Science.gov

Sample records for nucleus caudalis neurons

  1. Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats.

    PubMed

    Takehana, Shiori; Sekiguchi, Kenta; Inoue, Maki; Kubota, Yoshiko; Ito, Yukihiko; Yui, Kei; Shimazu, Yoshihito; Takeda, Mamoru

    2016-01-01

    Although a modulatory role has been reported for the red wine polyphenol resveratrol on several types of ion channels and excitatory synaptic transmission in the nervous system, the acute effects of resveratrol in vivo, particularly on nociceptive transmission of the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous resveratrol administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 18 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was inhibited by resveratrol (0.5-2 mg/kg, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. These inhibitory effects were reversed after approximately 20 min. The relative magnitude of inhibition by resveratrol of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. These results suggest that, in the absence of inflammatory or neuropathic pain, acute intravenous resveratrol administration suppresses trigeminal sensory transmission, including nociception, and so resveratrol may be used as a complementary and alternative medicine therapeutic agent for the treatment of trigeminal nociceptive pain, including hyperalgesia.

  2. Acute intravenous administration of dietary constituent theanine suppresses noxious neuronal transmission of trigeminal spinal nucleus caudalis in rats.

    PubMed

    Takehana, Shiori; Kubota, Yoshiko; Uotsu, Nobuo; Yui, Kei; Shimazu, Yoshihito; Takeda, Mamoru

    2017-03-15

    Theanine is a non-dietary amino acid linked to the modulation of synaptic transmission in the central nervous system, although the acute effects of theanine in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The present study investigated whether acute intravenous theanine administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 15 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats, and responses to non-noxious and noxious mechanical stimuli were analyzed. The mean firing frequency of SpVc WDR neurons in response to all mechanical stimuli was dose-dependently inhibited by theanine (10, 50, and 100mM, i.v.) with the maximum inhibition of discharge frequency reached within 5min. These inhibitory effects were reversed after approximately 10min. The relative magnitude of theanine's inhibition of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. Iontophoretic application of l-glutamate induced the mean firing frequency of SpVc WDR neuron responding to noxious mechanical stimulation was also inhibited by intravenous administration of 100mM theanine. These results suggest that acute intravenous theanine administration suppresses glutaminergic noxious synaptic transmission in the SpVc, implicating theanine as a potential complementary and alternative therapeutic agent for the treatment of trigeminal nociceptive pain.

  3. Nucleus caudalis lesioning: Case report of chronic traumatic headache relief

    PubMed Central

    Sandwell, Stephen E.; El-Naggar, Amr O.

    2011-01-01

    Background: The nucleus caudalis dorsal root entry zone (DREZ) surgery is used to treat intractable central craniofacial pain. This is the first journal publication of DREZ lesioning used for the long-term relief of an intractable chronic traumatic headache. Case Description: A 40-year-old female experienced new-onset bi-temporal headaches following a traumatic head injury. Despite medical treatment, her pain was severe on over 20 days per month, 3 years after the injury. The patient underwent trigeminal nucleus caudalis DREZ lesioning. Bilateral single-row lesions were made at 1-mm interval between the level of the obex and the C2 dorsal nerve roots, using angled radiofrequency electrodes, brought to 80°C for 15 seconds each, along a path 1 to 1.2 mm posterior to the accessory nerve rootlets. The headache improved, but gradually returned. Five years later, her headaches were severe on over 24 days per month. The DREZ surgery was then repeated. Her headaches improved and the relief has continued for 5 additional years. She has remained functional, with no limitation in instrumental activities of daily living. Conclusions: The nucleus caudalis DREZ surgery brought long-term relief to a patient suffering from chronic traumatic headache. PMID:22059123

  4. Inflammation enhanced brain-derived neurotrophic factor-induced suppression of the voltage-gated potassium currents in small-diameter trigeminal ganglion neurons projecting to the trigeminal nucleus interpolaris/caudalis transition zone.

    PubMed

    Takeda, M; Takahashi, M; Matsumoto, S

    2014-03-07

    We recently indicated that brain-derived neurotrophic factor (BDNF) enhances the excitability of small-diameter trigeminal ganglion (TRG) neurons projecting onto the trigeminal nucleus interpolaris/caudalis (Vi/Vc) transition zone via a paracrine mechanism following masetter muscle (MM) inflammation. The present study investigated whether modulation of voltage-gated potassium (K) channels by BDNF contributes to this hyperexcitability effect. To induce inflammation we injected complete Freund's adjuvant (CFA) into the MM. The escape threshold from mechanical stimulation applied to skin above the inflamed MM was significantly lower than in naïve rats. TRG neurons innervating the site of inflammation were subsequently identified by fluorogold (FG) labeling, and microbeads (MB) were used to label neurons projecting specifically to the Vi/Vc region. BDNF significantly decreased the total, transient (IA), and sustained (IK) currents in FG-/MB-labeled small-diameter TRG neurons under voltage-clamp conditions in naïve and inflamed rats. The magnitude of inhibition of IA and IK currents by BDNF in FG-/MB-labeled TRG neurons was significantly greater in inflamed rats than in naïve rats, and BDNF inhibited IA to a significantly greater extent than IK. Furthermore, co-administration of K252a, a tyrosine kinase inhibitor, abolished the suppression of IA and IK currents by BDNF. These results suggested that the inhibitory effects of BDNF on IA and IK currents in small-diameter TRG neurons projecting onto the Vi/Vc potentiate neuronal excitability, and in turn, contribute to MM inflammatory hyperalgesia. These findings support the development of voltage-gated K(+) channel openers and tyrosine kinase inhibitors as potential therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia.

  5. Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats.

    PubMed

    Hegarty, Deborah M; Hermes, Sam M; Largent-Milnes, Tally M; Aicher, Sue A

    2014-11-01

    We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings.

  6. Differential effects of the cannabinoid receptor agonist, WIN 55,212-2, on lamina I and lamina V spinal trigeminal nucleus caudalis neurons

    PubMed Central

    Ogawa, Akiko; Meng, Ian D.

    2009-01-01

    Direct application of cannabinoids to the medullary dorsal horn (MDH) inhibits lamina V nociceptive neurons. The present study compared the effect of the cannabinoid receptor agonist, WIN 55,212-2 (WIN-2) on the activity of lamina I and lamina V MDH neurons using extracellular single unit recording in anesthetized rats. Activity evoked by a contact thermode was measured before and after local application of WIN-2 (0.5-2.0 μg/μl) to the brainstem. Fast and slow heat ramps were used to differentiate between activity evoked primarily by A-delta and C primary afferent fibers, respectively. In lamina V neurons, WIN-2 produced a concentration dependent decrease in activity evoked by both fast and slow heat, reaching significance at 1.0 μg/μl. In lamina I neurons, WIN-2 administration inhibited slow heat evoked activity beginning at 1.0 μg/μl but had no significant effect on fast heat evoked activity, even at the highest concentration (2.0 μg/μl). In separate experiments, the effect of intrathecal administration of WIN-2 to the MDH on head withdrawal latencies elicited by fast and slow heat ramps applied to the whisker pad was assessed in lightly anesthetized rats. Head withdrawal latencies elicited by slow but not fast heat stimulation were increased by WIN-2. Taken together, these results emphasize the importance of lamina I neurons in the control of a nociceptive heat-evoked reflex. PMID:19114295

  7. Eye Movements and Abducens Motoneuron Behavior after Cholinergic Activation of the Nucleus Reticularis Pontis Caudalis

    PubMed Central

    Márquez-Ruiz, Javier; Escudero, Miguel

    2010-01-01

    Study Objectives: The aim of this work was to characterize eye movements and abducens (ABD) motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis (NRPC). Methods: Six female adult cats were prepared for chronic recording of eye movements (using the scleral search-coil technique), electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves in the lateral geniculate nucleus, and ABD motoneuron activities after microinjections of the cholinergic agonist carbachol into the NRPC. Results: Unilateral microinjections of carbachol in the NRPC induced tonic and phasic phenomena in the oculomotor system. Tonic effects consisted of ipsiversive rotation to the injected side, convergence, and downward rotation of the eyes. Phasic effects consisted of bursts of rhythmic rapid eye movements directed contralaterally to the injected side along with PGO-like waves in the lateral geniculate and ABD nuclei. Although tonic effects were dependent on the level of drowsiness, phasic effects were always present and appeared along with normal saccades when the animal was vigilant. ABD motoneurons showed phasic activities associated with ABD PGO-like waves during bursts of rapid eye movements, and tonic and phasic activities related to eye position and velocity during alertness. Conclusion The cholinergic activation of the NRPC induces oculomotor phenomena that are somewhat similar to those described during REM sleep. A precise comparison of the dynamics and timing of the eye movements further suggests that a temporal organization of both NRPCs is needed to reproduce the complexity of the oculomotor behavior during REM sleep. Citation: Márquez-Ruiz J; Escudero M. Eye movements and abducens motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis. SLEEP 2010;33(11):1517-1527. PMID:21102994

  8. ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue

    PubMed Central

    Nakaya, Yuka; Tsuboi, Yoshiyuki; Okada-Ogawa, Akiko; Shinoda, Masamichi; Kubo, Asako; Chen, Jui Yen; Noma, Noboru; Batbold, Dulguun; Imamura, Yoshiki; Sessle, Barry J

    2016-01-01

    Background Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. Results The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of

  9. The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

    PubMed

    Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

    2016-04-01

    It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory.

  10. The non-peptide neurokinin-1 antagonist, RPR 100893, decreases c-fos expression in trigeminal nucleus caudalis following noxious chemical meningeal stimulation.

    PubMed

    Cutrer, F M; Moussaoui, S; Garret, C; Moskowitz, M A

    1995-02-01

    The effect of RPR 100893, a selective and specific neurokinin-1 antagonist, or its enantiomer RPR 103253 was examined on c-fos antigen expression in brain stem and upper cervical cord 2 h after intracisternal capsaicin injection (30.5 micrograms/ml) in pentobarbital-anesthetized Hartley guinea-pigs. Positive cells were counted at three levels corresponding to obex, -2.25 mm and -6.75 mm in 18 sections (50 microns). Immunoreactivity was strongly expressed within laminae I and IIo of trigeminal nucleus caudalis, area postrema and the leptomeninges. Moderate labeling was present in the nucleus of the solitary tract and the medullary lateral reticular nucleus, whereas few positive cells were found in the ventral portion of the medullary reticular nucleus and Rexed laminae III-V and X. The distribution of labeled cells was consistent with previously reported results following subarachnoid placement of the noxious agents, blood or carrageenin. Pretreatment with RPR 100893 (1, 10 and 100 micrograms/kg, i.v.) but not its enantiomer (100 micrograms/kg, i.v.) 30 min prior to capsaicin injection significantly reduced the number of positive cells in the trigeminal nucleus caudalis (P < 0.01) in a dose-dependent manner, but not within area postrema or nucleus of the solitary tract. These results indicate that (i) the instillation of capsaicin into the subarachnoid space is an effective stimulus for the induction of c-fos antigen within trigeminal nucleus caudalis, presumably through activation of trigeminovascular afferents, and (ii) the neurokinin-1 antagonist RPR 100893 reduces the number of positive cells selectively within this nucleus. The findings are significant because drugs which alleviate vascular headaches decrease the number of c-fos-positive cells within trigeminal nucleus caudalis following noxious meningeal stimulation. Hence, strategies aimed at blocking the neurokinin-1 receptor may be useful for treating migraine and cluster headache.

  11. Cross-desensitization of responses of rat trigeminal subnucleus caudalis neurons to cinnamaldehyde and menthol

    PubMed Central

    Zanotto, Karen L.; Iodi Carstens, M.; Carstens, E.

    2008-01-01

    Most cold-sensitive subnucleus caudalis (Vc) neurons are also excited by the TRPM8 agonist menthol and the TRPA1 agonist cinnamaldehyde (CA). We investigated how interactions among menthol, CA and noxious cooling and heating of the tongue affected responses of superficial Vc units recorded in thiopental-anesthetized rats. Units responded to 1% CA which enhanced cold- and heat-evoked responses 5 min later. They responded more strongly to 10% CA which initially depressed cold responses, followed by enhancement at 5 min without affecting responses to heat. Following 10% CA, the mean response to 1% menthol was significantly lower than when menthol was tested first. After menthol, the subsequent response to CA was significantly weaker compared to the mean CA-evoked response when it was tested first. These results demonstrate mutual cross-desensitization between CA and menthol. The response to CA was enhanced following prior application of 10% ethanol (menthol vehicle). Prior application of menthol did not prevent the biphasic effect of 10% CA on cold-evoked responses, nor did prior application of CA prevent menthol enhancement of cold-evoked responses. Responses to noxious heat were unaffected by 10% CA and menthol regardless of the order of chemical presentation. These data indicate that superficial Vc neurons receive convergent input from primary afferents expressing TRPM8 and TRPA1. The mutual cross-desensitization between CA and menthol, and differential modulation of cold- vs. heat-evoked responses, suggests a direct inhibition of TRPM8 and TRPA1 expressed in peripheral nerve endings by CA and menthol, respectively, rather than a central site of interaction. PMID:18060696

  12. The role of trigeminal nucleus caudalis orexin 1 receptor in orofacial pain-induced anxiety in rat.

    PubMed

    Bahaaddini, Mehri; Khatamsaz, Saeed; Esmaeili-Mahani, Saeed; Abbasnejad, Mehdi; Raoof, Maryam

    2016-10-19

    The relationship between anxiety and pain has received special attention. Orexins (A and B) are hypothalamic neuropeptides that have diverse functions in the regulation of different physiological and behavioral responses. This study was designed to evaluate the role of orexin 1 receptors (OX1R) within trigeminal nucleus caudalis (TNC) in anxiety following the induction of orofacial pain. The subcutaneous injection of capsaicin (CAP) into the rat upper lip region produced pain responses. OX1R agonist (orexin A) and antagonist (SB-334867) were microinjected into the TNC before the administration of CAP. Anxiety behaviors were investigated using elevated plus maze (EPM) and open-field tests. The results showed that CAP injection significantly decreases the percentage of time spent in the open arms of the EPM and the time spent in the center of the open field. Surprisingly, orexin (50, 100, and 150 pM/rat) significantly exaggerated the CAP effects, whereas SB-334867 (20, 40 nM/rat) significantly inhibited the CAP-induced anxiety. The CAP-injected group showed a significant decrease in the percentage of entries to open arms in the EPM and the number of visits in the center area of the open field compared with the control group. Orexin significantly potentiated the mentioned effects of CAP, whereas SB-334867 (40, 80 nM/rat) exerted a significant inhibitory effect on CAP-induced anxiety. The overall results indicated that the TNC OX1Rs play an important role in orofacial pain-induced anxiety.

  13. Functional expression of 5-HT7 receptor on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice.

    PubMed

    Yang, Eun Ju; Han, Seong Kyu; Park, Soo Joung

    2013-10-25

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc; medullary dorsal horn) receives and processes orofacial nociceptive inputs, and serotonergic fibers involved in the descending modulation of nociception are more densely distributed in the superficial laminae of the Vc. This study investigated the direct effects of 5-HT1A/7 receptor agonist 8-OH-DPAT on SG neurons of the Vc to assess functional expression of the 5-HT7 receptor using gramicidin-perforated patch-clamp in postnatal day (PND) 5-84 male mice. Of the 70 SG neurons tested, bath application of 8-OH-DPAT (30μM) induced depolarization (n=33), hyperpolarization (n=16) or no response (n=21). In another 10 SG neurons, 8-OH-DPAT in the presence of 5-HT1A receptor antagonist WAY-100635 (1μM) elicited either depolarization (n=6) or no response (n=4); hyperpolarization was not observed. The 8-OH-DPAT-induced depolarization was significantly blocked by the selective 5-HT7 receptor antagonist SB-269970 (10μM; n=8), but not by WAY-100635 (1μM; n=5). The depolarizing effect of 8-OH-DPAT was maintained in the presence of TTX, CNQX, AP5, picrotoxin, and strychnine, indicating direct postsynaptic action of 8-OH-DPAT on SG neurons (n=6). 5-HT7 receptor mRNA was also detected in five of 21 SG neurons by single-cell RT-PCR. The mean amplitude of 8-OH-DPAT-induced depolarization in PND 5-21 mice (n=21) was significantly larger than that in PND 22-84 mice (n=12), although the proportion of SG neurons responding to 8-OH-DPAT by depolarization did not differ significantly between two age groups of mice. These results indicate that 5-HT7 receptors are functionally expressed in a subpopulation of SG neurons of the Vc and activation of 5-HT7 receptors plays an important role in modulating orofacial nociceptive processing in the SG neurons of the Vc.

  14. The effect of capsaicin on expression patterns of CGRP in trigeminal ganglion and trigeminal nucleus caudalis following experimental tooth movement in rats

    PubMed Central

    ZHOU, Yang; LONG, Hu; YE, Niansong; LIAO, Lina; YANG, Xin; JIAN, Fan; WANG, Yan; LAI, Wenli

    2016-01-01

    ABSTRACT Objectives The aim of this study was to explore the effect of capsaicin on expression patterns of calcitonin gene-related peptide (CGRP) in the trigeminal ganglion (TG) and trigeminal subnucleus caudalis (Vc) following experimental tooth movement. Material and Methods Male Sprague-Dawley rats were used in this study and divided into small-dose capsaicin+force group, large-dose capsaicin+force group, saline+force group, and no force group. Closed coil springs were used to mimic orthodontic forces in all groups except for the no force group, in which springs were inactivated. Capsaicin and saline were injected into periodontal tissues. Rats were euthanized at 0 h, 12 h, 1 d, 3 d, 5 d, and 7 d following experimental tooth movement. Then, TG and Vc were obtained for immunohistochemical staining and western blotting against CGRP. Results Immunohistochemical results indicated that CGRP positive neurons were located in the TG, and CGRP immunoreactive fibers were distributed in the Vc. Immunohistochemical semiquantitative analysis and western blotting analysis demonstrated that CGRP expression levels both in TG and Vc were elevated at 12 h, 1 d, 3 d, 5 d, and 7 d in the saline + force group. However, both small-dose and large-dose capsaicin could decrease CGRP expression in TG and Vc at 1 d and 3 d following experimental tooth movement, as compared with the saline + force group. Conclusions These results suggest that capsaicin could regulate CGRP expression in TG and Vc following experimental tooth movement in rats. PMID:28076465

  15. Activation of glycine and extrasynaptic GABA(A) receptors by taurine on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis.

    PubMed

    Nguyen, Thi Thanh Hoang; Bhattarai, Janardhan Prasad; Park, Soo Joung; Han, Seong Kyu

    2013-01-01

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC) with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10  μM to 3 mM) showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3  μM and 723  μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50  μM) and almost completely blocked by strychnine (2  μM), suggesting that taurine-mediated responses are via glycine receptor (GlyR) activation. In addition, taurine (1 mM) activated extrasynaptic GABA(A) receptor (GABA(A)R)-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABA(A)Rs on the SG neurons.

  16. Effect of persistent monoarthritis of the temporomandibular joint region on acute mustard oil-induced excitation of trigeminal subnucleus caudalis neurons in male and female rats.

    PubMed

    Bereiter, David A; Okamoto, Keiichiro; Bereiter, Dominique F

    2005-09-01

    The effect of persistent inflammation of the temporomandibular (TMJ) region on Fos-like immunoreactivity (Fos-LI) evoked by acute noxious stimulation of the same or opposite TMJ was assessed in male and cycling female rats. Two weeks after inflammation of the TMJ by complete Freund's adjuvant (CFA, 25 microg) the selective small fiber excitant, mustard oil (MO, 20%), was injected into the arthritic or opposite TMJ under barbiturate anesthesia. MO stimulation of the arthritic TMJ increased Fos-LI ipsilateral, but not contralateral, to MO compared to naïve subjects in superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C2) junction independent of sex hormone status. Unexpectedly, MO stimulation of the opposite TMJ in arthritic rats also produced a greater Fos-LI response ipsilateral to MO than naïve animals. Fos-LI produced in the dorsal paratrigeminal region (dPa5) and Vc/C2 junction after MO stimulation of the normal TMJ was significantly greater in proestrous than diestrous females or male monoarthritic rats. In contrast to naïve animals, Fos-LI was produced in deep laminae at the Vc/C2 junction ipsilateral to MO in CFA-treated animals independent of the site of prior CFA inflammation or sex hormone status. These results indicated that persistent monoarthritis of the TMJ region enhanced the excitability of trigeminal brainstem neurons to subsequent TMJ injury that occurred bilaterally in multiple regions of the lower trigeminal brainstem complex and depended on sex hormone status.

  17. Subthalamic Nucleus Stimulation Modulates Thalamic Neuronal Activity

    PubMed Central

    Xu, Weidong; Russo, Gary S.; Hashimoto, Takao; Zhang, Jianyu; Vitek, Jerrold L.

    2009-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is an effective tool for the treatment of advanced Parkinson’s disease. The mechanism by which STN DBS elicits its beneficial effect, however, remains unclear. We previously reported STN stimulation increased the rate and produced a more regular and periodic pattern of neuronal activity in the internal segment of the globus pallidus (GPi). Here we extend our observations to neurons in the pallidal (ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)) and cerebellar (ventralis lateralis posterior pars oralis (VPLo)) receiving areas of the motor thalamus during STN DBS. Stimulation parameters that produced improvement in rigidity and bradykinesia resulted in changes in the pattern and power of oscillatory activity of neuronal activity that were similar in both regions of the motor thalamus. Neurons in both VA/VLo and VPLo tended to become more periodic and regular with a shift in oscillatory activity from low to high frequencies. Burst activity was reduced in VA/VLo, but was not significantly changed in VPLo. There was also a significant shift in the population of VA/VLo neurons that were inhibited during STN DBS, while VPLo neurons tended to be activated. These data are consistent with the hypothesis that STN DBS increases output from the nucleus and produces a change in the pattern and periodicity of neuronal activity in the basal ganglia thalamic network, and that these changes include cerebellar pathways likely via activation of adjacent cerebello-thalamic fiber bundles. PMID:19005057

  18. Calretinin Neurons in the Rat Suprachiasmatic Nucleus.

    PubMed

    Moore, Robert Y

    2016-08-01

    The hypothalamic suprachiasmatic nucleus (SCN), a circadian pacemaker, is present in all mammalian brains. It has a complex organization of peptide-containing neurons that is similar among species, but calcium-binding proteins are expressed variably. Neurons containing calretinin have been described in the SCN in a number of species but not with association to circadian function. The objective of the present study is to characterize a calretinin neuron (CAR) group in the rat anterior hypothalamus anatomically and functionally with a detailed description of its location and a quantitative analysis of neuronal calretinin immunoreactivity at 3 times of day, 0600, 1400, and 1900 h, from animals in either light-dark or constant dark conditions. CAR neurons occupy a region in the dorsal and lateral SCN with a circadian rhythm in CAR immunoreactivity with a peak at 0600 h and a rhythm in cytoplasmic CAR distribution with a peak at 1400 h. CAR neurons should be viewed as an anatomical and functional component of the rat SCN that expands the definition from observations with cell stains. CAR neurons are likely to modulate temporal regulation of calcium in synaptic transmission.

  19. The topography of regio caudalis hypothalami in goose (Anser anser F. domestica).

    PubMed

    Rehák, P; Kostová, D; Boda, K

    1986-01-01

    We studied the topography of the caudal hypothalamic region of the goose on brain sections stained with luxol fast blue and cresyl violet in combination according to Klüver-Barrera (1953), or with cresyl violet (Nissl method). In the regio caudalis hypothalami of this bird we identified in agreement with Nomina anatomica avium (Breazile 1979): nucleus premamillaris (PM), nucleus mamillaris lateralis (ML), nucleus mamillaris medialis (MM), nucleus supramamillaris interstitialis (SMI) and nucleus intercalatus (Ic).

  20. Comparing Realistic Subthalamic Nucleus Neuron Models

    NASA Astrophysics Data System (ADS)

    Njap, Felix; Claussen, Jens C.; Moser, Andreas; Hofmann, Ulrich G.

    2011-06-01

    The mechanism of action of clinically effective electrical high frequency stimulation is still under debate. However, recent evidence points at the specific activation of GABA-ergic ion channels. Using a computational approach, we analyze temporal properties of the spike trains emitted by biologically realistic neurons of the subthalamic nucleus (STN) as a function of GABA-ergic synaptic input conductances. Our contribution is based on a model proposed by Rubin and Terman and exhibits a wide variety of different firing patterns, silent, low spiking, moderate spiking and intense spiking activity. We observed that most of the cells in our network turn to silent mode when we increase the GABAA input conductance above the threshold of 3.75 mS/cm2. On the other hand, insignificant changes in firing activity are observed when the input conductance is low or close to zero. We thus reproduce Rubin's model with vanishing synaptic conductances. To quantitatively compare spike trains from the original model with the modified model at different conductance levels, we apply four different (dis)similarity measures between them. We observe that Mahalanobis distance, Victor-Purpura metric, and Interspike Interval distribution are sensitive to different firing regimes, whereas Mutual Information seems undiscriminative for these functional changes.

  1. Serotonin neurons in the dorsal raphe nucleus encode reward signals

    PubMed Central

    Li, Yi; Zhong, Weixin; Wang, Daqing; Feng, Qiru; Liu, Zhixiang; Zhou, Jingfeng; Jia, Chunying; Hu, Fei; Zeng, Jiawei; Guo, Qingchun; Fu, Ling; Luo, Minmin

    2016-01-01

    The dorsal raphe nucleus (DRN) is involved in organizing reward-related behaviours; however, it remains unclear how genetically defined neurons in the DRN of a freely behaving animal respond to various natural rewards. Here we addressed this question using fibre photometry and single-unit recording from serotonin (5-HT) neurons and GABA neurons in the DRN of behaving mice. Rewards including sucrose, food, sex and social interaction rapidly activate 5-HT neurons, but aversive stimuli including quinine and footshock do not. Both expected and unexpected rewards activate 5-HT neurons. After mice learn to wait for sucrose delivery, most 5-HT neurons fire tonically during waiting and then phasically on reward acquisition. Finally, GABA neurons are activated by aversive stimuli but inhibited when mice seek rewards. Thus, DRN 5-HT neurons positively encode a wide range of reward signals during anticipatory and consummatory phases of reward responses. Moreover, GABA neurons play a complementary role in reward processing. PMID:26818705

  2. Glycine immunoreactivity of multipolar neurons in the ventral cochlear nucleus which project to the dorsal cochlear nucleus.

    PubMed

    Doucet, J R; Ross, A T; Gillespie, M B; Ryugo, D K

    1999-06-14

    Certain distinct populations of neurons in the dorsal cochlear nucleus are inhibited by a neural source that is responsive to a wide range of acoustic frequencies. In this study, we examined the glycine immunoreactivity of two types of ventral cochlear nucleus neurons (planar and radiate) in the rat which project to the dorsal cochlear nucleus (DCN) and thus, might be responsible for this inhibition. Previously, we proposed that planar neurons provided a tonotopic and narrowly tuned input to the DCN, whereas radiate neurons provided a broadly tuned input and thus, were strong candidates as the source of broadband inhibition (Doucet and Ryugo [1997] J. Comp. Neurol. 385:245-264). We tested this idea by combining retrograde labeling and glycine immunohistochemical protocols. Planar and radiate neurons were first retrogradely labeled by injecting biotinylated dextran amine into a restricted region of the dorsal cochlear nucleus. The labeled cells were visualized using streptavidin conjugated to indocarbocyanine (Cy3), a fluorescent marker. Sections that contained planar or radiate neurons were then processed for glycine immunocytochemistry using diaminobenzidine as the chromogen. Immunostaining of planar neurons was light, comparable to that of excitatory neurons (pyramidal neurons in the DCN), whereas immunostaining of radiate neurons was dark, comparable to that of glycinergic neurons (cartwheel cells in the dorsal cochlear nucleus and principal cells in the medial nucleus of the trapezoid body). These results are consistent with the hypothesis that radiate neurons in the ventral cochlear nucleus subserve the wideband inhibition observed in the dorsal cochlear nucleus.

  3. Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens.

    PubMed

    Tecuapetla, Fatuel; Patel, Jyoti C; Xenias, Harry; English, Daniel; Tadros, Ibrahim; Shah, Fulva; Berlin, Joshua; Deisseroth, Karl; Rice, Margaret E; Tepper, James M; Koos, Tibor

    2010-05-19

    Recent evidence suggests the intriguing possibility that midbrain dopaminergic (DAergic) neurons may use fast glutamatergic transmission to communicate with their postsynaptic targets. Because of technical limitations, direct demonstration of the existence of this signaling mechanism has been limited to experiments using cell culture preparations that often alter neuronal function including neurotransmitter phenotype. Consequently, it remains uncertain whether glutamatergic signaling between DAergic neurons and their postsynaptic targets exists under physiological conditions. Here, using an optogenetic approach, we provide the first conclusive demonstration that mesolimbic DAergic neurons in mice release glutamate and elicit excitatory postsynaptic responses in projection neurons of the nucleus accumbens. In addition, we describe the properties of the postsynaptic glutamatergic responses of these neurons during experimentally evoked burst firing of DAergic axons that reproduce the reward-related phasic population activity of the mesolimbic projection. These observations indicate that, in addition to DAergic mechanisms, mesolimbic reward signaling may involve glutamatergic transmission.

  4. Glutamatergic Signaling by Mesolimbic Dopamine Neurons in the Nucleus Accumbens

    PubMed Central

    Tecuapetla, Fatuel; Patel, Jyoti C.; Xenias, Harry; English, Daniel; Tadros, Ibrahim; Shah, Fulva; Berlin, Joshua; Deisseroth, Karl; Rice, Margaret E.; Tepper, James M.

    2010-01-01

    Recent evidence suggests the intriguing possibility that midbrain dopaminergic (DAergic) neurons may use fast glutamatergic transmission to communicate with their postsynaptic targets. Because of technical limitations, direct demonstration of the existence of this signaling mechanism has been limited to experiments using cell culture preparations that often alter neuronal function including neurotransmitter phenotype. Consequently, it remains uncertain whether glutamatergic signaling between DAergic neurons and their postsynaptic targets exists under physiological conditions. Here, using an optogenetic approach, we provide the first conclusive demonstration that mesolimbic DAergic neurons in mice release glutamate and elicit excitatory postsynaptic responses in projection neurons of the nucleus accumbens. In addition, we describe the properties of the postsynaptic glutamatergic responses of these neurons during experimentally evoked burst firing of DAergic axons that reproduce the reward-related phasic population activity of the mesolimbic projection. These observations indicate that, in addition to DAergic mechanisms, mesolimbic reward signaling may involve glutamatergic transmission. PMID:20484653

  5. Neuronal Complexity in Subthalamic Nucleus is Reduced in Parkinson's Disease.

    PubMed

    Vyas, Saurabh; Huang, He; Gale, John T; Sarma, Sridevi V; Montgomery, Erwin B

    2016-01-01

    Several theories posit increased Subthalamic Nucleus (STN) activity is causal to Parkinsonism, yet in our previous study we showed that activity from 113 STN neurons from two epilepsy patients and 103 neurons from nine Parkinson's disease (PD) patients demonstrated no significant differences in frequencies or in the coefficients of variation of mean discharge frequencies per 1-s epochs. We continued our analysis using point process modeling to capture higher order temporal dynamics; in particular, bursting, beta-band oscillations, excitatory and inhibitory ensemble interactions, and neuronal complexity. We used this analysis as input to a logistic regression classifier and were able to differentiate between PD and epilepsy neurons with an accuracy of 92%. We also found neuronal complexity, i.e., the number of states in a neuron's point process model, and inhibitory ensemble dynamics, which can be interpreted as a reduction in complexity, to be the most important features with respect to classification accuracy. Even in a dataset with no significant differences in firing rate, we observed differences between PD and epilepsy for other single-neuron measures. Our results suggest PD comes with a reduction in neuronal "complexity," which translates to a neuron's ability to encode information; the more complexity, the more information the neuron can encode. This is also consistent with studies correlating disease to loss of variability in neuronal activity, as the lower the complexity, the less variability.

