and every 15-months thereafter, and classified as having normal cognition, MCI (amnestic, aMCI and nonamnestic, naMCI), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. MAIN OUTCOMES AND MEASURES Mild cognitive impairment, AD dementia, longitudinal change in cognitive performance measures. RESULTS Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by decrease in number of correct responses in B-SIT score, and an increased risk of aMCI. Compared to the upper B-SIT quartile (Q4, best scores), hazard ratios (HR) were 1.12; P = 0.68 for Q3; HR, 1.95; P =0.003 for Q2; and HR, 2.18; P = 0.001 (worst scores; p for trend <0.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD, with a significant dose-response with worsening B-SIT quartiles. Compared to Q4, HR estimates were 3.02, P = 0.038 for Q3; HR, 3.63; P = 0.024 for Q2; and HR, 5.20; P = 0.001 for Q1. After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10; p < 0.001), and improved the model concordance. CONCLUSIONS AND RELEVANCE Olfactory impairment predicts incident aMCI and progression from aMCI to AD. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life, and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress. PMID:26569387

Modulation of cerebral haemodynamic response to olfactory stimuli by emotional valence detected by functional magnetic resonance imaging

PubMed Central

Caous, Cristofer André; Tobo, Patrícia Renovato; Talarico, Vânia Hercília; Gonçales, Luciana Ribeiro Lopes; Yoshimine, Elise; da Cruz Jr, Antonio Cesário; Albuquerque, Cristóvão; Amaro Jr, Edson

2015-01-01

Olfactory perception, although restricted to just a few contexts in everyday life, is key in medicine. Several dementia conditions have been associated with early loss of olfactory discrimination. Despite the fact that several brain areas have been associated with olfaction in functional magnetic resonance imaging (fMRI), the mechanisms by which emotional valence is conveyed to the brain are not fully understood. Methods In this study, we compared cerebral activations by olfactory stimuli using different emotional valence stimuli on event-related fMRI. We used three standard olfactory odorants with different valence (positive, neutral and negative). Forty-three healthy subjects (22 males) were scanned on a 3.0T MR system. Olfactory stimulation was attained through a delivery system synchronized with image acquisition and subjects´ breathing instructions. fMRI data analysis was performed by the FSL package (Oxford University) including head movement correction, GLM modeling of the neurovascular (BOLD) response and group activation maps produced at p<0.05and corrected for multiple comparison. Results Increased cerebral responses within the anterior cingulate, amygdaloid nuclei, as well as the dorsolateral prefrontal, occipital and orbitofrontal cortices were observed in positive and negative valence conditions, while response to neutral valence arousal was less intense and not observed in the amygdaloid complex. The most significant statistical response aroused from the stimuli clusters was observed in the negative condition. Conclusion The results of the present study support the hypothesis that neutral stimuli may be more sensitive to early losses in pathological conditions, particularly dementia. PMID:29213990

Rats Remember Items in Context Using Episodic Memory.

PubMed

Panoz-Brown, Danielle; Corbin, Hannah E; Dalecki, Stefan J; Gentry, Meredith; Brotheridge, Sydney; Sluka, Christina M; Wu, Jie-En; Crystal, Jonathon D

2016-10-24

Vivid episodic memories in people have been characterized as the replay of unique events in sequential order [1-3]. Animal models of episodic memory have successfully documented episodic memory of a single event (e.g., [4-8]). However, a fundamental feature of episodic memory in people is that it involves multiple events, and notably, episodic memory impairments in human diseases are not limited to a single event. Critically, it is not known whether animals remember many unique events using episodic memory. Here, we show that rats remember many unique events and the contexts in which the events occurred using episodic memory. We used an olfactory memory assessment in which new (but not old) odors were rewarded using 32 items. Rats were presented with 16 odors in one context and the same odors in a second context. To attain high accuracy, the rats needed to remember item in context because each odor was rewarded as a new item in each context. The demands on item-in-context memory were varied by assessing memory with 2, 3, 5, or 15 unpredictable transitions between contexts, and item-in-context memory survived a 45 min retention interval challenge. When the memory of item in context was put in conflict with non-episodic familiarity cues, rats relied on item in context using episodic memory. Our findings suggest that rats remember multiple unique events and the contexts in which these events occurred using episodic memory and support the view that rats may be used to model fundamental aspects of human cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Associative Processes in Early Olfactory Preference Acquisition

PubMed Central

Sullivan, Regina M.; Wilson, Donald A.; Leon, Michael

2007-01-01

Acquisition of behavioral conditioned responding and learned odor preferences during olfactory classical conditioning in rat pups requires forward or simultaneous pairings of the conditioned stimulus (CS) and the unconditioned stimulus (US). Other temporal relationships between the CS and US do not usually result in learning. The present study examined the influence of this CS-US relationship upon the neural olfactory bulb modifications that are acquired during early classical conditioning. Wistar rat pups were trained from Postnatal Days (PN) 1-18 with either forward (odor overlapping temporally with reinforcing stroking) or backward (stroking followed by odor) CS-US pairings. On PN 19, pups received either a behavioral odor preference test to the odor CS or an injection of 14C 2-DG and exposure to the odor CS, or olfactory bulb single unit responses were recorded in response to exposure to the odor CS. Only pups that received forward presentations of the CS and US exhibited both a preference for the CS and modified olfactory bulb neural responses to the CS. These results, then, suggest that the modified olfactory bulb neural responses acquired during classical conditioning are guided by the same temporal constraints as those which govern the acquisition of behavioral conditioned responses. PMID:17572798

Detection of Volatile Indicators of Illicit Substances by the Olfactory Receptors of Drosophila melanogaster

PubMed Central

Marshall, Brenton; Warr, Coral G.

2010-01-01

Insects can detect a large range of odors with a numerically simple olfactory system that delivers high sensitivity and accurate discrimination. Therefore, insect olfactory receptors hold great promise as biosensors for detection of volatile organic chemicals in a range of applications. The array of olfactory receptor neurons of Drosophila melanogaster is rapidly becoming the best-characterized natural nose. We have investigated the suitability of Drosophila receptors as detectors for volatiles with applications in law enforcement, emergency response, and security. We first characterized responses of the majority of olfactory neuron types to a set of diagnostic odorants. Being thus able to correctly identify neurons, we then screened for responses from 38 different types of neurons to 35 agents. We identified 13 neuron types with responses to 13 agents. As individual Drosophila receptor genes have been mapped to neuron types, we can infer which genes confer responsiveness to the neurons. The responses were confirmed for one receptor by expressing it in a nonresponsive neuron. The fly olfactory system is mainly adapted to detect volatiles from fermenting fruits. However, our findings establish that volatiles associated with illicit substances, many of which are of nonnatural origin, are also detected by Drosophila receptors. PMID:20530374

Role of neuropeptide Y (NPY) in the regulation of reproduction: study based on catfish model.

PubMed

Subhedar, Nishikant; Gaikwad, Archana; Biju, K C; Saha, Subhash

2005-04-01

Significance of NPY in the regulation of GnRH-LH axis was evaluated. Considerable NPY immunoreactivity was seen in the components like olfactory system, basal telencephalon, preoptic and tuberal areas, and the pituitary gland that serve as neuroanatomical substrates for processing reproductive information. Close anatomical association as well as colocalizations of NPY and GnRH were seen in the olfactory receptor neurons, olfactory nerve fibers and their terminals in the glomeruli, ganglion cells of nervus terminalis, medial olfactory tracts, fibers in the ventral telencephalon and pituitary. In the pituitary, NPY fibers seem to innervate the GnRH as well as LH cells. Intracranial administration of NPY resulted in significant increase in the GnRH immunoreactivity in all the components of the olfactory system. In the pituitary, NPY augmented the population of GnRH fibers and LH cells. HPLC analysis showed that salmon GnRH content in the olfactory organ, bulb, preoptic area+telencephalon and pituitary was also significantly increased following NPY treatment. NPY may play a role in positive regulation of GnRH throughout the neuraxis and also up-regulate the LH cells in the pituitary.

NMDA receptors in mouse anterior piriform cortex initialize early odor preference learning and L-type calcium channels engage for long-term memory.

PubMed

Mukherjee, Bandhan; Yuan, Qi

2016-10-14

The interactions of L-type calcium channels (LTCCs) and NMDA receptors (NMDARs) in memories are poorly understood. Here we investigated the specific roles of anterior piriform cortex (aPC) LTCCs and NMDARs in early odor preference memory in mice. Using calcium imaging in aPC slices, LTCC activation was shown to be dependent on NMDAR activation. Either D-APV (NMDAR antagonist) or nifedipine (LTCC antagonist) reduced somatic calcium transients in pyramidal cells evoked by lateral olfactory tract stimulation. However, nifedipine did not further reduce calcium in the presence of D-APV. In mice that underwent early odor preference training, blocking NMDARs in the aPC prevented short-term (3 hr) and long-term (24 hr) odor preference memory, and both memories were rescued when BayK-8644 (LTCC agonist) was co-infused. However, activating LTCCs in the absence of NMDARs resulted in loss of discrimination between the conditioned odor and a similar odor mixture at 3 hr. Elevated synaptic AMPAR expression at 3 hr was prevented by D-APV infusion but restored when LTCCs were directly activated, mirroring the behavioral outcomes. Blocking LTCCs prevented 24 hr memory and spared 3 hr memory. These results suggest that NMDARs mediate stimulus-specific encoding of odor memory while LTCCs mediate intracellular signaling leading to long-term memory.

Evolution of olfaction in non-avian theropod dinosaurs and birds

PubMed Central

Zelenitsky, Darla K.; Therrien, François; Ridgely, Ryan C.; McGee, Amanda R.; Witmer, Lawrence M.

2011-01-01

Little is known about the olfactory capabilities of extinct basal (non-neornithine) birds or the evolutionary changes in olfaction that occurred from non-avian theropods through modern birds. Although modern birds are known to have diverse olfactory capabilities, olfaction is generally considered to have declined during avian evolution as visual and vestibular sensory enhancements occurred in association with flight. To test the hypothesis that olfaction diminished through avian evolution, we assessed relative olfactory bulb size, here used as a neuroanatomical proxy for olfactory capabilities, in 157 species of non-avian theropods, fossil birds and living birds. We show that relative olfactory bulb size increased during non-avian maniraptoriform evolution, remained stable across the non-avian theropod/bird transition, and increased during basal bird and early neornithine evolution. From early neornithines through a major part of neornithine evolution, the relative size of the olfactory bulbs remained stable before decreasing in derived neoavian clades. Our results show that, rather than decreasing, the importance of olfaction actually increased during early bird evolution, representing a previously unrecognized sensory enhancement. The relatively larger olfactory bulbs of earliest neornithines, compared with those of basal birds, may have endowed neornithines with improved olfaction for more effective foraging or navigation skills, which in turn may have been a factor allowing them to survive the end-Cretaceous mass extinction. PMID:21490022

Ultrastructural localization of connexins (Cx36, Cx43, Cx45), glutamate receptors and aquaporin-4 in rodent olfactory mucosa, olfactory nerve and olfactory bulb

PubMed Central

RASH, JOHN E.; DAVIDSON, KIMBERLY G. V.; KAMASAWA, NAOMI; YASUMURA, THOMAS; KAMASAWA, MASAMI; ZHANG, CHUNBO; MICHAELS, ROBIN; RESTREPO, DIEGO; OTTERSEN, OLE P.; OLSON, CARL O.; NAGY, JAMES I.

2006-01-01

Odorant/receptor binding and initial olfactory information processing occurs in olfactory receptor neurons (ORNs) within the olfactory epithelium. Subsequent information coding involves high-frequency spike synchronization of paired mitral/tufted cell dendrites within olfactory bulb (OB) glomeruli via positive feedback between glutamate receptors and closely-associated gap junctions. With mRNA for connexins Cx36, Cx43 and Cx45 detected within ORN somata and Cx36 and Cx43 proteins reported in ORN somata and axons, abundant gap junctions were proposed to couple ORNs. We used freeze-fracture replica immunogold labeling (FRIL) and confocal immunofluorescence microscopy to examine Cx36, Cx43 and Cx45 protein in gap junctions in olfactory mucosa, olfactory nerve and OB in adult rats and mice and early postnatal rats. In olfactory mucosa, Cx43 was detected in gap junctions between virtually all intrinsic cell types except ORNs and basal cells; whereas Cx45 was restricted to gap junctions in sustentacular cells. ORN axons contained neither gap junctions nor any of the three connexins. In OB, Cx43 was detected in homologous gap junctions between almost all cell types except neurons and oligodendrocytes. Cx36 and, less abundantly, Cx45 were present in neuronal gap junctions, primarily at “mixed” glutamatergic/electrical synapses between presumptive mitral/tufted cell dendrites. Genomic analysis revealed multiple miRNA (micro interfering RNA) binding sequences in 3′-untranslated regions of Cx36, Cx43 and Cx45 genes, consistent with cell-type-specific post-transcriptional regulation of connexin synthesis. Our data confirm absence of gap junctions between ORNs, and support Cx36- and Cx45-containing gap junctions at glutamatergic mixed synapses between mitral/tufted cells as contributing to higher-order information coding within OB glomeruli. PMID:16841170

Relationships between pathologic subjective halitosis, olfactory reference syndrome, and social anxiety in young Japanese women.

PubMed

Tsuruta, Miho; Takahashi, Toru; Tokunaga, Miki; Iwasaki, Masanori; Kataoka, Shota; Kakuta, Satoko; Soh, Inho; Awano, Shuji; Hirata, Hiromi; Kagawa, Masaharu; Ansai, Toshihiro

2017-03-14

Pathologic subjective halitosis is known as a halitosis complaint without objective confirmation of halitosis by others or by halitometer measurements; it has been reported to be associated with social anxiety disorder. Olfactory reference syndrome is a preoccupation with the false belief that one emits a foul and offensive body odor. Generally, patients with olfactory reference syndrome are concerned with multiple body parts. However, the mouth is known to be the most common source of body odor for those with olfactory reference syndrome, which could imply that the two conditions share similar features. Therefore, we investigated potential causal relationships among pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupations with body part odors. A total of 1360 female students (mean age 19.6 ± 1.1 years) answered a self-administered questionnaire regarding pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupation with odors of body parts such as mouth, body, armpits, and feet. The scale for pathologic subjective halitosis followed that developed by Tsunoda et al.; participants were divided into three groups based on their scores (i.e., levels of pathologic subjective halitosis). A Bayesian network was used to analyze causal relationships between pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupations with body part odors. We found statistically significant differences in the results for olfactory reference syndrome and social anxiety among the various levels of pathologic subjective halitosis (P < 0.001). Residual analyses indicated that students with severe levels of pathologic subjective halitosis showed greater preoccupations with mouth and body odors (P < 0.05). Bayesian network analysis showed that social anxiety directly influenced pathologic subjective halitosis and olfactory reference syndrome. Preoccupations with mouth and body odors also influenced pathologic subjective halitosis. Social anxiety may be a causal factor of pathologic subjective halitosis and olfactory reference syndrome.

Constant Light Desynchronizes Olfactory versus Object and Visuospatial Recognition Memory Performance

PubMed Central

Tam, Shu K.E.; Hasan, Sibah; Brown, Laurence A.; Jagannath, Aarti; Hankins, Mark W.; Foster, Russell G.; Vyazovskiy, Vladyslav V.

2017-01-01

Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light (rLL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genes Period1 and Period2 (Per1 and Per2), as well as the immediate-early gene Fos in the SCN, dorsal hippocampus, and olfactory bulb. Under rLL, rhythmic Per1 and Fos expression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly, Per1 and Fos expression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist under rLL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals. SIGNIFICANCE STATEMENT A master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by synchronizing peripheral clocks throughout the brain and body. Without the SCN, these peripheral clocks rapidly become desynchronized. Here, we provide a unique demonstration that, under lighting conditions in which the central clock in the SCN is dampened, peripheral oscillators in the hippocampus and olfactory bulb become desynchronized, along with the behavioral processes mediated by these clocks. Multiple clocks that adopt different phase relationships may enable processes occurring in different brain regions to be optimized to specific phases of the 24 h day. Moreover, such a dispersed network of dissociable circadian clocks may provide greater flexibility when faced with conflicting environmental signals (e.g., seasonal changes in photoperiod). PMID:28264977

Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets.

PubMed

Mizunami, Makoto; Nemoto, Yuko; Terao, Kanta; Hamanaka, Yoshitaka; Matsumoto, Yukihisa

2014-01-01

Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca(2+)/CaM and cAMP signaling participates in long-term memory (LTM) formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM). Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca(2+) influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC) activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca(2+) signaling and cAMP signaling for LTM formation, a new role of CaMKII in learning and memory.

Color-dependent learning in restrained Africanized honey bees.

PubMed

Jernigan, C M; Roubik, D W; Wcislo, W T; Riveros, A J

2014-02-01

Associative color learning has been demonstrated to be very poor using restrained European honey bees unless the antennae are amputated. Consequently, our understanding of proximate mechanisms in visual information processing is handicapped. Here we test learning performance of Africanized honey bees under restrained conditions with visual and olfactory stimulation using the proboscis extension response (PER) protocol. Restrained individuals were trained to learn an association between a color stimulus and a sugar-water reward. We evaluated performance for 'absolute' learning (learned association between a stimulus and a reward) and 'discriminant' learning (discrimination between two stimuli). Restrained Africanized honey bees (AHBs) readily learned the association of color stimulus for both blue and green LED stimuli in absolute and discriminatory learning tasks within seven presentations, but not with violet as the rewarded color. Additionally, 24-h memory improved considerably during the discrimination task, compared with absolute association (15-55%). We found that antennal amputation was unnecessary and reduced performance in AHBs. Thus color learning can now be studied using the PER protocol with intact AHBs. This finding opens the way towards investigating visual and multimodal learning with application of neural techniques commonly used in restrained honey bees.

Expression of Olfactory Signaling Genes in the Eye

PubMed Central

Velmeshev, Dmitry; Faghihi, Mohammad; Shestopalov, Valery I.; Slepak, Vladlen Z.

2014-01-01

Purpose To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on G protein-coupled receptors. Methods Total RNA from the mouse cornea was subjected to next-generation sequencing using the Illumina platform. The data was analyzed with TopHat and CuffLinks software packages. Expression of a representative group of genes detected by RNA-seq was further analyzed by RT-PCR and in situ hybridization using RNAscope technology and fluorescent microscopy. Results We generated more than 46 million pair-end reads from mouse corneal RNA. Bioinformatics analysis revealed that the mouse corneal transcriptome reconstructed from these reads represents over 10,000 gene transcripts. We identified 194 GPCR transcripts, of which 96 were putative olfactory receptors. RT-PCR analysis confirmed the presence of several olfactory receptors and related genes, including olfactory marker protein and the G protein associated with olfaction, Gαolf. In situ hybridization showed that mRNA for olfactory marker protein, Gαolf and possibly some olfactory receptors were found in the corneal epithelial cells. In addition to the corneal epithelium, Gαolf was present in the ganglionic and inner nuclear layers of the retina. One of the olfactory receptors, Olfr558, was present primarily in vessels of the eye co-stained with antibodies against alpha-smooth muscle actin, indicating expression in arterioles. Conclusions Several species of mRNA encoding putative olfactory receptors and related genes are expressed in the mouse cornea and other parts of the eye indicating they may play a role in sensing chemicals in the ocular environment. PMID:24789354

Effect of ginkgo biloba and dexamethasone in the treatment of 3-methylindole-induced anosmia mouse model.

PubMed

Lee, Chul Hee; Mo, Ji-Hun; Shim, Seung Hee; Ahn, Jung-Min; Kim, Jeong-Whun

2008-01-01

Olfactory loss is a challenging disease. Although glucocorticoid is sometimes used for the treatment of anosmia, it has been reported that it potentiated neural damage in the early phase of treatment. This study is designed to identify the effect of ginkgo biloba, an antioxidant that acts as a free radical scavenger, in the treatment of olfactory injury aggravated by dexamethasone. Anosmia mouse model was induced by i.p. injection of 3-methylindole (3-MI). Twenty-five mice were divided into one control group without anosmia and four anosmia treatment groups (given treatments of dexamethasone and/or ginkgo biloba). The effects of treatment were evaluated by behavioral test, Western blot, and immunohistochemistry 2 weeks after 3-MI injection. Induction of anosmia was confirmed by behavioral tests. The thickness and cell number of olfactory neuroepithelium were decreased more significantly in the dexamethasone treatment group than in the combination treatment group. The expression of olfactory marker protein (OMP) in olfactory epithelium was more decreased also in the dexamethasone treatment group than in the combination treatment group. The expression of OMP was decreased significantly in the olfactory bulbs of anosmia groups but there were no differences between the anosmia treatment groups. Dexamethasone treatment was associated with further deterioration of olfactory injury by 3-MI and it was recovered by combination treatment of dexamethasone and ginkgo biloba. The antioxidant effect of ginkgo biloba might play a role in restoration of olfactory loss and it was effective only when oxidative stress is maximized by dexamethasone.

Olfactory bulb and olfactory sulcus depths are associated with disease duration and attack frequency in multiple sclerosis patients.

PubMed

Tanik, Nermin; Serin, Halil Ibrahim; Celikbilek, Asuman; Inan, Levent Ertugrul; Gundogdu, Fatma

2015-11-15

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease that progresses to axonal loss and demyelinization. Olfactory dysfunction in patients with MS has been reported frequently. We were interested in the associations of olfactory bulb (OB) and olfactory sulcus depth (OSD) with disease duration and attack frequency. We included 25 patients with MS and 30 age- and sex-matched controls in this study. The Expanded Disability Status Scale, Beck Depression Inventory, and Mini Mental State Examination were applied. OB, OSD, and magnetic resonance imaging plaque numbers were calculated. OB volume and OSD in patients with MS were significantly lower than those in the control group (right and left OB: p<0.001; right OSD: p=0.001; and left OSD: p=0.039). Disease duration was negatively correlated with right and left OB volume (right OB: r=-0.434, p=0.030 and left OB: r=-0.518, p=0.008). Attack frequency was negatively correlated with left OB volume and left OSD (left OB: r=-0.428, p=0.033 and left OSD: r=-0.431, p=0.032). The OB and OSD were atrophied significantly in patients with MS, and this was correlated with disease duration and attack frequency. The left side tended to be dominant. Copyright © 2015 Elsevier B.V. All rights reserved.

Lesion of olfactory epithelium attenuates expression of morphine-induced behavioral sensitization and reinstatement of drug-primed conditioned place preference in mice.

PubMed

Niu, Haichen; Zheng, Yingwei; Huma, Tanzeel; Rizak, Joshua D; Li, Ling; Wang, Guimei; Ren, He; Xu, Liqi; Yang, Jianzhen; Ma, Yuanye; Lei, Hao

2013-01-01

Previous studies have shown that olfactory impairment by disrupting the olfactory epithelium prior to morphine administration attenuated the development addiction-related behaviors. However, it is unclear whether olfactory impairment will affect the expression of already established addiction-related behaviors. To address this issue, mice were conditioned with morphine to induce behavioral sensitization and condition placed preference (CPP). After an abstinence period, the animals were subjected to either an intranasal ZnSO(4) effusion (ZnE) or sham treatment with saline. Behavioral sensitization and CPP reinstatement were evaluated 24h later, as well as the expression of c-Fos protein, a marker of activated neural sites, in brain regions of interest. It was found that ZnE treatment attenuated morphine-induced behavioral sensitization and reinstatement of CPP. Compared to the saline-treated ones, the ZnE-treated animals showed reduced c-Fos expression in the nucleus accumbens (NAc) associated with behavioral sensitization, and in the NAc, cingulate cortex, dentate gyrus, amygdala, lateral hypothalamus and ventral tegmental area associated with CPP reinstatement. Together, these results demonstrated that acute olfactory impairment could attenuate already established addiction-related behaviors and expression of c-Fos in drug addiction related brain regions, perhaps by affecting the coordination between reward and motivational systems in the brain. Copyright © 2012 Elsevier Inc. All rights reserved.

A cortical pathway to olfactory naming: evidence from primary progressive aphasia

PubMed Central

Rogalski, Emily; Harrison, Theresa; Mesulam, M.-Marsel; Gottfried, Jay A.