  6. Developmental Changes in Synaptic Distribution in Arcuate Nucleus Neurons

    PubMed Central

    Kirigiti, Melissa A.; Baquero, Karalee C.; Lee, Shin J.; Smith, M. Susan; Grove, Kevin L.

    2015-01-01

    Neurons coexpressing neuropeptide Y, agouti-related peptide, and GABA (NAG) play an important role in ingestive behavior and are located in the arcuate nucleus of the hypothalamus. NAG neurons receive both GABAergic and glutamatergic synaptic inputs, however, the developmental time course of synaptic input organization of NAG neurons in mice is unknown. In this study, we show that these neurons have low numbers of GABAergic synapses and that GABA is inhibitory to NAG neurons during early postnatal period. In contrast, glutamatergic inputs onto NAG neurons are relatively abundant by P13 and are comparatively similar to the levels observed in the adult. As mice reach adulthood (9–10 weeks), GABAergic tone onto NAG neurons increases. At this age, NAG neurons received similar numbers of inhibitory and EPSCs. To further differentiate age-associated changes in synaptic distribution, 17- to 18-week-old lean and diet-induced obesity (DIO) mice were studied. Surprisingly, NAG neurons from lean adult mice exhibit a reduction in the GABAergic synapses compared with younger adults. Conversely, DIO mice display reductions in the number of GABAergic and glutamatergic inputs onto NAG neurons. Based on these experiments, we propose that synaptic distribution in NAG neurons is continuously restructuring throughout development to accommodate the animals' energy requirements. PMID:26041922

  7. Response Properties of Cochlear Nucleus Neurons in Monkeys

    PubMed Central

    Roth, G. Linn; Recio, A.

    2009-01-01

    Much of what is known about how the cochlear nuclei participate in mammalian hearing comes from studies of non-primate mammalian species. To determine to what extent the cochlear nuclei of primates resemble those of other mammalian orders, we have recorded responses to sound in three primate species: marmosets, Cynomolgus macaques, and squirrel monkeys. These recordings show that the same types of temporal firing patterns are found in primates that have been described in other mammals. Responses to tones of neurons in the ventral cochlear nucleus have similar tuning, latencies, post-stimulus time and interspike interval histograms as those recorded in non-primate cochlear nucleus neurons. In the dorsal cochlear nucleus, too, responses were similar. From these results it is evident that insights gained from non-primate studies can be applied to the peripheral auditory system of primates. PMID:19531377

  8. Isoperiodic neuronal activity in suprachiasmatic nucleus of the rat

    NASA Technical Reports Server (NTRS)

    Miller, J. D.; Fuller, C. A.

    1992-01-01

    A subpopulation of neurons in the suprachiasmatic nucleus (SCN) is shown here to exhibit isoperiodic bursting activity. The period of discharge in these cells may be lengthened or the periodicity may be transiently disrupted by photic stimulation. It is suggested that many, if not all, of these cells are vasoactive intestinal polypeptide (VIP) neurons. It is shown that the ultradian periodicity of these cells, estimates of the VIP neuron population size in the SCN, effects of partial lesions on tau (period), and estimates of the phase stability of SCN-driven circadian rhythms are consistent with a strongly coupled, multioscillator model of circadian rhythmicity, in which the oscillator population constitutes a restricted subset of the SCN neuronal population.

  9. Subthalamic nucleus neuronal activity in Parkinson's disease and epilepsy subjects.

    PubMed

    Montgomery, Erwin B

    2008-01-01

    Activity from 113 subthalamic nucleus (STN) neurons from two epilepsy patients and 103 neurons from 9 Parkinson's disease (PD) patients undergoing DBS surgery showed no significant differences in frequencies (PD, mean 7.5+/-7.0 spikes/s (sps), epilepsy mean 7.8+/-8.5 sps) or in the coefficients of variation of mean discharge frequencies per 1s epochs. A striking relationship between mean discharge frequencies per 1 s epochs and the standard deviations for both groups were consistent with a random Poisson processes. These and similar findings call into question theories that posit increased STN activity is causal to parkinsonism.

  10. Heterogeneity of firing properties among rat thalamic reticular nucleus neurons

    PubMed Central

    Lee, Sang-Hun; Govindaiah, G; Cox, Charles L

    2007-01-01

    The thalamic reticular nucleus (TRN) provides inhibitory innervation to most thalamic relay nuclei and receives excitatory innervation from both cortical and thalamic neurons. Ultimately, information transfer through the thalamus to the neocortex is strongly influenced by TRN. In addition, the reciprocal synaptic connectivity between TRN with associated thalamic relay nuclei is critical in generating intrathalamic rhythmic activities that occur during certain arousal states and pathophysiological conditions. Despite evidence suggesting morphological heterogeneity amongst TRN neurons, the heterogeneity of intrinsic properties of TRN neurons has not been systematically examined. One key characteristic of virtually all thalamic neurons is the ability to produce action potentials in two distinct modes: burst and tonic. In this study, we have examined the prevalence of burst discharge within TRN neurons. Our intracellular recordings revealed that TRN neurons can be differentiated by their action potential discharge modes. The majority of neurons in the dorsal TRN (56%) lack burst discharge, and the remaining neurons (35%) show an atypical burst that consists of an initial action potential followed by small amplitude, long duration depolarizations. In contrast, most neurons in ventral TRN (82%) display a stereotypical burst discharge consisting of a transient, high frequency discharge of multiple action potentials. TRN neurons that lack burst discharge typically did not produce low threshold calcium spikes or produced a significantly reduced transient depolarization. Our findings clearly indicate that TRN neurons can be differentiated by differences in their spike discharge properties and these subtypes are not uniformly distributed within TRN. The functional consequences of such intrinsic differences may play an important role in modality-specific thalamocortical information transfer as well as overall circuit level activities. PMID:17463035

  11. Integration of sensory quanta in cuneate nucleus neurons in vivo.

    PubMed

    Bengtsson, Fredrik; Brasselet, Romain; Johansson, Roland S; Arleo, Angelo; Jörntell, Henrik

    2013-01-01

    Discriminative touch relies on afferent information carried to the central nervous system by action potentials (spikes) in ensembles of primary afferents bundled in peripheral nerves. These sensory quanta are first processed by the cuneate nucleus before the afferent information is transmitted to brain networks serving specific perceptual and sensorimotor functions. Here we report data on the integration of primary afferent synaptic inputs obtained with in vivo whole cell patch clamp recordings from the neurons of this nucleus. We find that the synaptic integration in individual cuneate neurons is dominated by 4-8 primary afferent inputs with large synaptic weights. In a simulation we show that the arrangement with a low number of primary afferent inputs can maximize transfer over the cuneate nucleus of information encoded in the spatiotemporal patterns of spikes generated when a human fingertip contact objects. Hence, the observed distributions of synaptic weights support high fidelity transfer of signals from ensembles of tactile afferents. Various anatomical estimates suggest that a cuneate neuron may receive hundreds of primary afferents rather than 4-8. Therefore, we discuss the possibility that adaptation of synaptic weight distribution, possibly involving silent synapses, may function to maximize information transfer in somatosensory pathways.

  12. Synaptic mechanisms underlying cholinergic control of thalamic reticular nucleus neurons

    PubMed Central

    Beierlein, Michael

    2014-01-01

    Neuronal networks of the thalamus are the target of extensive cholinergic projections from the basal forebrain and the brainstem. Activation of these afferents can regulate neuronal excitability, transmitter release, and firing patterns in thalamic networks, thereby altering the flow of sensory information during distinct behavioural states. However, cholinergic regulation in the thalamus has been primarily examined by using receptor agonist and antagonist, which has precluded a detailed understanding of the spatiotemporal dynamics that govern cholinergic signalling under physiological conditions. This review summarizes recent studies on cholinergic synaptic transmission in the thalamic reticular nucleus (TRN), a brain structure intimately involved in the control of sensory processing and the generation of rhythmic activity in the thalamocortical system. This work has shown that acetylcholine (ACh) released from individual axons can rapidly and reliably activate both pre- and postsynaptic cholinergic receptors, thereby controlling TRN neuronal activity with high spatiotemporal precision. PMID:24973413

  13. Oxytocin excites nucleus accumbens shell neurons in vivo.

    PubMed

    Moaddab, Mahsa; Hyland, Brian I; Brown, Colin H

    2015-09-01

    Oxytocin modulates reward-related behaviors. The nucleus accumbens shell (NAcSh) is a major relay in the brain reward pathway and expresses oxytocin receptors, but the effects of oxytocin on the activity of NAcSh neurons in vivo are unknown. Hence, we used in vivo extracellular recording to show that intracerebroventricular (ICV) oxytocin administration (0.2μg) robustly increased medial NAcSh neuron mean firing rate; this increase was almost exclusively evident in slow-firing neurons and was not associated with any change in firing pattern. To determine whether oxytocin excitation of medial NAcSh neurons is modulated by drugs that impact the brain reward pathway, we next tested the effects of ICV oxytocin following repeated morphine treatment. In morphine-treated rats, ICV oxytocin did not affect the mean firing rate of medial NAcSh neurons. Taken together, these results show that oxytocin excites medial NAcSh neurons but does not do so after repeated morphine. This could be an important factor in oxytocin modulation of reward-related behaviors, such as drug addiction.

  14. Simultaneous electrophysiological recording and calcium imaging of suprachiasmatic nucleus neurons.

    PubMed

    Irwin, Robert P; Allen, Charles N

    2013-12-08

    Simultaneous electrophysiological and fluorescent imaging recording methods were used to study the role of changes of membrane potential or current in regulating the intracellular calcium concentration. Changing environmental conditions, such as the light-dark cycle, can modify neuronal and neural network activity and the expression of a family of circadian clock genes within the suprachiasmatic nucleus (SCN), the location of the master circadian clock in the mammalian brain. Excitatory synaptic transmission leads to an increase in the postsynaptic Ca(2+) concentration that is believed to activate the signaling pathways that shifts the rhythmic expression of circadian clock genes. Hypothalamic slices containing the SCN were patch clamped using microelectrodes filled with an internal solution containing the calcium indicator bis-fura-2. After a seal was formed between the microelectrode and the SCN neuronal membrane, the membrane was ruptured using gentle suction and the calcium probe diffused into the neuron filling both the soma and dendrites. Quantitative ratiometric measurements of the intracellular calcium concentration were recorded simultaneously with membrane potential or current. Using these methods it is possible to study the role of changes of the intracellular calcium concentration produced by synaptic activity and action potential firing of individual neurons. In this presentation we demonstrate the methods to simultaneously record electrophysiological activity along with intracellular calcium from individual SCN neurons maintained in brain slices.

  15. Recording Gamma Band Oscillations in Pedunculopontine Nucleus Neurons.

    PubMed

    Urbano, Francisco J; Luster, Brennon R; D'Onofrio, Stasia; Mahaffey, Susan; Garcia-Rill, Edgar

    2016-09-14

    Synaptic efferents from the PPN are known to modulate the neuronal activity of several intralaminar thalamic regions (e.g., the centrolateral/parafascicular; Cl/Pf nucleus). The activation of either the PPN or Cl/Pf nuclei in vivo has been described to induce the arousal of the animal and an increment in gamma band activity in the cortical electroencephalogram (EEG). The cellular mechanisms for the generation of gamma band oscillations in Reticular Activating System (RAS) neurons are the same as those found to generate gamma band oscillations in other brains nuclei. During current-clamp recordings of PPN neurons (from parasagittal slices from 9 - 25 day-old rats), the use of depolarizing square steps rapidly activated voltage-dependent potassium channels that prevented PPN neurons from being depolarized beyond -25 mV. Injecting 1 - 2 sec long depolarizing current ramps gradually depolarized PPN membrane potential resting values towards 0 mV. However, injecting depolarizing square pulses generated gamma-band oscillations of membrane potential that showed to be smaller in amplitude compared to the oscillations generated by ramps. All experiments were performed in the presence of voltage-gated sodium channels and fast synaptic receptors blockers. It has been shown that the activation of high-threshold voltage-dependent calcium channels underlie gamma-band oscillatory activity in PPN neurons. Specific methodological and pharmacological interventions are described here, providing the necessary tools to induce and sustain PPN subthreshold gamma band oscillation in vitro.

  16. MATURATION OF FIRING PATTERN IN CHICK VESTIBULAR NUCLEUS NEURONS

    PubMed Central

    SHAO, M.; HIRSCH, J. C.; PEUSNER, K. D.

    2007-01-01

    The principal cells of the chick tangential nucleus are vestibular nucleus neurons participating in the vestibuloocular and vestibulocollic reflexes. In birds and mammals, spontaneous and stimulus-evoked firing of action potentials is essential for vestibular nucleus neurons to generate mature vestibular reflex activity. The emergence of spike-firing pattern and the underlying ion channels were studied in morphologically-identified principal cells using whole-cell patch-clamp recordings from brain slices of late-term embryos (embryonic day 16) and hatchling chickens (hatching day 1 and hatching day 5). Spontaneous spike activity emerged around the perinatal period, since at embryonic day 16 none of the principal cells generated spontaneous action potentials. However, at hatching day 1, 50% of the cells fired spontaneously (range, 3 to 32 spikes/s), which depended on synaptic transmission in most cells. By hatching day 5, 80% of the principal cells could fire action potentials spontaneously (range, 5 to 80 spikes/s), and this activity was independent of synaptic transmission and showed faster kinetics than at hatching day 1. Repetitive firing in response to depolarizing pulses appeared in the principal cells starting around embryonic day 16, when < 20% of the neurons fired repetitively. However, almost 90% of the principal cells exhibited repetitive firing on depolarization at hatching day 1, and 100% by hatching day 5. From embryonic day 16 to hatching day 5, the gain for evoked spike firing increased almost 10-fold. At hatching day 5, a persistent sodium channel was essential for the generation of spontaneous spike activity, while a small conductance, calcium-dependent potassium current modulated both the spontaneous and evoked spike firing activity. Altogether, these in vitro studies showed that during the perinatal period, the principal cells switched from displaying no spontaneous spike activity at resting membrane potential and generating one spike on

  17. Maturation of firing pattern in chick vestibular nucleus neurons.

    PubMed

    Shao, M; Hirsch, J C; Peusner, K D

    2006-08-25

    The principal cells of the chick tangential nucleus are vestibular nucleus neurons participating in the vestibuloocular and vestibulocollic reflexes. In birds and mammals, spontaneous and stimulus-evoked firing of action potentials is essential for vestibular nucleus neurons to generate mature vestibular reflex activity. The emergence of spike-firing pattern and the underlying ion channels were studied in morphologically-identified principal cells using whole-cell patch-clamp recordings from brain slices of late-term embryos (embryonic day 16) and hatchling chickens (hatching day 1 and hatching day 5). Spontaneous spike activity emerged around the perinatal period, since at embryonic day 16 none of the principal cells generated spontaneous action potentials. However, at hatching day 1, 50% of the cells fired spontaneously (range, 3 to 32 spikes/s), which depended on synaptic transmission in most cells. By hatching day 5, 80% of the principal cells could fire action potentials spontaneously (range, 5 to 80 spikes/s), and this activity was independent of synaptic transmission and showed faster kinetics than at hatching day 1. Repetitive firing in response to depolarizing pulses appeared in the principal cells starting around embryonic day 16, when <20% of the neurons fired repetitively. However, almost 90% of the principal cells exhibited repetitive firing on depolarization at hatching day 1, and 100% by hatching day 5. From embryonic day 16 to hatching day 5, the gain for evoked spike firing increased almost 10-fold. At hatching day 5, a persistent sodium channel was essential for the generation of spontaneous spike activity, while a small conductance, calcium-dependent potassium current modulated both the spontaneous and evoked spike firing activity. Altogether, these in vitro studies showed that during the perinatal period, the principal cells switched from displaying no spontaneous spike activity at resting membrane potential and generating one spike on

  18. Planar multipolar cells in the cochlear nucleus project to medial olivocochlear neurons in mouse.

    PubMed

    Darrow, Keith N; Benson, Thane E; Brown, M Christian

    2012-05-01

    Medial olivocochlear (MOC) neurons originate in the superior olivary complex and project to the cochlea, where they act to reduce the effects of noise masking and protect the cochlea from damage. MOC neurons respond to sound via a reflex pathway; however, in this pathway the cochlear nucleus cell type that provides input to MOC neurons is not known. We investigated whether multipolar cells of the ventral cochlear nucleus have projections to MOC neurons by labeling them with injections into the dorsal cochlear nucleus. The projections of one type of labeled multipolar cell, planar neurons, were traced into the ventral nucleus of the trapezoid body, where they were observed terminating on MOC neurons (labeled in some cases by a second cochlear injection of FluoroGold). These terminations formed what appear to be excitatory synapses, i.e., containing small, round vesicles and prominent postsynaptic densities. These data suggest that cochlear nucleus planar multipolar neurons drive the MOC neuron's response to sound.

  19. Characterization of Ca(2+) channels in rat subthalamic nucleus neurons.

    PubMed

    Song, W J; Baba, Y; Otsuka, T; Murakami, F

    2000-11-01

    The subthalamic nucleus (STN) plays a key role in motor control. Although previous studies have suggested that Ca(2+) conductances may be involved in regulating the activity of STN neurons, Ca(2+) channels in this region have not yet been characterized. We have therefore investigated the subtypes and functional characteristics of Ca(2+) conductances in STN neurons, in both acutely isolated and slice preparations. Acutely isolated STN cells were identified by retrograde filling with the fluorescent dye, Fluoro-Gold. In acutely isolated STN neurons, Cd(2+)-sensitive, depolarization-activated Ba(2+) currents were observed in all cells studied. The current-voltage relationship and current kinetics were characteristic of high-voltage-activated Ca(2+) channels. The steady-state voltage-dependent activation curves and inactivation curves could both be fitted with a single Boltzmann function. Currents evoked with a prolonged pulse, however, inactivated with multiple time constants, suggesting either the presence of more than one Ca(2+) channel subtype or multiple inactivation processes with a single channel type in STN neurons. Experiments using organic Ca(2+) channel blockers revealed that on average, 21% of the current was nifedipine sensitive, 52% was sensitive to omega-conotoxin GVIA, 16% was blocked by a high concentration of omega-agatoxin IVA (200 nM), and the remainder of the current (9%) was resistant to the co-application of all blockers. These currents had similar voltage dependencies, but the nifedipine-sensitive current and the resistant current activated at slightly lower voltages. omega-Agatoxin IVA at 20 nM was ineffective in blocking the current. Together, the above results suggest that acutely isolated STN neurons have all subtypes of high-voltage-activated Ca(2+) channels except for P-type, but have no low-voltage-activated channels. Although acutely isolated neurons provide a good preparation for whole cell voltage-clamp study, dendritic processes are

  20. The interfascicular trigeminal nucleus: a precerebellar nucleus in the mouse defined by retrograde neuronal tracing and genetic fate mapping.

    PubMed

    Fu, Yuhong; Tvrdik, Petr; Makki, Nadja; Machold, Robert; Paxinos, George; Watson, Charles

    2013-02-15

    We have found a previously unreported precerebellar nucleus located among the emerging fibers of the motor root of the trigeminal nerve in the mouse, which we have called the interfascicular trigeminal nucleus (IF5). This nucleus had previously been named the tensor tympani part of the motor trigeminal nucleus (5TT) in rodent brain atlases, because it was thought to be a subset of small motor neurons of the motor trigeminal nucleus innervating the tensor tympani muscle. However, following injection of retrograde tracer in the cerebellum, the labeled neurons in IF5 were found to be choline acetyltransferase (ChAT) negative, indicating that they are not motor neurons. The cells of IF5 are strongly labeled in mice from Wnt1Cre and Atoh1 CreER lineage fate mapping, in common with the major precerebellar nuclei that arise from the rhombic lip and that issue mossy fibers. Analysis of sections from mouse Hoxa3, Hoxb1, and Egr2 Cre labeled lineages shows that the neurons of IF5 arise from rhombomeres caudal to rhombomere 4, most likely from rhombomeres 6-8. We conclude that IF5 is a significant precerebellar nucleus in the mouse that shares developmental gene expression characteristics with mossy fiber precerebellar nuclei that arise from the caudal rhombic lip.

  1. MDMA modulates spontaneous firing of subthalamic nucleus neurons in vitro.

    PubMed

    Liebig, Luise; von Ameln-Mayerhofer, Andreas; Hentschke, Harald

    2015-01-01

    3,4-Methylene-dioxy-N-methylamphetamine (MDMA, 'ecstasy') has a broad spectrum of molecular targets in the brain, among them receptors and transporters of the serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic systems. Its action on the serotonergic system modulates motor systems in rodents and humans. Although parts of the basal ganglia could be identified as mediators of the motor effects of MDMA, very little is known about the role of the subthalamic nucleus (STN). Therefore, this study investigated the modulation of spontaneous action potential activity of the STN by MDMA (2.5-20 µM) in vitro. MDMA had very heterogeneous effects, ranging from a complete but reversible inhibition to a more than twofold increase in firing at 5 µM. On average, MDMA excited STN neurons moderately, but lost its excitatory effect in the presence of the 5-HT(2A) antagonist MDL 11,939. 5-HT(1A) receptors did not appear to play a major role. Effects of MDMA on transporters for serotonin (SERT) and norepinephrine (NET) were investigated by coapplication of the reuptake inhibitors citalopram and desipramine, respectively. Similar to the effects of 5-HT(2A) receptor blockade, antagonism of SERT and NET bestowed an inhibitory effect on MDMA. From these results, we conclude that both the 5-HT and the noradrenergic system mediate MDMA-induced effects on STN neurons.

  2. A light and electron microscope study of rat abducens nucleus neurons projecting to the cerebellar flocculus.

    PubMed Central

    Rodella, L; Rezzani, R; Corsetti, G; Simonetti, C; Stacchiotti, A; Ventura, R G

    1995-01-01

    Injection of horseradish peroxidase (HRP) into the cerebellar flocculus of the rat was employed to identify neurons in the abducens nucleus that project to the flocculus. The number, ultrastructural features and precise localisation of these neurons in the nucleus were examined. They were present bilaterally and represented about 7% of the total neuronal population of each nucleus. They were localised principally in the dorsomedial area of the cranial half of each nucleus and did not display the typical ultrastructural features of motoneurons. It is concluded that the localisation and ultrastructural characteristics of these HRP-positive neurons are useful for distinguishing them from other neuronal populations within the nucleus. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:7649835

  3. Characteristics of rostral solitary tract nucleus neurons with identified afferent connections that project to the parabrachial nucleus in rats.

    PubMed

    Suwabe, Takeshi; Bradley, Robert M

    2009-07-01

    Afferent information derived from oral chemoreceptors is transmitted to second-order neurons in the rostral solitary tract nucleus (rNST) and then relayed to other CNS locations responsible for complex sensory and motor behaviors. Here we investigate the characteristics of rNST neurons sending information rostrally to the parabrachial nucleus (PBN). Afferent connections to these rNST-PBN projection neurons were identified by anterograde labeling of the chorda tympani (CT), glossopharyngeal (IX), and lingual (LV) nerves. We used voltage- and current-clamp recordings in brain slices to characterize the expression of both the transient A-type potassium current, IKA and the hyperpolarization-activated inward current, Ih, important determinants of neuronal repetitive discharge characteristics. The majority of rNST-PBN neurons express IKA, and these IKA-expressing neurons predominate in CT and IX terminal fields but were expressed in approximately half of the neurons in the LV field. rNST-PBN neurons expressing Ih were evenly distributed among CT, IX and LV terminal fields. However, expression patterns of IKA and Ih differed among CT, IX, and LV fields. IKA-expressing neurons frequently coexpress Ih in CT and IX terminal fields, whereas neurons in LV terminal field often express only Ih. After GABAA receptor block all rNST-PBN neurons responded to afferent stimulation with all-or-none excitatory synaptic responses. rNST-PBN neurons had either multipolar or elongate morphologies and were distributed throughout the rNST, but multipolar neurons were more often encountered in CT and IX terminal fields. No correlation was found between the biophysical and morphological characteristics of the rNST-PBN projection neurons in each terminal field.

  4. Responses of primate caudal parabrachial nucleus and Kolliker-fuse nucleus neurons to whole body rotation

    NASA Technical Reports Server (NTRS)

    Balaban, Carey D.; McGee, David M.; Zhou, Jianxun; Scudder, Charles A.

    2002-01-01

    The caudal aspect of the parabrachial (PBN) and Kolliker-Fuse (KF) nuclei receive vestibular nuclear and visceral afferent information and are connected reciprocally with the spinal cord, hypothalamus, amygdala, and limbic cortex. Hence, they may be important sites of vestibulo-visceral integration, particularly for the development of affective responses to gravitoinertial challenges. Extracellular recordings were made from caudal PBN cells in three alert, adult female Macaca nemestrina through an implanted chamber. Sinusoidal and position trapezoid angular whole body rotation was delivered in yaw, roll, pitch, and vertical semicircular canal planes. Sites were confirmed histologically. Units that responded during rotation were located in lateral and medial PBN and KF caudal to the trochlear nerve at sites that were confirmed anatomically to receive superior vestibular nucleus afferents. Responses to whole-body angular rotation were modeled as a sum of three signals: angular velocity, a leaky integration of angular velocity, and vertical position. All neurons displayed angular velocity and integrated angular velocity sensitivity, but only 60% of the neurons were position-sensitive. These responses to vertical rotation could display symmetric, asymmetric, or fully rectified cosinusoidal spatial tuning about a best orientation in different cells. The spatial properties of velocity and integrated velocity and position responses were independent for all position-sensitive neurons; the angular velocity and integrated angular velocity signals showed independent spatial tuning in the position-insensitive neurons. Individual units showed one of three different orientations of their excitatory axis of velocity rotation sensitivity: vertical-plane-only responses, positive elevation responses (vertical plane plus ipsilateral yaw), and negative elevation axis responses (vertical plane plus negative yaw). The interactions between the velocity and integrated velocity components

  5. Convergence of limb, visceral, and vertical semicircular canal or otolith inputs onto vestibular nucleus neurons

    NASA Technical Reports Server (NTRS)

    Jian, B. J.; Shintani, T.; Emanuel, B. A.; Yates, B. J.

    2002-01-01

    The major goal of this study was to determine the patterns of convergence of non-labyrinthine inputs from the limbs and viscera onto vestibular nucleus neurons receiving signals from vertical semicircular canals or otolith organs. A secondary aim was to ascertain whether the effects of non-labyrinthine inputs on the activity of vestibular nucleus neurons is affected by bilateral peripheral vestibular lesions. The majority (72%) of vestibular nucleus neurons in labyrinth-intact animals whose firing was modulated by vertical rotations responded to electrical stimulation of limb and/or visceral nerves. The activity of even more vestibular nucleus neurons (93%) was affected by limb or visceral nerve stimulation in chronically labyrinthectomized preparations. Some neurons received non-labyrinthine inputs from a variety of peripheral sources, including antagonist muscles acting at the same joint, whereas others received inputs from more limited sources. There was no apparent relationship between the spatial and dynamic properties of a neuron's responses to tilts in vertical planes and the non-labyrinthine inputs that it received. These data suggest that non-labyrinthine inputs elicited during movement will modulate the processing of information by the central vestibular system, and may contribute to the recovery of spontaneous activity of vestibular nucleus neurons following peripheral vestibular lesions. Furthermore, some vestibular nucleus neurons with non-labyrinthine inputs may be activated only during particular behaviors that elicit a specific combination of limb and visceral inputs.

  6. Distribution of the neuronal inputs to the ventral premammillary nucleus of male and female rats☆

    PubMed Central

    Cavalcante, Judney Cley; Bittencourt, Jackson Cioni; Elias, Carol Fuzeti

    2014-01-01

    The ventral premammillary nucleus (PMV) expresses dense collections of sex steroid receptors and receptors for metabolic cues, including leptin, insulin and ghrelin. The PMV responds to opposite sex odor stimulation and projects to areas involved in reproductive control, including direct innervation of gonadotropin releasing hormone neurons. Thus, the PMV is well positioned to integrate metabolic and reproductive cues, and control downstream targets that mediate reproductive function. In fact, lesions of PMV neurons blunt female reproductive function and maternal aggression. However, although the projections of PMV neurons have been well documented, little is known about the neuronal inputs received by PMV neurons. To fill this gap, we performed a systematic evaluation of the brain sites innervating the PMV neurons of male and female rats using the retrograde tracer subunit B of the cholera toxin (CTb). In general, we observed that males and females show a similar pattern of afferents. We also noticed that the PMV is preferentially innervated by neurons located in the forebrain, with very few projections coming from brainstem nuclei. The majority of inputs originated from the medial nucleus of the amygdala, the bed nucleus of the stria terminalis and the medial preoptic nucleus. A moderate to high density of afferents was also observed in the ventral subiculum, the arcuate nucleus and the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus. Our findings strengthen the concept that the PMV is part of the vomeronasal system and integrates the brain circuitry controlling reproductive functions. PMID:25084037

  7. [Reactions of caudate nucleus neurons to presentation of acoustic clicks to cats in a chronic experiment].

    PubMed

    Litvinova, A N; Lukhanina, E P

    1980-01-01

    Background and evoked activities of the caudate nucleus neurons to repetitive auditory clicks were recorded extracellularly in chronic experiments with partial restrained cats. Four types of background neuronal activity were distinguished. 44% of recorded units altered their background activity during auditory click applications. Five types of neuronal responses were found: phasic activation, phasic inhibition, tonic activation, tonic inhibition, mixed tonic reactions. Tonic activation was predominant. The phasic responses persisted under prolonged presentation of clicks. Partial or total attenuation of tonic responses during frequent repetition of clicks occurred in 33% of responding units. The question is discussed on the convergence of specific and unspecific influences on the caudate nucleus neurons.

  8. Preliminary findings on the nucleus of large neurons in Lophius piscatorius L. (Osteichthyes, Lophiiformes).

    PubMed

    Benedetti, I; Mola, L

    1991-01-01

    Some Teleosts belonging to the orders Batrachoidiformes, Lophiiformes, Perciformes and Tetraodontiformes show a cluster of large neurons dorsally located at the boundary between the spinal cord and medulla oblongata. These elements have traditionally been grouped with the supramedullary neurons aligned in the dorso-medial region of the spinal cord of other teleosts (see Marini and Benedetti, in press). However, recent morphological and immunohistochemical studies have suggested that the neurons grouped in a cluster on the spinal cord of Lophius piscatorius may not be of the same nature as the supramedullary neurons aligned within the dorsal gray matter of the spinal cord (Benedetti and Mola, 1988; Mola, 1990). Over the course of these previous investigations, it seemed that the nucleus of the neurons in the cluster showed more abundant chromatin than other neurons in the dorsal spinal cord. This prompted a series of investigations on the nucleus of these neurons.

  9. [The neuronal responses of the caudate nucleus in the cat to sensory stimulation].

    PubMed

    Rodionova, E I; Pigarev, I N

    1990-01-01

    Responses of caudate neurons to a large variety of visual and other sensory stimuli were studied in alert cats. Sharp drops in the spontaneous activity of the unknown origin and differences in the activity level were revealed in adjacent parts of the caudate nucleus. The following types of neurons were recorded: neurons responding to visual stimulation; neurons responding to somatic stimulation; neurons responding to combined visual-somatic stimulation. The best response was observed to moving visual stimuli that attracted the animal's attention, alimentary objects specifically. The caudate nucleus of each hemisphere contained representation of both contra- and ipsilateral half of the animal body. Cell responses to sensory stimuli from the caudate nucleus have been compared with those from some cortical areas.

  10. Morphometric study on the development of magnocellular neurons of the supraoptic nucleus utilising immunohistochemical methods.

    PubMed Central

    Lazcano, M A; Bentura, M L; Toledano, A

    1990-01-01

    Vasopressin (VP)- and oxytocin (OXY)-producing neurons, components of the rat supraoptic nucleus, have been located with immunohistochemical methods, with the purpose of studying their morphofunctional characteristics during different phases of life (embryonic, juvenile, adult and senile). To carry out this study, an IBAS I (Kontron) computerised image analyser has been utilised. The hormone VP is first detected in the neuronal cytoplasm of 21 days old rat embryos and the hormone OXY appears in the neuronal cytoplasm later, in the newborn phase. The neuronal area with a positive reaction for the two neurohormones has been evaluated and it has been found that the quantity of reaction substance is proportional to the age. In the adult period, VP neurons possess a reaction area (198 microns 2) greater than that of OXY neurons (153 microns 2). In the SON, there are two neuronal shapes, fusiform and round; these shapes coexist in both hormonal types of neurons. Until Day 15 of postnatal development, the SON neurons are intermixed in the interior of the nucleus but in this period a neuronal redistribution is initiated. In the adult phase, OXY neurons are situated preferentially in the anterior, posterior and dorsal parts and VP neurons in the ventral and posterior parts, with both neurons being present in the intermediate part of the SON. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Figs. 12-14 Fig. 15 Fig. 16 PMID:2182586

  11. Target neurons of floccular middle zone inhibition in medial vestibular nucleus.

    PubMed

    Sato, Y; Kanda, K; Kawasaki, T

    1988-04-19

    Unitary activities of 288 neurons were recorded extracellularly in the medial vestibular nucleus (MV) in anesthetized cats. In 19 neurons, located in the rostral part of the MV adjacent to the stria acustica, floccular middle zone stimulation resulted in cessation of spontaneous discharges. Systematic microstimulation in the brainstem during recording of 16 of 19 target neurons of floccular middle zone inhibition revealed that the target neurons projected to the ipsilateral abducens nucleus (ABN), and not to the contralateral ABN nor the oculomotor nucleus. The conjugate ipsilateral horizontal eye movement elicited by middle zone stimulation may be mediated by this pathway to motoneurons and internuclear neurons in the ipsilateral ABN. In additional experiments, the MV neurons responding antidromically to ipsilateral ABN stimulation and orthodromically to ipsilateral 8 nerve stimulation were recorded extracellularly. In only 7 of 36 recorded neurons, middle zone stimulation depressed the orthodromic and spontaneous activities. Many neurons were free of floccular inhibition. As to the route of floccular inhibitory control over the vestibulo-ocular reflex (VOR) during visual-vestibular stimulation, we propose that the interaction of target and VOR relay neurons takes place at the ipsilateral ABN and modulates the VOR, in addition to well known Ito's proposal that the interaction of the floccular output and the VOR takes place at secondary vestibular neurons and modulates the VOR.

  12. Characterization of neurons of the nucleus tractus solitarius pars centralis.

    PubMed

    Baptista, V; Zheng, Z L; Coleman, F H; Rogers, R C; Travagli, R A

    2005-08-09

    Esophageal sensory afferent inputs terminate principally in the central subnucleus of the tractus solitarius (cNTS). Neurons of the cNTS comprise two major neurochemical subpopulations. One contains neurons that are nitric oxide synthase (NOS) immunoreactive (-IR) while the other comprises neurons that are tyrosine hydroxylase (TH)-IR. We have shown recently that TH-IR neurons are involved in esophageal-distention induced gastric relaxation. We used whole cell patch clamp techniques in rat brainstem slices combined with immunohistochemical and morphological reconstructions to characterize cNTS neurons. Postrecording reconstruction of cNTS neurons revealed two morphological neuronal subtypes; one group of cells (41 out of 131 neurons, i.e., 31%) had a multipolar soma, while the other group (87 out of 131 neurons, i.e., 66%) had a bipolar soma. Of the 43 cells in which we conducted a neurochemical examination, 15 displayed TH-IR (9 with bipolar morphology, 6 with multipolar morphology) while the remaining 28 neurons did not display TH-IR (18 with bipolar morphology, 10 with multipolar morphology). Even though the range of electrophysiological properties varied significantly, morphological or neurochemical distinctions did not reveal characteristics peculiar to the subgroups. Spontaneous excitatory postsynaptic currents (sEPSC) recorded in cNTS neurons had a frequency of 1.5 +/- 0.15 events s(-1) and an amplitude of 27 +/- 1.2 pA (Vh = -50 mV) and were abolished by pretreatment with 30 muM AP-5 and 10 muM CNQX, indicating the involvement of both NMDA and non-NMDA receptors. Some cNTS neurons also received a GABAergic input that was abolished by perfusion with 30-50 muM bicuculline. In conclusion, our data show that despite the heterogeneity of morphological and neurochemical membrane properties, the electrophysiological characteristics of cNTS neurons are not a distinguishing feature.

  13. Neuronal cell death in the arcuate nucleus of the medulla oblongata in stillbirth.

    PubMed

    Folkerth, Rebecca D; Zanoni, Sallie; Andiman, Sarah E; Billiards, Saraid S

    2008-02-01

    The hypothesis that unexplained stillbirth arises in a similar manner as the sudden infant death syndrome (SIDS) is based in part on shared neuropathologic features between the two entities, including hypoxic-ischemic lesions such as white matter and brainstem gliosis, as well as aplasia or hypoplasia of the arcuate nucleus on the ventral surface of the medulla. The arcuate nucleus is the putative homologue of the respiratory chemosensory region at the ventral medullary surface in animals that is involved in central chemosensitivity. To determine arcuate nucleus pathology in stillbirth, and its co-occurrence with evidence of hypoxia-ischemia, we reviewed brain specimens from the archives of our hospitals from 22 consecutive stillbirths from 22 to 41 gestational weeks. Explained causes of death (n=17) included nuchal cord, acute chorioamnionitis, placental abruption, and fetal glomerulosclerosis; 5 cases were unexplained. In 12 brains, we observed nuclear karyorrhexis and/or pyknosis with cytoplasmic hypereosinophilia in neurons in the arcuate nucleus in both explained (n=8) and unexplained (n=4) cases (54.5% of total cases). Three additional cases had arcuate aplasia (n=1) or hypoplasia (n=2) (13.6% of total cases); one of the latter cases also had neuronal necrosis in the hypoplastic arcuate. The degree of gliosis in the region of the arcuate nucleus was variable across all cases, without statistically significant differences between groups with and without arcuate nucleus necrosis. Other lesions in association with (n=14) and without (n=8) arcuate nucleus abnormalities were diffuse cerebral white matter gliosis, periventricular leukomalacia (PVL), and neuronal necrosis in the hippocampus, basal ganglia, thalamus, basis pontis, and brainstem tegmentum. In 16/20 (80.0%) cases (with or without histologic necrosis of the arcuate), immunostaining with caspase-3 demonstrated positive neurons. Our findings suggest that neuronal pathology in the arcuate nucleus may be

  14. Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder.

    PubMed

    Valencia Garcia, Sara; Libourel, Paul-Antoine; Lazarus, Michael; Grassi, Daniela; Luppi, Pierre-Hervé; Fort, Patrice

    2017-02-01

    SEE SCHENCK AND MAHOWALD DOI101093/AWW329 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Idiopathic REM sleep behaviour disorder is characterized by the enactment of violent dreams during paradoxical (REM) sleep in the absence of normal muscle atonia. Accumulating clinical and experimental data suggest that REM sleep behaviour disorder might be due to the neurodegeneration of glutamate neurons involved in paradoxical sleep and located within the pontine sublaterodorsal tegmental nucleus. The purpose of the present work was thus to functionally determine first, the role of glutamate sublaterodorsal tegmental nucleus neurons in paradoxical sleep and second, whether their genetic inactivation is sufficient for recapitulating REM sleep behaviour disorder in rats. For this goal, we first injected two retrograde tracers in the intralaminar thalamus and ventral medulla to disentangle neuronal circuits in which sublaterodorsal tegmental nucleus is involved; second we infused bilaterally in sublaterodorsal tegmental nucleus adeno-associated viruses carrying short hairpin RNAs targeting Slc17a6 mRNA [which encodes vesicular glutamate transporter 2 (vGluT2)] to chronically impair glutamate synaptic transmission in sublaterodorsal tegmental nucleus neurons. At the neuroanatomical level, sublaterodorsal tegmental nucleus neurons specifically activated during paradoxical sleep hypersomnia send descending efferents to glycine/GABA neurons within the ventral medulla, but not ascending projections to the intralaminar thalamus. These data suggest a crucial role of sublaterodorsal tegmental nucleus neurons rather in muscle atonia than in paradoxical sleep generation. In line with this hypothesis, 30 days after adeno-associated virus injections into sublaterodorsal tegmental nucleus rats display a decrease of 30% of paradoxical sleep daily quantities, and a significant increase of muscle tone during paradoxical sleep concomitant to a tremendous increase of abnormal motor dream

  15. Peripherally injected CCK-8S activates CART positive neurons of the paraventricular nucleus in rats

    PubMed Central

    Noetzel, Steffen; Inhoff, Tobias; Goebel, Miriam; Taché, Yvette; Veh, Rüdiger W.; Bannert, Norbert; Grötzinger, Carsten; Wiedenmann, Bertram; Klapp, Burghard F.; Mönnikes, Hubert; Kobelt, Peter

    2014-01-01

    Cholecystokinin (CCK) plays a role in the short-term inhibition of food intake. Cocaine- and amphetamine-regulated transcript (CART) peptide has been observed in neurons of the paraventricular nucleus (PVN). It has been reported that intracerebroventricular injection of CART peptide inhibits food intake in rodents. The aim of the study was to determine whether intraperitoneally (ip) injected CCK-8S affects neuronal activity of PVN-CART neurons. Ad libitum fed male Sprague-Dawley rats received 6 or 10 μg/kg CCK-8S or 0.15 M NaCl ip (n = 4/group). The number of c-Fos-immunoreactive neurons was determined in the PVN, arcuate nucleus (ARC), and the nucleus of the solitary tract (NTS). CCK-8S dose-dependently increased the number of c-Fos-immunoreactive neurons in the PVN (mean ± SEM: 102 ± 6 vs. 150 ± 5 neurons/section, p < 0.05) and compared to vehicle treated rats (18 ± 7, p < 0.05 vs. 6 and 10 μg/kg CCK-8S). CCK-8S at both doses induced an increase in the number of c-Fos-immunoreactive neurons in the NTS (65 ± 13, p < 0.05, and 182 ± 16, p < 0.05). No effect on the number of c-Fos neurons was observed in the ARC. Immunostaining for CART and c-Fos revealed a dose-dependent increase of activated CART neurons (19 ± 3 vs. 29 ± 7; p < 0.05), only few activated CART neuron were observed in the vehicle group (1 ± 0). The present observation shows that CCK-8S injected ip induces an increase in neuronal activity in PVN-CART neurons and suggests that CART neurons in the PVN may play a role in the mediation of peripheral CCK-8S's anorexigenic effects. PMID:20307613

  16. From Synapse to Nucleus and Back Again – Communication Over Distance Within Neurons

    PubMed Central

    Fainzilber, Mike; Budnik, Vivian; Segal, Rosalind A.; Kreutz, Michael R.

    2011-01-01

    How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at SfN 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, utilizing motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions. PMID:22072654

  17. Rostrocaudal changes in neuronal cell size in human lateral vestibular nucleus.

    PubMed

    Diaz, C; Suarez, C; Navarro, A; Gonzalez del Rey, C; Tolivia, J

    1993-07-09

    A cytoarchitectonic and morphometric study of the human lateral vestibular nucleus (LVN) is presented. In sagittal sections, the LVN appears as a triangular cell group rostrally located near the motor trigeminal nucleus and caudally near the vestibular root. The estimated volume is 13.49 mm3 with a neuronal population of 25,046 cells and 1855 neurons/mm3 in density. The average neuronal cross-sectional area changes from a minimum caudally (380.02 +/- 7.23 microns 2) to a maximum rostrally (825.16 +/- 25.10 microns 2). Four types of neurons can be observed: small (< 200 microns 2), medium (200-500 microns 2), large (500-100 microns 2) and giant or Deiter's cells (> 1000 microns 2). The small and medium cells constitute 62%, large cells 26% and the giant cells only 12% of the neuronal population.

  18. Regular theta-firing neurons in the nucleus incertus during sustained hippocampal activation.

    PubMed

    Martínez-Bellver, Sergio; Cervera-Ferri, Ana; Martínez-Ricós, Joana; Ruiz-Torner, Amparo; Luque-Garcia, Aina; Luque-Martinez, Aina; Blasco-Serra, Arantxa; Guerrero-Martínez, Juan; Bataller-Mompeán, Manuel; Teruel-Martí, Vicent

    2015-04-01

    This paper describes the existence of theta-coupled neuronal activity in the nucleus incertus (NI). Theta rhythm is relevant for cognitive processes such as spatial navigation and memory processing, and can be recorded in a number of structures related to the hippocampal activation including the NI. Strong evidence supports the role of this tegmental nucleus in neural circuits integrating behavioural activation with the hippocampal theta rhythm. Theta oscillations have been recorded in the local field potential of the NI, highly coupled to the hippocampal waves, although no rhythmical activity has been reported in neurons of this nucleus. The present work analyses the neuronal activity in the NI in conditions leading to sustained hippocampal theta in the urethane-anaesthetised rat, in order to test whether such activation elicits a differential firing pattern. Wavelet analysis has been used to better define the neuronal activity already described in the nucleus, i.e., non-rhythmical neurons firing at theta frequency (type I neurons) and fast-firing rhythmical neurons (type II). However, the most remarkable finding was that sustained stimulation activated regular-theta neurons (type III), which were almost silent in baseline conditions and have not previously been reported. Thus, we describe the electrophysiological properties of type III neurons, focusing on their coupling to the hippocampal theta. Their spike rate, regularity and phase locking to the oscillations increased at the beginning of the stimulation, suggesting a role in the activation or reset of the oscillation. Further research is needed to address the specific contribution of these neurons to the entire circuit.

  19. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J

    2016-06-23

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.

  20. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

    PubMed Central

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  1. Neuronal architecture in the rat central nucleus of the amygdala: a cytological, hodological, and immunocytochemical study.

    PubMed

    Cassell, M D; Gray, T S; Kiss, J Z

    1986-04-22

    The organization of neurons in the rat central nucleus of the amygdala (CNA) has been examined by using Nissl stain and immunocytochemical and retrograde tracing techniques. Four main subdivisions were identified on the basis of quantitative analyses of Nissl-stained material: medial (CM), lateral (CL), lateral capsular (CLC), and ventral (CV). An intermediate subdivision (CI), previously described by McDonald ('82), was apparent only in animals that had HRP-WGA injected into the bed nucleus of the stria terminalis. Large populations of neurotensin-, corticotropin-releasing factor (CRF)-, and enkephalin-immunoreactive neurons were present within the lateral divisions (mainly CL), although they were also seen within CM. Somatostatin-immunoreactive neurons were distributed mainly within CL and CM. Within CL, neurotensin- and enkephalin-immunoreactive neurons were more numerous laterally whereas CRF- and somatostatin-immunoreactive neurons were more numerous medially. Substance P-immunoreactive neurons were almost exclusively confined to CM. Only a few cholecystokinin- and vasoactive-polypeptide-immunoreactive neurons were seen in the CNA, and they were observed within CL, CV, and CM. The majority of neurons projecting to the dorsal medulla, hypothalamus, and ventral tegmental area were located within CM, although a significant number of cells were also seen within CL. Efferent projections to the bed nucleus of the stria terminalis were found to arise from neurons located within all subdivisions of the CNA. Thus, the distributional patterns of peptidergic and efferent neurons were not confined to individual cytoarchitectonically- defined subdivisions of the CNA. Rather, the results suggest overlapping medial to the lateral trends. Comparisons with the results of previous studies indicate that peptidergic and afferent terminal distribution patterns are more restricted to individual cytoarchitectonically defined subregions of the CNA. These observations suggest that the

  2. Characteristics of GABAergic and cholinergic neurons in perinuclear zone of mouse supraoptic nucleus

    PubMed Central

    Ennis, Matthew; Szabó, Gábor; Armstrong, William E.

    2014-01-01

    The perinuclear zone (PNZ) of the supraoptic nucleus (SON) contains some GABAergic and cholinergic neurons thought to innervate the SON proper. In mice expressing enhanced green fluorescent protein (eGFP) in association with glutamate decarboxylase (GAD)65 we found an abundance of GAD65-eGFP neurons in the PNZ, whereas in mice expressing GAD67-eGFP, there were few labeled PNZ neurons. In mice expressing choline acetyltransferase (ChAT)-eGFP, large, brightly fluorescent and small, dimly fluorescent ChAT-eGFP neurons were present in the PNZ. The small ChAT-eGFP and GAD65-eGFP neurons exhibited a low-threshold depolarizing potential consistent with a low-threshold spike, with little transient outward rectification. Large ChAT-eGFP neurons exhibited strong transient outward rectification and a large hyperpolarizing spike afterpotential, very similar to that of magnocellular vasopressin and oxytocin neurons. Thus the large soma and transient outward rectification of large ChAT-eGFP neurons suggest that these neurons would be difficult to distinguish from magnocellular SON neurons in dissociated preparations by these criteria. Large, but not small, ChAT-eGFP neurons were immunostained with ChAT antibody (AB144p). Reconstructed neurons revealed a few processes encroaching near and passing through the SON from all types but no clear evidence of a terminal axon arbor. Large ChAT-eGFP neurons were usually oriented vertically and had four or five dendrites with multiple branches and an axon with many collaterals and local arborizations. Small ChAT-eGFP neurons had a more restricted dendritic tree compared with parvocellular GAD65 neurons, the latter of which had long thin processes oriented mediolaterally. Thus many of the characteristics found previously in unidentified, small PNZ neurons are also found in identified GABAergic neurons and in a population of smaller ChAT-eGFP neurons. PMID:25376783

  3. Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus

    PubMed Central

    Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Šťastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

    2015-01-01

    Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson’s disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well. PMID:25713375

  4. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.

    PubMed

    Krashes, Michael J; Shah, Bhavik P; Madara, Joseph C; Olson, David P; Strochlic, David E; Garfield, Alastair S; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen D; Lowell, Bradford B

    2014-03-13

    Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.

  5. Neuronal Entropy-Rate Feature of Entopeduncular Nucleus in Rat Model of Parkinson's Disease.

    PubMed

    Darbin, Olivier; Jin, Xingxing; Von Wrangel, Christof; Schwabe, Kerstin; Nambu, Atsushi; Naritoku, Dean K; Krauss, Joachim K; Alam, Mesbah

    2016-03-01

    The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25 Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

  6. Interactions between Brainstem Noradrenergic Neurons and the Nucleus Accumbens Shell in Modulating Memory for Emotionally Arousing Events

    ERIC Educational Resources Information Center

    Kerfoot, Erin C.; Williams, Cedric L.

    2011-01-01

    The nucleus accumbens shell (NAC) receives axons containing dopamine-[beta]-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these…

  7. Modulation of Hippocampal Theta Oscillations and Spatial Memory by Relaxin-3 Neurons of the Nucleus Incertus

    ERIC Educational Resources Information Center

    Ma, Sherie; Olucha-Bordonau, Francisco E.; Hossain, M. Akhter; Lin, Feng; Kuei, Chester; Liu, Changlu; Wade, John D.; Sutton, Steven W.; Nunez, Angel; Gundlach, Andrew L.

    2009-01-01

    Hippocampal theta rhythm is thought to underlie learning and memory, and it is well established that "pacemaker" neurons in medial septum (MS) modulate theta activity. Recent studies in the rat demonstrated that brainstem-generated theta rhythm occurs through a multisynaptic pathway via the nucleus incertus (NI), which is the primary source of the…

  8. Synaptic input to vasopressin neurons of the paraventricular nucleus (PVN)

    SciTech Connect

    Silverman, A.J.; Oldfield, B.J.

    1984-01-01

    Following injections of horseradish peroxidase into the PVN, retrogradely filled cells were found in regions of the limbic system known to contain glucocorticoid concentrating neurons. To determine if these regions which include the lateral septum, medial amygdala and ventral subiculum have a monosynaptic input to vasopressin neurons the authors developed a double label ultrastructural technique to simultaneously visualize immunoreactive neuropeptide and anterogradely transported HRP. Following injections of tracer into all three of these regions, HRP labeled fibers were seen at the light microscopic level to form a halo in the perinuclear, cell poor zone around the PVN. Ultrastructural examination of this area resulted in the discovery of a small number of limbic system synapses on vasopressin dendrites. In a similar fashion they were interested in determining the distribution of noradrenergic terminals on vasopressin neurons in the various subnuclei of the PVN. The authors have combined immunocytochemistry for vasopressin with radioautography for /sup 3/H-norepinephrine (NE) at the ultrastructural level. NE terminals were numerous in the periventricular zone, innervating both vasopressin containing dendrites and non-immunoreactive dendrites and cell bodies. These studies demonstrate the need for ultrastructural analysis of synaptic input to neurosecretory cells.

  9. Immunohistochemical study of neurons in the rat abducens nucleus that project to the flocculus.

    PubMed Central

    Rodella, L; Rezzani, R; Bianchi, R

    1996-01-01

    The neurons of the rat abducens nucleus that project to the flocculus of the cerebellum were studied by double labelling using the retrograde transport of horseradish peroxidase (HRP) and choline acetyltransferase (ChAT) immunohistochemistry. Double-labelled cells were present bilaterally in the dorsal and dorsomedial zones of the cranial pole of the nucleus. They represented about half of the total number of HRP-positive neurons. These findings show the existence of a bilateral projection from the abducens nucleus to the flocculus which uses acetylcholine as a neurotransmitter. This projection could be part of the system of the nerve circuits through which the cerebellum modulates visual activities. Images Fig. 3 Fig. 4 Fig. 5 PMID:8763489

  10. Cholinergic and non-cholinergic mesopontine tegmental neurons projecting to the subthalamic nucleus in the rat

    PubMed Central

    Kita, Takako; Kita, Hitoshi

    2010-01-01

    The subthalamic nucleus (STN) receives cholinergic and non-cholinergic projections from the mesopontine tegmentum. This study investigated the numbers and distributions of neurons involved in these projections in rats using Fluorogold (FG) retrograde tracing combined with immunostaining of choline acetyltransferase and a neuron-specific nuclear protein. The results suggest that a small population of cholinergic neurons mainly in the caudoventral part of the pedunculopontine tegmental nucleus (PPN), approximately 360 neurons (≈10% of total) in the homolateral and 80 neurons (≈2%) in the contralateral PPN, projects to the STN. In contrast, the number of non-cholinergic neurons projecting to the STN was estimated to be 9 times as much, with approximately 3300 in the homolateral side and 1300 neurons in the contralateral side. A large gathering of the FG-labeled non-cholinergic neurons was found rostrodorsomedial to the caudolateral PPN. The biotinylated dextran amine (BDA) anterograde tracing method was used to substantiate the mesopontine-STN projections. Injection of BDA into the caudoventral PPN labeled numerous thin fibers with small en-passant varicosities in the STN. Injection of BDA into the non-cholinergic neuron-rich area labeled a moderate number of thicker fibers with patches of aggregates of larger boutons. The densities of labeled fibers and the number of retrogradely labeled cells in the mesopontine tegmentum suggested that the terminal field formed in the STN by each cholinergic neuron is more extensive than that by each non-cholinergic neuron. The findings suggest that cholinergic and non-cholinergic mesopontine afferents may carry different information to the STN. PMID:21198985

  11. Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus.

    PubMed

    Cabral, Agustina; Portiansky, Enrique; Sánchez-Jaramillo, Edith; Zigman, Jeffrey M; Perello, Mario

    2016-05-01

    Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin's orexigenic action vs. its role as a stress signal are anatomically dissociated.

  12. Adiponectin modulates excitability of rat paraventricular nucleus neurons by differential modulation of potassium currents.

    PubMed

    Hoyda, Ted D; Ferguson, Alastair V

    2010-07-01

    The adipocyte-derived hormone adiponectin acts at two seven-transmembrane domain receptors, adiponectin receptor 1 and adiponectin receptor 2, present in the paraventricular nucleus of the hypothalamus to regulate neuronal excitability and endocrine function. Adiponectin depolarizes rat parvocellular preautonomic neurons that secrete either thyrotropin releasing hormone or oxytocin and parvocellular neuroendocrine corticotropin releasing hormone neurons, leading to an increase in plasma adrenocorticotropin hormone concentrations while also hyperpolarizing a subgroup of neurons. In the present study, we investigate the ionic mechanisms responsible for these changes in excitability in parvocellular paraventricular nucleus neurons. Patch clamp recordings of currents elicited from slow voltage ramps and voltage steps indicate that adiponectin inhibits noninactivating delayed rectifier potassium current (I(K)) in a majority of neurons. This inhibition produced a broadening of the action potential in cells that depolarized in the presence of adiponectin. The depolarizing effects of adiponectin were abolished in cells pretreated with tetraethyl ammonium (0/15 cells depolarize). Slow voltage ramps performed during adiponectin-induced hyperpolarization indicate the activation of voltage-independent potassium current. These hyperpolarizing responses were abolished in the presence of glibenclamide [an ATP-sensitive potassium (K(ATP)) channel blocker] (0/12 cells hyperpolarize). The results presented in this study suggest that adiponectin controls neuronal excitability through the modulation of different potassium conductances, effects which contribute to changes in excitability and action potential profiles responsible for peptidergic release into the circulation.

  13. Neuron types and organisation of the rabbit dorsal lateral geniculate nucleus.

    PubMed Central

    Caballero, J L; Ostos, M V; Abadía-Fenoll, F

    1986-01-01

    The Golgi technique was employed in order to study the types of neurons composing the dorsal lateral geniculate nucleus and to elucidate its organisational features in the rabbit. Four types of neurons were identified based on differences in perikaryon size or the particular features of their dendrites and dendritic appendages. Types 1 and 2 were comparable to the relay cells previously identified in functional and morphological studies in other mammals as projecting upon the visual cortex. Type 3 cells were morphologically identified as interneurons. Type 4 neurons, not described in detail in the present paper, were observed along the nuclear periphery underlying the optic tract. Types 1 and 2 neurons along with their dendritic trees were orientated in planes which converged radially in the anteromedial region of the nucleus. Retinal afferent fibres from the optic tract traversed the nucleus as part of a longitudinal fibre system, running parallel to the planes of cell orientation, to establish synapses with the relay neurons. Images Fig. 3 Fig. 5 Fig. 7 Fig. 8 PMID:3693085

  14. Neuron types in the rat dorsal lateral geniculate nucleus identified in Nissl and deimpregnated Golgi preparations.

    PubMed

    Werner, L; Brauer, K

    1984-01-01

    To identify geniculo-cortical relay neurons (GCR-neurons) and interneurons (I-neurons) in Nissl stained sections of the albino rat's (Wistar strain) dorsal lateral geniculate nucleus (dLGN) we combined a Golgi deimpregnation technique (Fairén et al. 1977) with the Nissl staining. The two types of neurons show numerous characteristic features in Golgi preparations (Brauer and Schober 1973, Grossman et al. 1973, Brauer et al. 1974, Winkelmann et al. 1976, 1979). After application of the combined method it is obvious that neuronal somata exhibit also features which make it possible to identify these types of neurons in Nissl stained series. GCR-neurons are characterized by a very broad cytoplasmic portion, whereas a particularly thin cytoplasm rim is typical of I-neurons. Our findings confirm former results obtained by analysis of Nissl material (Werner and Kruger 1973, Werner et al. 1975, Werner and Winkelmann 1976, Werner et al. 1984). In these investigations, special attention was paid to cytoplasmic and nuclear characteristics in order to elucidate the ratio of GCR-/I-neurons (13:1) and the internal dLGN topography. It is still discussed if the described cytological features can be taken as basis for the classification of GCR- and I-neurons in other species.

  15. Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus

    PubMed Central

    Chua, Streamson; Jo, Young-Hwan

    2016-01-01

    The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC), plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT)-expressing neurons in the ARC. Gene expression patterns are remarkably distinct in each individual cholinergic neuron. Two-thirds of cholinergic neurons express tyrosine hydroxylase (Th) mRNA. A large subset of these Th-positive cholinergic neurons is GABAergic as they express the GABA synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter transcripts. Some cholinergic neurons also express the vesicular glutamate transporter transcript gene. POMC and POMC-processing enzyme transcripts are found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene expression patterns in individual cholinergic cells appear to be highly regulated in a cell-specific manner. In fact, membrane receptor transcripts are clustered with their respective intracellular signaling and downstream targets. This novel population of cholinergic neurons may be part of the neural circuitries that detect homeostatic need for food and control the drive to eat. PMID:27611685

  16. [Local GABA-ergic modulation of serotonergic neuron activity in the nucleus raphe magnus].

    PubMed

    Iniushkin, A N; Merkulova, N A; Orlova, A O; Iniushkina, E M

    2009-07-01

    In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. Local applications of 5-HT induced an increase in IPCSs frequency and amplitude in 45% of serotonergic cells. The effect suppressed by the blocker of fast sodium channels tetradotoxin. Antagonist of GABA receptor gabazine blocked IPSCs in neurons both sensitive and non-sensitive to 5-HT action. Applications of GABA induced a membrane current (I(GABA)), which was completely blocked by gabazine. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons.

  17. Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability.

    PubMed

    Ziminski, Joseph J; Hessler, Sabine; Margetts-Smith, Gabriella; Sieburg, Meike C; Crombag, Hans S; Koya, Eisuke

    2017-03-22

    Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFP+ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFP+ neurons were more excitable than surrounding GFP- neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell.SIGNIFICANCE STATEMENT Sparsely distributed sets of neurons called "neuronal ensembles" encode learned associations about food and cues predictive of its availability. Widespread changes in neuronal excitability have been observed in limbic brain areas after associative learning, but little is known about the excitability changes that

  18. Thresholds of cat cochlear nucleus neurons to microwave pulses.

    PubMed

    Seaman, R L; Lebovitz, R M

    1989-01-01

    Action potentials of neurons in cat dorsal and posteroventral cochlear nuclei were recorded extracellularly with glass microelectrodes while the head of the cat was exposed to microwave pulses at 915 MHz using a diathermy applicator. Response thresholds to acoustic tones, acoustic clicks, and microwave pulses were determined for auditory units with characteristic frequencies (CFs) from 278 Hz to 39.2 kHz. Tests with pulsatile stimuli were performed for durations of 20-700 mus, principally 20, 70, and 200 mus. Brainstem midline specific absorption rate (SAR) threshold was as small as 11.1 mW/g per pulse, and specific absorption (SA) threshold was a small as 0.6 muJ/g per pulse. Microwave thresholds were generally lower for CF less than 9 kHz, as were most acoustic thresholds. However, microwave threshold was only weakly related to click threshold and CF-tone threshold of each unit.

  19. Cytoarchitectural impairments in the medium spiny neurons of the Nucleus Accumbens core of hyperactive juvenile rats.