2013-01-01

It is notoriously difficult to name odours. Without the benefit of non-olfactory information, even common household smells elude our ability to name them. The neuroscientific basis for this olfactory language ‘deficit’ is poorly understood, and even basic models to explain how odour inputs gain access to transmodal representations required for naming have not been put forward. This study used patients with primary progressive aphasia, a clinical dementia syndrome characterized by primary deficits in language, to investigate the interactions between olfactory inputs and lexical access by assessing behavioural performance of olfactory knowledge and its relationship to brain atrophy. We specifically hypothesized that the temporal pole would play a key role in linking odour object representations to transmodal networks, given its anatomical proximity to olfactory and visual object processing areas. Behaviourally, patients with primary progressive aphasia with non-semantic subtypes were severely impaired on an odour naming task, in comparison with an age-matched control group. However, with the availability of picture cues or word cues, odour matching performance approached control levels, demonstrating an inability to retrieve but not to recognize the name and nature of the odorant. The magnitude of cortical thinning in the temporal pole was found to correlate with reductions in odour familiarity and odour matching to visual cues, whereas the inferior frontal gyrus correlated with both odour naming and matching. Volumetric changes in the mediodorsal thalamus correlated with the proportion of categorical mismatch errors, indicating a possible role of this region in error-signal monitoring to optimize recognition of associations linked to the odour. A complementary analysis of patients with the semantic subtype of primary progressive aphasia, which is associated with marked temporopolar atrophy, revealed much more pronounced impairments of odour naming and matching. In identifying the critical role of the temporal pole and inferior frontal gyrus in transmodal linking and verbalization of olfactory objects, our findings provide a new neurobiological foundation for understanding why even common odours are hard to name. PMID:23471695

Olfactory cleft computed tomography analysis and olfaction in chronic rhinosinusitis

PubMed Central

Kohli, Preeti; Schlosser, Rodney J.; Storck, Kristina

2016-01-01

Background: Volumetric analysis of the olfactory cleft by using computed tomography has been associated with olfaction in patients with chronic rhinosinusitis (CRS). However, existing studies have not comprehensively measured olfaction, and it thus remains unknown whether correlations differ across specific dimensions of odor perception. Objective: To use comprehensive measures of patient-reported and objective olfaction to evaluate the relationship between volumetric olfactory cleft opacification and olfaction. Methods: Olfaction in patients with CRS was evaluated by using “Sniffin' Sticks” tests and a modified version of the Questionnaire of Olfactory Disorders. Olfactory cleft opacification was quantified by using two- and three-dimensional, computerized volumetric analysis. Correlations between olfactory metrics and olfactory cleft opacification were then calculated. Results: The overall CRS cohort included 26 patients without nasal polyposis (CRSsNP) (68.4%) and 12 patients with nasal polyposis (CRSwNP) (31.6%). Across the entire cohort, total olfactory cleft opacification was 82.8%, with greater opacification in the CRSwNP subgroup compared with CRSsNP (92.3 versus 78.4%, p < 0.001). The percent total volume opacification correlated with the total Sniffin' Sticks score (r = −0.568, p < 0.001) as well as individual threshold, discrimination, and identification scores (p < 0.001 for all). Within the CRSwNP subgroup, threshold (r = −0.616, p = 0.033) and identification (r = −0.647, p = 0.023) remained highly correlated with total volume opacification. In patients with CRSsNP, the threshold correlated with total volume scores (r = −0.457, p = 0.019), with weaker and nonsignificant correlations for discrimination and identification. Correlations between total volume opacification and the Questionnaire of Olfactory Disorders were qualitatively similar to objective olfactory findings in both CRSwNP (r = −0.566, p = 0.070) and CRSsNP (r = −0.310, p = 0.141) subgroups, although neither reached significance. When examined by two-dimensional planes, the percent opacification of the anterior plane had the strongest correlations with objective olfaction. Conclusion: Olfactory cleft opacification correlated with objective measures of olfaction in patients with CRS, which correlated with threshold values in patients with CRSsNP and all dimensions of olfaction in those with CRSwNP. PMID:28124650

Immunization Against Specific Fragments of Neurotrophin p75 Receptor Protects Forebrain Cholinergic Neurons in the Olfactory Bulbectomized Mice

PubMed Central

Bobkova, Natalia; Vorobyov, Vasily; Medvinskaya, Natalia; Nesterova, Inna; Tatarnikova, Olga; Nekrasov, Pavel; Samokhin, Alexander; Deev, Alexander; Sengpiel, Frank; Koroev, Dmitry; Volpina, Olga

2016-01-01

Alzheimer’s disease (AD) is characterized by progressive cognitive impairment associated with marked cholinergic neuron loss and amyloid-β (Aβ) peptide accumulation in the brain. The cytotoxicity in AD is mediated, at least in part, by Aβ binding with the extracellular domain of the p75 neurotrophin receptor (p75NTR), localized predominantly in the membranes of acetylcholine-producing neurons in the basal forebrain. Hypothesizing that an open unstructured loop of p75NTR might be the effective site for Aβ binding, we have immunized both olfactory bulbectomized (OBX) and sham-operated (SO) mice (n = 82 and 49, respectively) with synthetic peptides, structurally similar to different parts of the loops, aiming to block them by specific antibodies. OBX-mice have been shown in previous studies, and confirmed in the present one, to be characterized by typical behavioral, morphological, and biochemical AD hallmarks, including cholinergic deficits in forebrain neurons. Immunization of OBX- or SO-mice with KLH conjugated fragments of p75NTR induced high titers of specific serum antibodies for each of nine chosen fragments. However, maximal protective effects on spatial memory, evaluated in a Morris water maze, and on activity of choline acetyltransferase in forebrain neurons, detected by immunoreactivity to specific antibodies, were revealed only for peptides with amino acid residue sequences of 155–164 and 167–176. We conclude that the approach based on immunological blockade of specific p75NTR sites, linked with the cytotoxicity, is a useful and effective tool for study of AD-associated mechanisms and for development of highly selective therapy of cholinergic malfunctioning in AD patients. PMID:27163825

Odor Experiences during Preimaginal Stages Cause Behavioral and Neural Plasticity in Adult Honeybees

PubMed Central

Ramírez, Gabriela; Fagundez, Carol; Grosso, Juan P.; Argibay, Pablo; Arenas, Andrés; Farina, Walter M.

2016-01-01

In eusocial insects, experiences acquired during the development have long-term consequences on mature behavior. In the honeybee that suffers profound changes associated with metamorphosis, the effect of odor experiences at larval instars on the subsequent physiological and behavioral response is still unclear. To address the impact of preimaginal experiences on the adult honeybee, colonies containing larvae were fed scented food. The effect of the preimaginal experiences with the food odor was assessed in learning performance, memory retention and generalization in 3–5- and 17–19 day-old bees, in the regulation of their expression of synaptic-related genes and in the perception and morphology of their antennae. Three-five day old bees that experienced 1-hexanol (1-HEX) as food scent responded more to the presentation of the odor during the 1-HEX conditioning than control bees (i.e., bees reared in colonies fed unscented food). Higher levels of proboscis extension response (PER) to 1-HEX in this group also extended to HEXA, the most perceptually similar odor to the experienced one that we tested. These results were not observed for the group tested at older ages. In the brain of young adults, larval experiences triggered similar levels of neurexins (NRXs) and neuroligins (Nlgs) expression, two proteins that have been involved in synaptic formation after associative learning. At the sensory periphery, the experience did not alter the number of the olfactory sensilla placoidea, but did reduce the electrical response of the antennae to the experienced and novel odor. Our study provides a new insight into the effects of preimaginal experiences in the honeybee and the mechanisms underlying olfactory plasticity at larval stage of holometabolous insects. PMID:27375445

Odor Experiences during Preimaginal Stages Cause Behavioral and Neural Plasticity in Adult Honeybees.

PubMed

Ramírez, Gabriela; Fagundez, Carol; Grosso, Juan P; Argibay, Pablo; Arenas, Andrés; Farina, Walter M

2016-01-01

In eusocial insects, experiences acquired during the development have long-term consequences on mature behavior. In the honeybee that suffers profound changes associated with metamorphosis, the effect of odor experiences at larval instars on the subsequent physiological and behavioral response is still unclear. To address the impact of preimaginal experiences on the adult honeybee, colonies containing larvae were fed scented food. The effect of the preimaginal experiences with the food odor was assessed in learning performance, memory retention and generalization in 3-5- and 17-19 day-old bees, in the regulation of their expression of synaptic-related genes and in the perception and morphology of their antennae. Three-five day old bees that experienced 1-hexanol (1-HEX) as food scent responded more to the presentation of the odor during the 1-HEX conditioning than control bees (i.e., bees reared in colonies fed unscented food). Higher levels of proboscis extension response (PER) to 1-HEX in this group also extended to HEXA, the most perceptually similar odor to the experienced one that we tested. These results were not observed for the group tested at older ages. In the brain of young adults, larval experiences triggered similar levels of neurexins (NRXs) and neuroligins (Nlgs) expression, two proteins that have been involved in synaptic formation after associative learning. At the sensory periphery, the experience did not alter the number of the olfactory sensilla placoidea, but did reduce the electrical response of the antennae to the experienced and novel odor. Our study provides a new insight into the effects of preimaginal experiences in the honeybee and the mechanisms underlying olfactory plasticity at larval stage of holometabolous insects.

Combustion-Derived Nanoparticles in Key Brain Target Cells and Organelles in Young Urbanites: Culprit Hidden in Plain Sight in Alzheimer's Disease Development.

PubMed

González-Maciel, Angélica; Reynoso-Robles, Rafael; Torres-Jardón, Ricardo; Mukherjee, Partha S; Calderón-Garcidueñas, Lilian

2017-01-01

Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains. Using transmission electron microscopy, we documented CDNPs in neurons, glia, choroid plexus, and neurovascular units of young MC residents versus matched clean air controls. CDNPs are associated with pathology in mitochondria, endoplasmic reticulum (ER), mitochondria-ER contacts (MERCs), axons,and dendrites. There is a significant difference in size and numbers between spherical CDNPs (>85%) and the angular, euhedral endogenous NPs (<15%). Spherical CDNPs (dogs 21.2±7.1 nm in diameter versus humans 29.1±11.2 nm, p = 0.002) are present in neurons, glia, choroid plexus, endothelium, nasal and olfactory epithelium, and in CSF at significantly higher in numbers in MC residents (p < 0.0001). Degenerated MERCs, abnormal mitochondria, and dilated ER are widespread, and CDNPs in close contact with neurofilaments, glial fibers, and chromatin are a potential source for altered microtubule dynamics, mitochondrial dysfunction, accumulation and aggregation of unfolded proteins, abnormal endosomal systems, altered insulin signaling, calcium homeostasis, apoptotic signaling, autophagy, and epigenetic changes. Highly oxidative, ubiquitous CDNPs constitute a novel path into AD pathogenesis. Exposed children and young adults need early neuroprotection and multidisciplinary prevention efforts to modify the course of AD at early stages.

Convergence of multimodal sensory pathways to the mushroom body calyx in Drosophila melanogaster

PubMed Central

Yagi, Ryosuke; Mabuchi, Yuta; Mizunami, Makoto; Tanaka, Nobuaki K.

2016-01-01

Detailed structural analyses of the mushroom body which plays critical roles in olfactory learning and memory revealed that it is directly connected with multiple primary sensory centers in Drosophila. Connectivity patterns between the mushroom body and primary sensory centers suggest that each mushroom body lobe processes information on different combinations of multiple sensory modalities. This finding provides a novel focus of research by Drosophila genetics for perception of the external world by integrating multisensory signals. PMID:27404960

What is CAR doing in the middle of the adult neurogenic road?

PubMed Central

Junyent, Felix; Coré, Nathalie; Cremer, Harold

2017-01-01

ABSTRACT The molecular and cellular basis of adult neurogenesis has attracted considerable attention for fundamental and clinical applications because neural stem cells and newborn neurons may, one day, be harnessed to replace neurons and allow cognitive improvement in the diseased brain. In rodents, neural progenitors are located in the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the generation of newborn neurons is associated with plasticity, including regulation of memory. The role of subventricular zone neural precursors that migrate to the olfactory bulb is less characterized. Identifying factors that impact neural stem cell proliferation, migration and differentiation is therefore sine qua non before we can harness their potential. Here, we expand upon our recent results showing that CAR, the coxsackievirus and adenovirus receptor, is among the developing list of key players when it comes to the complex process of integrating newborn neurons into existing circuits in the mature brain. PMID:28516108

Protein tyrosine phosphatase receptor type R deficient mice exhibit increased exploration in a new environment and impaired novel object recognition memory.