    PubMed

    González-Burgos, I; García-Martínez, S; Velázquez-Zamora, D A; Ponce-Rolón, R

    2010-10-01

    Dopaminergic activity in the Nucleus Accumbens has been strongly implicated in the motor hyperactivity associated with Attention deficit hyperactivity disorder. Dopaminergic and glutamatergic terminals converge on the dendritic spines of medium spiny neurons of the nucleus accumbens core, which modulate the excitatory glutamatergic activity. In this work, a Golgi study was carried out to investigate the effects of dopamine depletion on the cytoarchitecture of dendritic spines of nucleus accumbens core medium spiny neurons. The dopaminergic system of newborn male rats was lesioned intracisternally by using 6-hydroxydopamine, and subsequently, the motor activity, spine density, and the proportion of thin, stubby, mushroom, wide, branched, and double spines was compared to those in control and intact animals. Motor activity was significantly increased in the dopamine-depleted animals and while the spine density was reduced, there was no change in the proportion of the specific types of spines. Larger thin spines were observed in the dopamine-depleted animals. Indeed, dopamine depletion may lead to spine retraction due to the disregulation of spine development, and/or an increase in glutamatergic activity. The enlargement of thin spines may suggest a compensatory mechanism to increase the efficiency of synaptic inputs in response to a decrease in spines number. Together, the present findings suggest an alteration to the excitatory/inhibitory balance on dendritic spines of medium spiny neurons of the nucleus accumbens core in hyperactive juvenile rats following early dopamine depletion.

  20. Tremor-correlated neuronal activity in the subthalamic nucleus of Parkinsonian patients.

    PubMed

    Amtage, Florian; Henschel, Kathrin; Schelter, Björn; Vesper, Jan; Timmer, Jens; Lücking, Carl Hermann; Hellwig, Bernhard

    2008-09-19

    Tremor in Parkinson's disease (PD) is generated by an oscillatory neuronal network consisting of cortex, basal ganglia and thalamus. The subthalamic nucleus (STN) which is part of the basal ganglia is of particular interest, since deep brain stimulation of the STN is an effective treatment for PD including Parkinsonian tremor. It is controversial if and how the STN contributes to tremor generation. In this study, we analyze neuronal STN activity in seven patients with Parkinsonian rest tremor who underwent stereotactic surgery for deep brain stimulation. Surface EMG was recorded from the wrist flexors and extensors. Simultaneously, neuronal spike activity was registered in different depths of the STN using an array of five microelectrodes. After spike-sorting, spectral coherence was analyzed between spike activity of STN neurons and tremor activity. Significant coherence at the tremor frequency was detected between EMG and neuronal STN activity in 76 out of 145 neurons (52.4%). In contrast, coherence in the beta band occurred only in 10 out of 145 neurons (6.9%). Tremor-coherent STN activity was widely distributed over the STN being more frequent in its dorsal parts (70.8-88.9%) than in its ventral parts (25.0-48.0%). Our results suggest that synchronous neuronal STN activity at the tremor frequency contributes to the pathogenesis of Parkinsonian tremor. The wide-spread spatial distribution of tremor-coherent spike activity argues for the recruitment of an extended network of subthalamic neurons for tremor generation.

  1. MCT2 Expression and Lactate Influx in Anorexigenic and Orexigenic Neurons of the Arcuate Nucleus

    PubMed Central

    Cortes-Campos, Christian; Elizondo, Roberto; Carril, Claudio; Martínez, Fernando; Boric, Katica; Nualart, Francisco; Garcia-Robles, Maria Angeles

    2013-01-01

    Hypothalamic neurons of the arcuate nucleus control food intake, releasing orexigenic and anorexigenic neuropeptides in response to changes in glucose concentration. Several studies have suggested that the glucosensing mechanism is governed by a metabolic interaction between neurons and glial cells via lactate flux through monocarboxylate transporters (MCTs). Hypothalamic glial cells (tanycytes) release lactate through MCT1 and MCT4; however, similar analyses in neuroendocrine neurons have yet to be undertaken. Using primary rat hypothalamic cell cultures and fluorimetric assays, lactate incorporation was detected. Furthermore, the expression and function of MCT2 was demonstrated in the hypothalamic neuronal cell line, GT1-7, using kinetic and inhibition assays. Moreover, MCT2 expression and localization in the Sprague Dawley rat hypothalamus was analyzed using RT-PCR, in situ hybridization and Western blot analyses. Confocal immunohistochemistry analyses revealed MCT2 localization in neuronal but not glial cells. Moreover, MCT2 was localized to ∼90% of orexigenic and ∼60% of anorexigenic neurons as determined by immunolocalization analysis of AgRP and POMC with MCT2-positives neurons. Thus, MCT2 distribution coupled with lactate uptake by hypothalamic neurons suggests that hypothalamic neurons control food intake using lactate to reflect changes in glucose levels. PMID:23638108

  2. Genetic identity of thermosensory relay neurons in the lateral parabrachial nucleus

    PubMed Central

    Kim, Minjee; Mahoney, Carrie E.; Abbott, Stephen B. G.; Agostinelli, Lindsay J.; Garfield, Alastair S.; Krashes, Michael J.; Lowell, Bradford B.; Scammell, Thomas E.

    2015-01-01

    The parabrachial nucleus is important for thermoregulation because it relays skin temperature information from the spinal cord to the hypothalamus. Prior work in rats localized thermosensory relay neurons to its lateral subdivision (LPB), but the genetic and neurochemical identity of these neurons remains unknown. To determine the identity of LPB thermosensory neurons, we exposed mice to a warm (36°C) or cool (4°C) ambient temperature. Each condition activated neurons in distinct LPB subregions that receive input from the spinal cord. Most c-Fos+ neurons in these LPB subregions expressed the transcription factor marker FoxP2. Consistent with prior evidence that LPB thermosensory relay neurons are glutamatergic, all FoxP2+ neurons in these subregions colocalized with green fluorescent protein (GFP) in reporter mice for Vglut2, but not for Vgat. Prodynorphin (Pdyn)-expressing neurons were identified using a GFP reporter mouse and formed a caudal subset of LPB FoxP2+ neurons, primarily in the dorsal lateral subnucleus (PBdL). Warm exposure activated many FoxP2+ neurons within PBdL. Half of the c-Fos+ neurons in PBdL were Pdyn+, and most of these project into the preoptic area. Cool exposure activated a separate FoxP2+ cluster of neurons in the far-rostral LPB, which we named the rostral-to-external lateral subnucleus (PBreL). These findings improve our understanding of LPB organization and reveal that Pdyn-IRES-Cre mice provide genetic access to warm-activated, FoxP2+ glutamatergic neurons in PBdL, many of which project to the hypothalamus. PMID:26491097

  3. Genetic identity of thermosensory relay neurons in the lateral parabrachial nucleus.

    PubMed

    Geerling, Joel C; Kim, Minjee; Mahoney, Carrie E; Abbott, Stephen B G; Agostinelli, Lindsay J; Garfield, Alastair S; Krashes, Michael J; Lowell, Bradford B; Scammell, Thomas E

    2016-01-01

    The parabrachial nucleus is important for thermoregulation because it relays skin temperature information from the spinal cord to the hypothalamus. Prior work in rats localized thermosensory relay neurons to its lateral subdivision (LPB), but the genetic and neurochemical identity of these neurons remains unknown. To determine the identity of LPB thermosensory neurons, we exposed mice to a warm (36°C) or cool (4°C) ambient temperature. Each condition activated neurons in distinct LPB subregions that receive input from the spinal cord. Most c-Fos+ neurons in these LPB subregions expressed the transcription factor marker FoxP2. Consistent with prior evidence that LPB thermosensory relay neurons are glutamatergic, all FoxP2+ neurons in these subregions colocalized with green fluorescent protein (GFP) in reporter mice for Vglut2, but not for Vgat. Prodynorphin (Pdyn)-expressing neurons were identified using a GFP reporter mouse and formed a caudal subset of LPB FoxP2+ neurons, primarily in the dorsal lateral subnucleus (PBdL). Warm exposure activated many FoxP2+ neurons within PBdL. Half of the c-Fos+ neurons in PBdL were Pdyn+, and most of these project into the preoptic area. Cool exposure activated a separate FoxP2+ cluster of neurons in the far-rostral LPB, which we named the rostral-to-external lateral subnucleus (PBreL). These findings improve our understanding of LPB organization and reveal that Pdyn-IRES-Cre mice provide genetic access to warm-activated, FoxP2+ glutamatergic neurons in PBdL, many of which project to the hypothalamus.

  4. Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B.

    PubMed

    Goodman, Robert L; Lehman, Michael N; Smith, Jeremy T; Coolen, Lique M; de Oliveira, Cleusa V R; Jafarzadehshirazi, Mohammad R; Pereira, Alda; Iqbal, Javed; Caraty, Alain; Ciofi, Philippe; Clarke, Iain J

    2007-12-01

    Kisspeptin is a potent stimulator of GnRH secretion that has been implicated in the feedback actions of ovarian steroids. In ewes, the majority of hypothalamic kisspeptin neurons are found in the arcuate nucleus (ARC), with a smaller population located in the preoptic area. Most arcuate kisspeptin neurons express estrogen receptor-alpha, as do a set of arcuate neurons that contain both dynorphin and neurokinin B (NKB), suggesting that all three neuropeptides are colocalized in the same cells. In this study we tested this hypothesis using dual immunocytochemistry and also determined if kisspeptin neurons contain MSH or agouti-related peptide. To assess colocalization of kisspeptin and dynorphin, we used paraformaldehyde-fixed tissue from estrogen-treated ovariectomized ewes in the breeding season (n = 5). Almost all ARC, but no preoptic area, kisspeptin neurons contained dynorphin. Similarly, almost all ARC dynorphin neurons contained kisspeptin. In experiment 2 we examined colocalization of kisspeptin and NKB in picric-acid fixed tissue collected from ovary intact ewes (n = 9). Over three quarters of ARC kisspeptin neurons also expressed NKB, and a similar percentage of NKB neurons contained kisspeptin. In contrast, no kisspeptin neurons stained for MSH or agouti-related peptide. These data demonstrate that, in the ewe, a high percentage of ARC kisspeptin neurons also produce dynorphin and NKB, and we propose that a single subpopulation of ARC neurons contains all three neuropeptides. Because virtually all of these neurons express estrogen and progesterone re-ceptors, they are likely to relay the feedback effects of these steroids to GnRH neurons to regulate reproductive function.

  5. Sulfated cholecystokinin-8 activates phospho-mTOR immunoreactive neurons of the paraventricular nucleus in rats

    PubMed Central

    Frommelt, Lisa; Inhoff, Tobias; Lommel, Reinhardt; Stengel, Andreas; Taché, Yvette; Grötzinger, Carsten; Bannert, Norbert; Wiedenmann, Bertram; Klapp, Burghard F.; Kobelt, Peter

    2014-01-01

    The serin/threonin-kinase, mammalian target of rapamycin (mTOR) was detected in the arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN) and suggested to play a role in the integration of satiety signals. Since cholecystokinin (CCK) plays a role in the short-term inhibition of food intake and induces c-Fos in PVN neurons, the aim was to determine whether intraperitoneally injected CCK-8S affects the neuronal activity in cells immunoreactive for phospho-mTOR in the PVN. Ad libitum fed male Sprague-Dawley rats received 6 or 10 μg/kg CCK-8S or 0.15 M NaCl ip (n=4/group). The number of c-Fosimmunoreactive (ir) neurons was assessed in the PVN, ARC and in the nucleus of the solitary tract (NTS). CCK-8S increased the number of c-Fos-ir neurons in the PVN (6 μg: 103 ± 13 vs. 10 μg: 165 ± 14 neurons/section; p<0.05) compared to vehicle treated rats (4 ± 1, p<0.05), but not in the ARC. CCK-8S also dose-dependently increased the number of c-Fos neurons in the NTS. Staining for phospho-mTOR and c-Fos in the PVN showed a dose-dependent increase of activated phospho-mTOR neurons (17 ± 3 vs. 38 ± 2 neurons/section; p<0.05), while no activated phospho-mTOR neurons were observed in the vehicle group. Triple staining in the PVN showed activation of phospho-mTOR neurons co-localized with oxytocin, corresponding to 9.8 ± 3.6% and 19.5 ± 3.3% of oxytocin neurons respectively. Our observations indicate that peripheral CCK-8S activates phospho-mTOR neurons in the PVN and suggest that phospho-mTOR plays a role in the mediation of CCK-8S's anorexigenic effects. PMID:20933028

  6. Molecular Properties of Kiss1 Neurons in the Arcuate Nucleus of the Mouse

    PubMed Central

    Gottsch, Michelle L.; Popa, Simina M.; Lawhorn, Janessa K.; Qiu, Jian; Tonsfeldt, Karen J.; Bosch, Martha A.; Kelly, Martin J.; Rønnekleiv, Oline K.; Sanz, Elisenda; McKnight, G. Stanley; Clifton, Donald K.; Palmiter, Richard D.

    2011-01-01

    Neurons that produce kisspeptin play a critical role in reproduction. However, understanding the molecular physiology of kisspeptin neurons has been limited by the lack of an in vivo marker for those cells. Here, we report the development of a Kiss1-CreGFP knockin mouse, wherein the endogenous Kiss1 promoter directs the expression of a Cre recombinase-enhanced green fluorescent protein (GFP) fusion protein. The pattern of GFP expression in the brain of the knockin recapitulates what has been described earlier for Kiss1 in the male and female mouse, with prominent expression in the arcuate nucleus (ARC) (in both sexes) and the anteroventral periventricular nucleus (in females). Single-cell RT-PCR showed that the Kiss1 transcript is expressed in 100% of GFP-labeled cells, and the CreGFP transcript was regulated by estradiol in the same manner as the Kiss1 gene (i.e. inhibited in the ARC and induced in the anteroventral periventricular nucleus). We used this mouse to evaluate the biophysical properties of kisspeptin (Kiss1) neurons in the ARC of the female mouse. GFP-expressing Kiss1 neurons were identified in hypothalamic slice preparations of the ARC and patch clamped. Whole-cell (and loose attached) recordings revealed that Kiss1 neurons exhibit spontaneous activity and expressed both h- (pacemaker) and T-type calcium currents, and hyperpolarization-activated cyclic nucleotide-regulated 1–4 and CaV3.1 channel subtypes (measured by single cell RT-PCR), respectively. N-methyl-D-aspartate induced bursting activity, characterized by depolarizing/hyperpolarizing oscillations. Therefore, Kiss1 neurons in the ARC share molecular and electrophysiological properties of other CNS pacemaker neurons. PMID:21933870

  7. Nuclear configuration and neuronal types of the nucleus niger in the brain of the human adult.

    PubMed

    Braak, H; Braak, E

    1986-01-01

    The pigmentoarchitectonic analysis of the human nucleus niger reveals three main territories: Pars compacta, pars diffusa and pars reticulata. Seven subnuclei are recognized within the pars compacta. The nerve cell types forming the nucleus niger were investigated using a Golgi de-impregnation technique in combination with counterstaining of intraneuronally deposited pigment granules. Three principal types of neurons were defined: Type I was a medium-sized to large neuron, mainly encountered in the pars compacta, giving off a few thick and sparsely branching dendrites. These cells were richly endowed with elongated patches of Nissl material that were mainly found in the peripheral portions of the dendrites. One pole of the cell body contained tightly packed neuromelanin granules. Type II neurons were mainly found in the pars reticulata. They were variable in size and shape and generated, similar to type I neurons, extended and sparsely branching dendrites. Type II neurons were devoid of neuromelanin. A considerable number of these cells were lacking in lipofuscin deposits as well. Type III neurons occurred in all portions of the nuclear complex. The small cell body gave rise to a few thin and spineless dendrites. The axon and filiform processes of the dendrites showed small varicosities irregularly spaced apart. The pale cytoplasm contained small and intensely stained lipofuscin granules, which did not tend to agglomerate. Intraneuronally deposited neuromelanin and lipofuscin pigment can be considered a natural marker of the neuronal type in the nucleus niger of the human adult. The technique and the data provide a basis for investigations of the aged and the diseased human brain.

  8. A cluster analysis of the neurons of the rat interpeduncular nucleus.

    PubMed Central

    Gioia, M; Vizzotto, L; Bianchi, R

    1994-01-01

    The morphometric characteristics of the neurons of the interpeduncular nucleus (IPN) in the rat were investigated by cluster analysis in order to identify neuronal groups which are morphometrically homogeneous, and to define their position and density in the IPN subnuclei. Two clusters of cells were detected. Cluster 1 neurons had a larger perikaryal size with a mean cross-sectional area of 170 microns2 and a high nuclear/cytoplasmic ratio. They were located mainly in the pars dorsalis (37%) and pars medialis (34%) rather than in the pars lateralis (29%). Cluster 1 neurons were also more frequent at the rostral (31%) and caudal (57%) poles than in the central part of the IPN. Cluster 2 cells showed a smaller mean perikaryal area (110 microns2), a small nucleus and abundant cytoplasm. They were equally distributed throughout the whole IPN. These findings suggest the existence of a magnocellular region at the rostral pole of the IPN which has not been described previously. The presence of IPN regions endowed with specific cytoarchitectural characteristics is discussed with respect to the complex neurochemical organisation of the nucleus. Images Fig. 1 Fig. 2 Fig. 4 PMID:7649781

  9. Local synaptic release of glutamate from neurons in the rat hypothalamic arcuate nucleus.

    PubMed Central

    Belousov, A B; van den Pol, A N

    1997-01-01

    1. The hypothalamic arcuate nucleus (ARC) contains neuroendocrine neurons that regulate endocrine secretions by releasing substances which control anterior pituitary hormonal release into the portal blood stream. Many neuroactive substances have been identified in the ARC, but the existence of excitatory neurons in the ARC and the identity of an excitatory transmitter have not been investigated physiologically. 2. In the present experiments using whole-cell current- and voltage-clamp recording of neurons from cultures and slices of the ARC, we demonstrate for the first time that some of the neurons in the ARC secrete glutamate as their transmitter. 3. Using microdrop stimulation of presynaptic neurons in ARC slices, we found that local axons from these glutamatergic neurons make local synaptic contact with other neurons in the ARC and that all evoked excitatory postsynaptic potentials could be blocked by the selective ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) and D,L-2-amino-5-phosphonovalerate (AP5; 100 microM). To determine the identity of ARC neurons postsynaptic to local glutamatergic neurons, we used antidromic stimulation to reveal that many of these cells were neuroendocrine neurons by virtue of their maintaining axon terminals in the median eminence. 4. In ARC cultures, postsynaptic potentials, both excitatory and inhibitory, were virtually eliminated by the glutamate receptor antagonists AP5 and CNQX, underlining the functional importance of glutamate within this part of the neuroendocrine brain. 5. GABA was secreted by a subset of ARC neurons from local axons. The GABAA receptor antagonist bicuculline released glutamatergic neurons from chronic inhibition mediated by synaptically released GABA, resulting in further depolarization and an increase in the amplitude and frequency of glutamate-mediated excitatory postsynaptic potentials. Images Figure 1 PMID:9130170

  10. Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

    PubMed Central

    Boychuk, Carie R.; Gyarmati, Peter; Xu, Hong

    2015-01-01

    Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated. PMID:26084907

  11. Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii.

    PubMed

    Boychuk, Carie R; Gyarmati, Peter; Xu, Hong; Smith, Bret N

    2015-08-01

    Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated.

  12. Globus Pallidus Externus Neurons Expressing parvalbumin Interconnect the Subthalamic Nucleus and Striatal Interneurons

    PubMed Central

    Saunders, Arpiar; Huang, Kee Wui; Sabatini, Bernardo Luis

    2016-01-01

    The globus pallidus externus (GP) is a nucleus of the basal ganglia (BG), containing GABAergic projection neurons that arborize widely throughout the BG, thalamus and cortex. Ongoing work seeks to map axonal projection patterns from GP cell types, as defined by their electrophysiological and molecular properties. Here we use transgenic mice and recombinant viruses to characterize parvalbumin expressing (PV+) GP neurons within the BG circuit. We confirm that PV+ neurons 1) make up ~40% of the GP neurons 2) exhibit fast-firing spontaneous activity and 3) provide the major axonal arborization to the STN and substantia nigra reticulata/compacta (SNr/c). PV+ neurons also innervate the striatum. Retrograde labeling identifies ~17% of pallidostriatal neurons as PV+, at least a subset of which also innervate the STN and SNr. Optogenetic experiments in acute brain slices demonstrate that the PV+ pallidostriatal axons make potent inhibitory synapses on low threshold spiking (LTS) and fast-spiking interneurons (FS) in the striatum, but rarely on spiny projection neurons (SPNs). Thus PV+ GP neurons are synaptically positioned to directly coordinate activity between BG input nuclei, the striatum and STN, and thalamic-output from the SNr. PMID:26905595

  13. [Responses of the reticular nucleus neurons and dorsal thalamic nuclei neurons in the cat during extinction of a conditioned instrumental reflex].

    PubMed

    Moldavan, M G

    1991-01-01

    Activity of 66 neurons of the reticular nucleus (R), 31 neurons of the ventroposterolateral nucleus and 14 neurons of the posterolateral nucleus-pulvinar complex of the thalamus was investigated during extinction of the conditioned instrumental alimentary reflex. The quantity of R neurons that show initial excitation in response to the conditional stimulus in the first 300 ms decreased during extinction. Conditioned placing reactions and late excitatory and inhibitory neuronal responses in the R and dorsal thalamic nuclei with latency above 300 ms disappeared during extinction simultaneously. The background unit activity decreased during extinction in the 2/3 of investigated neurons of R and dorsal thalamic nuclei. It is suggested that the efferent influence from the R decreased during extinction.

  14. Evidence that Neurons of the Sublaterodorsal Tegmental Nucleus Triggering Paradoxical (REM) Sleep Are Glutamatergic

    PubMed Central

    Clément, Olivier; Sapin, Emilie; Bérod, Anne; Fort, Patrice; Luppi, Pierre-Hervé

    2011-01-01

    Study Objectives: To determine whether sublaterodorsal tegmental nucleus (SLD) neurons triggering paradoxical (REM) sleep (PS) are glutamatergic. Design: Three groups of rats were used: controls, rats deprived of PS for 72 h, and rats allowed to recover for 3 h after deprivation. Brain sections were processed for double labeling combining Fos immunohistochemistry and vesicular glutamate transporter 2 (vGLUT2) in situ hybridization. Measurements and Results: The number of single Fos+ and Fos/vGLUT2+ double-labeled neurons was counted for each experimental condition. A very large number of Fos+ neurons expressing vGLUT2 mRNA specifically after PS hypersomnia was counted in the SLD. These double-labeled cells accounted for 84% of the total number of Fos+ cells. Conclusions: This finding adds further evidence to the concept that PS-on neurons of the SLD generating PS are of small size and glutamatergic in nature. By means of their descending projections to medullary and/or spinal glycinergic/GABAergic premotoneurons, they may be especially important for the induction of muscle atonia during PS, a disturbed phenomenon in narcolepsy and REM sleep behavior disorder. Citation: Clément O; Sapin E; Bérod A; Fort P; Luppi PH. Evidence that neurons of the sublaterodorsal tegmental nucleus triggering paradoxical (REM) sleep are glutamatergic. SLEEP 2011;34(4):419-423. PMID:21461384

  15. Neurons in the Nucleus Accumbens Promote Selection Bias for Nearer Objects

    PubMed Central

    Morrison, Sara E.

    2014-01-01

    Both animals and humans often prefer rewarding options that are nearby over those that are distant, but the neural mechanisms underlying this bias are unclear. Here we present evidence that a proximity signal encoded by neurons in the nucleus accumbens drives proximate reward bias by promoting impulsive approach to nearby reward-associated objects. On a novel decision-making task, rats chose the nearer option even when it resulted in greater effort expenditure and delay to reward; therefore, proximate reward bias was unlikely to be caused by effort or delay discounting. The activity of individual neurons in the nucleus accumbens did not consistently encode the reward or effort associated with specific alternatives, suggesting that it does not participate in weighing the values of options. In contrast, proximity encoding was consistent and did not depend on the subsequent choice, implying that accumbens activity drives approach to the nearest rewarding option regardless of its specific associated reward size or effort level. PMID:25319709

  16. Spinally projecting neurons of the dorsal column nucleus in a reptile: locus of origin and trajectory of termination.

    PubMed

    Pritz, M B

    1996-01-01

    Interconnections between the dorsal column nucleus and the spinal cord were investigated in a reptile, Caiman crocodilus. After placement of an anterograde tracer into the dorsal column nucleus, descending fibers are seen to leave this nucleus to enter the dorsal funiculus where they course ventrally to terminate in lamina V of the spinal cord as far caudally as C2. Placement of a retrograde tracer into cut fibers of the cervical spinal cord identified the relay cells of the dorsal column nucleus that project to the spinal cord. These neurons were mainly clustered in a caudal and ventral part of this nucleus. The soma of these spinally projecting cells were small and were generally round or oval in shape. A number of these neurons had the long axis of their soma oriented dorsoventrally, with a primary dendrite extending dorsally. Fibers in the dorsal funiculus that originated from the spinal cord enter the caudal part of the dorsal column nucleus and turn ventral. In the dorsal column nucleus, these axons run parallel to the vertically oriented dendrites of these spinally projecting cells before termination in close relation to the cell bodies of these neurons. Quantitative observations (mean +/- standard error) were made on well labeled neurons and included several measurements: area, perimeter, and degree of eccentricity (greatest width/greatest length) in both the transverse as well as the sagittal plane. These spinally projecting neurons in Caiman are located in the dorsal column nucleus in a position similar to that of spinally projecting cells in cats.

  17. Electrical and morphological characteristics of anteroventral periventricular nucleus kisspeptin and other neurons in the female mouse.

    PubMed

    Ducret, Eric; Gaidamaka, Galina; Herbison, Allan E

    2010-05-01

    Neurons in the rodent anteroventral periventricular nucleus (AVPV) play a key role in integrating circadian and gonadal steroid hormone information in the control of fertility. In particular, estradiol-sensitive kisspeptin neurons located in the AVPV, and adjacent structures [together termed the rostral periventricular area of the third ventricle (RP3V)], are critical for puberty onset and the preovulatory LH surge. The present study aimed to establish the morphological and electrical firing characteristics of RP3V neurons, including kisspeptin neurons, in the adult female mouse. Cell-attached electrical recordings, followed by juxtacellular dye filling, of 129 RP3V neurons in the acute brain slice preparation revealed these cells to exhibit multipolar (53%), bipolar (43%), or unipolar (4%) dendritic morphologies along with silent (16%), irregular (41%), bursting (25%), or tonic (34%) firing patterns. Postrecording immunocytochemistry identified 17 of 100 filled RP3V cells as being kisspeptin neurons, all of which exhibited complex multipolar dendritic trees and significantly (P < 0.05) higher bursting or high tonic firing rates compared with nonkisspeptin neurons. The firing pattern of RP3V neurons fluctuated across the estrous cycle with a significant (P < 0.05) switch from irregular to tonic firing patterns found on proestrus. A similar nonsignificant trend was found for kisspeptin neurons. All RP3V neurons responded to gamma-aminobutyric acid and glutamate, about 10% to RFamide-related peptide-3, about 5% to vasopressin, 0% to vasoactive intestinal peptide, and 0% to kisspeptin. These studies provide a morphological and electrical description of AVPV/RP3V neurons and demonstrate their cycle-dependent firing patterns along with an unexpected lack of acute response to the circadian neuropeptides.

  18. Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion.

    PubMed

    Lamy, Christophe M; Sanno, Hitomi; Labouèbe, Gwenaël; Picard, Alexandre; Magnan, Christophe; Chatton, Jean-Yves; Thorens, Bernard

    2014-03-04

    Glucose-sensing neurons in the brainstem participate in the regulation of energy homeostasis but have been poorly characterized because of the lack of specific markers to identify them. Here we show that GLUT2-expressing neurons of the nucleus of the tractus solitarius form a distinct population of hypoglycemia-activated neurons. Their response to low glucose is mediated by reduced intracellular glucose metabolism, increased AMP-activated protein kinase activity, and closure of leak K(+) channels. These are GABAergic neurons that send projections to the vagal motor nucleus. Light-induced stimulation of channelrhodospin-expressing GLUT2 neurons in vivo led to increased parasympathetic nerve firing and glucagon secretion. Thus GLUT2 neurons of the nucleus tractus solitarius link hypoglycemia detection to counterregulatory response. These results may help identify the cause of hypoglycemia-associated autonomic failure, a major threat in the insulin treatment of diabetes.

  19. Dendritic geometry shapes neuronal cAMP signalling to the nucleus.

    PubMed

    Li, Lu; Gervasi, Nicolas; Girault, Jean-Antoine

    2015-02-18

    Neurons have complex dendritic trees, receiving numerous inputs at various distances from the cell body. Yet the rules of molecular signal propagation from dendrites to nuclei are unknown. DARPP-32 is a phosphorylation-regulated signalling hub in striatal output neurons. We combine diffusion-reaction modelling and live imaging to investigate cAMP-activated DARPP-32 signalling to the nucleus. The model predicts maximal effects on the nucleus of cAMP production in secondary dendrites, due to segmental decrease of dendrite diameter. Variations in branching, perikaryon size or spines have less pronounced effects. Biosensor kinase activity measurement following cAMP or dopamine uncaging confirms these predictions. Histone 3 phosphorylation, regulated by this pathway, is best stimulated by cAMP released in secondary-like dendrites. Thus, unexpectedly, the efficacy of diffusion-based signalling from dendrites to nucleus is not inversely proportional to the distance. We suggest a general mechanism by which dendritic geometry counterbalances the effect of dendritic distance for signalling to the nucleus.

  20. Orexin action on oxytocin neurons in the paraventricular nucleus of the hypothalamus.

    PubMed

    Maejima, Yuko; Takahashi, Shinichi; Takasu, Katsuya; Takenoshita, Seiichi; Ueta, Yoichi; Shimomura, Kenju

    2017-04-12

    Oxytocin neurons in the paraventricular nucleus (PVN) of the hypothalamus play an important role in food intake regulation. It has been shown that the secretion of oxytocin from the hypothalamus shows a diurnal circadian rhythmic pattern and disturbance of this pattern leads to the development of obesity. However, whether oxytocin secretion from the PVN has a diurnal pattern remains unknown. Here, we show that oxytocin secretion from the PVN does have a diurnal pattern and that the terminals of orexin neurons, the neuropeptide responsible for regulating the sleep-wake rhythm, are synapsed with PVN oxytocin neurons. Using transgenic rats selectively expressing monomeric red fluorescent protein 1 in oxytocin neurons, we found that orexin-A inhibits the activities of PVN oxytocin neurons by inhibiting glutamatergic excitatory synaptic input. These data suggest that orexin is a possible candidate to regulate the circadian rhythm of PVN oxytocin neurons. The circadian rhythmic secretion of oxytocin is considered to play an important role in maintaining homeostasis, including body weight regulation. Our present data indicate a possible contribution of orexin toward the development of circadian rhythm in PVN oxytocin neurons.

  1. Neuronal Activity in the Subthalamic Nucleus Modulates the Release of Dopamine in the Monkey Striatum

    PubMed Central

    Shimo, Yasushi; Wichmann, Thomas

    2009-01-01

    The primate subthalamic nucleus (STN) is commonly seen as a relay nucleus between the external and internal pallidal segments, and as an input station for cortical and thalamic information into the basal ganglia. In rodents, STN activity is also known to influence neuronal activity in the dopaminergic substantia nigra pars compacta (SNc) through inhibitory and excitatory mono- and polysynaptic pathways. Although the anatomical connections between STN and SNc are not entirely the same in primates as in rodents, the electrophysiologic and microdialysis experiments presented here show directly that this functional interaction can also be demonstrated in primates. In three Rhesus monkeys, extracellular recordings from SNc during microinjections into the STN revealed that transient pharmacologic activation of the subthalamic nucleus by the acetylcholine-receptor agonist carbachol substantially increased burst firing of single nigral neurons. Transient inactivation of the STN with microinjections of the GABA-A-receptor agonist muscimol had the opposite effect. While the firing rates of individual SNc neurons changed in response to the activation or inactivation of the STN, these changes were not consistent across the entire population of SNc cells. Permanent lesions of the STN, produced in two animals with the fiber-sparing neurotoxin ibotenic acid, reduced burst firing and firing rates of SNc neurons, and substantially decreased dopamine levels in the primary recipient area of SNc projections, the striatum, as measured with microdialysis. These results suggest that activity in the primate SNc is prominently influenced by neuronal discharge in the STN, which may thus alter dopamine release in the striatum. PMID:19087163

  2. [Effect of the intermittent hypoxic training on the functioning of peptidergic neurons of the paraventricular hypothalamic nucleus and brain stem neurons in rats].

    PubMed

    Abramov, A V

    1998-03-01

    Internittent hypoxic training (IHT) increased the quantity and secretory activity of peptidergic neurons of the paraventricular hypothalamic nucleus (PHN) and activated neurons of the dorsal motor nucleus of n.vagus. These structures seem to take part in realisation of the IHT activating effect on condition of the pancreatic delta-cells. The effect involves insulin-stimulating and insuloprotective effects realised via hypothalamic and neuro-conducting ways of regulation of the endocrine pancreas with a direct participation of hypothalamic neuropeptides.

  3. Activity Parameters of Subthalamic Nucleus Neurons Selectively Predict Motor Symptom Severity in Parkinson's Disease

    PubMed Central

    Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A.; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A.; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K.

    2014-01-01

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype. PMID:24790198

  4. Activity parameters of subthalamic nucleus neurons selectively predict motor symptom severity in Parkinson's disease.

    PubMed

    Sharott, Andrew; Gulberti, Alessandro; Zittel, Simone; Tudor Jones, Adam A; Fickel, Ulrich; Münchau, Alexander; Köppen, Johannes A; Gerloff, Christian; Westphal, Manfred; Buhmann, Carsten; Hamel, Wolfgang; Engel, Andreas K; Moll, Christian K E

    2014-04-30

    Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥ 10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype.

  5. Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons.

    PubMed

    Habib, Naomi; Li, Yinqing; Heidenreich, Matthias; Swiech, Lukasz; Avraham-Davidi, Inbal; Trombetta, John J; Hession, Cynthia; Zhang, Feng; Regev, Aviv

    2016-08-26

    Single-cell RNA sequencing (RNA-Seq) provides rich information about cell types and states. However, it is difficult to capture rare dynamic processes, such as adult neurogenesis, because isolation of rare neurons from adult tissue is challenging and markers for each phase are limited. Here, we develop Div-Seq, which combines scalable single-nucleus RNA-Seq (sNuc-Seq) with pulse labeling of proliferating cells by 5-ethynyl-2'-deoxyuridine (EdU) to profile individual dividing cells. sNuc-Seq and Div-Seq can sensitively identify closely related hippocampal cell types and track transcriptional dynamics of newborn neurons within the adult hippocampal neurogenic niche, respectively. We also apply Div-Seq to identify and profile rare newborn neurons in the adult spinal cord, a noncanonical neurogenic region. sNuc-Seq and Div-Seq open the way for unbiased analysis of diverse complex tissues.

  6. Thalamic VPM nucleus in the behaving monkey. I. Multimodal and discriminative properties of thermosensitive neurons.

    PubMed

    Bushnell, M C; Duncan, G H; Tremblay, N

    1993-03-01

    1. The role of the thalamic ventroposterior medial (VPM) nucleus in the discriminative aspects of nociception and thermoreception was evaluated in alert, trained rhesus monkeys. Single-unit responses were recorded from VPM while the monkeys performed a battery of tasks involving noxious heat, innocuous cool, and air-puff stimuli presented to the face. The discriminative ability of the monkey was compared directly with the responses of single neurons, to determine whether the neuronal response could subserve the monkey's discriminative behavior. 2. Most thermally sensitive neurons exhibited multimodal properties. Only 18% responded exclusively to heat (HT-Heat neurons), whereas 27% responded to innocuous mechanical, as well as noxious mechanical and heat stimuli (WDR-Heat). Twenty-three percent responded to innocuous mechanical stimuli and innocuous skin cooling (Mechano-Cool), and 32% responded to mechanical, innocuous cool, and noxious heat stimuli (WDR-Heat-Cool). 3. Almost all mechanical receptive fields were confined to one division of the trigeminal nerve. This was true for all of the above categories of VPM neurons, even those showing highly convergent properties (WDR-Heat-Cool). 4. Heat-activated neurons produced graded responses to noxious skin heating in the 46 to 49 degrees C range. Stimulus-response functions of neurons that responded to both heat and cool did not differ from those of neurons that responded exclusively to skin heating. 5. When the monkeys were detecting small changes in the intensity of a noxious heat stimulus (e.g., from 47 to 47.1-47.8 degrees C), heat-activated neurons responded to the smallest temperature changes that could be detected by the monkeys. Further, there was a high correlation between the monkey's success in detecting the stimulus changes and the magnitude of the neuronal responses to those changes. 6. Although the responsiveness of VPM cool-activated neurons was not compared with the monkeys' threshold for detecting

  7. The development and migration of large multipolar neurons into the cochlear nucleus of the North American opossum.

    PubMed

    Willard, F H; Martin, G F

    1986-06-01

    We have studied the maturation of the inferior colliculus and cochlear nuclei of the North American opossum with particular emphasis on the large multipolar neurons of the cochlear nucleus. These neurons include the principal and giant cells of the dorsal cochlear nucleus (DCN) and the large neurons of the ventral cochlear nucleus (VCN), all of which can be labelled by horseradish peroxidase (HRP) injections into the contralateral inferior colliculus (IC). The size of these neurons, their characteristic Nissl patterns, and their labelling density after injections into the IC render them distinguishable from other neurons in this nuclei, even in young animals. In Nissl-stained sections of newborn opossums, a band of horizontally oriented neurons can be identified dorsomedial to the vestibular nerve root. This band extends from an apparent cytogenetic zone close to the sulcus limitans, to, but not within, the presumptive cochlear nucleus. Between birth and estimated postnatal day 22 (EPND 22) the band shifts laterally, eventually becoming incorporated into the cochlear nucleus. Many neurons in this band have perinuclear caps of Nissl substance similar to those present in the principal cells of the adult DCN. Injections of HRP into the IC as early as EPND 5 (17 days after conception) labelled neurons in the band referred to above but not in the presumptive cochlear nucleus. By EPND 15, labelled cells were clustered mainly within the nucleus proper. Most of these cells were located in the DCN, but a few were scattered in the dorsocentral VCN. Consistent labelling of small neurons in VCN was not obtained until sometime later. From EPND 15 to EPND 20 most of the labelled cells in DCN reoriented in the vertical plane, aligned in layer II, and differentiated into principal neurons. Some, however, remained deep to layer II and differentiated into giant neurons. The heavily labelled cells in VCN differentiated into large neurons. Our results suggest that the large multipolar

  8. Nucleus accumbens neuronal activity correlates to the animal's behavioral response to acute and chronic methylphenidate.

    PubMed

    Claussen, Catherine M; Chong, Samuel L; Dafny, Nachum

    2014-04-22

    Acute and chronic methylphenidate (MPD) exposure was recorded simultaneously for the rat's locomotor activity and the nucleus accumbens (NAc) neuronal activity. The evaluation of the neuronal events was based on the animal's behavior response to chronic MPD administration: 1) Animals exhibiting behavioral sensitization, 2) Animals exhibiting behavioral tolerance. The experiment lasted for 10days with four groups of animals; saline, 0.6, 2.5, and 10.0mg/kg MPD. For the main behavioral findings, about half of the animals exhibited behavioral sensitization or behavioral tolerance to 0.6, 2.5, and/or 10mg/kg MPD respectively. Three hundred and forty one NAc neuronal units were evaluated. Approximately 80% of NAc units responded to 0.6, 2.5, and 10.0mg/kg MPD. When the neuronal activity was analyzed based on the animals' behavioral response to chronic MPD exposure, significant differences were seen between the neuronal population responses recorded from animals that expressed behavioral sensitization when compared to the NAc neuronal responses recorded from animals exhibiting behavioral tolerance. Three types of neurophysiological sensitization and neurophysiological tolerance can be recognized following chronic MPD administration to the neuronal populations. Collectively, these findings show that the same dose of chronic MPD can elicit either behavioral tolerance or behavioral sensitization. Differential statistical analyses were used to verify our hypothesis that the neuronal activity recorded from animals exhibiting behavioral sensitization will respond differently to MPD compared to those animals exhibiting behavioral tolerance, thus, suggesting that it is essential to record the animal's behavior concomitantly with neuronal recordings.

  9. Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation.

    PubMed

    Young, E D; Sachs, M B

    2008-06-12

    The strength of synapses between auditory nerve (AN) fibers and ventral cochlear nucleus (VCN) neurons is an important factor in determining the nature of neural integration in VCN neurons of different response types. Synaptic strength was analyzed using cross-correlation of spike trains recorded simultaneously from an AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as chopper, primarylike, and onset using previously defined criteria, although onset neurons usually were not analyzed because of their low discharge rates. The correlograms showed an excitatory peak (EP), consistent with monosynaptic excitation, in AN-VCN pairs with similar best frequencies (49% 24/49 of pairs with best frequencies within +/-5%). Chopper and primarylike neurons showed similar EPs, except that the primarylike neurons had shorter latencies and shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical bushy cells were not observed, probably because of the low probability of recording from one. The small EPs observed in primarylike neurons, presumably spherical bushy cells, could be derived from small terminals that accompany end bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were consistent with the smaller synaptic terminals on multipolar and globular bushy cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of threshold, showing that VCN responses to steady tones shift from a 1:1 relationship between AN and VCN spikes at low sound levels to a more autonomous mode of firing at high levels. In the high level mode, the pattern of output spikes seems to be determined by the properties of the postsynaptic spike generator rather than the input spike patterns. The EP amplitudes did not change significantly when the presynaptic spike was preceded by either a short or long interspike interval, suggesting that synaptic depression and facilitation have little effect under the conditions studied

  10. Burst-firing activity of presumed 5-HT neurones of the rat dorsal raphe nucleus: electrophysiological analysis by antidromic stimulation.

    PubMed

    Hajós, M; Sharp, T

    1996-11-18

    We recently reported raphe neurones which frequently fired spikes in short bursts. However, the action potentials were broad and the neurones fired in a slow and regular pattern, suggesting they were an unusual type of 5-hydroxytryptamine (5-HT) neurone. In the present study, we investigated whether these putative burst-firing 5-HT neurones project to the forebrain and whether all spikes fired in bursts propagate along the axon. In anaesthetised rats, electrical stimulation of the medial forebrain bundle evoked antidromic spikes in both burst-firing neurones and in single-spiking, classical 5-HT neurones recorded in the dorsal raphe nucleus. Although the antidromic spike latency of the single-spiking and burst-firing neurones showed a clear overlap, burst-firing neurones had a significantly shorter latency than single-spiking neurones. For both burst-firing neurones and classical 5-HT neurones, antidromic spikes made collisions with spontaneously occurring spikes. Furthermore, in all burst-firing neurones tested, first, second and third order spikes in a burst could be made to collide with antidromic spike. Interestingly, in a small number of burst-firing neurones, antidromic stimulation evoked spike doublets, similar to those recorded spontaneously. From these data we conclude that burst-firing neurones in the dorsal raphe nucleus project to the forebrain, and each spike generated by the burst propagates along the axon and could thereby release transmitter (5-HT).

  11. Distinct Firing Properties of Vasoactive Intestinal Peptide-Expressing Neurons in the Suprachiasmatic Nucleus

    PubMed Central

    Hermanstyne, Tracey O.; Simms, Carrie L.; Carrasquillo, Yarimar; Herzog, Erik D.; Nerbonne, Jeanne M.

    2016-01-01

    The suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behavior. Previous studies suggest a critical role for neurons expressing vasoactive intestinal peptide (VIP) in coordinating rhythmicity and synchronization in the SCN. Here we examined the firing properties of VIP-expressing SCN neurons in acute brain slices. Active and passive membrane properties were measured in VIP and in non-VIP neurons during the day and at night. Current-clamp recordings revealed that both VIP and non-VIP neurons were spontaneously active, with higher firing rates during the day than at night. Average firing frequencies, however, were higher in VIP neurons (3.1 ± 0.2 Hz, day and 2.4 ± 0.2 Hz, night) than in non-VIP neurons (1.8 ± 0.2 Hz, day and 0.9 ± 0.2 Hz, night), both day and night. The waveforms of individual action potentials in VIP and non-VIP neurons were also distinct. Action potential durations (APD50) were shorter in VIP neurons (3.6 ± 0.1 ms, day and 2.9 ± 0.1 ms, night) than in non-VIP neurons (4.4 ± 0.3 ms, day and 3.5 ± 0.2 ms, night) throughout the light-dark cycle. In addition, after hyper polarization (AHP) amplitudes were larger in VIP neurons (21 ± 0.8 mV, day and 24.9 ± 0.9 mV, night) than in non-VIP neurons (17.2 ± 1.1 mV, day and 20.5 ± 1.2 mV, night) during the day and at night. Furthermore, significant day/night differences were observed in APD50 and AHP amplitudes in both VIP and non-VIP SCN neurons, consistent with rhythmic changes in ionic conductances that contribute to shaping the firing properties of both cell types. The higher day and night firing rates of VIP neurons likely contribute to synchronizing electrical activity in the SCN. PMID:26712166

  12. Opioids inhibit visceral afferent activation of catecholamine neurons in the solitary tract nucleus.

    PubMed

    Cui, R J; Roberts, B L; Zhao, H; Andresen, M C; Appleyard, S M

    2012-10-11

    Brainstem A2/C2 catecholamine (CA) neurons within the solitary tract nucleus (NTS) influence many homeostatic functions, including food intake, stress, respiratory and cardiovascular reflexes. They also play a role in both opioid reward and withdrawal. Injections of opioids into the NTS modulate many autonomic functions influenced by catecholamine neurons including food intake and cardiac function. We recently showed that NTS-CA neurons are directly activated by incoming visceral afferent inputs. Here we determined whether opioid agonists modulate afferent activation of NTS-CA neurons using transgenic mice with EGFP expressed under the control of the tyrosine hydroxylase promoter (TH-EGFP) to identify catecholamine neurons. The opioid agonist Met-enkephalin (Met-Enk) significantly attenuated solitary tract-evoked excitatory postsynaptic currents (ST-EPSCs) in NTS TH-EGFP neurons by 80%, an effect reversed by wash or the mu opioid receptor-specific antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP). Met-Enk had a significantly greater effect to inhibit afferent inputs onto TH-EGFP-positive neurons than EGFP-negative neurons, which were only inhibited by 50%. The mu agonist, DAMGO, also inhibited the ST-EPSC in TH-EGFP neurons in a dose-dependent manner. In contrast, neither the delta agonist DPDPE, nor the kappa agonist, U69,593, consistently inhibited the ST-EPSC amplitude. Met-Enk and DAMGO increased the paired pulse ratio, decreased the frequency, but not amplitude, of mini-EPSCs and had no effect on holding current, input resistance or current-voltage relationships in TH-EGFP neurons, suggesting a presynaptic mechanism of action on afferent terminals. Met-Enk significantly reduced both the basal firing rate of NTS TH-EGFP neurons and the ability of afferent stimulation to evoke an action potential. These results suggest that opioids inhibit NTS-CA neurons by reducing an excitatory afferent drive onto these neurons through presynaptic inhibition of

  13. Activation of neurons in the hypothalamic dorsomedial nucleus via hypothalamic projections of the nucleus of the solitary tract following refeeding of fasted rats.

    PubMed

    Renner, Eva; Szabó-Meltzer, Kinga I; Puskás, Nela; Tóth, Zsuzsanna E; Dobolyi, Arpád; Palkovits, Miklós

    2010-01-01

    We report that satiation evokes neuronal activity in the ventral subdivision of the hypothalamic dorsomedial nucleus (DMH) as indicated by increased c-fos expression in response to refeeding in fasted rats. The absence of significant Fos activation following food presentation without consumption suggests that satiation but not craving for food elicits the activation of ventral DMH neurons. The distribution pattern of the prolactin-releasing peptide (PrRP)-immunoreactive (ir) network showed remarkable correlations with the distribution of activated neurons within the DMH. The PrRP-ir fibers and terminals were immunolabeled with tyrosine hydroxylase, suggesting their origin in lower brainstem instead of local, hypothalamic PrRP cells. PrRP-ir fibers arising from neurons of the nucleus of the solitary tract could be followed to the hypothalamus. Unilateral transections of these fibers at pontine and caudal hypothalamic levels resulted in a disappearance of the dense PrRP-ir network in the ventral DMH while PrRP immunoreactivity was increased in transected fibers caudal to the knife cuts as well as in perikarya of the nucleus of the solitary tract ipsilateral to the transections. In accord with these changes, the number of Fos-expressing neurons following refeeding declined in the ipsilateral but remained high in the contralateral DMH. However, the Fos response in the ventral DMH was not attenuated following chemical lesion (neonatal monosodium glutamate treatment) of the hypothalamic arcuate nucleus, another possible source of DMH inputs. These findings suggest that PrRP projections from the nucleus of the solitary tract contribute to the activation of ventral DMH neurons during refeeding, possibly by transferring information on cholecystokinin-mediated satiation.

  14. [Neuronal mechanisms of motor signal transmission in thalamic Voi nucleus in spasmodic torticollis patients].

    PubMed

    Sedov, A S; Raeva, S N; Pavlenko, V B

    2014-01-01

    Neural mechanisms of motor signal transmission in ventrooral (Voi) nucleus of motor thalamus during the realization-of voluntary and involuntary abnormal (dystonic) movements in patients with spasmodic torticollis were investigated by means of microelectrode technique. The high reactivity of the cellular Voi elements to various functional (mainly motor) tests was proved. Analysis of neuronal activity showed: (1) the difference of neural mechanisms of motor signal transmission in the realization of voluntary movement with and without the involvement of the pathological axial neck muscles, as well as passive and abnormal involuntary dystonic movements; (2) significance of sensory component in the mechanisms of sensorimotor interactions during realization of voluntary and involuntary dystonic head and neck movements, causing the activation of the axial neck muscles; (3) important role of the rhythmic and synchronized neuronal activity in motor signal transmission during the realization of active and passive movements. Participation of Voi nucleus in pathological mechanisms of spasmodic torticollis was shown. The data obtained can be used for identificatiori of Voi thalamic nucleus during stereotactic neurosurgical operations in patients with spasmodic torticollis for selection the optimum destruction (stimulation) target and reduction of postoperative effects.

  15. Serotonin activates catecholamine neurons in the solitary tract nucleus by increasing spontaneous glutamate inputs.

    PubMed

    Cui, Ran Ji; Roberts, Brandon L; Zhao, Huan; Zhu, Mingyan; Appleyard, Suzanne M

    2012-11-14

    Serotonin (5-HT) is a critical neurotransmitter in the control of autonomic functions. 5-HT(3) receptors participate in vagal afferent feedback to decrease food intake and regulate cardiovascular reflexes; however, the phenotype of the solitary tract nucleus (NTS) neurons involved is not known. A(2)/C(2) catecholamine (CA) neurons in the NTS are directly activated by visceral afferents and are important for the control of food intake and cardiovascular function, making them good candidates to respond to and mediate the effects of serotonin at the level of the NTS. This study examines serotonin's effects on NTS-CA neurons using patch-clamp techniques and transgenic mice expressing an enhanced green fluorescent protein driven by the tyrosine hydroxylase (TH) promoter (TH-EGFP) to identify catecholamine neurons. Serotonin increased the frequency of spontaneous glutamate excitatory postsynaptic currents (sEPSCs) in >90% of NTS-TH-EGFP neurons, an effect blocked by the 5-HT(3) receptor antagonist ondansetron and mimicked by the 5-HT(3) receptor agonists SR5227 and mCPBG. In contrast, 5-HT(3) receptor agonists increased sEPSCs on a minority (<30%) of non-TH neurons. 5-HT(3) receptor agonists increased the frequency, but not the amplitude, of mini-EPSCs, suggesting that their actions are presynaptic. 5-HT(3) receptor agonists increased the firing rate of TH-EGFP neurons, an effect dependent on the increased spontaneous glutamate inputs as it was blocked by the ionotropic glutamate antagonist NBQX, but independent of visceral afferent activation. These results demonstrate a cellular mechanism by which serotonin activates NTS-TH neurons and suggest a pathway by which it can increase catecholamine release in target regions to modulate food intake, motivation, stress, and cardiovascular function.

  16. Dissociation between two subgroups of the suprachiasmatic nucleus affected by the number of damped oscillated neurons

    NASA Astrophysics Data System (ADS)

    Gu, Changgui; Yang, Huijie; Rohling, Jos HT

    2017-03-01

    In mammals, the main clock located in the suprachiasmatic nucleus (SCN) of the brain synchronizes the body rhythms to the environmental light-dark cycle. The SCN is composed of about 2 ×104 neurons which can be classified into three oscillatory phenotypes: self-sustained oscillators, damped oscillators, and arrhythmic neurons. Exposed to an artificial external light-dark cycle with a period of 22 h instead of 24 h , two subgroups of the SCN can become desynchronized (dissociated). The ventrolateral (VL) subgroup receives photic input and is entrained to the external cycle and a dorsomedial (DM) subgroup oscillates with its endogenous (i.e., free running) period and is synchronized to the external light-dark cycle through coupling from the VL. In the present study, we examined the effects of damped oscillatory neurons on the dissociation between VL and DM under an external 22 h cycle. We found that, with increasing numbers of damped oscillatory neurons located in the VL, the dissociation between the VL and DM emerges, but if these neurons are increasingly present in the DM the dissociation disappears. Hence, the damped oscillatory neurons in different subregions of the SCN play distinct roles in the dissociation between the two subregions of the SCN. This shows that synchrony between SCN subregions is affected by the number of damped oscillatory neurons and the location of these cells. We suggest that more knowledge on the number and the location of these cells may explain why some species do show a dissociation between the subregions and others do not, as the distribution of oscillatory types of neurons offers a plausible and novel candidate mechanism to explain heterogeneity.

  17. Sudden Death Following Selective Neuronal Lesions in the Rat Nucleus Tractus Solitarii

    PubMed Central

    Talman, William T.; Lin, Li-Hsien

    2013-01-01

    In efforts to assess baroreflex and cardiovascular responses in rats in which substance P (SP) or catecholamine transmission had been eliminated we studied animals after bilateral injections into the nucleus tractus solitarii (NTS) of SP or stabilized SP (SSP) conjugated to saporin (SP-SAP or SSP-SAP respectively) or SAP conjugated to an antibody to dopamine-β-hydroxylase (anti-DBH-SAP). We found that SP- and SSP-SAP eliminated NTS neurons that expressed the SP neurokinin-1 receptor (NK1R) while anti-DBH-SAP eliminated NTS neurons expressing tyrosine hydroxylase (TH) and DBH. The toxins were selective. Thus SP-or SSP-SAP did not eliminate TH/DBH neurons and anti-DBH-SAP did not eliminate NK1R neurons in the NTS. Each toxin, however, led to chronic lability of arterial blood pressure, diminished baroreflex function, cardiac ventricular irritability, coagulation necrosis of cardiac myocytes and, in some animals, sudden death associated with asystole. However, when TH/DBH neurons were targeted and eliminated by injection of 6-hydroxydopamine (6-OHDA), none of the cardiovascular or cardiac changes occurred. The studies reviewed here reveal that selective lesions of the NTS lead to altered baroreflex control and to cardiac changes that may lead to sudden death. Though the findings could support a role for SP or catecholamines in baroreflex transmission neither is proven in that NK1R colocalizes with glutamate receptors. Thus neurons with both are lost when treated with SP- or SSP-SAP. In addition, loss of catecholamine neurons after treatment with 6-OHDA does not affect cardiovascular control. Thus, the effect of the toxins may depend on an action of SAP independent of the effects of the SAP conjugates on targeted neuronal types. PMID:23245583

  18. TASK-2 Channels Contribute to pH Sensitivity of Retrotrapezoid Nucleus Chemoreceptor Neurons

    PubMed Central

    Wang, Sheng; Benamer, Najate; Zanella, Sébastien; Kumar, Natasha N.; Shi, Yingtang; Bévengut, Michelle; Penton, David; Guyenet, Patrice G.; Lesage, Florian

    2013-01-01

    Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) display properties expected of central respiratory chemoreceptors; they are directly activated by CO2/H+ via an unidentified pH-sensitive background K+ channel and, in turn, facilitate brainstem networks that control breathing. Here, we used a knock-out mouse model to examine whether TASK-2 (K2P5), an alkaline-activated background K+ channel, contributes to RTN neuronal pH sensitivity. We made patch-clamp recordings in brainstem slices from RTN neurons that were identified by expression of GFP (directed by the Phox2b promoter) or β-galactosidase (from the gene trap used for TASK-2 knock-out). Whereas nearly all RTN cells from control mice were pH sensitive (95%, n = 58 of 61), only 56% of GFP-expressing RTN neurons from TASK-2−/− mice (n = 49 of 88) could be classified as pH sensitive (>30% reduction in firing rate from pH 7.0 to pH 7.8); the remaining cells were pH insensitive (44%). Moreover, none of the recorded RTN neurons from TASK-2−/− mice selected based on β-galactosidase activity (a subpopulation of GFP-expressing neurons) were pH sensitive. The alkaline-activated background K+ currents were reduced in amplitude in RTN neurons from TASK-2−/− mice that retained some pH sensitivity but were absent from pH-insensitive cells. Finally, using a working heart–brainstem preparation, we found diminished inhibition of phrenic burst amplitude by alkalization in TASK-2−/− mice, with apneic threshold shifted to higher pH levels. In conclusion, alkaline-activated TASK-2 channels contribute to pH sensitivity in RTN neurons, with effects on respiration in situ that are particularly prominent near apneic threshold. PMID:24107938

  19. Serotonin Activates Catecholamine Neurons in the Solitary Tract Nucleus by Increasing Spontaneous Glutamate Inputs

    PubMed Central

    Cui, Ran Ji; Roberts, Brandon L.; Zhao, Huan; Zhu, Mingyan

    2012-01-01

    Serotonin (5-HT) is a critical neurotransmitter in the control of autonomic functions. 5-HT3 receptors participate in vagal afferent feedback to decrease food intake and regulate cardiovascular reflexes; however, the phenotype of the solitary tract nucleus (NTS) neurons involved is not known. A2/C2 catecholamine (CA) neurons in the NTS are directly activated by visceral afferents and are important for the control of food intake and cardiovascular function, making them good candidates to respond to and mediate the effects of serotonin at the level of the NTS. This study examines serotonin's effects on NTS-CA neurons using patch-clamp techniques and transgenic mice expressing an enhanced green fluorescent protein driven by the tyrosine hydroxylase (TH) promoter (TH-EGFP) to identify catecholamine neurons. Serotonin increased the frequency of spontaneous glutamate excitatory postsynaptic currents (sEPSCs) in >90% of NTS-TH-EGFP neurons, an effect blocked by the 5-HT3 receptor antagonist ondansetron and mimicked by the 5-HT3 receptor agonists SR5227 and mCPBG. In contrast, 5-HT3 receptor agonists increased sEPSCs on a minority (<30%) of non-TH neurons. 5-HT3 receptor agonists increased the frequency, but not the amplitude, of mini-EPSCs, suggesting that their actions are presynaptic. 5-HT3 receptor agonists increased the firing rate of TH-EGFP neurons, an effect dependent on the increased spontaneous glutamate inputs as it was blocked by the ionotropic glutamate antagonist NBQX, but independent of visceral afferent activation. These results demonstrate a cellular mechanism by which serotonin activates NTS-TH neurons and suggest a pathway by which it can increase catecholamine release in target regions to modulate food intake, motivation, stress, and cardiovascular function. PMID:23152635

  20. Neurotensin excitation of serotonergic neurons in the rat nucleus raphe magnus: ionic and molecular mechanisms.

    PubMed

    Li, A H; Yeh, T H; Tan, P P; Hwang, H M; Wang, H L

    2001-06-01

    To understand the cellular and molecular mechanisms by which neurotensin (NT) induces an analgesic effect in the nucleus raphe magnus (NRM), whole-cell patch-clamp recordings were performed to investigate the electrophysiological effects of NT on acutely dissociated NRM neurons. Two subtypes of neurons, primary serotonergic and secondary non-serotonergic cells, were identified from acutely isolated NRM neurons. During current-clamp recordings, NT depolarized NRM serotonergic neurons and evoked action potentials. Voltage-clamp recordings showed that NT excited serotonergic neurons by enhancing a voltage-insensitive and non-selective cationic conductance. Both SR48692, a selective antagonist of subtype 1 neurotensin receptor (NTR-1), and SR 142948A, a non-selective antagonist of NTR-1 and subtype 2 neurotensin receptor (NTR-2), failed to prevent neurotensin from exciting NRM serotonergic neurons. NT-evoked cationic current was inhibited by the intracellular administration of GDP-beta-S. NT failed to induce cationic currents after dialyzing serotonergic neurons with the anti-G(alphaq/11) antibody. Cellular Ca(2+) imaging study using fura-2 showed that NT induced the calcium release from the intracellular store. NT-evoked current was blocked after the internal perfusion of heparin, an IP(3) receptor antagonist, or BAPTA, a fast Ca(2+) chelator. It is concluded that neurotensin enhancement of the cationic conductance of NRM serotonergic neurons is mediated by a novel subtype of neurotensin receptors. The coupling mechanism via G(alphaq/11) proteins is likely to involve the generation of IP(3), and subsequent IP(3)-evoked Ca(2+) release from intracellular stores results in activating the non-selective cationic conductance.

  1. Projections from a single NUCB2/nesfatin-1 neuron in the paraventricular nucleus to different brain regions involved in feeding.

    PubMed

    Maejima, Yuko; Kumamoto, Kensuke; Takenoshita, Seiichi; Shimomura, Kenju

    2016-12-01

    The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/nesfatin-1-containing neurons are distributed in the brain regions involved in feeding regulation, including the hypothalamic paraventricular nucleus (PVN). Functionally, NUCB2/nesfatin-1 neurons in the PVN regulate feeding through the hypothalamus and brain stem. However, the neural network of PVN NUCB2/nesfatin-1 neurons has yet to be elucidated. Axon collateral branches allow individual neurons to target multiple neurons. In some cases, each target neuron can be located in different nuclei. Here we show that a single neuron in the PVN projects axonal collaterals to both the dorsal vagal complex (DVC) and the arcuate nucleus (ARC), which are important brain regions for feeding regulation. In this study, after injection of different retrograde tracers into the DVC and ARC, both tracer-labeled neurons were detected in the identical PVN neuron, indicating the axon collateral projections from the single PVN neuron to the DVC and ARC. Furthermore, immunohistochemical analysis revealed that approximately 50 % of the neurons with axon collateral projections from the PVN to the DVC and ARC were found to be NUCB2/nesfatin-1 neurons. Our data suggest that a single NUCB2/nesfatin-1 neuron in the PVN projects to both the ARC and the DVC with axon collateral projection. Although the physiological significance remains to be elucidated, our data offer new perspectives on NUCB2/nesfatin-1 function at the neural network level and food intake regulation.