PubMed

Erkens, Mirthe; Bakker, Brenda; van Duijn, Lucette M; Hendriks, Wiljan J A J; Van der Zee, Catharina E E M

2014-05-15

Mouse gene Ptprr encodes multiple protein tyrosine phosphatase receptor type R (PTPRR) isoforms that negatively regulate mitogen-activated protein kinase (MAPK) signaling pathways. In the mouse brain, PTPRR proteins are expressed in cerebellum, olfactory bulb, hippocampus, amygdala and perirhinal cortex but their precise role in these regions remains to be determined. Here, we evaluated phenotypic consequences of loss of PTPRR activity and found that basal smell was normal for Ptprr(-/-) mice. Also, spatial learning and fear-associated contextual learning were unaffected. PTPRR deficiency, however, resulted in impaired novel object recognition and a striking increase in exploratory activity in a new environment. The data corroborate the importance of proper control of MAPK signaling in cerebral functions and put forward PTPRR as a novel target to modulate synaptic processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Predictors of quality of life outcomes in chronic rhinosinusitis after sinus surgery.

PubMed

Katotomichelakis, Michael; Simopoulos, Efthimios; Tripsianis, Gregory; Balatsouras, Dimitrios; Danielides, Gerasimos; Kourousis, Christos; Livaditis, Miltos; Danielides, Vassilios

2014-04-01

The predictive value of olfaction for quality of life (QoL) recovery after endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) is still underestimated. The aim of this study was to explore the proportion of patients suffering from CRS who experience clinically significant QoL improvement after ESS and identify pre-operative clinical phenotypes that best predict surgical outcomes for QoL, focusing mainly on the role of patients' olfaction. One hundred eleven patients following ESS for CRS and 48 healthy subjects were studied. Olfactory function was expressed by the combined "Threshold Discrimination Identification" score using "Sniffin' sticks" test pre-treatment and 12 months after treatment. All subjects completed validated, widely used QoL questionnaires, specific for olfaction (Questionnaire of Olfactory Deficits: QOD), for assessing psychology (Beck Depression Inventory: BDI) and for general health (Short Form-36: SF-36). Statistically significant improvement of olfactory function by 41.8% and of all QoL questionnaires scores (all p < 0.001) was observed on the 12-month follow-up examination. Clinically significant improvement for QoL was measured in a proportion of 56.8% of patients on QOD, 64.9% on SF-36 and 49.5% on BDI scales results. Although olfactory dysfunction, nasal polyps, female gender, high socio-economic status and non-smoking habits were significantly associated with better QoL results, multivariate logistic regression analysis revealed that only olfactory dysfunction and nasal polyps were independent predictors significantly associated with higher likelihood of clinically significant improvement in all QoL questionnaire results. Olfactory dysfunction and nasal polyps were independent pre-operative predictors for surgical outcomes with regard to QoL results.

Olfactory dysfunction, olfactory bulb pathology and urban air pollution

PubMed Central

Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Osnaya, Norma; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Herritt, Lou; Brooks, Diane; Keefe, Sheyla; Palacios-Moreno, Juan; Villarreal-Calderon, Rodolfo; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Delgado-Chávez, Ricardo; Aiello-Mora, Mario; Maronpot, Robert R.; Doty, Richard L

2010-01-01

Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8 ± 8.5 y were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC / 25 controls 21.2 ±2.7 y. MC subjects had significantly lower UPSIT scores: 34.24 ± 0.42 versus controls 35.76 ± 0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE ε 4 carriers failed 2.4 ± 0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36 ± 0.16 items, p = 0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid βA42 (29/35) and/or α-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration. PMID:19297138

[Olfactory sensory perception].

PubMed

Fuentes, Aler; Fresno, María Javiera; Santander, Hugo; Valenzuela, Saúl; Gutiérrez, Mario Felipe; Miralles, Rodolfo

2011-03-01

The five senses have had a fundamental importance for survival and socialization of human beings. From an evolutionary point of view the sense of smell is the oldest. This sense has a strong representation within the genome, allowing the existence of many types of receptors that allow us to capture multiple volatile odor producing molecules, sending electrical signals to higher centers to report the outside world. Several cortical areas are activated in the brain, which are interconnected to form an extensive and complex neural network, linking for example, areas involved with memory and emotions, thus giving this sense of perceptual richness. While the concept of flavor is largely related to the sense of taste, smell provides the necessary integration with the rest of the senses and higher functions. Fully understanding the sense of smell is relevant to health professionals. Knowing the characteristics of the receptors, the transduction processes and convergence of information in the higher centers involved, we can properly detect olfactory disorders in our patients.

An olfactory subsystem that detects carbon disulfide and mediates food-related social learning.

PubMed

Munger, Steven D; Leinders-Zufall, Trese; McDougall, Lisa M; Cockerham, Renee E; Schmid, Andreas; Wandernoth, Petra; Wennemuth, Gunther; Biel, Martin; Zufall, Frank; Kelliher, Kevin R

2010-08-24

Olfactory signals influence social interactions in a variety of species. In mammals, pheromones and other social cues can promote mating or aggression behaviors; can communicate information about social hierarchies, genetic identity and health status; and can contribute to associative learning. However, the molecular, cellular, and neural mechanisms underlying many olfactory-mediated social interactions remain poorly understood. Here, we report that a specialized olfactory subsystem that includes olfactory sensory neurons (OSNs) expressing the receptor guanylyl cyclase GC-D, the cyclic nucleotide-gated channel subunit CNGA3, and the carbonic anhydrase isoform CAII (GC-D(+) OSNs) is required for the acquisition of socially transmitted food preferences (STFPs) in mice. Using electrophysiological recordings from gene-targeted mice, we show that GC-D(+) OSNs are highly sensitive to the volatile semiochemical carbon disulfide (CS(2)), a component of rodent breath and a known social signal mediating the acquisition of STFPs. Olfactory responses to CS(2) are drastically reduced in mice lacking GC-D, CNGA3, or CAII. Disruption of this sensory transduction cascade also results in a failure to acquire STFPs from either live or surrogate demonstrator mice or to exhibit hippocampal correlates of STFP retrieval. Our findings indicate that GC-D(+) OSNs detect chemosignals that facilitate food-related social interactions. Copyright 2010 Elsevier Ltd. All rights reserved.

Sad man's nose: Emotion induction and olfactory perception.

PubMed

Flohr, Elena L R; Erwin, Elena; Croy, Ilona; Hummel, Thomas

2017-03-01

Emotional and olfactory processing is frequently shown to be closely linked both anatomically and functionally. Depression, a disease closely related to the emotional state of sadness, has been shown to be associated with a decrease in olfactory sensitivity. The present study focuses on the state of sadness in n = 31 healthy subjects in order to investigate the specific contribution of this affective state in the modulation of olfactory processing. A sad or indifferent affective state was induced using 2 movies that were presented on 2 separate days. Afterward, chemosensory-evoked potentials were recorded after stimulation with an unpleasant (hydrogen sulfide: "rotten eggs") or a pleasant (phenyl ethyl alcohol: "rose") odorant. Latencies of N1 and P2 peaks were longer after induction of the sad affective state. Additionally, amplitudes were lower in a sad affective state when being stimulated with the unpleasant odorant. Processing of olfactory input has thus been reduced under conditions of the sad affective state. We argue that the affective state per se could at least partially account for the reduced olfactory sensitivity in depressed patients. To our knowledge, the present study is the first to show influence of affective state on chemosensory event-related potentials. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Is the brain of migraineurs "different" even in dreams?

PubMed

Lovati, C; DeAngeli, F; D'Amico, D; Giani, L; D'Alessandro, C M; Zardoni, M; Scaglione, V; Castoldi, D; Capiluppi, E; Curone, M; Bussone, G; Mariani, C

2014-05-01

Migraineurs brain is hyper-excitable and hypo-metabolic. Dreaming is a mental state characterized by hallucinatory features in which imagery, emotion, motor skills and memory are created de novo. To evaluate dreams in different kinds of headache. We included 219 controls; 148 migraineurs (66 with aura-MA, 82 without aura-MO); 45 tension type headache (TTH) patients. ICHD-II diagnostic criteria were used. Ad hoc questionnaire was used to evaluate oneiric activity. The Generalized Anxiety Disorder Questionnaire, and the Patient Health Questionnaire were administered to evaluate anxiety and mood. The prevalence of dreamers was similar in different groups. Frequency of visual and auditory dreams was not different between groups. Migraineurs, particularly MA, had an increased frequency of taste dreams (present in 19.6 % of controls, 40.9 % of MA, 23.2 % of MO, 11.1 % of TTH, p < 0.01), and of olfactory dreams (present in 20 % of controls, 36 % of MA, 35 % of MO and 20 % of TTH, p < 0.01). Anxiety and mood did not influence these results. The increased frequency of taste and olfactory dreams among migraineurs seems to be specific, possibly reflecting a particular sensitivity of gustative and olfactory brain structures, as suggested by osmofobia and nausea, typical of migraine. This may suggest the role of some cerebral structures, such as amygdala and hypothalamus, which are known to be involved in migraine mechanisms as well in the biology of sleep and dreaming.

Olfactory priming reinstates extinguished chocolate-induced conditioned place preference.

PubMed

La Mela, Immacolata; Latagliata, Emanuele Claudio; Patrono, Enrico; Puglisi-Allegra, Stefano; Ventura, Rossella

2010-02-01

A major problem in the dietary treatment of disorders associated with excessive eating, such as obesity, is the high rate of relapse into maladaptive eating habits after withdrawal from consumption of palatable, energy-dense food. As olfaction has a major role in appetite and eating behavior, in this study we used a reinstatement model based on conditioned place preference to investigate the ability of olfactory priming to reinstate extinguished chocolate-induced conditioned place preference in sated mice. We found that olfactory priming, which was ineffective in inducing conditioned place preference in the control group, reactivated place preference following the extinction procedure in the experimental group. These results extend previous reports of the reinstatement of food seeking induced by pellet priming and, for the first time, show the possibility of using olfactory priming in an animal model of relapse. In light of the major role of olfactory inputs in appetite and of cues in relapse, the present results indicate that smell is an important factor to consider in the treatment of eating disorders. 2009 Elsevier Ltd. All rights reserved.

The olfactory system as the gateway to the neural correlates of consciousness

PubMed Central

Merrick, Christina; Godwin, Christine A.; Geisler, Mark W.; Morsella, Ezequiel

2014-01-01

How consciousness is generated by the nervous system remains one of the greatest mysteries in science. Investigators from diverse fields have begun to unravel this puzzle by contrasting conscious and unconscious processes. In this way, it has been revealed that the two kinds of processes differ in terms of the underlying neural events and associated cognitive mechanisms. We propose that, for several reasons, the olfactory system provides a unique portal through which to examine this contrast. For this purpose, the olfactory system is beneficial in terms of its (a) neuroanatomical aspects, (b) phenomenological and cognitive/mechanistic properties, and (c) neurodynamic (e.g., brain oscillations) properties. In this review, we discuss how each of these properties and aspects of the olfactory system can illuminate the contrast between conscious and unconscious processing in the brain. We conclude by delineating the most fruitful avenues of research and by entertaining hypotheses that, in order for an olfactory content to be conscious, that content must participate in a network that is large-scale, both in terms of the neural systems involved and the scope of information integration. PMID:24454300

Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice.

PubMed

Yassine, Nour; Lazaris, Anelise; Dorner-Ciossek, Cornelia; Després, Olivier; Meyer, Laurence; Maitre, Michel; Mensah-Nyagan, Ayikoe Guy; Cassel, Jean-Christophe; Mathis, Chantal

2013-03-01

The retinal degeneration Pde6b(rd1) (rd) mutation can be a major pitfall in behavioral studies using tg2576 mice bred on a B6:SJL genetic background, 1 of the most widely used models of Alzheimer's disease. After a pilot study in wild type mice, performance of 8- and 16-month-old tg2576 mice were assessed in several behavioral tasks with the challenge of selecting 1 or more task(s) showing robust memory deficits on this genetic background. Water maze acquisition was impossible in rd homozygotes, whereas Y-maze alternation, object recognition, and olfactory discrimination were unaffected by both the transgene and the rd mutation. Spatial memory retention of 8- and 16-month-old tg2576 mice, however, was dramatically affected independently of the rd mutation when mice had to recognize a spatial configuration of objects or to perform the Barnes maze. Thus, the latter tasks appear extremely useful to evaluate spatial memory deficits and to test cognitive therapies in tg2576 mice and other mouse models bred on a background susceptible to visual impairment. Copyright © 2013 Elsevier Inc. All rights reserved.

Histological and Lectin Histochemical Studies on the Olfactory and Respiratory Mucosae of the Sheep

PubMed Central

IBRAHIM, Dalia; NAKAMUTA, Nobuaki; TANIGUCHI, Kazumi; YAMAMOTO, Yoshio; TANIGUCHI, Kazuyuki

2013-01-01

ABSTRACT The olfactory and respiratory mucosae of the Corriedale sheep were examined using lectin histochemistry in order to clarify the histochemical and glycohistochemical differences between these two tissues. The olfactory epithelium was stained with 13 lectins out of 21 lectins examined, while the respiratory epithelium was positive to 16 lectins. The free border of both of the olfactory and respiratory epithelia was stained with 12 lectins: Wheat germ agglutinin (WGA), succinylated-wheat germ agglutinin (s-WGA), Lycopersicon esculentum lectin (LEL), Solanum tuberosum lectin (STL), Datura stramonium lectin (DSL), Soybean agglutinin (SBA), Bandeiraea simplicifolia lectin-I (BSL-I), Ricinus communis agglutinin-I (RCA-120), Erythrina cristagalli lectin (ECL), Concanavalin A (Con A), Phaseolus vulgaris agglutinin-E (PHA-E) and Phaseolus vulgaris agglutinin-L (PHA-L). The associated glands of the olfactory mucosa, Bowman’s glands, were stained with 13 lectins. While both the goblet cells and mucous nasal glands were stained with 8 lectins; five of them (WGA, s-WGA, STL, Vicia villosa agglutinin (VVA) and ECL) were mutually positive among the Bowman’s glands, mucous nasal glands and the goblet cells. These findings indicate that the glycohistochemical characteristics of the free borders of both olfactory and respiratory epithelia are similar to each other, suggesting that secretions from the Bowman’s glands and those of the goblet cells and mucous nasal glands are partially exchanged between the surface of two epithelia to contribute the functions of the respiratory epithelium and the olfactory receptor cells, respectively. PMID:24200894

Concise review: Patient-derived olfactory stem cells: new models for brain diseases.

PubMed

Mackay-Sim, Alan

2012-11-01

Traditional models of brain diseases have had limited success in driving candidate drugs into successful clinical translation. This has resulted in large international pharmaceutical companies moving out of neuroscience research. Cells are not brains, obviously, but new patient-derived stem models have the potential to elucidate cell biological aspects of brain diseases that are not present in worm, fly, or rodent models, the work horses of disease investigations and drug discovery. Neural stem cells are present in the olfactory mucosa, the organ of smell in the nose. Patient-derived olfactory mucosa has demonstrated disease-associated differences in a variety of brain diseases and recently olfactory mucosa stem cells have been generated from patients with schizophrenia, Parkinson's disease, and familial dysautonomia. By comparison with cells from healthy controls, patient-derived olfactory mucosa stem cells show disease-specific alterations in gene expression and cell functions including: a shorter cell cycle and faster proliferation in schizophrenia, oxidative stress in Parkinson's disease, and altered cell migration in familial dysautonomia. Olfactory stem cell cultures thus reveal patient-control differences, even in complex genetic diseases such as schizophrenia and Parkinson's disease, indicating that multiple genes of small effect can converge on shared cell signaling pathways to present as a disease-specific cellular phenotype. Olfactory mucosa stem cells can be maintained in homogeneous cultures that allow robust and repeatable multiwell assays suitable for screening libraries of drug candidate molecules. Copyright © 2012 AlphaMed Press.

Enhanced olfactory sensitivity in autism spectrum conditions.

PubMed

Ashwin, Chris; Chapman, Emma; Howells, Jessica; Rhydderch, Danielle; Walker, Ian; Baron-Cohen, Simon

2014-01-01

People with autism spectrum conditions (ASC) report heightened olfaction. Previous sensory experiments in people with ASC have reported hypersensitivity across visual, tactile, and auditory domains, but not olfaction. The aims of the present study were to investigate olfactory sensitivity in ASC, and to test the association of sensitivity to autistic traits. We recruited 17 adult males diagnosed with ASC and 17 typical adult male controls and tested their olfactory sensitivity using the Alcohol Sniff Test (AST), a standardised clinical evaluation of olfactory detection. The AST involves varying the distance between subject and stimulus until an odour is barely detected. Participants with ASC also completed the Autism Spectrum Quotient (AQ) as a measure of autism traits. The ASC group detected the odour at a mean distance of 24.1 cm (SD =11.5) from the nose, compared to the control group, who detected it at a significantly shorter mean distance of 14.4 cm (SD =5.9). Detection distance was independent of age and IQ for both groups, but showed a significant positive correlation with autistic traits in the ASC group (r =0.522). This is the first experimental demonstration, as far as the authors are aware, of superior olfactory perception in ASC and showing that greater olfactory sensitivity is correlated with a higher number of autistic traits. This is consistent with results from previous findings showing hypersensitivity in other sensory domains and may help explain anecdotal and questionnaire accounts of heightened olfactory sensitivity in ASC. Results are discussed in terms of possible underlying neurophysiology.

Body Odor Trait Disgust Sensitivity Predicts Perception of Sweat Biosamples.

PubMed

Liuzza, Marco Tullio; Olofsson, Jonas K; Sabiniewicz, Agnieszka; Sorokowska, Agnieszka

2017-07-01

Body odors are potent triggers of disgust and regulate social behaviors in many species. The role of olfaction in disgust-associated behaviors has received scant attention in the research literature, in part because olfactory disgust assessments have required laboratory testing with odors. We have devised the "Body Odor Disgust Scale" (BODS) to facilitate research on olfactory disgust. In this study, we evaluated whether individual differences in BODS scores would be associated with the perception of disgust for sweat samples in a laboratory setting. Results show that BODS was a strong predictor of disgust ratings of sweat samples even when controlling for general disgust sensitivity. In contrast, odor intensity ratings were unrelated to BODS scores. Our findings suggest that the BODS scores reflect body odor disgust perception. The BODS scale might facilitate research on olfactory disgust responses and associated behaviors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evidence that thyroid hormone induces olfactory cellular proliferation in salmon during a sensitive period for imprinting.

PubMed

Lema, Sean C; Nevitt, Gabrielle A

2004-09-01

Salmon have long been known to imprint and home to natal stream odors, yet the mechanisms driving olfactory imprinting remain obscure. The timing of imprinting is associated with elevations in plasma thyroid hormone levels, with possible effects on growth and proliferation of the peripheral olfactory system. Here, we begin to test this idea by determining whether experimentally elevated plasma levels of 3,5,3'-triiodothyronine (T(3)) influence cell proliferation as detected by the 5-bromo-2'-deoxyuridine (BrdU) cell birth-dating technique in the olfactory epithelium of juvenile coho salmon (Oncorhynchus kisutch). We also explore how natural fluctuations in thyroxine (T(4)) relate to proliferation in the epithelium during the parr-smolt transformation. In both studies, we found that BrdU labeled both single and clusters of mitotic cells. The total number of BrdU-labeled cells in the olfactory epithelium was significantly greater in fish with artificially elevated T(3) compared with placebo controls. This difference in proliferation was restricted to the basal region of the olfactory epithelium, where multipotent progenitor cells differentiate into olfactory receptor neurons. The distributions of mitotic cluster sizes differed significantly from a Poisson distribution for both T(3) and placebo treatments, suggesting that proliferation tends to be non-random. Over the course of the parr-smolt transformation, changes in the density of BrdU cells showed a positive relationship with natural fluctuations in plasma T(4). This relationship suggests that even small changes in thyroid activity can stimulate the proliferation of neural progenitor cells in the salmon epithelium. Taken together, our results establish a link between the thyroid hormone axis and measurable anatomical changes in the peripheral olfactory system.

Development of the terminal nerve system in the shark Scyliorhinus canicula.

PubMed

Quintana-Urzainqui, Idoia; Anadón, Ramón; Candal, Eva; Rodríguez-Moldes, Isabel

2014-01-01

The nervus terminalis (or terminal nerve) system was discovered in an elasmobranch species more than a century ago. Over the past century, it has also been recognized in other vertebrate groups, from agnathans to mammals. However, its origin, functions or relationship with the olfactory system are still under debate. Despite the abundant literature about the nervus terminalis system in adult elasmobranchs, its development has been overlooked. Studies in other vertebrates have reported newly differentiated neurons of the terminal nerve system migrating from the olfactory epithelium to the telencephalon as part of a 'migratory mass' of cells associated with the olfactory nerve. Whether the same occurs in developing elasmobranchs (adults showing anatomically separated nervus terminalis and olfactory systems) has not yet been determined. In this work we characterized for the first time the development of the terminal nerve and ganglia in an elasmobranch, the lesser spotted dogfish (Scyliorhinus canicula), by means of tract-tracing techniques combined with immunohistochemical markers for the terminal nerve (such as FMRF-amide peptide), for the developing components of the olfactory system (Gα0 protein, GFAP, Pax6), and markers for early postmitotic neurons (HuC/D) and migrating immature neurons (DCX). We discriminated between embryonic olfactory and terminal nerve systems and determined that both components may share a common origin in the migratory mass. We also localized the exact point where they split off near the olfactory nerve-olfactory bulb junction. The study of the development of the terminal nerve system in a basal gnathostome contributes to the knowledge of the ancestral features of this system in vertebrates, shedding light on its evolution and highlighting the importance of elasmobranchs for developmental and evolutionary studies. © 2014 S. Karger AG, Basel.

Non-motor parkinsonian pathology in aging A53T α-synuclein mice is associated with progressive synucleinopathy and altered enzymatic function.

PubMed

Farrell, Kaitlin F; Krishnamachari, Sesha; Villanueva, Ernesto; Lou, Haiyan; Alerte, Tshianda N M; Peet, Eloise; Drolet, Robert E; Perez, Ruth G

2014-02-01

Aging, the main risk factor for Parkinson's disease (PD), is associated with increased α-synuclein levels in substantia nigra pars compacta (SNc). Excess α-synuclein spurs Lewy-like pathology and dysregulates the activity of protein phosphatase 2A (PP2A). PP2A dephosphorylates many neuroproteins, including the catecholamine rate-limiting enzyme, tyrosine hydroxylase (TH). A loss of nigral dopaminergic neurons induces PD movement problems, but before those abnormalities occur, behaviors such as olfactory loss, anxiety, and constipation often manifest. Identifying mouse models with early PD behavioral changes could provide a model in which to test emerging therapeutic compounds. To this end, we evaluated mice expressing A53T mutant human (A53T) α-synuclein for behavior and α-synuclein pathology in olfactory bulb, adrenal gland, and gut. Aging A53T mice exhibited olfactory loss and anxiety that paralleled olfactory and adrenal α-synuclein aggregation. PP2A activity was also diminished in olfactory and adrenal tissues harboring insoluble α-synuclein. Low adrenal PP2A activity co-occurred with TH hyperactivity, making this the first study to link adrenal synucleinopathy to anxiety and catecholamine dysregulation. Aggregated A53T α-synuclein recombinant protein also had impaired stimulatory effects on soluble recombinant PP2A. Collectively, the data identify an excellent model in which to screen compounds for their ability to block the spread of α-synuclein pathology associated with pre-motor stages of PD. © 2013 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

A Synergistic Transcriptional Regulation of Olfactory Genes Drives Blood-Feeding Associated Complex Behavioral Responses in the Mosquito Anopheles culicifacies.