  2. Mathematical Model of Neuronal Morphology: Prenatal Development of the Human Dentate Nucleus

    PubMed Central

    Rajković, Katarina; Bačić, Goran; Ristanović, Dušan; Milošević, Nebojša T.

    2014-01-01

    The aim of the study was to quantify the morphological changes of the human dentate nucleus during prenatal development using mathematical models that take into account main morphometric parameters. The camera lucida drawings of Golgi impregnated neurons taken from human fetuses of gestational ages ranging from 14 to 41 weeks were analyzed. Four morphometric parameters, the size of the neuron, the dendritic complexity, maximum dendritic density, and the position of maximum density, were obtained using the modified Scholl method and fractal analysis. Their increase during the entire prenatal development can be adequately fitted with a simple exponential. The three parameters describing the evolution of branching complexity of the dendritic arbor positively correlated with the increase of the size of neurons, but with different rate constants, showing that the complex development of the dendritic arbor is complete during the prenatal period. The findings of the present study are in accordance with previous crude qualitative data on prenatal development of the human dentate nucleus, but provide much greater amount of fine details. The mathematical model developed here provides a sound foundation enabling further studies on natal development or analyzing neurological disorders during prenatal development. PMID:24995329

  3. Oxytocin in Brattleboro rats: increased synthesis is contrasted by blunted intrahypothalamic release from supraoptic nucleus neurones.

    PubMed

    Zelena, D; Pintér, O; Langnaese, K; Richter, K; Landgraf, R; Makara, G B; Engelmann, M

    2013-08-01

    Adult male Brattleboro rats were used to investigate the impact of the congenital absence of vasopressin on the release pattern of oxytocin (OXT) within the hypothalamic supraoptic nucleus (SON) in response to a 10-min forced swimming session and osmotic stimulation. Both immunohistochemical and in situ hybridisation data suggest that vasopressin-deficient animals have more oxytocin-synthesising neurones in the SON than homozygous wild-type controls. Unexpectedly, both forced swimming and peripheral osmotic stimulation resulted in a blunted release profile of oxytocin within the SON of vasopressin-deficient rats compared to controls. A similar intranuclear OXT response to direct osmotic stimulation of the SON by retrodialysis with hypertonic Ringer's solution in both genotypes confirmed the capability of SON neurones to locally release oxytocin in vasopressin-deficient rats, indicating an altered processing of information originating from multisynaptic inputs rather than a deficit in release capacity. Taken together with data obtained in previous studies, the present findings provide evidence suggesting that autocrine and paracrine signalling of magnocellular neurones differs within the paraventricular nucleus and the SON. Thus, significant alterations in intra-SON oxytocin mRNA levels cannot easily be extrapolated to intranuclear release profiles and the local signal intensity of this neuropeptide after physiological stimulation.

  4. Activity of Caudate Nucleus Neurons in a Visual Fixation Paradigm in Behaving Cats

    PubMed Central

    Nagypál, Tamás; Gombkötő, Péter; Barkóczi, Balázs; Benedek, György; Nagy, Attila

    2015-01-01

    Beside its motor functions, the caudate nucleus (CN), the main input structure of the basal ganglia, is also sensitive to various sensory modalities. The goal of the present study was to investigate the effects of visual stimulation on the CN by using a behaving, head-restrained, eye movement-controlled feline model developed recently for this purpose. Extracellular multielectrode recordings were made from the CN of two cats in a visual fixation paradigm applying static and dynamic stimuli. The recorded neurons were classified in three groups according to their electrophysiological properties: phasically active (PAN), tonically active (TAN) and high-firing (HFN) neurons. The response characteristics were investigated according to this classification. The PAN and TAN neurons were sensitive primarily to static stimuli, while the HFN neurons responded primarily to changes in the visual environment i.e. to optic flow and the offset of the stimuli. The HFNs were the most sensitive to visual stimulation; their responses were stronger than those of the PANs and TANs. The majority of the recorded units were insensitive to the direction of the optic flow, regardless of group, but a small number of direction-sensitive neurons were also found. Our results demonstrate that both the static and the dynamic components of the visual information are represented in the CN. Furthermore, these results provide the first piece of evidence on optic flow processing in the CN, which, in more general terms, indicates the possible role of this structure in dynamic visual information processing. PMID:26544604

  5. Human Subthalamic Nucleus Theta and Beta Oscillations Entrain Neuronal Firing During Sensorimotor Conflict

    PubMed Central

    Zavala, Baltazar; Damera, Srikanth; Dong, Jian Wilson; Lungu, Codrin; Brown, Peter; Zaghloul, Kareem A.

    2017-01-01

    Recent evidence has suggested that prefrontal cortical structures may inhibit impulsive actions during conflict through activation of the subthalamic nucleus (STN). Consistent with this hypothesis, deep brain stimulation to the STN has been associated with altered prefrontal cortical activity and impaired response inhibition. The interactions between oscillatory activity in the STN and its presumably antikinetic neuronal spiking, however, remain poorly understood. Here, we simultaneously recorded intraoperative local field potential and spiking activity from the human STN as participants performed a sensorimotor action selection task involving conflict. We identified several STN neuronal response types that exhibited different temporal dynamics during the task. Some neurons showed early, cue-related firing rate increases that remained elevated longer during high conflict trials, whereas other neurons showed late, movement-related firing rate increases. Notably, the high conflict trials were associated with an entrainment of individual neurons by theta- and beta-band oscillations, both of which have been observed in cortical structures involved in response inhibition. Our data suggest that frequency-specific activity in the beta and theta bands influence STN firing to inhibit impulsivity during conflict. PMID:26494798

  6. Orexins excite neurons of the rat cerebellar nucleus interpositus via orexin 2 receptors in vitro.

    PubMed

    Yu, Lei; Zhang, Xiao-Yang; Zhang, Jun; Zhu, Jing-Ning; Wang, Jian-Jun

    2010-03-01

    Orexins are newfound hypothalamic neuropeptides implicated in the regulation of feeding behavior, sleep-wakefulness cycle, nociception, addiction, emotions, as well as narcolepsy. However, little is known about roles of orexins in motor control. Therefore, the present study was designed to investigate the effect of orexins on neuronal activity in the cerebellum, an important subcortical center for motor control. In this study, perfusing slices with orexin A (100 nM-1 microM) or orexin B (100 nM-1 microM) both produced neurons in the rat cerebellar interpositus nucleus (IN) a concentration-dependent excitatory response (96/143, 67.1%). Furthermore, both of the excitations induced by orexin A and B were not blocked by the low-Ca(2+)/high-Mg(2+) medium (n = 8), supporting a direct postsynaptic action of the peptides. Highly selective orexin 1 receptor antagonist SB-334867 did not block the excitatory response of cerebellar IN neurons to orexins (n = 22), but [Ala(11), D-Leu(15)] orexin B, a highly selective orexin 2 receptor (OX(2)R) agonist, mimicked the excitatory effect of orexins on the cerebellar neurons (n = 18). These results demonstrate that orexins excite the cerebellar IN neurons through OX(2)R and suggest that the central orexinergic nervous system may actively participate in motor control through its modulation on one of the final outputs of the spinocerebellum.

  7. Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons

    PubMed Central

    van Welie, Ingrid

    2011-01-01

    Large conductance K+ (BK) channels are a key determinant of neuronal excitability. Medial vestibular nucleus (MVN) neurons regulate eye movements to ensure image stabilization during head movement, and changes in their intrinsic excitability may play a critical role in plasticity of the vestibulo-ocular reflex. Plasticity of intrinsic excitability in MVN neurons is mediated by kinases, and BK channels influence excitability, but whether endogenous BK channels are directly modulated by kinases is unknown. Double somatic patch-clamp recordings from MVN neurons revealed large conductance potassium channel openings during spontaneous action potential firing. These channels displayed Ca2+ and voltage dependence in excised patches, identifying them as BK channels. Recording isolated single channel currents at physiological temperature revealed a novel kinase-mediated bidirectional control in the range of voltages over which BK channels are activated. Application of activated Ca2+/calmodulin-dependent kinase II (CAMKII) increased BK channel open probability by shifting the voltage activation range towards more hyperpolarized potentials. An opposite shift in BK channel open probability was revealed by inhibition of phosphatases and was occluded by blockade of protein kinase C (PKC), suggesting that active PKC associated with BK channel complexes in patches was responsible for this effect. Accordingly, direct activation of endogenous PKC by PMA induced a decrease in BK open probability. BK channel activity affects excitability in MVN neurons and bidirectional control of BK channels by CAMKII, and PKC suggests that cellular signaling cascades engaged during plasticity may dynamically control excitability by regulating BK channel open probability. PMID:21307321

  8. Reduced neuronal size and dendritic length in the medial superior olivary nucleus of albino rabbits.

    PubMed

    Conlee, J W; Parks, T N; Creel, D J

    1986-01-15

    We have previously demonstrated that circumscribed structural and functional abnormalities exist in the brainstem auditory system of albino cats. Anomalies in the auditory brainstem evoked response of albino cats were correlated with anatomical defects in the medial superior olivary nucleus (MSO) of the same animals. To examine whether a similar syndrome is present in other albino mammals, we studied the MSO of albino and pigmented rabbits using both Nissl-stained and Golgi-impregnated material. Neurons in the MSO of the albinos were significantly smaller (24%) than those in the pigmented rabbits and there was no overlap in the size distributions between the two groups. Neurons in the abducens nucleus of the albinos were also 14% smaller than in the pigmented rabbits, but this difference was not statistically reliable. The broad overlap in the distributions of neuronal size in the abducens nucleus between groups indicated that not all cells in the albino brainstem are significantly smaller than normal. In the Golgi-impregnated material, the mean total dendritic length for the 'marginal' cell type in the MSO was 39% shorter in albinos than in the pigmented animals. The branching density of dendrites was also significantly reduced in the albinos. Mean total dendritic length for cerebellar granule cells was a statistically insignificant 6% longer in the albinos, demonstrating that dendritic structure is not uniformly affected in all regions of the albino brain. The demonstration of similar anatomical differences in albino rabbits and cats indicates that whatever process produces these effects is not species-specific and may be common to the albinos of other mammalian species. The evidence that the amount of cochlear melanin may be related to differences in auditory function further suggests that the differences in the MSO of the albinos may ultimately be related to absence of inner ear pigmentation and not to other gene effects.

  9. Activation of metabotropic glutamate receptors regulates ribosomes of cochlear nucleus neurons.

    PubMed

    Carzoli, Kathryn L; Hyson, Richard L

    2014-01-01

    The brain stem auditory system of the chick is an advantageous model for examining changes that occur as a result of deafness. Elimination of acoustic input through cochlear ablation results in the eventual death of approximately 30% of neurons in the chick cochlear nucleus, nucleus magnocellularis (NM). One early change following deafness is an alteration in NM ribosomes, evidenced both by a decrease in protein synthesis and reduction in antigenicity for Y10B, a monoclonal antibody that recognizes a ribosomal epitope. Previous studies have shown that mGluR activation is necessary to maintain Y10B antigenicity and NM viability. What is still unclear, however, is whether or not mGluR activation is sufficient to prevent deafness-induced changes in these neurons, or if other activity-dependent factors are also necessary. The current study investigated the ability of mGluR activation to regulate cochlear nucleus ribosomes in the absence of auditory nerve input. In vitro methods were employed to periodically pressure eject glutamate or mGluR agonists over neurons on one side of a slice preparation leaving the opposite side of the same slice untreated. Immunohistochemistry was then performed using Y10B in order to assess ribosomal changes. Application of glutamate and both group I and II selective mGluR agonists effectively rescued ribosomal antigenicity on the treated side of the slice in comparison to ribosomes on the untreated side. These findings suggest that administration of mGluR agonists is sufficient to reduce the early interruption of normal ribosomal integrity that is typically seen following loss of auditory nerve activity.

  10. Disinhibition of neurons of the nucleus of solitary tract that project to the superior salivatory nucleus causes choroidal vasodilation: Implications for mechanisms underlying choroidal baroregulation.

    PubMed

    Li, Chunyan; Fitzgerald, Malinda E C; Del Mar, Nobel; Reiner, Anton

    2016-10-28

    Preganglionic neurons in the superior salivatory nucleus (SSN) that mediate parasympathetic vasodilation of choroidal blood vessels receive a major excitatory input from the baroresponsive part of the nucleus of the solitary tract (NTS). This input appears likely to mediate choroidal vasodilation during systemic hypotension, which prevents decreases in choroidal blood flow (ChBF) due to reduced perfusion pressure. It is uncertain, however, how low blood pressure signals to NTS from the aortic depressor nerve (ADN), which fires at a low rate during systemic hypotension, could yield increased firing in the NTS output to SSN. The simplest hypothesis is that SSN-projecting NTS neurons are under the inhibitory control of ADN-receptive GABAergic NTS neurons. As part of evaluating this hypothesis, we assessed if SSN-projecting NTS neurons, in fact, receive prominent inhibitory input and if blocking GABAergic modulation of them increases ChBF. We found that SSN-projecting NTS neuronal perikarya identified by retrograde labeling are densely coated with GABAergic terminals, but lightly coated with excitatory terminals. We also found that, infusion of the GABA-A receptor antagonist GABAzine into NTS increased ChBF. Our results are consistent with the possibility that low blood pressure signals from the ADN produce vasodilation in choroid by causing diminished activity in ADN-receptive NTS neurons that tonically suppress SSN-projecting NTS neurons.

  11. Estrogen replacement modulates voltage-gated potassium channels in rat presympathetic paraventricular nucleus neurons

    PubMed Central

    2013-01-01

    Background The hypothalamic paraventricular nucleus (PVN) is an important site in the regulation of the autonomic nervous system. Specifically, PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) play a regulatory role in the determination of the sympathetic outflow in the cardiovascular system. In the PVN-RVLM neurons, the estrogen receptor β is expressed. However, to date, the effects of estrogen on PVN-RVLM neurons have not been reported. The present study investigated estrogen-mediated modulation of two voltage-gated potassium channel (Kv) subunits, Kv4.2 and Kv4.3, that are expressed predominantly in PVN neurons and the functional current of Kv4.2 and Kv4.3, the transient outward potassium current (IA). Results Single-cell real-time RT-PCR analysis showed that 17β-estradiol (E2) replacement (once daily for 4 days) selectively down-regulated Kv4.2 mRNA levels in the PVN-RVLM neurons of ovariectomized female rats. There was no change in Kv4.3 levels. Whole-cell patch-clamp recordings demonstrated that E2 also diminished IA densities. Interestingly, these effects were most apparent in the dorsal cap parvocellular subdivision of the PVN. E2 also shortened a delay in the excitation of the PVN-RVLM neurons. Conclusions These findings demonstrate that E2 exerts an inhibitory effect on the functions of IA, potentially by selectively down-regulating Kv4.2 but not Kv4.3 in PVN-RVLM neurons distributed in a specific parvocellular subdivision. PMID:24180323

  12. Segregation of tactile input features in neurons of the cuneate nucleus.

    PubMed

    Jörntell, Henrik; Bengtsson, Fredrik; Geborek, Pontus; Spanne, Anton; Terekhov, Alexander V; Hayward, Vincent

    2014-09-17

    Our tactile perception of external objects depends on skin-object interactions. The mechanics of contact dictates the existence of fundamental spatiotemporal input features-contact initiation and cessation, slip, and rolling contact-that originate from the fact that solid objects do not interpenetrate. However, it is unknown whether these features are represented within the brain. We used a novel haptic interface to deliver such inputs to the glabrous skin of finger/digit pads and recorded from neurons of the cuneate nucleus (the brain's first level of tactile processing) in the cat. Surprisingly, despite having similar receptive fields and response properties, each cuneate neuron responded to a unique combination of these inputs. Hence, distinct haptic input features are encoded already at subcortical processing stages. This organization maps skin-object interactions into rich representations provided to higher cortical levels and may call for a re-evaluation of our current understanding of the brain's somatosensory systems.

  13. Nkx6-1 controls the identity and fate of red nucleus and oculomotor neurons in the mouse midbrain

    PubMed Central

    Prakash, Nilima; Puelles, Eduardo; Freude, Kristine; Trümbach, Dietrich; Omodei, Daniela; Di Salvio, Michela; Sussel, Lori; Ericson, Johan; Sander, Maike; Simeone, Antonio; Wurst, Wolfgang

    2009-01-01

    Summary Little is known about the cues controlling the generation of motoneuron populations in the mammalian ventral midbrain. We show that Otx2 provides the crucial anterior-posterior positional information for the generation of red nucleus neurons in the murine midbrain. Moreover, the homeodomain transcription factor Nkx6-1 controls the proper development of the red nucleus and of the oculomotor and trochlear nucleus neurons. Nkx6-1 is expressed in ventral midbrain progenitors and acts as a fate determinant of the Brn3a+ (also known as Pou4f1) red nucleus neurons. These progenitors are partially dorsalized in the absence of Nkx6-1, and a fraction of their postmitotic offspring adopts an alternative cell fate, as revealed by the activation of Dbx1 and Otx2 in these cells. Nkx6-1 is also expressed in postmitotic Isl1+ oculomotor and trochlear neurons. Similar to hindbrain visceral (branchio-) motoneurons, Nkx6-1 controls the proper migration and axon outgrowth of these neurons by regulating the expression of at least three axon guidance/neuronal migration molecules. Based on these findings, we provide additional evidence that the developmental mechanism of the oculomotor and trochlear neurons exhibits more similarity with that of special visceral motoneurons than with that controlling the generation of somatic motoneurons located in the murine caudal hindbrain and spinal cord. PMID:19592574

  14. Behavioral flexibility is increased by optogenetic inhibition of neurons in the nucleus accumbens shell during specific time segments

    PubMed Central

    Aquili, Luca; Liu, Andrew W.; Shindou, Mayumi; Shindou, Tomomi; Wickens, Jeffery R.

    2014-01-01

    Behavioral flexibility is vital for survival in an environment of changing contingencies. The nucleus accumbens may play an important role in behavioral flexibility, representing learned stimulus–reward associations in neural activity during response selection and learning from results. To investigate the role of nucleus accumbens neural activity in behavioral flexibility, we used light-activated halorhodopsin to inhibit nucleus accumbens shell neurons during specific time segments of a bar-pressing task requiring a win–stay/lose–shift strategy. We found that optogenetic inhibition during action selection in the time segment preceding a lever press had no effect on performance. However, inhibition occurring in the time segment during feedback of results—whether rewards or nonrewards—reduced the errors that occurred after a change in contingency. Our results demonstrate critical time segments during which nucleus accumbens shell neurons integrate feedback into subsequent responses. Inhibiting nucleus accumbens shell neurons in these time segments, during reinforced performance or after a change in contingencies, increases lose–shift behavior. We propose that the activity of nucleus shell accumbens shell neurons in these time segments plays a key role in integrating knowledge of results into subsequent behavior, as well as in modulating lose–shift behavior when contingencies change. PMID:24639489

  15. Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus.

    PubMed

    Zhou, Li; Liu, Ming-Zhe; Li, Qing; Deng, Juan; Mu, Di; Sun, Yan-Gang

    2017-03-21

    Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN.

  16. Propofol facilitated excitatory postsynaptic currents frequency on nucleus tractus solitarii (NTS) neurons.

    PubMed

    Jin, Zhenhua; Choi, Myung-Jin; Park, Cheung-Seog; Park, Young Seek; Jin, Young-Ho

    2012-01-13

    Propofol, an intravenous anesthetic, is broadly used for general anesthesia and diagnostic sedations due to its fast onset and recovery. Propofol depresses respiratory and cardiovascular reflex responses, however, their underlying mechanisms are not well known. Cardiorespiratory information from visceral afferent vagus nerves is integrated in the nucleus tractus solitarii (NTS). Cardiac and respiratory signals transducing vagal afferent neurons release the excitatory neurotransmitter glutamate onto NTS neurons in an activity dependent manner and trigger negative feedback reflex responses. In this experiment, the effects of propofol on glutamatergic synaptic responses at NTS neurons was tested using patch clamp methods. Glutamatergic excitatory postsynaptic currents (EPSC) were recorded at chloride reversal potential (-49mV) without γ-aminobutyric acid type A (GABA(A)) receptor antagonists. Propofol (≥3μM) facilitated frequency of the spontaneous EPSCs in a concentration dependent manner without altering amplitude and decay time. The GABA(A) receptor selective antagonist, gabazine (6μM), attenuated propofol effects on glutamate release. Propofol (10μM) evoked glutamate release was also blocked in the presence of the voltage dependent Na(+) and Ca(2+) channel blockers TTX (0.3μM) and Cd(2+) (0.2mM), respectively. In addition, the Na(+)-K(+)-Cl(-) cotransporter type 1 antagonist bumetanide (10μM) also inhibited propofol evoked increase in sEPSC frequency. These results suggest that propofol evoked glutamate release onto NTS neurons by GABA(A) receptor-mediated depolarization of the presynaptic excitatory terminals.

  17. GABAergic signaling induces divergent neuronal Ca2+ responses in the suprachiasmatic nucleus network

    PubMed Central

    Allen, Charles N.

    2013-01-01

    Intercellular communication between γ-aminobutyric acid (GABA)ergic suprachiasmatic nucleus (SCN) neurons facilitates light-induced phase changes and synchronization of individual neural oscillators within the SCN network. We used ratiometric Ca2+ imaging techniques to record changes in the intracellular calcium concentration ([Ca2+]i) to study the role of GABA in interneuronal communication and the response of the SCN neuronal network to optic nerve stimulations that mimic entraining light signals. Stimulation of the retinohypothalamic tract (RHT) evoked divergent Ca2+ responses in neurons that varied regionally within the SCN with a pattern that correlated with those evoked by pharmacological GABA applications. GABAA and GABAB receptor agonists and antagonists were used to evaluate components of the GABA-induced changes in [Ca2+]i. Application of the GABAA receptor antagonist gabazine induced changes in baseline [Ca2+]i in a direction opposite to that evoked by GABA, and similarly altered the RHT stimulation-induced Ca2+ response. GABA application induced Ca2+ responses varied in time and region within the SCN network. The NKCC1 cotransporter blocker, bumetanide, and L-type calcium channel blocker, nimodipine, attenuated the GABA-induced rise of [Ca2+]i. These results suggest that physiological GABA induces opposing effects on [Ca2+]i based on the chloride equilibrium potential, and may play an important role in neuronal Ca2+ balance, synchronization and modulation of light input signaling in the SCN network. PMID:19821838

  18. Learning-related neuronal activity in the ventral lateral geniculate nucleus during associative cerebellar learning

    PubMed Central

    Kashef, Alireza; Campolattaro, Matthew M.

    2014-01-01

    During delay eyeblink conditioning, rats learn to produce an eyelid-closure conditioned response (CR) to a conditioned stimulus (CS), such as a light, which precedes and coterminates with an unconditioned stimulus (US). Previous studies have suggested that the ventral lateral geniculate nucleus (LGNv) might play an important role in visual eyeblink conditioning by supplying visual sensory input to the pontine nuclei (PN) and also receiving feedback from the cerebellum. No prior study has investigated LGNv neuronal activity during eyeblink conditioning. The present study used multiple tetrodes to monitor single-unit activity in the rat LGNv during pre-exposure (CS only), unpaired CS/US, and paired CS-US training conditions. This behavioral-training sequence was used to investigate nonassociative- and associative-driven neuronal activity in the LGNv during training. LGNv neuronal activity habituated during unpaired training and then recovered from habituation during subsequent paired training, which may indicate that the LGNv plays a role in attention to the CS. The amplitude of LGNv neuronal activity correlated with CR production during paired but not unpaired CS/US training. Cerebellar feedback to the LGNv may play a role in modulating LGNv activity and attention to the CS during paired training. Based on the present findings, we hypothesize that the role of LGNv in visual eyeblink conditioning goes beyond simply routing visual CS information to the PN and involves modulation of attention. PMID:25122718

  19. Role of the flocculus in mediating vestibular nucleus neuron plasticity during vestibular compensation in the rat

    PubMed Central

    Johnston, Alex R; Seckl, Jonathan R; Dutia, Mayank B

    2002-01-01

    We investigated the role of the cerebellar flocculus in mediating the adaptive changes that occur in the intrinsic properties of brainstem medial vestibular nucleus (MVN) neurons during vestibular compensation. Ipsi-lesional, but not contra-lesional, flocculectomy prevented the compensatory increase in intrinsic excitability (CIE) that normally occurs in the de-afferented MVN neurons within 4 h after unilateral labyrinthectomy (UL). Flocculectomy did not, however, prevent the down-regulation of efficacy of GABA receptors that also occurs in these neurons after UL, indicating that these responses of the MVN neurons to deafferentation are discrete, parallel processes. CIE was also abolished by intra-floccular microinjection of the metabotropic glutamate receptor (mGluR) antagonist AIDA, and the protein kinase C inhibitor bisindolymaleimide I (BIS-I). The serene-threonine kinase inhibitor H-7 had no effect when microinjected at the time of de-afferentation, but abolished CIE if microinjected 2 h later. These cellular effects are in line with the recently reported retardatory effects of BIS-I and H-7 on behavioural recovery after UL. They demonstrate that the increase in intrinsic excitability in MVN neurons during vestibular compensation is cerebellum dependent, and requires mGluR activation and protein phosphorylation in cerebellar cortex. Furthermore, microinjection of the glucocorticoid receptor (GR) antagonist RU38486 into the ipsi-lesional flocculus also abolished CIE in MVN neurons. Thus an important site for glucocorticoids in facilitating vestibular compensation is within the cerebellar cortex. These observations ascribe functional significance to the high levels of GR and 11-β-HSD Type 1 expression in cerebellum. PMID:12482895

  20. Inhibitory effects of propofol on excitatory synaptic transmission in supraoptic nucleus neurons in vitro.

    PubMed

    Zhang, Huan-Huan; Zheng, Chao; Wang, Bang-An; Wang, Meng-Ya

    2015-12-25

    The present study was designed to investigate the inhibitory effects of intravenous general anesthetic propofol (0.1-3.0 mmol/L) on excitatory synaptic transmission in supraoptic nucleus (SON) neurons of rats, and to explore the underlying mechanisms by using intracellular recording technique and hypothalamic slice preparation. It was observed that stimulation of the dorsolateral region of SON could elicit the postsynaptic potentials (PSPs) in SON neurons. Of the 8 tested SON neurons, the PSPs of 7 (88%, 7/8) neurons were decreased by propofol in a concentration-dependent manner, in terms of the PSPs' amplitude (P < 0.01), area under curve, duration, half-width and 10%-90% decay time (P < 0.05). The PSPs were completely and reversibly abolished by 1.0 mmol/L propofol at 2 out of 7 tested cells. The depolarization responses induced by pressure ejection of exogenous glutamate were reversibly and concentration-dependently decreased by bath application of propofol. The PSPs and glutamate-induced responses recorded simultaneously were reversibly and concentration-dependently decreased by propofol, but 0.3 mmol/L propofol only abolished PSPs. The excitatory postsynaptic potentials (EPSPs) of 7 cells increased in the condition of picrotoxin (30 µmol/L, a GABA(A) receptor antagonist) pretreatment. On this basis, the inhibitory effects of propofol on EPSPs were decreased. These data indicate that the presynaptic and postsynaptic mechanisms may be both involved in the inhibitory effects of propofol on excitatory synaptic transmission in SON neurons. The inhibitory effects of propofol on excitatory synaptic transmission of SON neurons may be related to the activation of GABA(A) receptors, but at a high concentration, propofol may also act directly on glutamate receptors.

  1. Components of after-hyperpolarization in magnocellular neurones of the rat supraoptic nucleus in vitro

    PubMed Central

    Greffrath, Wolfgang; Martin, Erich; Reuss, Stefan; Boehmer, Gerd

    1998-01-01

    The pharmacological sensitivity of hyperpolarizing components of spike train after-potentials was examined in sixty-one magnocellular neurones of the rat supraoptic nucleus using intracellular recording techniques in a brain slice preparation.In 26 % of all neurones a slow after-hyperpolarization (AHP) was observed in addition to a fast AHP. In 31 % of all neurones a depolarizing after-potential (DAP) was observed.The fast AHP was blocked by apamin whereas the slow AHP was blocked by charybdotoxin (ChTX). The DAP was enhanced by ChTX or a DAP was unmasked if not present during the control period.Low concentrations of TEA (0.15–1.5 mm) induced effects on the slow AHP and the DAP essentially resembling those of ChTX. The same was true for the effects of CoCl2 (1 mm).Spike train after-potentials were not affected by either iberiotoxin (IbTX), a selective high-conductance potassium (BK) channel antagonist, or margatoxin (MgTX), a Kv1.3 α-subunit antagonist.Kv1.3 α-subunit immunohistochemistry revealed that these units are not expressed in the somato-dendritic region of supraoptic neurones.The effects of ChTX, IbTX, MgTX, TEA, CoCl2 and CdCl2 on spike train after-potentials are interpreted in terms of an induction of the slow AHP by the activation of calcium-dependent potassium channels of intermediate single channel conductance (IK channels).The results suggest that at least the majority of supraoptic magnocellular neurones share the capability of generating both a slow AHP and a DAP. The slow AHP may act to control the expression of the DAP, thus regulating the excitability of magnocellular neurones. The interaction of the slow AHP and the DAP may be important for the control of phasic discharge. PMID:9806998

  2. Biphasic cholinergic synaptic transmission controls action potential activity in thalamic reticular nucleus neurons.

    PubMed

    Sun, Yan-Gang; Pita-Almenar, Juan D; Wu, Chia-Shan; Renger, John J; Uebele, Victor N; Lu, Hui-Chen; Beierlein, Michael

    2013-01-30

    Cholinergic neurons in the basal forebrain and the brainstem form extensive projections to a number of thalamic nuclei. Activation of cholinergic afferents during distinct behavioral states can regulate neuronal firing, transmitter release at glutamatergic and GABAergic synapses, and synchrony in thalamic networks, thereby controlling the flow of sensory information. These effects are thought to be mediated by slow and persistent increases in extracellular ACh levels, resulting in the modulation of populations of thalamic neurons over large temporal and spatial scales. However, the synaptic mechanisms underlying cholinergic signaling in the thalamus are not well understood. Here, we demonstrate highly reliable cholinergic transmission in the mouse thalamic reticular nucleus (TRN), a brain structure essential for sensory processing, arousal, and attention. We find that ACh release evoked by low-frequency stimulation leads to biphasic excitatory-inhibitory (E-I) postsynaptic responses, mediated by the activation of postsynaptic α4β2 nicotinic ACh receptors (nAChRs) and M2 muscarinic ACh receptors (mAChRs), respectively. In addition, ACh can bind to mAChRs expressed near cholinergic release sites, resulting in autoinhibition of release. We show that the activation of postsynaptic nAChRs by transmitter release from only a small number of individual axons is sufficient to trigger action potentials in TRN neurons. Furthermore, short trains of cholinergic synaptic inputs can powerfully entrain ongoing TRN neuronal activity. Our study demonstrates fast and precise synaptic E-I signaling mediated by ACh, suggesting novel computational mechanisms for the cholinergic control of neuronal activity in thalamic circuits.