PubMed

Das De, Tanwee; Thomas, Tina; Verma, Sonia; Singla, Deepak; Chauhan, Charu; Srivastava, Vartika; Sharma, Punita; Kumari, Seena; Tevatiya, Sanjay; Rani, Jyoti; Hasija, Yasha; Pandey, Kailash C; Dixit, Rajnikant

2018-01-01

Decoding the molecular basis of host seeking and blood feeding behavioral evolution/adaptation in the adult female mosquitoes may provide an opportunity to design new molecular strategy to disrupt human-mosquito interactions. Although there is a great progress in the field of mosquito olfaction and chemo-detection, little is known about the sex-specific evolution of the specialized olfactory system of adult female mosquitoes that enables them to drive and manage the complex blood-feeding associated behavioral responses. A comprehensive RNA-Seq analysis of prior and post blood meal olfactory system of An. culicifacies mosquito revealed a minor but unique change in the nature and regulation of key olfactory genes that may play a pivotal role in managing diverse behavioral responses. Based on age-dependent transcriptional profiling, we further demonstrated that adult female mosquito's chemosensory system gradually learned and matured to drive the host-seeking and blood feeding behavior at the age of 5-6 days. A time scale expression analysis of Odorant Binding Proteins (OBPs) unravels unique association with a late evening to midnight peak biting time. Blood meal-induced switching of unique sets of OBP genes and Odorant Receptors (Ors) expression coincides with the change in the innate physiological status of the mosquitoes. Blood meal follows up experiments further provide enough evidence that how a synergistic and concurrent action of OBPs-Ors may drive "prior and post blood meal" associated complex behavioral events. A dominant expression of two sensory appendages proteins (SAP-1 & SAP2) in the legs of An. culicifacies suggests that this mosquito species may draw an extra advantage of having more sensitive appendages than An. stephensi , an urban malarial vector in the Indian subcontinents. Finally, our molecular modeling analysis predicts crucial amino acid residues for future functional characterization of the sensory appendages proteins which may play a central role in regulating multiple behaviors of An. culicifacies mosquito. SIGNIFICANCE   Evolution and adaptation of blood feeding behavior not only favored the reproductive success of adult female mosquitoes but also make them important disease-transmitting vectors. An environmental exposure after emergence may favor the broadly tuned olfactory system of mosquitoes to drive complex behavioral responses. But, how these olfactory derived genetic factors manage female specific "pre and post" blood meal associated complex behavioral responses are not well known. Our findings suggest that a synergistic action of olfactory factors may govern an innate to prime learning strategy to facilitate rapid blood meal acquisition and downstream behavioral activities. A species-specific transcriptional profiling and an in-silico analysis predict that "sensory appendages protein" may be a unique target to design disorientation strategy against the mosquito Anopheles culicifacies .

Brain architecture of the largest living land arthropod, the Giant Robber Crab Birgus latro (Crustacea, Anomura, Coenobitidae): evidence for a prominent central olfactory pathway?

PubMed Central

2010-01-01

Background Several lineages within the Crustacea conquered land independently during evolution, thereby requiring physiological adaptations for a semi-terrestrial or even a fully terrestrial lifestyle. Birgus latro Linnaeus, 1767, the giant robber crab or coconut crab (Anomura, Coenobitidae), is the largest land-living arthropod and inhabits Indo-Pacific islands such as Christmas Island. B. latro has served as a model in numerous studies of physiological aspects related to the conquest of land by crustaceans. From an olfactory point of view, a transition from sea to land means that molecules need to be detected in gas phase instead of in water solution. Previous studies have provided physiological evidence that terrestrial hermit crabs (Coenobitidae) such as B. latro have a sensitive and well differentiated sense of smell. Here we analyze the brain, in particular the olfactory processing areas of B. latro, by morphological analysis followed by 3 D reconstruction and immunocytochemical studies of synaptic proteins and a neuropeptide. Results The primary and secondary olfactory centers dominate the brain of B. latro and together account for ca. 40% of the neuropil volume in its brain. The paired olfactory neuropils are tripartite and composed of more than 1,000 columnar olfactory glomeruli, which are radially arranged around the periphery of the olfactory neuropils. The glomeruli are innervated ca. 90,000 local interneurons and ca. 160,000 projection neurons per side. The secondary olfactory centers, the paired hemiellipsoid neuropils, are targeted by the axons of these olfactory projection neurons. The projection neuron axonal branches make contact to ca. 250.000 interneurons (per side) associated with the hemiellipsoid neuropils. The hemiellipsoid body neuropil is organized into parallel neuropil lamellae, a design that is quite unusual for decapod crustaceans. The architecture of the optic neuropils and areas associated with antenna two suggest that B. latro has visual and mechanosensory skills that are comparable to those of marine Crustacea. Conclusions In parallel to previous behavioral findings that B. latro has aerial olfaction, our results indicate that their central olfactory pathway is indeed most prominent. Similar findings from the closely related terrestrial hermit crab Coenobita clypeatus suggest that in Coenobitidae, olfaction is a major sensory modality processed by the brain, and that for these animals, exploring the olfactory landscape is vital for survival in their terrestrial habitat. Future studies on terrestrial members of other crustacean taxa such as Isopoda, Amphipoda, Astacida, and Brachyura will shed light on how frequently the establishment of an aerial sense of olfaction evolved in Crustacea during the transition from sea to land. Amounting to ca. 1,000,000, the numbers of interneurons that analyse the olfactory input in B. latro brains surpasses that in other terrestrial arthropods, as e.g. the honeybee Apis mellifera or the moth Manduca sexta, by two orders of magnitude suggesting that B. latro in fact is a land-living arthropod that has devoted a substantial amount of nervous tissue to the sense of smell. PMID:20831795

Reciprocal synapses between mushroom body and dopamine neurons form a positive feedback loop required for learning.

PubMed

Cervantes-Sandoval, Isaac; Phan, Anna; Chakraborty, Molee; Davis, Ronald L

2017-05-10

Current thought envisions dopamine neurons conveying the reinforcing effect of the unconditioned stimulus during associative learning to the axons of Drosophila mushroom body Kenyon cells for normal olfactory learning. Here, we show using functional GFP reconstitution experiments that Kenyon cells and dopamine neurons from axoaxonic reciprocal synapses. The dopamine neurons receive cholinergic input via nicotinic acetylcholine receptors from the Kenyon cells; knocking down these receptors impairs olfactory learning revealing the importance of these receptors at the synapse. Blocking the synaptic output of Kenyon cells during olfactory conditioning reduces presynaptic calcium transients in dopamine neurons, a finding consistent with reciprocal communication. Moreover, silencing Kenyon cells decreases the normal chronic activity of the dopamine neurons. Our results reveal a new and critical role for positive feedback onto dopamine neurons through reciprocal connections with Kenyon cells for normal olfactory learning.

Individual significance of olfaction: development of a questionnaire.

PubMed

Croy, Ilona; Buschhüter, Dorothee; Seo, Han-Seok; Negoias, Simona; Hummel, Thomas

2010-01-01

Clinical experience shows that the individual significance of olfactory function varies between subjects. In order to estimate these individual differences we developed a questionnaire to study the subjective importance of the sense of smell. Questions were arranged within three subscales: association with olfactory sensations, application of the sense of smell, and the readiness to draw consequences from the olfactory perception. The questionnaire was shown to be time efficient, suitable for normosmic subjects and patients with hyposmia or anosmia. It exhibited a good internal reliability (Cronbach's Alpha = 0.77). First results in 123 subjects indicate that the subjective importance of the sense of smell stays at the same level throughout life-span despite of a decreased olfactory sensitivity. Furthermore, women reported a higher importance of olfaction. It is hoped that this questionnaire will contribute to clarify, for example, cross-cultural differences in the perception of odours.

Quantitative comparative analysis of the nasal chemosensory organs of anurans during larval development and metamorphosis highlights the relative importance of chemosensory subsystems in the group.

PubMed

Jungblut, Lucas David; Reiss, John O; Paz, Dante A; Pozzi, Andrea G

2017-09-01

The anuran peripheral olfactory system is composed of a number of subsystems, represented by distinct neuroepithelia. These include the main olfactory epithelium and vomeronasal organ (found in most tetrapods) and three specialized epithelia of anurans: the buccal-exposed olfactory epithelium of larvae, and the olfactory recess and middle chamber epithelium of postmetamorphic animals. To better characterize the developmental changes in these subsystems across the life cycle, morphometric changes of the nasal chemosensory organs during larval development and metamorphosis were analyzed in three different anuran species (Rhinella arenarum, Hypsiboas pulchellus, and Xenopus laevis). We calculated the volume of the nasal chemosensory organs by measuring the neuroepithelial area from serial histological sections at four different stages. In larvae, the vomeronasal organ was relatively reduced in R. arenarum compared with the other two species; the buccal-exposed olfactory epithelium was absent in X. laevis, and best developed in H. pulchellus. In postmetamorphic animals, the olfactory epithelium (air-sensitive organ) was relatively bigger in terrestrial species (R. arenarum and H. pulchellus), whereas the vomeronasal and the middle chamber epithelia (water-sensitive organs) was best developed in X. laevis. A small olfactory recess (likely homologous with the middle chamber epithelium) was found in R. arenarum juveniles, but not in H. pulchellus. These results support the association of the vomeronasal and middle chamber epithelia with aquatic olfaction, as seen by their enhanced development in the secondarily aquatic juveniles of X. laevis. They also support a role for the larval buccal-exposed olfactory epithelium in assessment of oral contents: it was absent in X. laevis, an obligate suspension feeder, while present in the two grazing species. These initial quantitative results give, for the first time, insight into the functional importance of the peripheral olfactory subsystems across the anuran life cycle. © 2017 Wiley Periodicals, Inc.

Olfactory system gamma oscillations: the physiological dissection of a cognitive neural system

PubMed Central

Rojas-Líbano, Daniel

2008-01-01

Oscillatory phenomena have been a focus of dynamical systems research since the time of the classical studies on the pendulum by Galileo. Fast cortical oscillations also have a long and storied history in neurophysiology, and olfactory oscillations have led the way with a depth of explanation not present in the literature of most other cortical systems. From the earliest studies of odor-evoked oscillations by Adrian, many reports have focused on mechanisms and functional associations of these oscillations, in particular for the so-called gamma oscillations. As a result, much information is now available regarding the biophysical mechanisms that underlie the oscillations in the mammalian olfactory system. Recent studies have expanded on these and addressed functionality directly in mammals and in the analogous insect system. Sub-bands within the rodent gamma oscillatory band associated with specific behavioral and cognitive states have also been identified. All this makes oscillatory neuronal networks a unique interdisciplinary platform from which to study neurocognitive and dynamical phenomena in intact, freely behaving animals. We present here a summary of what has been learned about the functional role and mechanisms of gamma oscillations in the olfactory system as a guide for similar studies in other cortical systems. PMID:19003484

Brain architecture in the terrestrial hermit crab Coenobita clypeatus (Anomura, Coenobitidae), a crustacean with a good aerial sense of smell

PubMed Central

Harzsch, Steffen; Hansson, Bill S

2008-01-01

Background During the evolutionary radiation of Crustacea, several lineages in this taxon convergently succeeded in meeting the physiological challenges connected to establishing a fully terrestrial life style. These physiological adaptations include the need for sensory organs of terrestrial species to function in air rather than in water. Previous behavioral and neuroethological studies have provided solid evidence that the land hermit crabs (Coenobitidae, Anomura) are a group of crustaceans that have evolved a good sense of aerial olfaction during the conquest of land. We wanted to study the central olfactory processing areas in the brains of these organisms and to that end analyzed the brain of Coenobita clypeatus (Herbst, 1791; Anomura, Coenobitidae), a fully terrestrial tropical hermit crab, by immunohistochemistry against synaptic proteins, serotonin, FMRFamide-related peptides, and glutamine synthetase. Results The primary olfactory centers in this species dominate the brain and are composed of many elongate olfactory glomeruli. The secondary olfactory centers that receive an input from olfactory projection neurons are almost equally large as the olfactory lobes and are organized into parallel neuropil lamellae. The architecture of the optic neuropils and those areas associated with antenna two suggest that C. clypeatus has visual and mechanosensory skills that are comparable to those of marine Crustacea. Conclusion In parallel to previous behavioral findings of a good sense of aerial olfaction in C. clypeatus, our results indicate that in fact their central olfactory pathway is most prominent, indicating that olfaction is a major sensory modality that these brains process. Interestingly, the secondary olfactory neuropils of insects, the mushroom bodies, also display a layered structure (vertical and medial lobes), superficially similar to the lamellae in the secondary olfactory centers of C. clypeatus. More detailed analyses with additional markers will be necessary to explore the question if these similarities have evolved convergently with the establishment of superb aerial olfactory abilities or if this design goes back to a shared principle in the common ancestor of Crustacea and Hexapoda. PMID:18590553

Food Avoidance Learning in Squirrel Monkeys and Common Marmosets

PubMed Central

Laska, Matthias; Metzker, Karin

1998-01-01

Using a conditioned food avoidance learning paradigm, six squirrel monkeys (Saimiri sciureus) and six common marmosets (Callithrix jacchus) were tested for their ability to (1) reliably form associations between visual or olfactory cues of a potential food and its palatability and (2) remember such associations over prolonged periods of time. We found (1) that at the group level both species showed one-trial learning with the visual cues color and shape, whereas only the marmosets were able to do so with the olfactory cue, (2) that all individuals from both species learned to reliably avoid the unpalatable food items within 10 trials, (3) a tendency in both species for quicker acquisition of the association with the visual cues compared with the olfactory cue, (4) a tendency for quicker acquisition and higher reliability of the aversion by the marmosets compared with the squirrel monkeys, and (5) that all individuals from both species were able to reliably remember the significance of the visual cues, color and shape, even after 4 months, whereas only the marmosets showed retention of the significance of the olfactory cues for up to 4 weeks. Furthermore, the results suggest that in both species tested, illness is not a necessary prerequisite for food avoidance learning but that the presumably innate rejection responses toward highly concentrated but nontoxic bitter and sour tastants are sufficient to induce robust learning and retention. PMID:10454364

Association between olfactory identification and parkinsonism in patients with non-affective psychosis.

PubMed

Meijer, Julia H; van Harten, Peter; Meijer, Carin J; Koeter, Maarten W; Bruggeman, Richard; Cahn, Wiepke; Kahn, René S; de Haan, L

2016-10-01

Olfactory identification deficits (OIDs) are seen in schizophrenia patients and individuals at increased risk for psychosis but its pathophysiology remains unclear. Although dopaminergic imbalance is known to lie at the core of schizophrenia symptomatology, its role in the development of OIDs has not been elucidated yet. This study investigated the association between OIDs and symptoms of parkinsonism as a derivative of dopaminergic functioning. In 320 patients diagnosed with non-affective psychosis, olfactory identification performance was assessed by means of the Sniffin' Sticks task. Level of parkinsonian symptoms was assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS-III). By means of multiple linear regression with bootstrapping, the association between UPDRS and Sniffin' Sticks score was investigated while correcting for potential confounders. A Bonferroni corrected P-value of 0.007 was used. Higher UPDRS scores significantly predicted worse olfactory identification in patients with non-affective psychosis with an unadjusted b = -0.07 (95% CI -0.10 to -0.04) and an adjusted b = -0.04 (95% CI -0.07 to -0.01). Results provide preliminary evidence that the same vulnerability may underlie the development of parkinsonism and OIDs in patients with non-affective psychosis. Further investigation should evaluate the clinical value of OIDs as a marker of dopaminergic vulnerability that may predict psychosis. © 2014 Wiley Publishing Asia Pty Ltd.

Sensory Impairments and Cognitive Function in Middle-Aged Adults.

PubMed

Schubert, Carla R; Cruickshanks, Karen J; Fischer, Mary E; Chen, Yanjun; Klein, Barbara E K; Klein, Ronald; Pinto, A Alex

2017-08-01

Hearing, visual, and olfactory impairments have been associated with cognitive impairment in older adults but less is known about associations with cognitive function in middle-aged adults. Sensory and cognitive functions were measured on participants in the baseline examination (2005-2008) of the Beaver Dam Offspring Study. Cognitive function was measured with the Trail Making tests A (TMTA) and B (TMTB) and the Grooved Peg Board test. Pure-tone audiometry, Pelli-Robson letter charts, and the San Diego Odor Identification test were used to measure hearing, contrast sensitivity, and olfaction, respectively. There were 2,836 participants aged 21-84 years with measures of hearing, visual, olfactory, and cognitive function at the baseline examination. Nineteen percent of the cohort had one sensory impairment and 3% had multiple sensory impairments. In multivariable adjusted linear regression models that included all three sensory impairments, hearing impairment, visual impairment, and olfactory impairment were each independently associated with poorer performance on the TMTA, TMTB, and Grooved Peg Board (p < .05 for all sensory impairments in all models). Participants with a sensory impairment took on average from 2 to 10 seconds longer than participants without the corresponding sensory impairment to complete these tests. Results were similar in models that included adjustment for hearing aid use. Hearing, visual and olfactory impairment were associated with poorer performance on cognitive function tests independent of the other sensory impairments and factors associated with cognition. Sensory impairments in midlife are associated with subtle deficits in cognitive function which may be indicative of early brain aging. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chemical factors determine olfactory system beta oscillations in waking rats.

PubMed

Lowry, Catherine A; Kay, Leslie M

2007-07-01

Recent studies have pointed to olfactory system beta oscillations of the local field potential (15-30 Hz) and their roles both in learning and as specific responses to predator odors. To describe odorant physical properties, resultant behavioral responses and changes in the central olfactory system that may induce these oscillations without associative learning, we tested rats with 26 monomolecular odorants spanning 6 log units of theoretical vapor pressure (estimate of relative vapor phase concentration) and 10 different odor mixtures. We found odorant vapor phase concentration to be inversely correlated with investigation time on the first presentation, after which investigation times were brief and not different across odorants. Analysis of local field potentials from the olfactory bulb and anterior piriform cortex shows that beta oscillations in waking rats occur specifically in response to the class of volatile organic compounds with vapor pressures of 1-120 mmHg. Beta oscillations develop over the first three to four presentations and are weakly present for some odorants in anesthetized rats. Gamma oscillations show a smaller effect that is not restricted to the same range of odorants. Olfactory bulb theta oscillations were also examined as a measure of effective afferent input strength, and the power of these oscillations did not vary systematically with vapor pressure, suggesting that it is not olfactory bulb drive strength that determines the presence of beta oscillations. Theta band coherence analysis shows that coupling strength between the olfactory bulb and piriform cortex increases linearly with vapor phase concentration, which may facilitate beta oscillations above a threshold.

Effects of nutritional status and cognitive ability on olfactory function in geriatric patients.

PubMed

Jin, Sung-Yong; Jeong, Hye Seon; Lee, Jin Woo; Kwon, Ki Ryun; Rha, Ki-Sang; Kim, Yong Min

2016-02-01

The aim of this study was to investigate the prevalence of olfactory dysfunction and evaluate the relationship between olfactory function and nutritional status, comorbidity, and the results of a neurocognitive test in geriatric patients who do not suffer from neurodegenerative disease. A total of 45 patients who visited the Geriatric Health Center of Chungnam National University Hospital were enrolled in this study. Olfactory function was assessed using a Korean Version of Sniffin' Stick Test II. Cognitive status of all participants was assessed with the MMSE-K (Korean version of the Mini-Mental State Examination). Nutritional status was assessed with body mass index, Mini-Nutritional Assessment (MNA), and serum total protein and albumin. A total of 45 participants were enrolled in this study. Of these subjects, 28 were men and 17 were women, with a mean age of 71.7±5.16 years. Nine (20%) were normosmia, 13 (28.9%) were hyposmia, and 23 (51.1%) were anosmia. Thirty-six patients (80%) suffered from olfactory dysfunction (anosmia or hyposmia). MMSE score showed significant correlation with MNA score. There were significant negative correlations between age and total TDI (threshold, discrimination, and identification) score, discrimination score, identification score, and MMSE score. MMSE score showed significant correlation with discrimination score and identification score. However, MNA score did not show any significant correlation with olfactory function test results. Although olfactory function was not influenced by nutritional status, abilities of discrimination and identification of odors were associated with cognitive function in geriatric patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Respective Role of the Dorsal Hippocampus and the Entorhinal Cortex during the Recombination of Previously Learned Olfactory-Tactile Associations in the Rat

ERIC Educational Resources Information Center

Boisselier, Lise; Ferry, Barbara; Gervais, Rémi

2017-01-01

The hippocampal formation has been extensively described as a key component for object recognition in conjunction with place and context. The present study aimed at describing neural mechanisms in the hippocampal formation that support olfactory-tactile (OT) object discrimination in a task where space and context were not taken into account. The…

Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with Different Surface Characteristics and Sizes in Excised Porcine Olfactory Epithelium.

PubMed

Mistry, Alpesh; Stolnik, Snjezana; Illum, Lisbeth

2015-08-03

The ability to deliver therapeutically relevant amounts of drugs directly from the nasal cavity to the central nervous system to treat neurological diseases is dependent on the availability of efficient drug delivery systems. Increased delivery and/or therapeutic effect has been shown for drugs encapsulated in nanoparticles; however, the factors governing the transport of the drugs and/or the nanoparticles from the nasal cavity to the brain are not clear. The present study evaluates the potential transport of nanoparticles across the olfactory epithelium in relation to nanoparticle characteristics. Model systems, 20, 100, and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS), were assessed for transport across excised porcine olfactory epithelium mounted in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the donor chamber of the diffusion cell, accompanied by fluorescence microscopy of dismounted tissues, revealed a loss of nanoparticle content from the donor suspension and their association with the excised tissue, depending on the surface properties and particle size. Chitosan surface modification of PS nanoparticles resulted in the highest tissue association among the tested systems, with the associated nanoparticles primarily located in the mucus, whereas the polysorbate 80-modified nanoparticles showed some penetration into the epithelial cell layer. Assessment of the bioelectrical properties, metabolic activity, and histology of the excised olfactory epithelium showed that C-PS nanoparticles applied in pH 6.0 buffer produced a damaging effect on the epithelial cell layer in a size-dependent manner, with fine 20 nm sized nanoparticles causing substantial tissue damage relative to that with the 100 and 200 nm counterparts. Although histology showed that the olfactory tissue was affected by the application of citrate buffer that was augmented by addition of chitosan in solution, this was not reflected in the bioelectrical parameters and the metabolic activity of the tissue. Regarding transport across the excised olfactory tissue, none of the nanoparticle systems tested, irrespective of particle size or surface modification, was transported across the epithelium to appear in measurable amounts in the receiver chamber.

The Multibasic Cleavage Site in H5N1 Virus Is Critical for Systemic Spread along the Olfactory and Hematogenous Routes in Ferrets

PubMed Central

Schrauwen, Eefje J. A.; Herfst, Sander; Leijten, Lonneke M.; van Run, Peter; Bestebroer, Theo M.; Linster, Martin; Bodewes, Rogier; Kreijtz, Joost H. C. M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.; Kuiken, Thijs

2012-01-01

The route by which highly pathogenic avian influenza (HPAI) H5N1 virus spreads systemically, including the central nervous system (CNS), is largely unknown in mammals. Especially, the olfactory route, which could be a route of entry into the CNS, has not been studied in detail. Although the multibasic cleavage site (MBCS) in the hemagglutinin (HA) of HPAI H5N1 viruses is a major determinant of systemic spread in poultry, the association between the MBCS and systemic spread in mammals is less clear. Here we determined the virus distribution of HPAI H5N1 virus in ferrets in time and space—including along the olfactory route—and the role of the MBCS in systemic replication. Intranasal inoculation with wild-type H5N1 virus revealed extensive replication in the olfactory mucosa, from which it spread to the olfactory bulb and the rest of the CNS, including the cerebrospinal fluid (CSF). Virus spread to the heart, liver, pancreas, and colon was also detected, indicating hematogenous spread. Ferrets inoculated intranasally with H5N1 virus lacking an MBCS demonstrated respiratory tract infection only. In conclusion, HPAI H5N1 virus can spread systemically via two different routes, olfactory and hematogenous, in ferrets. This systemic spread was dependent on the presence of the MBCS in HA. PMID:22278228

PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

PubMed

Mayanagi, Taira; Yasuda, Hiroki; Sobue, Kenji

2015-10-21

Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors. These abnormal behaviors are caused by impaired glutamatergic synapse transmission accompanied by tiny-headed immature dendritic spines in the PFC, due to aberrant Rap2 activation, which has roles in synapse formation and plasticity. PSD-Zip70 modulates the Rap2 activity by interacting with SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) in the postsynapse. Furthermore, suppression of the aberrant Rap2 activation in the PFC rescued the behavioral defects in PSD-Zip70KO mice. Our data demonstrate a critical role for PSD-Zip70 in Rap2-dependent spine synapse development in the PFC and underscore the importance of this regulation in PFC-dependent behaviors. PSD-Zip70 deficiency causes behavioral defects in working memory and cognition, and enhanced anxiety due to prefrontal hypofunction. This study revealed that PSD-Zip70 plays essential roles in glutamatergic synapse maturation via modulation of the Rap2 activity in the PFC. PSD-Zip70 interacts with both SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) and modulates the Rap2 activity in postsynaptic sites. Our results provide a novel Rap2-specific regulatory mechanism in synaptic maturation involving PSD-Zip70. Copyright © 2015 the authors 0270-6474/15/3514327-14$15.00/0.

The Anterior Thalamus is Critical for Overcoming Interference in a Context-Dependent Odor Discrimination Task

PubMed Central

Law, L. Matthew; Smith, David M.