  3. Control of ventricular excitability by neurons of the dorsal motor nucleus of the vagus nerve

    PubMed Central

    Machhada, Asif; Ang, Richard; Ackland, Gareth L.; Ninkina, Natalia; Buchman, Vladimir L.; Lythgoe, Mark F.; Trapp, Stefan; Tinker, Andrew; Marina, Nephtali; Gourine, Alexander V.

    2015-01-01

    Background The central nervous origins of functional parasympathetic innervation of cardiac ventricles remain controversial. Objective This study aimed to identify a population of vagal preganglionic neurons that contribute to the control of ventricular excitability. An animal model of synuclein pathology relevant to Parkinson’s disease was used to determine whether age-related loss of the activity of the identified group of neurons is associated with changes in ventricular electrophysiology. Methods In vivo cardiac electrophysiology was performed in anesthetized rats in conditions of selective inhibition of the dorsal vagal motor nucleus (DVMN) neurons by pharmacogenetic approach and in mice with global genetic deletion of all family members of the synuclein protein. Results In rats anesthetized with urethane (in conditions of systemic beta-adrenoceptor blockade), muscarinic and neuronal nitric oxide synthase blockade confirmed the existence of a tonic parasympathetic control of cardiac excitability mediated by the actions of acetylcholine and nitric oxide. Acute DVMN silencing led to shortening of the ventricular effective refractory period (vERP), a lowering of the threshold for triggered ventricular tachycardia, and prolongation of the corrected QT (QTc) interval. Lower resting activity of the DVMN neurons in aging synuclein-deficient mice was found to be associated with vERP shortening and QTc interval prolongation. Conclusion Activity of the DVMN vagal preganglionic neurons is responsible for tonic parasympathetic control of ventricular excitability, likely to be mediated by nitric oxide. These findings provide the first insight into the central nervous substrate that underlies functional parasympathetic innervation of the ventricles and highlight its vulnerability in neurodegenerative diseases. PMID:26051529

  4. Descending projections from the nucleus accumbens shell excite activity of taste-responsive neurons in the nucleus of the solitary tract in the hamster.

    PubMed

    Li, Cheng-Shu; Lu, Da-Peng; Cho, Young K

    2015-06-01

    The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second relays in the rodent central taste pathway. A series of electrophysiological experiments revealed that spontaneous and taste-evoked activities of brain stem gustatory neurons are altered by descending input from multiple forebrain nuclei in the central taste pathway. The nucleus accumbens shell (NAcSh) is a key neural substrate of reward circuitry, but it has not been verified as a classical gustatory nucleus. A recent in vivo electrophysiological study demonstrated that the NAcSh modulates the spontaneous and gustatory activities of hamster pontine taste neurons. In the present study, we investigated whether activation of the NAcSh modulates gustatory responses of the NST neurons. Extracellular single-unit activity was recorded from medullary neurons in urethane-anesthetized hamsters. After taste response was confirmed by delivery of sucrose, NaCl, citric acid, and quinine hydrochloride to the anterior tongue, the NAcSh was stimulated bilaterally with concentric bipolar stimulating electrodes. Stimulation of the ipsilateral and contralateral NAcSh induced firings from 54 and 37 of 90 medullary taste neurons, respectively. Thirty cells were affected bilaterally. No inhibitory responses or antidromic invasion was observed after NAcSh activation. In the subset of taste cells tested, high-frequency electrical stimulation of the NAcSh during taste delivery enhanced taste-evoked neuronal firing. These results demonstrate that two-thirds of the medullary gustatory neurons are under excitatory descending influence from the NAcSh, which is a strong indication of communication between the gustatory pathway and the mesolimbic reward pathway.

  5. Mechanism of phase splitting in two coupled groups of suprachiasmatic-nucleus neurons

    NASA Astrophysics Data System (ADS)

    Gu, Changgui; Wang, Jianxiong; Wang, Jiaxiang; Liu, Zonghua

    2011-04-01

    The phase-splitting behavior of coupled suprachiasmatic-nucleus neurons has been observed in many mammals, and its mechanism is still not completely understood. Based on our previous work [C. Gu, J. Wang, and Z. Liu, Phys. Rev. E JTBIAP1539-375510.1103/PhysRevE.80.03090480, 030904(R) (2009)] on the free-running periods of neurons in the suprachiasmatic nucleus, we present here a modified Goodwin oscillator model to explain the mechanism of phase splitting. In contrast to the previous phase model, the modified Goodwin oscillator model contains the information on both the phase and amplitude and, thus, can show more features than the purely phase model, including all three behaviors of synchronization, phase splitting, and amplitude death and the distributed periodicity in the regions of synchronization and phase splitting, etc. An analytic phase model is extracted from the modified Goodwin oscillator model to explain the dependence of periodicity on the parameters. Moreover, both the modified Goodwin oscillator model and the analytic phase model show that the ensemble frequency can be enhanced or reduced by the time delay.

  6. Corticotropin releasing factor excites neurons of posterior hypothalamic nucleus to produce tachycardia in rats

    PubMed Central

    Gao, He-Ren; Zhuang, Qian-Xing; Li, Bin; Li, Hong-Zhao; Chen, Zhang-Peng; Wang, Jian-Jun; Zhu, Jing-Ning

    2016-01-01

    Corticotropin releasing factor (CRF), a peptide hormone involved in the stress response, holds a key position in cardiovascular regulation. Here, we report that the central effect of CRF on cardiovascular activities is mediated by the posterior hypothalamic nucleus (PH), an important structure responsible for stress-induced cardiovascular changes. Our present results demonstrate that CRF directly excites PH neurons via two CRF receptors, CRFR1 and CRFR2, and consequently increases heart rate (HR) rather than the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). Bilateral vagotomy does not influence the tachycardia response to microinjection of CRF into the PH, while β adrenergic receptor antagonist propranolol almost totally abolishes the tachycardia. Furthermore, microinjecting CRF into the PH primarily increases neuronal activity of the rostral ventrolateral medulla (RVLM) and rostral ventromedial medulla (RVMM), but does not influence that of the dorsal motor nucleus of the vagus nerve (DMNV). These findings suggest that the PH is a critical target for central CRF system in regulation of cardiac activity and the PH-RVLM/RVMM-cardiac sympathetic nerve pathways, rather than PH-DMNV-vagus pathway, may contribute to the CRF-induced tachycardia. PMID:26831220

  7. Corticotropin releasing factor excites neurons of posterior hypothalamic nucleus to produce tachycardia in rats.

    PubMed

    Gao, He-Ren; Zhuang, Qian-Xing; Li, Bin; Li, Hong-Zhao; Chen, Zhang-Peng; Wang, Jian-Jun; Zhu, Jing-Ning

    2016-02-01

    Corticotropin releasing factor (CRF), a peptide hormone involved in the stress response, holds a key position in cardiovascular regulation. Here, we report that the central effect of CRF on cardiovascular activities is mediated by the posterior hypothalamic nucleus (PH), an important structure responsible for stress-induced cardiovascular changes. Our present results demonstrate that CRF directly excites PH neurons via two CRF receptors, CRFR1 and CRFR2, and consequently increases heart rate (HR) rather than the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). Bilateral vagotomy does not influence the tachycardia response to microinjection of CRF into the PH, while β adrenergic receptor antagonist propranolol almost totally abolishes the tachycardia. Furthermore, microinjecting CRF into the PH primarily increases neuronal activity of the rostral ventrolateral medulla (RVLM) and rostral ventromedial medulla (RVMM), but does not influence that of the dorsal motor nucleus of the vagus nerve (DMNV). These findings suggest that the PH is a critical target for central CRF system in regulation of cardiac activity and the PH-RVLM/RVMM-cardiac sympathetic nerve pathways, rather than PH-DMNV-vagus pathway, may contribute to the CRF-induced tachycardia.

  8. Electrophysiological characteristics of inhibitory neurons of the prepositus hypoglossi nucleus as analyzed in Venus-expressing transgenic rats.

    PubMed

    Shino, M; Kaneko, R; Yanagawa, Y; Kawaguchi, Y; Saito, Y

    2011-12-01

    The identification and characterization of excitatory and inhibitory neurons are significant steps in understanding neural network functions. In this study, we investigated the intrinsic electrophysiological properties of neurons in the prepositus hypoglossi nucleus (PHN), a brainstem structure that is involved in gaze holding, using whole-cell recordings in brainstem slices from vesicular GABA transporter (VGAT)-Venus transgenic rats, in which inhibitory neurons express the fluorescent protein Venus. To characterize the intrinsic properties of these neurons, we recorded afterhyperpolarization (AHP) profiles and firing patterns from Venus-expressing [Venus⁺] and Venus-non-expressing [Venus⁻] PHN neurons. Although both types of neurons showed a wide variety of AHP profiles and firing patterns, oscillatory firing was specific to Venus⁺ neurons, while a firing pattern showing only a few spikes was specific to Venus⁻ neurons. In addition, AHPs without a slow component and delayed spike generation were preferentially displayed by Venus⁺ neurons, whereas a firing pattern with constant interspike intervals was preferentially displayed by Venus⁻ neurons. We evaluated the mRNAs expression of glutamate decarboxylase (GAD65, GAD67) and glycine transporter 2 (GlyT2) to determine whether the recorded Venus⁺ neurons were GABAergic or glycinergic. Of the 67 Venus⁺ neurons tested, GlyT2 expression alone was detected in only one neuron. Approximately 40% (28/67) expressed GAD65 and/or GAD67 (GABAergic neuron), and the remainder (38/67) expressed both GAD(s) and GlyT2 (GABA&GLY neuron). These results suggest that most inhibitory PHN neurons use either GABA or both GABA and glycine as neurotransmitters. Although the overall distribution of firing patterns in GABAergic neurons was similar to that of GABA&GLY neurons, only GABA&GLY neurons exhibited a firing pattern with a long first interspike interval. These differential electrophysiological properties will be useful

  9. Responses from two firing patterns in inferior colliculus neurons to stimulation of the lateral lemniscus dorsal nucleus

    PubMed Central

    Li, Xiao-ting; Wang, Ning-yu; Wang, Yan-jun; Xu, Zhi-qing; Liu, Jin-feng; Bai, Yun-fei; Dai, Jin-sheng; Zhao, Jing-yi

    2016-01-01

    The γ-aminobutyric acid neurons (GABAergic neurons) in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the whole-cell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns: sustained-regular (n = 4) and sustained-adapting firing patterns (n = 3). The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies. PMID:27335563

  10. Growth and atrophy of neurons labeled at their birth in a song nucleus of the zebra finch

    SciTech Connect

    Konishi, M.; Akutagawa, E. )

    1990-05-01

    The robust nucleus of the archistriatum (RA) is one of the forebrain nuclei that control song production in birds. In the zebra finch (Poephila guttata), this nucleus contains more and larger neurons in the male than in the female. A single injection of tritiated thymidine into the egg on the 6th or 7th day of incubation resulted in labeling of many RA neurons with tritium. The size of tritium-labeled neurons and the tissue volume containing them did not differ between the sexes at 15 days after hatching. In the adult brain, tritium-labeled neurons and the tissue volume containing them were much larger in the male than in the female. Also, tritium-labeled RA neurons were large in females which received an implant of estrogen immediately after hatching. The gender differences in the neuron size and nuclear volume of the zebra finch RA are, therefore, due not to the replacement of old neurons by new ones during development but to the growth and atrophy of neurons born before hatching. Similarly, the masculinizing effects of estrogen on the female RA are due not to neuronal replacement but to the prevention of atrophy and promotion of growth in preexisting neurons.

  11. Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms.

    PubMed

    Lee, Ivan T; Chang, Alexander S; Manandhar, Manabu; Shan, Yongli; Fan, Junmei; Izumo, Mariko; Ikeda, Yuichi; Motoike, Toshiyuki; Dixon, Shelley; Seinfeld, Jeffrey E; Takahashi, Joseph S; Yanagisawa, Masashi

    2015-03-04

    Circadian behavior in mammals is orchestrated by neurons within the suprachiasmatic nucleus (SCN), yet the neuronal population necessary for the generation of timekeeping remains unknown. We show that a subset of SCN neurons expressing the neuropeptide neuromedin S (NMS) plays an essential role in the generation of daily rhythms in behavior. We demonstrate that lengthening period within Nms neurons is sufficient to lengthen period of the SCN and behavioral circadian rhythms. Conversely, mice without a functional molecular clock within Nms neurons lack synchronous molecular oscillations and coherent behavioral daily rhythms. Interestingly, we found that mice lacking Nms and its closely related paralog, Nmu, do not lose in vivo circadian rhythms. However, blocking vesicular transmission from Nms neurons with intact cell-autonomous clocks disrupts the timing mechanisms of the SCN, revealing that Nms neurons define a subpopulation of pacemakers that control SCN network synchrony and in vivo circadian rhythms through intercellular synaptic transmission.

  12. Dependence of the activity of interpositus and red nucleus neurons on sensory input data generated by movement.

    PubMed

    Burton, J E; Onoda, N

    1978-08-18

    Cats performed flexion movements of the forearm, and the discharge of interpositus and red nucleus neurons was examined for relationships to the motion and to the EMG activity of agonist and antagonist muscles. It is shown that, over a wide range in the time course of the motion, the activity of the neurons is covariant with both the EMG and the movement parameters, in particular, the velocity. Also, the discharge of the interpositus neurons is modulated in phase with the velocity of passive movement. It is concluded that during fast, intentional movements, sensory input data generated by motion is a major determinant of the output of the interpositus nucleus. Furthermore, the results are consistent with the concept that this output provides a continuous modulation of spinal segmental mechanisms by way of the red nucleus and rubrospinal tract.

  13. Chronic L-dopa decreases serotonin neurons in a subregion of the dorsal raphe nucleus.

    PubMed

    Stansley, Branden J; Yamamoto, Bryan K

    2014-11-01

    L-Dopa (l-3,4-dihydroxyphenylalanine) is the precursor to dopamine and has become the mainstay therapeutic treatment for Parkinson's disease. Chronic L-dopa is administered to recover motor function in Parkinson's disease patients. However, drug efficacy decreases over time, and debilitating side effects occur, such as dyskinesia and mood disturbances. The therapeutic effect and some of the side effects of L-dopa have been credited to its effect on serotonin (5-HT) neurons. Given these findings, it was hypothesized that chronic L-dopa treatment decreases 5-HT neurons in the dorsal raphe nucleus (DRN) and the content of 5-HT in forebrain regions in a manner that is mediated by oxidative stress. Rats were treated chronically with l-dopa (6 mg/kg; twice daily) for 10 days. Results indicated that the number of 5-HT neurons was significantly decreased in the DRN after l-dopa treatment compared with vehicle. This effect was more pronounced in the caudal-extent of the dorsal DRN, a subregion found to have a significantly higher increase in the 3,4-dihydroxyphenylacetic acid/dopamine ratio in response to acute L-dopa treatment. Furthermore, pretreatment with ascorbic acid (400 mg/kg) or deprenyl (2 mg/kg) prevented the l-dopa-induced decreases in 5-HT neurons. In addition, 5-HT content was decreased significantly in the DRN and prefrontal cortex by l-dopa treatment, effects that were prevented by ascorbic acid pretreatment. Taken together, these data illustrate that chronic L-dopa causes a 5-HT neuron loss and the depletion of 5-HT content in a subregion of the DRN as well as in the frontal cortex through an oxidative-stress mechanism.

  14. Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons

    PubMed Central

    Simon, Christen; Kezunovic, Nebojsa; Williams, D. Keith; Urbano, Francisco J.

    2011-01-01

    The dorsal subcoeruleus nucleus (SubCD) is involved in generating two signs of rapid eye movement (REM) sleep: muscle atonia and ponto-geniculo-occipital (PGO) waves. We tested the hypothesis that single cell and/or population responses of SubCD neurons are capable of generating gamma frequency activity in response to intracellular stimulation or receptor agonist activation. Whole cell patch clamp recordings (immersion chamber) and population responses (interface chamber) were conducted on 9- to 20-day-old rat brain stem slices. All SubCD neurons (n = 103) fired at gamma frequency when subjected to depolarizing steps. Two statistically distinct populations of neurons were observed, which were distinguished by their high (>80 Hz, n = 24) versus low (35–80 Hz, n = 16) initial firing frequencies. Both cell types exhibited subthreshold oscillations in the gamma range (n = 43), which may underlie the gamma band firing properties of these neurons. The subthreshold oscillations were blocked by the sodium channel blockers tetrodotoxin (TTX, n = 21) extracellularly and N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314) intracellularly (n = 5), indicating they were sodium channel dependent. Gamma frequency subthreshold oscillations were observed in response to the nonspecific cholinergic receptor agonist carbachol (CAR, n = 11, d = 1.08) and the glutamate receptor agonists N-methyl-d-aspartic acid (NMDA, n = 12, d = 1.09) and kainic acid (KA, n = 13, d = 0.96), indicating that cholinergic and glutamatergic inputs may be involved in the activation of these subthreshold currents. Gamma band activity also was observed in population responses following application of CAR (n = 4, P < 0.05), NMDA (n = 4, P < 0.05) and KA (n = 4, P < 0.05). Voltage-sensitive, sodium channel-dependent gamma band activity appears to be a part of the intrinsic membrane properties of SubCD neurons. PMID:21543743

  15. Increased glutamate synaptic transmission in the nucleus raphe magnus neurons from morphine-tolerant rats.

    PubMed

    Bie, Bihua; Pan, Zhizhong Z

    2005-02-09

    Currently, opioid-based drugs are the most effective pain relievers that are widely used in the treatment of pain. However, the analgesic efficacy of opioids is significantly limited by the development of tolerance after repeated opioid administration. Glutamate receptors have been reported to critically participate in the development and maintenance of opioid tolerance, but the underlying mechanisms remain unclear. Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia. Chronic morphine significantly increased glutamate synaptic transmission exclusively in one class of NRM cells that contains mu-opioid receptors in a morphine-tolerant state. The adenylyl cyclase activator forskolin and the cAMP analog 8-bromo-cAMP mimicked the chronic morphine effect in control neurons and their potency in enhancing the glutamate synaptic current was significantly increased in neurons from morphine-tolerant rats. MDL12330a, an adenylyl cyclase inhibitor, and H89, a protein kinase A (PKA) inhibitor, reversed the increase in glutamate synaptic transmission induced by chronic morphine. In addition, PMA, a phorbol ester activator of protein kinase C (PKC), also showed an increased potency in enhancing the glutamate synaptic current in these morphine-tolerant cells. The PKC inhibitor GF109203X attenuated the chronic morphine effect. Taken together, these results suggest that chronic morphine increases presynaptic glutamate release in mu receptor-containing NRM neurons in a morphine-tolerant state, and that the increased glutamate synaptic transmission appears to involve an upregulation of both the cAMP/PKA pathway and the PKC pathway. This glutamate-mediated activation of these NRM neurons that are thought to facilitate spinal pain transmission may contribute to

  16. Types of neurons of the subthalamic nucleus and zona incerta in the guinea pig--Nissl and Golgi study.

    PubMed

    Robak, A; Bogus-Nowakowska, K; Szteyn, S

    2000-01-01

    The studies were carried out on the subthalamus of adult guinea pigs. Golgi impregnation, Nissl and Klüver-Barrera methods were used for the study. In Nissl stained sections the subthalamic neuronal population consists of multipolar, fusiform, oval and pear-shaped perikarya. In two studied areas: nucleus subthalamicus (STN) and zona incerta (ZI) three types of neurons were distinguished. Type I, multipolar neurons with quadrangular, triangular or oval perikarya. They have 3-6 primary dendrites which run slightly wavy and spread out in all directions. Type II, bipolar neurons with fusiform or semilunar perikarya, they have two primary dendrites. Type III, pear-shaped neurons with 1-2 dendritic trunks arising from one pole of the neuron. In all types of neurons axon emerges from the perikaryon or initial segment of a dendritic trunk and can be followed at a maximum distance of about 50 microns.

  17. Suckling-induced activation of neuronal input to the dorsomedial nucleus of the hypothalamus: possible candidates for mediating the activation of DMH neuropeptide Y neurons during lactation.

    PubMed

    Chen, Peilin; Smith, M Susan

    2003-09-12

    Activation of the neuropeptide Y (NPY) neuronal system in the dorsomedial nucleus of the hypothalamus (DMH) during lactation in the rat is in part due to neural impulses arising from the suckling stimulus. However, the afferent neuronal input to the DMH that is activated during lactation and is responsible for activation of NPY neurons is currently unknown. Previously, using cFos as a marker for neuronal activation, we identified several brain areas in the lactating animals that were activated by the suckling stimulus. Thus, the objective of the present study was to determine if any of these suckling activated areas project directly to the DMH. The retrograde tracer, fluorogold (FG), was injected into the DMH on day 4 postpartum. FG-injected lactating rats were then deprived of their eight-pup litters on day 9 postpartum, and 48 h later, the pups were returned to the females to reinitiate the suckling stimulus for 90 min and induce cFos expression. The animals were then perfused and the brains were subjected to double-label immunohistochemistry to visualize both FG- and cFos-positive cells. Substantial numbers of FG/cFos double-labeled cells were found in forebrain regions, including the preoptic area, lateral septal nucleus, ventral subiculum, and supramammillary nucleus, and in brainstem regions, including the lateral parabrachial nucleus, periaqeductal gray, and ventrolateral medulla. In conclusion, these areas are potentially important candidates for mediating the activation of the NPY neuronal system in the DMH during lactation.

  18. Types of neurons in nucleus olivaris inferior of the European bison.

    PubMed

    Szteyn, S

    1988-01-01

    The studies were carried out on the medullae oblongatae of four European bisons. Preparations made by means of the Golgi technique, as well as preparations stained by the Klüver-Barrera methods, were used. Two types of neurons were distinguished in nucleus olivaris inferior of the European bison. Type I (about 90% of neurons) are multipolar cells whose perikaryons measure from 25 to 40 microns. The multipolar cells generate 5-6 thick dendrites which next give off a number of branches. The dendritic tree is ball-shaped. A single long, thin axon arises from the surface of the perikaryon or branches from the initial segment of one of the dendrites. The axon adopts a course along the plane corresponding to the transverse section of brain stem. Type II (about 10% of neurons) are pear-shaped and rounded cells measuring from 25 to 30 microns. These cells generate 2-3 thick dendritic trunks which are concentrated at one pole of the perikaryon. The dendritic tree has a stream-like form. A single short and rather thin axon emerges from the surface of the perikaryon. Its course corresponds to the long axis of brain stem.

  19. Involvement of subthalamic nucleus in the stimulatory effect of Delta(9)-tetrahydrocannabinol on dopaminergic neurons.

    PubMed

    Morera-Herreras, T; Ruiz-Ortega, J A; Gómez-Urquijo, S; Ugedo, L

    2008-02-06

    The cannabinoid CB1 receptor which is densely located in the basal ganglia is known to participate in the regulation of movement. The present study sought to determine the mechanisms underlying the effect of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) on neurons in the substantia nigra pars compacta (SNpc) using single-unit extracellular recordings in anesthetized rats. Administration of Delta(9)-THC (0.25-2 mg/kg, i.v.) increased the firing rate of SNpc neurons (maximal effect: 33.54+/-6.90%, n=8) without modifying other firing parameters (coefficient of variation and burst firing). This effect was completely blocked by the cannabinoid receptor antagonist rimonabant (0.5 mg/kg, i.v.). In addition, the blockade of excitatory amino acids receptors by kynurenic acid (0.5 microM, i.c.v.) or a chemical lesion of the subthalamic nucleus (STN) with ibotenic acid abolished Delta(9)-THC effect. These results indicate that CB1 receptor activation modulates SNpc neuronal activity by an indirect mechanism involving excitatory amino acids, probably released from STN axon terminals in the SNpc.

  20. Visually guided whole cell patch clamp of mouse supraoptic nucleus neurons in cultured and acute conditions.

    PubMed

    Stachniak, Tevye J E; Bourque, Charles W

    2006-07-01

    Recent advances in neuronal culturing techniques have supplied a new set of tools for studying neural tissue, providing effective means to study molecular aspects of regulatory elements in the supraoptic nucleus of the hypothalamus (SON). To combine molecular biology techniques with electrophysiological recording, we modified an organotypic culture protocol to permit transfection and whole cell patch-clamp recordings from SON cells. Neonatal mouse brain coronal sections containing the SON were dissected out, placed on a filter insert in culture medium, and incubated for at least 4 days to allow attachment to the insert. The SON was identifiable using gross anatomical landmarks, which remained intact throughout the culturing period. Immunohistochemical staining identified both vasopressinergic and oxytocinergic cells present in the cultures, typically appearing in well-defined clusters. Whole cell recordings from these cultures demonstrated that certain properties of the neonatal mouse SON were comparable to adult mouse magnocellular neurons. SON neurons in both neonatal cultures and acute adult slices showed similar sustained outward rectification above -60 mV and action potential broadening during evoked activity. Membrane potential, input resistance, and rapidly inactivating potassium current density (IA) were reduced in the cultures, whereas whole cell capacitance and spontaneous synaptic excitation were increased, perhaps reflecting developmental changes in cell physiology that warrant further study. The use of the outlined organotypic culturing procedures will allow the study of such electrophysiological properties of mouse SON using whole cell patch-clamp, in addition to various molecular, techniques that require longer incubation times.

  1. Orexins excite ventrolateral geniculate nucleus neurons predominantly via OX2 receptors.

    PubMed

    Chrobok, Lukasz; Palus, Katarzyna; Lewandowski, Marian Henryk

    2016-04-01

    Orexins/hypocretins are two neuropeptides that influence many behaviours, such as feeding, sleep or arousal. Orexin A/hypocretin-1 (OXA) and orexin B/hypocretin-2 (OXB) bind to two metabotropic receptors, named the OX1 and OX2 receptors. The lateral geniculate complex of the thalamus is one of the many targets of orexinergic fibres derived from the lateral hypothalamus, although the impact of orexins on the ventrolateral geniculate nucleus (VLG) is poorly understood. The VLG, an important relay station of the subcortical visual system, is implicated in visuomotor and/or circadian processes. Therefore, in this study we evaluated the effects of orexins on single VLG neurons using a patch-clamp technique in vitro. Surprisingly, orexins depolarised the majority of the recorded neurons regardless of their localisation in the borders of the VLG. In addition, data presented in this article show that neurons synthesising NO were also affected by OXA. Moreover, immunohistochemical staining of OXB revealed the moderate density of orexinergic fibbers in the VLG. Our study using specific orexin receptor antagonists suggests that the OX2 receptor has a dominant role in the observed effects of OXA. To our knowledge, this article is the first to show orexinergic modulation of the VLG. These findings strengthen the postulated link between orexins and the circadian system, and propose a new role of these neuropeptides in the modulation of visuomotor functions.

  2. Electrophysiological identification of mesencephalic ventromedial tegmental (VMT) neurons projecting to the frontal cortex, septum and nucleus accumbens.

    PubMed

    Deniau, J M; Thierry, A M; Feger, J

    1980-05-12

    The electrophysiological properties of neurons located in the mesencephalic ventromedial tegmentum (VMT) and the organization of the efferents of these neurons to the frontal cortex, the septum, the nucleus accumbens and the head of the striatum were studied in ketamine-anesthetized rats. The projections of the VMT cells were determined through use of the antidromic activation method. Our results show that VMT projections to different target areas originate mainly from different VMT neurons. However, in some cases single VMT neurons were found to send axon collaterals to two different areas. Three branching patterns were observed: septum-cortex, septum--nucleus accumbens and septum--striatum. The occasional observation of temporally distinct antodromic responses from a single area was considered to result from activation of different branches of the arborizing axon. The distribution of antidromic response latencies for VMT projections to each structure is discussed in relation to the question of dopaminergic versus non-dopaminergic mesolimbic and mesocortical systems.

  3. Development of neuronal types and laminar organization in the central nucleus of the inferior colliculus in the cat.

    PubMed

    González-Hernández, T H; Meyer, G; Ferres-Torres, R

    1989-01-01

    The development of neuronal morphology and laminar organization in the central nucleus of the inferior colliculus has been studied with the different Golgi methods in kittens and cats of 1 day-2 years of age. The different Golgi methods used allowed us to selectively visualize the axonal or dendritic component of the fibrodendritic laminae. The characteristic lamination of the central nucleus defined by the fiber system of the lateral lemniscus is already present at birth. The axonal component of the laminae is constituted by parallel condensations of varicose terminals, myelinated axons, and preterminal fibers, oriented from ventrolateral to dorsomedial. The laminae are smaller in the dorsolateral edge of the nucleus. Neurons are classified mainly on the basis of their dendritic trees and the axonal ramification patterns. Three main types are distinguished: spinous disk-shaped neurons, aspinous to sparsely spinous disk-shaped neurons, and large or giant multipolar neurons. Our results suggest that the basic structures of the central nucleus--neuronal types and lamination of the lemniscal fibers--are already established at birth. The different neuronal types can be distinguished from the first days of life according to the ramification pattern of dendritic and axonal arbors. The characteristics of the different cell types, such as the density and distribution of dendritic spines, and the presence of varicose dendritic branchlets, are recognizable from the second week. At the end of the first month, neurons display an adult-like morphology, although the density of dendritic spines is higher than in the adult. Our morphological data can be related to the development of response properties in the inferior colliculus.

  4. Dendritic arbor of neurons in the hypothalamic ventromedial nucleus in female prairie voles (Microtus ochrogaster).

    PubMed

    Ferri, Sarah L; Rohrbach, Carlos J; Way, Samantha E; Curtis, Kathleen S; Curtis, J Thomas; Flanagan-Cato, Loretta M

    2013-01-01

    Female mating behavior in rats is associated with hormone-induced changes in the dendritic arbor of neurons in the ventromedial nucleus of the hypothalamus (VMH), particularly the ventrolateral portion. Regulation of mating behavior in female prairie voles differs substantially from that in rats; therefore, we examined the dendritic morphology of VMH neurons in this species. Sexually naïve adult female prairie voles were housed with a male to activate the females' reproductive endocrine system. Following 48 h of cohabitation, females were tested for evidence of reproductive activation by assessing the level of male sexual interest, after which their brains were processed using Golgi impregnation, which allowed ventrolateral VMH neurons to be visualized and analyzed. Dendritic arborization in the female prairie vole VMH neurons was strikingly similar to that of female rats. The key difference was that in the prairie voles the long primary dendrites extended considerably further than those observed in rats. Although most female voles paired with males exhibited sexual activation, some females did not. These two groups displayed specific differences in their VMH dendrites. In particular, the long primary dendrites were longer in the reproductively active females compared with those in the non-activated females. Overall, dendrite lengths were positively correlated with plasma estradiol levels in females exposed to males, but not in unpaired females. Although causal relationships between the neuroendocrine events, dendrite length, and the outward, behavioral manifestation of reproductive activation cannot be determined from this study, these results suggest an association between ventrolateral VMH dendrite morphology and female mating behavior in prairie voles, akin to what has been observed in female rats.