2012-01-01

The anterior thalamus (AT) is anatomically interconnected with the hippocampus and other structures known to be involved in memory, and the AT is involved in many of the same learning and memory functions as the hippocampus. For example, like the hippocampus, the AT is involved in spatial cognition and episodic memory. The hippocampus also has a well-documented role in contextual memory processes, but it is not known whether the AT is similarly involved in contextual memory. In the present study, we assessed the role of the AT in contextual memory processes by temporarily inactivating the AT and training rats on a recently developed context-based olfactory list learning task, which was designed to assess the use of contextual information to resolve interference. Rats were trained on one list of odor discrimination problems, followed by training on a second list in either the same context or a different context. In order to induce interference, some of the odors appeared on both lists with their predictive value reversed. Control rats that learned the two lists in different contexts performed significantly better than rats that learned the two lists in the same context. However, AT lesions completely abolished this contextual learning advantage, a result that is very similar to the effects of hippocampal inactivation. These findings demonstrate that the AT, like the hippocampus, is involved in contextual memory and suggest that the hippocampus and AT are part of a functional circuit involved in contextual memory. PMID:23025833

Neurogenesis Inhibition Prevents Enriched Environment to Prolong and Strengthen Social Recognition Memory, But Not to Increase BDNF Expression.

PubMed

Pereira-Caixeta, Ana Raquel; Guarnieri, Leonardo O; Pena, Roberta R; Dias, Thomáz L; Pereira, Grace Schenatto

2017-07-01

Hippocampus-dependent memories, such as social recognition (SRM), are modulated by neurogenesis. However, the precise role of newborn neurons in social memory processing is still unknown. We showed previously that 1 week of enriched environment (EE) is sufficient to increase neurogenesis in the hippocampus (HIP) and the olfactory bulb (OB) of mice. Here, we tested the hypothesis that 1 week of EE would enhance SRM persistence and strength. In addition, as brain-derived neurotrophic factor (BDNF) may mediate some of the neurogenesis effects on memory, we also tested if 1 week of EE would increase BDNF expression in the HIP and OB. We also predicted that neurogenesis inhibition would block the gain of function caused by EE on both SRM and BDNF expression. We found that EE increased BDNF expression in the HIP and OB of mice; at the same time, it allowed SRM to last longer. In addition, mice on EE had their SRM unaffected by memory consolidation interferences. As we predicted, treatment with the anti-mitotic drug AraC blocked EE effects on SRM. Surprisingly, neurogenesis inhibition did not affect the BDNF expression, increased by EE. Together, our results suggest that newborn neurons improve SRM persistence through a BDNF-independent mechanism. Interestingly, this study on social memory uncovered an unexpected dissociation between the effect of adult neurogenesis and BDNF expression on memory persistence, reassuring the idea that not all neurogenesis effects on memory are BDNF-dependent.

The conserved, disease-associated RNA binding protein dNab2 interacts with the Fragile-X protein ortholog in Drosophila neurons

PubMed Central

Bienkowski, Rick S.; Banerjee, Ayan; Rounds, J. Christopher; Rha, Jennifer; Omotade, Omotola F.; Gross, Christina; Morris, Kevin J.; Leung, Sara W.; Pak, ChangHui; Jones, Stephanie K.; Santoro, Michael R.; Warren, Stephen T.; Zheng, James Q.; Bassell, Gary J.; Corbett, Anita H.; Moberg, Kenneth H.

2017-01-01

Summary The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA-binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with and the Fragile-X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory and their encoded proteins co-localize in puncta within neuronal processes. dNab2 regulates CaMKII but not futsch mRNA, implying a selective role in control of dFMRP-bound transcripts. Reciprocally, dFMRP and vertebrate FMRP restrict mRNA poly(A)-tail length similar to dNab2/ZC3H14. Parallel studies of murine hippocampal neurons indicate that ZC3H14 is also a cytoplasmic regulator of neuronal mRNAs. In sum these findings suggest that dNab2 represses expression of a subset of dFMRP-target mRNAs, which could underlie brain-specific defects in patients lacking ZC3H14. PMID:28793261

Neural correlates of olfactory learning paradigms in an identified neuron in the honeybee brain.

PubMed

Mauelshagen, J

1993-02-01

1. Sensitization and classical odor conditioning of the proboscis extension reflex were functionally analyzed by repeated intracellular recordings from a single identified neuron (PE1-neuron) in the central bee brain. This neuron belongs to the class of "extrinsic cells" arising from the pedunculus of the mushroom bodies and has extensive arborizations in the median and lateral protocerebrum. The recordings were performed on isolated bee heads. 2. Two different series of physiological experiments were carried out with the use of a similar temporal succession of stimuli as in previous behavioral experiments. In the first series, one group of animals was used for a single conditioning trial [conditioned stimulus (CS), carnation; unconditioned stimulus (US), sucrose solution to the antennae and proboscis), a second group was used for sensitization (sensitizing stimulus, sucrose solution to the antennae and/or proboscis), and the third group served as control (no sucrose stimulation). In the second series, a differential conditioning paradigm (paired odor CS+, carnation; unpaired odor CS-, orange blossom) was applied to test the associative nature of the conditioning effect. 3. The PE1-neuron showed a characteristic burstlike odor response before the training procedures. The treatments resulted in different spike-frequency modulations of this response, which were specific for the nonassociative and associative stimulus paradigms applied. During differential conditioning, there are dynamic up and down modulations of spike frequencies and of the DC potentials underlying the responses to the CS+. Overall, only transient changes in the minute range were observed. 4. The results of the sensitization procedures suggest two qualitatively different US pathways. The comparison between sensitization and one-trial conditioning shows differential effects of nonassociative and associative stimulus paradigms on the response behavior of the PE1-neuron. The results of the differential conditioning procedure reveal that the effect observed for the one-trial conditioning paradigm is of an associative nature and that there might be modulations, which are specific for single and multiple trial conditioning procedures. It is hypothesized that the PE1-neuron is a possible element involved in the short-term acquisition, rather than in the long-term storage, of an associative olfactory memory in the honeybee.

Peripheral and Central Olfactory Tuning in a Moth

PubMed Central

Ong, Rose C.

2012-01-01

Animals can be innately attracted to certain odorants. Because these attractants are particularly salient, they might be expected to induce relatively strong responses throughout the olfactory pathway, helping animals detect the most relevant odors but limiting flexibility to respond to other odors. Alternatively, specific neural wiring might link innately preferred odors to appropriate behaviors without a need for intensity biases. How nonpheromonal attractants are processed by the general olfactory system remains largely unknown. In the moth Manduca sexta, we studied this with a set of innately preferred host plant odors and other, neutral odors. Electroantennogram recordings showed that, as a population, olfactory receptor neurons (ORNs) did not respond with greater intensity to host plant odors, and further local field potential recordings showed that no specific amplification of signals induced by host plant odors occurred between the first olfactory center and the second. Moreover, when odorants were mutually diluted to elicit equally intense output from the ORNs, moths were able to learn to associate all tested odorants equally well with food reward. Together, these results suggest that, although nonpheromonal host plant odors activate broadly distributed responses, they may be linked to attractive behaviors mainly through specific wiring in the brain. PMID:22362866

Dop1 enhances conspecific olfactory attraction by inhibiting miR-9a maturation in locusts.

PubMed

Guo, Xiaojiao; Ma, Zongyuan; Du, Baozhen; Li, Ting; Li, Wudi; Xu, Lingling; He, Jing; Kang, Le

2018-03-22

Dopamine receptor 1 (Dop1) mediates locust attraction behaviors, however, the mechanism by which Dop1 modulates this process remains unknown to date. Here, we identify differentially expressed small RNAs associated with locust olfactory attraction after activating and inhibiting Dop1. Small RNA transcriptome analysis and qPCR validation reveal that Dop1 activation and inhibition downregulates and upregulates microRNA-9a (miR-9a) expression, respectively. miR-9a knockdown in solitarious locusts increases their attraction to gregarious volatiles, whereas miR-9a overexpression in gregarious locusts reduces olfactory attraction. Moreover, miR-9a directly targets adenylyl cyclase 2 (ac2), causing its downregulation at the mRNA and protein levels. ac2 responds to Dop1 and mediates locust olfactory attraction. Mechanistically, Dop1 inhibits miR-9a expression through inducing the dissociation of La protein from pre-miR-9a and resulting in miR-9a maturation inhibition. Our results reveal a Dop1-miR-9a-AC2 circuit that modulates locust olfactory attraction underlying aggregation. This study suggests that miRNAs act as key messengers in the GPCR signaling.

L1CAM/Neuroglian controls the axon–axon interactions establishing layered and lobular mushroom body architecture

PubMed Central

Siegenthaler, Dominique; Enneking, Eva-Maria; Moreno, Eliza

2015-01-01

The establishment of neuronal circuits depends on the guidance of axons both along and in between axonal populations of different identity; however, the molecular principles controlling axon–axon interactions in vivo remain largely elusive. We demonstrate that the Drosophila melanogaster L1CAM homologue Neuroglian mediates adhesion between functionally distinct mushroom body axon populations to enforce and control appropriate projections into distinct axonal layers and lobes essential for olfactory learning and memory. We addressed the regulatory mechanisms controlling homophilic Neuroglian-mediated cell adhesion by analyzing targeted mutations of extra- and intracellular Neuroglian domains in combination with cell type–specific rescue assays in vivo. We demonstrate independent and cooperative domain requirements: intercalating growth depends on homophilic adhesion mediated by extracellular Ig domains. For functional cluster formation, intracellular Ankyrin2 association is sufficient on one side of the trans-axonal complex whereas Moesin association is likely required simultaneously in both interacting axonal populations. Together, our results provide novel mechanistic insights into cell adhesion molecule–mediated axon–axon interactions that enable precise assembly of complex neuronal circuits. PMID:25825519

L1CAM/Neuroglian controls the axon-axon interactions establishing layered and lobular mushroom body architecture.

PubMed

Siegenthaler, Dominique; Enneking, Eva-Maria; Moreno, Eliza; Pielage, Jan

2015-03-30

The establishment of neuronal circuits depends on the guidance of axons both along and in between axonal populations of different identity; however, the molecular principles controlling axon-axon interactions in vivo remain largely elusive. We demonstrate that the Drosophila melanogaster L1CAM homologue Neuroglian mediates adhesion between functionally distinct mushroom body axon populations to enforce and control appropriate projections into distinct axonal layers and lobes essential for olfactory learning and memory. We addressed the regulatory mechanisms controlling homophilic Neuroglian-mediated cell adhesion by analyzing targeted mutations of extra- and intracellular Neuroglian domains in combination with cell type-specific rescue assays in vivo. We demonstrate independent and cooperative domain requirements: intercalating growth depends on homophilic adhesion mediated by extracellular Ig domains. For functional cluster formation, intracellular Ankyrin2 association is sufficient on one side of the trans-axonal complex whereas Moesin association is likely required simultaneously in both interacting axonal populations. Together, our results provide novel mechanistic insights into cell adhesion molecule-mediated axon-axon interactions that enable precise assembly of complex neuronal circuits. © 2015 Siegenthaler et al.

Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: a bold FMRI study.

PubMed

Lukas, Scott E; Lowen, Steven B; Lindsey, Kimberly P; Conn, Nina; Tartarini, Wendy; Rodolico, John; Mallya, Gopi; Palmer, Christopher; Penetar, David M

2013-09-01

Oral naltrexone reduces heavy drinking, but is less consistent as an abstinence promoter, whereas once-monthly extended-release naltrexone (XR-NTX) also maintains abstinence. The present study sought to determine if alcohol cue reactivity is attenuated by XR-NTX. Twenty-eight detoxified alcohol-dependent adult male and female volunteers received a single i.m. injection of either XR-NTX or placebo under double-blind conditions. An fMRI/cue reactivity procedure was conducted immediately before and two weeks after injection. At baseline, alcohol-related visual and olfactory cues elicited significant increases in orbital and cingulate gyri, inferior frontal and middle frontal gyri. Subsequently, brain activation was significantly altered in XR-NTX-treated individuals. These affected brain regions are associated with the integration of emotion, cognition, reward, punishment, and learning/memory, suggesting that XR-NTX attenuates the salience of alcohol-related cues. Such an effect on brain function may interrupt the processes associated with "slips" and relapse, which may account for XR-NTX's ability to maintain abstinence. Copyright © 2013 Elsevier Inc. All rights reserved.