  5. Subthreshold oscillation of the membrane potential in magnocellular neurones of the rat supraoptic nucleus

    PubMed Central

    Boehmer, Gerd; Greffrath, Wolfgang; Martin, Erich; Hermann, Sven

    2000-01-01

    Electrophysiological properties and ionic basis of subthreshold oscillation of the membrane potential were examined in 104 magnocellular neurones of the rat supraoptic nucleus using intracellular recording techniques in a brain slice preparation. Subthreshold oscillation of the membrane potential occurring in all neurones examined was voltage dependent. Oscillation was initiated 7-12 mV negative to the threshold of fast action potentials. Oscillation was the result of neither excitatory nor inhibitory synaptic activity nor of electric coupling. Frequency analyses revealed a broad band frequency distribution of subthreshold oscillation waves (range 10-70 Hz). The frequency band of 15-33 Hz was observed in neurones depolarized close to the threshold of discharge. Subthreshold oscillation was blocked by TTX (1.25-2.5 μM) as well as by TEA (15 mM). Subthreshold oscillation was not blocked by low Ca2+-high Mg2+ superfusate, CdCl2, TEA (1-4.5 mM), 4-aminopyridine, apamin, charybdotoxin, iberiotoxin, BaCl2, carbachol and CsCl. During application of TTX, stronger depolarization induced high-threshold oscillation of the membrane potential at a threshold of about -32 mV. These oscillation waves occurred at a mean frequency of about 35 Hz and were blocked by CdCl2. Effects of ion channel antagonists suggest that subthreshold oscillation is generated by the interaction of a subthreshold sodium current and a subthreshold potassium current. The generation of high-threshold oscillation during TTX involves a high-threshold calcium current. Subthreshold oscillation of the membrane potential may be important for the inter-neuronal synchronization of discharge and for the amplification of synaptic events. PMID:10878105

  6. Functional role of cyclic nucleotide-gated channels in rat medial vestibular nucleus neurons

    PubMed Central

    Podda, Maria Vittoria; D'Ascenzo, Marcello; Leone, Lucia; Piacentini, Roberto; Azzena, Gian Battista; Grassi, Claudio

    2008-01-01

    Although cyclic nucleotide-gated (CNG) channels are expressed in numerous brain areas, little information is available on their functions in CNS neurons. The aim of the present study was to define the distribution of CNG channels in the rat medial vestibular nucleus (MVN) and their possible involvement in regulating MVN neuron (MVNn) excitability. The majority of MVNn expressed both CNG1 and CNG2 A subunits. In whole-cell current-clamp experiments carried out on brainstem slices containing the MVNn, the membrane-permeant analogues of cyclic nucleotides, 8-Br-cGMP and 8-Br-cAMP (1 mm), induced membrane depolarizations (8.9 ± 0.8 and 9.2 ± 1.0 mV, respectively) that were protein kinase independent. The cGMP-induced depolarization was associated with a significant decrease in the membrane input resistance. The effects of cGMP on membrane potential were almost completely abolished by the CNG channel blockers, Cd2+ and l-cis-diltiazem, but they were unaffected by blockade of hyperpolarization-activated cyclic nucleotide-gated channels. In voltage-clamp experiments, 8-Br-cGMP induced non-inactivating inward currents (−22.2 ± 3.9 pA) with an estimated reversal potential near 0 mV, which were markedly inhibited by reduction of extracellular Na+ and Ca2+ concentrations. Membrane depolarization induced by CNG channel activation increased the firing rate of MVNn without changing the action potential shape. Collectively, these findings provide novel evidence that CNG channels affect membrane potential and excitability of MVNn. Such action should have a significant impact on the function of these neurons in sensory–motor integration processes. More generally, it might represent a broad mechanism for regulating the excitability of different CNS neurons. PMID:18048449

  7. GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic paraventricular nucleus stimulation.

    PubMed

    Rojas-Piloni, Gerardo; López-Hidalgo, Mónica; Martínez-Lorenzana, Guadalupe; Rodríguez-Jiménez, Javier; Condés-Lara, Miguel

    2007-03-16

    In anaesthetized rats, we tested whether the unit activity of dorsal horn neurons that receive nociceptive input is modulated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN). An electrophysiological mapping of dorsal horn neurons at L3-L4 let us choose cells responding to a receptive field located in the toes region of the left hindpaw. Dorsal horn neurons were classified according to their response properties to peripheral stimulation. Wide Dynamic Range (WDR) cells responding to electrical stimulation of the peripheral receptive field and presenting synaptic input of Adelta, Abeta, and C-fibers were studied. Suspected interneurons that are typically silent and lack peripheral receptive field responses were also analyzed. PVN electrical stimulation inhibits Adelta (-55.0+/-10.2%), C-fiber (-73.1+/-6.7%), and post-discharge (-75.0+/-8.9%) peripheral activation in WDR cells, and silent interneurons were activated. So, this last type of interneuron was called a PVN-ON cell. In WDR cells, the inhibition of peripheral responses caused by PVN stimulation was blocked by intrathecal administration of a specific oxytocin antagonist or bicuculline. However, PVN-ON cell activation was blocked by the same specific oxytocin antagonist, but not by bicuculline. Our results suggest that PVN stimulation inhibits nociceptive peripheral-evoked responses in WDR neurons by a descending oxytocinergic pathway mediated by GABAergic PVN-ON cells. We discuss our observation that the PVN electrical stimulation selectively inhibits Adelta and C-fiber activity without affecting Abeta fibers. We conclude that Adelta and C-fibers receive a presynaptic inhibition mediated by GABA.

  8. Early developmental stress negatively affects neuronal recruitment to avian song system nucleus HVC.

    PubMed

    Honarmand, Mariam; Thompson, Christopher K; Schatton, Adriana; Kipper, Silke; Scharff, Constance

    2016-01-01

    Adverse environmental conditions can impact the life history trajectory of animals. Adaptive responses enable individuals to cope with unfavorable conditions, but altered metabolism and resource allocation can bear long-term costs. In songbirds, early developmental stress can cause lifelong changes in learned song, a culturally transmitted trait, and nestlings experiencing developmental stress develop smaller song control nucleus HVCs. We investigated whether nutrition-related developmental stress impacts neurogenesis in HVC, which may explain how poor nutrition leads to smaller HVC volume. We provided different quality diets (LOW and HIGH) by varying the husks-to-seeds ratio to zebra finch families for the first 35 days after the young hatched (PHD). At PHD14-18 and again at nutritional independence (PHD35), juveniles were injected with different cell division markers. To monitor growth, we took body measures at PHD10, 17, and 35. At PHD35 the number of newly recruited neurons in HVC and the rate of proliferation in the adjacent ventricular zone (VZ) were counted. Males raised on the LOW diet for their first weeks of life had significantly fewer new neurons in HVC than males raised on the HIGH diet. At the time when these new HVC neurons were born and labeled in the VZ (PHD17) the birds exposed to the LOW diet had significantly lower body mass. At PHD35 body mass or neuronal proliferation no longer differed. Our study shows that even transitory developmental stress can have negative consequences on the cellular processes underlying the development of neural circuits.

  9. Sustained and transient neurones in the cat's retina and lateral geniculate nucleus

    PubMed Central

    Cleland, B. G.; Dubin, M. W.; Levick, W. R.

    1971-01-01

    1. Cat retinal ganglion cells may be subdivided into sustained and transient response-types by the application of a battery of simple tests based on responses to standing contrast, fine grating patterns, size and speed of contrasting targets, and on the presence or absence of the periphery effect. The classification is equivalent to the `X'/`Y' (linear/nonlinear) subdivision of Enroth-Cugell & Robson which is thus confirmed and extended. 2. The sustained/transient classification applied to both on-centre and off-centre cells. 3. Lateral geniculate neurones may be similarly classified by the same tests. Occasional concentrically organized cells had a mixture of sustained and transient properties. 4. A technique for simultaneous recording from a geniculate neurone and one or more retinal ganglion cells providing its excitatory input showed that the connexions were specific with respect to the sustained/transient classification as well as the on-centre/off-centre classification. Most geniculate neurones are excitatorily driven only by retinal ganglion cells of the same functional type. In a few cases the inputs were mixed but only with respect to the sustained/transient classification. 5. Sustained retinal ganglion cells had slower-conducting axons than the transient type. The same was true for lateral geniculate neurones but in this case the distributions showed considerable overlap. 6. The sustained/transient classification is the functional correlate for the well-known segregation of optic nerve fibres into two conduction groups. 7. The pathways carrying sustained and transient information remain essentially separate from retina through the lateral geniculate nucleus to the striate cortex. PMID:5097609

  10. Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro

    NASA Technical Reports Server (NTRS)

    Phelan, K. D.; Gallagher, J. P.

    1992-01-01

    We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

  11. Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

    PubMed Central

    Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

    2014-01-01

    We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that ‘cell cycle’-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9–10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9–10 HVR counterparts. However, voluntary running wheel access in our G9–10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

  12. Oscillatory entrainment of subthalamic nucleus neurons and behavioural consequences in rodents and primates.

    PubMed

    Syed, E C J; Benazzouz, A; Taillade, M; Baufreton, J; Champeaux, K; Falgairolle, M; Bioulac, B; Gross, C E; Boraud, T

    2012-11-01

    We investigated the functional role of oscillatory activity in the local field potential (LFP) of the subthalamic nucleus (STN) in the pathophysiology of Parkinson's disease (PD). It has been postulated that beta (15-30 Hz) oscillatory activity in the basal ganglia induces PD motor symptoms. To assess this hypothesis, an LFP showing significant power in the beta frequency range (23 Hz) was used as a stimulus both in vitro and in vivo. We first demonstrated in rat brain slices that STN neuronal activity was driven by the LFP stimulation. We then applied beta stimulation to the STN of 16 rats and two monkeys while quantifying motor behaviour. Although stimulation-induced behavioural effects were observed, stimulation of the STN at 23 Hz induced no significant decrease in motor performance in either rodents or primates. This study is the first to show LFP-induced behaviour in both rats and primates, and highlights the complex relationship between beta power and parkinsonian symptoms.

  13. Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward.

    PubMed

    Al-Hasani, Ream; McCall, Jordan G; Shin, Gunchul; Gomez, Adrian M; Schmitz, Gavin P; Bernardi, Julio M; Pyo, Chang-O; Park, Sung Il; Marcinkiewcz, Catherine M; Crowley, Nicole A; Krashes, Michael J; Lowell, Bradford B; Kash, Thomas L; Rogers, John A; Bruchas, Michael R

    2015-09-02

    The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease.

  14. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    PubMed Central

    da Silva, M.P.; Cedraz-Mercez, P.L.; Varanda, W.A.

    2014-01-01

    Physiological evidence indicates that the supraoptic nucleus (SON) is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs) responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1) the intrinsic membrane properties of the MNCs themselves and 2) synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO) may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON. PMID:24519124

  15. The types of neurons of the somatic oculomotor nucleus in the European bison. Nissl and Golgi studies.

    PubMed

    Szteyn, S; Robak, A; Równiak, M

    1997-01-01

    The neuronal structure of the somatic oculomotor nucleus (SON) was studied on the basis of Nissl and Golgi preparations, obtained from mesencephalons of 4 European bisons. We distinguished four types of neurons in the investigated nucleus: 1. The large multipolar nerve cells with 5-8 thick dendritic trunks and a thin axon which emerges directly from the soma. These are the most numerous neurons in the SON. 2. The small multipolar neurons. These cells have 4-6 thick dendritic trunks. An axon arises mostly from initial segment of one of the dendrites. This type represents about 8% neurons of SON. 3. The triangular neurons. From perikaryon 3 thick dendritic trunks emerge. A thin axon arises directly from the cell body. These cells make about 10% neurons of SON. 4. The pear-shaped cells which have 1 or 2 dendritic trunks concentrate at one pole of the neurons. In the SON there are about 2% pear-shaped cells. Their features correspond to the features attributed by many authors to the interneurons.

  16. Excitatory projections from the amygdala to neurons in the nucleus pontis oralis in the rat: an intracellular study.

    PubMed

    Xi, M; Fung, S J; Sampogna, S; Chase, M H

    2011-12-01

    There is a consensus that active (REM) sleep (AS) is controlled by cholinergic projections from the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT) to neurons in the nucleus pontis oralis (NPO) that generate AS (i.e. AS-Generator neurons). The present study was designed to provide evidence that other projections to the NPO, such as those from the amygdala, are also capable of inducing AS. Accordingly, the responses of neurons, recorded intracellularly in the NPO, were examined following stimulation of the ipsilateral central nucleus of the amygdala (CNA) in urethane-anesthetized rats. Single pulse stimulation in the CNA produced an early, fast depolarizing potential (EPSP) in neurons within the NPO. The mean latency to the onset of these excitatory postsynaptic potentials (EPSPs) was 3.6±0.2 ms. A late, small-amplitude inhibitory synaptic potential (IPSP) was present following EPSPs in a portion of the NPO neurons. Following stimulation of the CNA with a train of 8-10 pulses, NPO neurons exhibited a sustained depolarization (5-10 mV) of their resting membrane potential. When single subthreshold intracellular depolarizing current pulses were delivered to NPO neurons, CNA-induced EPSPs were sufficient to promote the discharge of these cells. Stimulation of the CNA with a short train of stimuli induced potent temporal facilitation of EPSPs in NPO neurons. Two forms of synaptic plasticity were revealed by the patterns of response of NPO neurons following stimulation of the CNA: paired-pulse facilitation (PPF) and post-tetanic potentiation (PTP). Six of recorded NPO neurons were identified morphologically with neurobiotin. They were medium to large, multipolar cells with diameters >20 μM, which resemble AS-on cells in the NPO. The present results demonstrate that amygdalar projections are capable of exerting a powerful excitatory postsynaptic drive that activates NPO neurons. Therefore, we suggest that the amygdala is capable of inducing AS via direct

  17. Segregation of Tactile Input Features in Neurons of the Cuneate Nucleus

    PubMed Central

    Jörntell, Henrik; Bengtsson, Fredrik; Geborek, Pontus; Spanne, Anton; Terekhov, Alexander V.; Hayward, Vincent

    2014-01-01

    Summary Our tactile perception of external objects depends on skin-object interactions. The mechanics of contact dictates the existence of fundamental spatiotemporal input features—contact initiation and cessation, slip, and rolling contact—that originate from the fact that solid objects do not interpenetrate. However, it is unknown whether these features are represented within the brain. We used a novel haptic interface to deliver such inputs to the glabrous skin of finger/digit pads and recorded from neurons of the cuneate nucleus (the brain’s first level of tactile processing) in the cat. Surprisingly, despite having similar receptive fields and response properties, each cuneate neuron responded to a unique combination of these inputs. Hence, distinct haptic input features are encoded already at subcortical processing stages. This organization maps skin-object interactions into rich representations provided to higher cortical levels and may call for a re-evaluation of our current understanding of the brain’s somatosensory systems. PMID:25175880

  18. Opioidergic projections to sleep-active neurons in the ventrolateral preoptic nucleus

    PubMed Central

    Greco, Mary-Ann; Fuller, Patrick; Jhou, Thomas C; Martin-Schild, S; Zadina, James E; Hu, Zhian; Shiromani, Priyattam; Lu, Jun

    2008-01-01

    Although opioids are known to influence sleep-wake regulation, the neuroanatomic substrate(s) mediating these effects remain unresolved. We hypothesized that the influence of opiates on sleep may be mediated, at least in part, by the ventrolateral preoptic nucleus (VLPO), a key cell group for producing behavioral sleep. By combining in situ hybridization for kappa and mu receptor mRNA with immunostaining of Fos expressed by VLPO cells during sleep we show that > 85% of sleep-active VLPO neurons contain mRNA for either or both opioid receptor. Microinfusions of a kappa receptor agonist into the VLPO region increased NREM sleep by 51% during the subjective night, whereas a mu receptor agonist increased wakefulness by 60% during the subjective day. The sleep- and wake- promoting effects of the kappa and mu agonists were blocked by prior administration of their respective antagonist. Combining retrograde tracing from the VLPO with immunohistochemistry for dynorphin (Dyn, the endogenous kappa receptor agonist) or endomorphin 1 (EM1, the endogenous mu receptor agonist) we show that the central lateral parabrachial subnucleus (PBcl) provides Dyn inputs to the VLPO, whereas hypothalamic histaminergic neurons provide EM1 inputs to the VLPO. In summary, results from the present study suggest that central opioid inputs to the VLPO may play a role in sleep-wake regulation and that the VLPO likely mediates the hypnotic response to high levels of opioid analgesics. PMID:18840417

  19. Collective behaviors of suprachiasm nucleus neurons under different light—dark cycles

    NASA Astrophysics Data System (ADS)

    Gu, Chang-Gui; Zhang, Xin-Hua; Liu, Zong-Hua

    2014-07-01

    The principal circadian clock in the suprachiasm nucleus (SCN) regulates the circadian rhythm of physiological and behavioral activities of mammals. Except for the normal function of the circadian rhythm, the ensemble of SCN neurons may show two collective behaviors, i.e., a free running period in the absence of a light—dark cycle and an entrainment ability to an external T cycle. Experiments show that both the free running periods and the entrainment ranges may vary from one species to another and can be seriously influenced by the coupling among the SCN neurons. We here review the recent progress on how the heterogeneous couplings influence these two collective behaviors. We will show that in the case of homogeneous coupling, the free running period increases monotonically while the entrainment range decreases monotonically with the increase of the coupling strength. While in the case of heterogenous coupling, the dispersion of the coupling strength plays a crucial role. It has been found that the free running period decreases with the increase of the dispersion while the entrainment ability is enhanced by the dispersion. These findings provide new insights into the mechanism of the circadian clock in the SCN.

  20. The cytoarchitectonic and neuronal structure of the red nucleus in guinea pig: Nissl and Golgi studies.

    PubMed

    Robak, A; Szteyn, S; Bogus-Nowakowska, K; Doboszyńska, T; Równiak, M

    2000-01-01

    The present studies were carried out on the brains of adult guinea pigs, Dunkin-Hartley strain. On the basis of preparations, they were stained according to the Nissl and the Klüver-Barrera method's; a short description of the cytoarchitectonics and the characteristics of the rubral cells were written. The red nucleus (RN) of the guinea pig is 1.2 mm in length. Three cellular parts in RN, and three classes (A, B, C) of the rubral cells were distinguished. Taking into consideration the predominant cell size, RN was divided into magnocellular part (RNm), parvocellular part (RNp) and intermediate part (RNi). On the basis of Golgi impregnated preparations four neuronal types (I, II, III, IV) were distinguished. To sum up, in the guinea pig were observed: the large, mainly multipolar (type I) and bipolar (type II) spiny being coarse (class A) in Nissl material; the medium-sized, triangular, aspiny (type III) corresponding to the fine cells (class B); and the small, both spiny and aspiny neurons (type IV), which are the fine or achromatic cells (classes B or C) in Nissl stained slices. The highest degree of dendritic branching was observed in type I, whereas the lowest in cells of types III and IV.

  1. Noradrenergic refinement of glutamatergic neuronal circuits in the lateral superior olivary nucleus before hearing onset.

    PubMed

    Hirao, Kenzo; Eto, Kei; Nakahata, Yoshihisa; Ishibashi, Hitoshi; Nagai, Taku; Nabekura, Junichi

    2015-09-01

    Neuronal circuit plasticity during development is fundamental for precise network formation. Pioneering studies of the developmental visual cortex indicated that noradrenaline (NA) is crucial for ocular dominance plasticity during the critical period in the visual cortex. Recent research demonstrated tonotopic map formation by NA during the critical period in the auditory system, indicating that NA also contributes to synaptic plasticity in this system. The lateral superior olive (LSO) in the auditory system receives glutamatergic input from the ventral cochlear nucleus (VCN) and undergoes circuit remodeling during postnatal development. LSO is innervated by noradrenergic afferents and is therefore a suitable model to study the function of NA in refinement of neuronal circuits. Chemical lesions of the noradrenergic system and chronic inhibition of α2-adrenoceptors in vivo during postnatal development in mice disrupted functional elimination and strengthening of VCN-LSO afferents. This was potentially mediated by activation of presynaptic α2-adrenoceptors and inhibition of glutamate release because NA presynaptically suppressed excitatory postsynaptic current (EPSC) through α2-adrenoceptors during the first two postnatal weeks in an in vitro study. Furthermore, NA and α2-adrenoceptor agonist induced long-term suppression of EPSCs and decreased glutamate release. These results suggest that NA has a critical role in synaptic refinement of the VCN-LSO glutamatergic pathway through failure of synaptic transmission. Because of the ubiquitous distribution of NA afferents and the extensive expression of α2-adrenoceptors throughout the immature brain, this phenomenon might be widespread in the developing central nervous system.

  2. Dopamine/Tyrosine Hydroxylase Neurons of the Hypothalamic Arcuate Nucleus Release GABA, Communicate with Dopaminergic and Other Arcuate Neurons, and Respond to Dynorphin, Met-Enkephalin, and Oxytocin

    PubMed Central

    Zhang, Xiaobing

    2015-01-01

    We employ transgenic mice with selective expression of tdTomato or cre recombinase together with optogenetics to investigate whether hypothalamic arcuate (ARC) dopamine/tyrosine hydroxylase (TH) neurons interact with other ARC neurons, how they respond to hypothalamic neuropeptides, and to test whether these cells constitute a single homogeneous population. Immunostaining with dopamine and TH antisera was used to corroborate targeted transgene expression. Using whole-cell recording on a large number of neurons (n = 483), two types of neurons with different electrophysiological properties were identified in the dorsomedial ARC where 94% of TH neurons contained immunoreactive dopamine: bursting and nonbursting neurons. In contrast to rat, the regular oscillations of mouse bursting neurons depend on a mechanism involving both T-type calcium and A-type potassium channel activation, but are independent of gap junction coupling. Optogenetic stimulation using cre recombinase-dependent ChIEF-AAV-DJ expressed in ARC TH neurons evoked postsynaptic GABA currents in the majority of neighboring dopamine and nondopamine neurons, suggesting for the first time substantial synaptic projections from ARC TH cells to other ARC neurons. Numerous met-enkephalin (mENK) and dynorphin-immunoreactive boutons appeared to contact ARC TH neurons. mENK inhibited both types of TH neuron through G-protein coupled inwardly rectifying potassium currents mediated by δ and μ opioid receptors. Dynorphin-A inhibited both bursting and nonbursting TH neurons by activating κ receptors. Oxytocin excited both bursting and nonbursting neurons. These results reveal a complexity of TH neurons that communicate extensively with neurons within the ARC. SIGNIFICANCE STATEMENT Here, we show that the great majority of mouse hypothalamic arcuate nucleus (ARC) neurons that synthesize TH in the dorsomedial ARC also contain immunoreactive dopamine, and show either bursting or nonbursting electrical activity. Unlike

  3. Effects of oleic acid on distinct populations of neurons in the hypothalamic arcuate nucleus are dependent on extracellular glucose levels.

    PubMed

    Wang, R; Cruciani-Guglielmacci, C; Migrenne, S; Magnan, C; Cotero, V E; Routh, V H

    2006-03-01

    Pharmacological manipulation of fatty acid metabolism in the hypothalamic arcuate nucleus (ARC) alters energy balance and glucose homeostasis. Thus, we tested the hypotheses that distinctive populations of ARC neurons are oleic acid (OA) sensors that exhibit a glucose dependency, independent of whether some of these OA sensors are also glucose-sensing neurons. We used patch-clamp recordings to investigate the effects of OA on ARC neurons in brain slices from 14- to 21-day-old Sprague-Dawley (SD) rats. Additionally, we recorded spontaneous discharge rate in ARC neurons in 8-wk-old fed and fasted SD rats in vivo. Patch-clamp studies showed that in 2.5 mM glucose 12 of 94 (13%) ARC neurons were excited by 2 microM OA (OA-excited or OAE neurons), whereas six of 94 (6%) were inhibited (OA-inhibited2.5 or OAI2.5 neurons). In contrast, in 0.1 mM glucose, OA inhibited six of 20 (30%) ARC neurons (OAI0.1 neurons); none was excited. None of the OAI0.1 neurons responded to OA in 2.5 mM glucose. Thus OAI2.5 and OAI0.1 neurons are distinct. Similarly, in seven of 20 fed rats (35%) the overall response was OAE-like, whereas in three of 20 (15%) it was OAI-like. In contrast, in fasted rats only OAI-like response were observed (three of 15; 20%). There was minimal overlap between OA-sensing neurons and glucose-sensing neurons. In conclusion, OA regulated three distinct subpopulations of ARC neurons in a glucose-dependent fashion. These data suggest that an interaction between glucose and fatty acids regulates OA sensing in ARC neurons.

  4. Depletion of glucose causes presynaptic inhibition of neuronal transmission in the rat dorsolateral septal nucleus.

    PubMed

    Akasu, T; Tsurusaki, M; Shoji, S

    1996-10-01

    The role of glucose in synaptic transmission was examined in the rat dorsolateral septal nucleus (DLSN) with single-microelectrode voltage-clamp and slice-patch technique. Removal of glucose from the oxygenated Krebs solution caused an outward current associated with an increased membrane conductance. The current-voltage relationship (I-V curve) showed that the hypoglycemia-induced outward current was reversed in polarity at the equilibrium potential for K+. Exposure of DLSN neurons to the glucose-free solution for 5-20 min depressed the excitatory postsynaptic current (EPSC), the inhibitory postsynaptic current (IPSC), and the late hyperpolarizing current (LHC). Replacement of glucose with 2-deoxy-D-glucose (2DG), an antimetabolic substrate, mimicked the deprivation of glucose. Mannoheptulose (10 mM) and dinitrophenol, inhibitors of glucose metabolism, also depressed the PSCs, even in the presence of 10 mM glucose. Glucose-free perfusion did not significantly depress the glutamate-induced inward current, indicating that the inhibition of the EPSC by the glucose-free perfusion was presynaptic. gamma-Aminobutyric acid (GABA)-induced outward currents were depressed by the glucose-free solution. Intracellular dialysis of DLSN neurons with a patch-pipette solution containing 5 mM ATP attenuated the hypoglycemia-induced outward current. Glucose-free superfusion consistently inhibited the IPSC and the LHC without changing the GABA-induced outward current in ATP-treated DLSN neurons. It is suggested that glucose metabolism directly regulates the release of both excitatory amino acids and GABA from the presynaptic nerve terminals.

  5. Responses of neurons in the nucleus of the basal optic root to translational and rotational flowfields.

    PubMed

    Wylie, D R; Frost, B J

    1999-01-01

    The nucleus of the basal optic root (nBOR) receives direct input from the contralateral retina and is the first step in a pathway dedicated to the analysis of optic flowfields resulting from self-motion. Previous studies have shown that most nBOR neurons exhibit direction selectivity in response to large-field stimuli moving in the contralateral hemifield, but a subpopulation of nBOR neurons has binocular receptive fields. In this study, the activity of binocular nBOR neurons was recorded in anesthetized pigeons in response to panoramic translational and rotational optic flow. Translational optic flow was produced by the "translator" projector described in the companion paper, and rotational optic flow was produced by a "planetarium projector" described by Wylie and Frost. The axis of rotation or translation could be positioned to any orientation in three-dimensional space. We recorded from 37 cells, most of which exhibited a strong contralateral dominance. Most of these cells were located in the caudal and dorsal aspects of the nBOR complex and many were localized to the subnucleus nBOR dorsalis. Other units were located outside the boundaries of the nBOR complex in the adjacent area ventralis of Tsai or mesencephalic reticular formation. Six cells responded best to rotational flowfields, whereas 31 responded best to translational flowfields. Of the rotation cells, three preferred rotation about the vertical axis and three preferred horizontal axes. Of the translation cells, 3 responded best to a flowfield simulating downward translation of the bird along a vertical axis, whereas the remaining 28 responded best to flowfields resulting from translation along axes in the horizontal plane. Seventeen of these cells preferred a flowfield resulting from the animal translating backward along an axis oriented approximately 45 degrees to the midline, but the best axes of the remaining eleven cells were distributed throughout the horizontal plane with no definitive

  6. Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory nerve activity

    PubMed Central

    Wang, Grace I.

    2012-01-01

    The spatio-temporal pattern of auditory nerve (AN) activity, representing the relative timing of spikes across the tonotopic axis, contains cues to perceptual features of sounds such as pitch, loudness, timbre, and spatial location. These spatio-temporal cues may be extracted by neurons in the cochlear nucleus (CN) that are sensitive to relative timing of inputs from AN fibers innervating different cochlear regions. One possible mechanism for this extraction is “cross-frequency” coincidence detection (CD), in which a central neuron converts the degree of coincidence across the tonotopic axis into a rate code by preferentially firing when its AN inputs discharge in synchrony. We used Huffman stimuli (Carney LH. J Neurophysiol 64: 437–456, 1990), which have a flat power spectrum but differ in their phase spectra, to systematically manipulate relative timing of spikes across tonotopically neighboring AN fibers without changing overall firing rates. We compared responses of CN units to Huffman stimuli with responses of model CD cells operating on spatio-temporal patterns of AN activity derived from measured responses of AN fibers with the principle of cochlear scaling invariance. We used the maximum likelihood method to determine the CD model cell parameters most likely to produce the measured CN unit responses, and thereby could distinguish units behaving like cross-frequency CD cells from those consistent with same-frequency CD (in which all inputs would originate from the same tonotopic location). We find that certain CN unit types, especially those associated with globular bushy cells, have responses consistent with cross-frequency CD cells. A possible functional role of a cross-frequency CD mechanism in these CN units is to increase the dynamic range of binaural neurons that process cues for sound localization. PMID:22972956

  7. Role of Na+/Ca2+ exchanger in Ca2+ homeostasis in rat suprachiasmatic nucleus neurons

    PubMed Central

    Wang, Yi-Chi; Chen, Ya-Shuan; Cheng, Ruo-Ciao

    2015-01-01

    Intracellular Ca2+ is critical to the central clock of the suprachiasmatic nucleus (SCN). However, the role of Na+/Ca2+ exchanger (NCX) in intracellular Ca2+ concentration ([Ca2+]i) homeostasis in the SCN is unknown. Here we show that NCX is an important mechanism for somatic Ca2+ clearance in SCN neurons. In control conditions Na+-free solution lowered [Ca2+]i by inhibiting TTX-sensitive as well as nimodipine-sensitive Ca2+ influx. With use of the Na+ ionophore monensin to raise intracellular Na+ concentration ([Na+]i), Na+-free solution provoked rapid Ca2+ uptake via reverse NCX. The peak amplitude of 0 Na+-induced [Ca2+]i increase was larger during the day than at night, with no difference between dorsal and ventral SCN neurons. Ca2+ extrusion via forward NCX was studied by determining the effect of Na+ removal on Ca2+ clearance after high-K+-induced Ca2+ loads. The clearance of Ca2+ proceeded with two exponential decay phases, with the fast decay having total signal amplitude of ∼85% and a time constant of ∼7 s. Na+-free solution slowed the fast decay rate threefold, whereas mitochondrial protonophore prolonged mostly the slow decay. In contrast, blockade of plasmalemmal and sarco(endo)plasmic reticulum Ca2+ pumps had little effect on the kinetics of Ca2+ clearance. RT-PCR indicated the expression of NCX1 and NCX2 mRNAs. Immunohistochemical staining showed the presence of NCX1 immunoreactivity in the whole SCN but restricted distribution of NCX2 immunoreactivity in the ventrolateral SCN. Together our results demonstrate an important role of NCX, most likely NCX1, as well as mitochondrial Ca2+ uptake in clearing somatic Ca2+ after depolarization-induced Ca2+ influx in SCN neurons. PMID:25568156

  8. Deep brain stimulation of the pedunculopontine tegmental nucleus modulates neuronal hyperactivity and enhanced beta oscillatory activity of the subthalamic nucleus in the rat 6-hydroxydopamine model.

    PubMed

    Alam, Mesbah; Heissler, Hans E; Schwabe, Kerstin; Krauss, Joachim K

    2012-01-01

    Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) area has been introduced as a novel surgical therapy for dopamine refractory gait problems, freezing and postural instability in the late stage of Parkinson's disease (PD). Lesions of the pedunculopontine tegmental (PPTg) nucleus, the equivalent of the PPN in rodents, were shown to reduce the elevated discharge rate of the subthalamic nucleus (STN) in the 6-hydroxydopamine (6-OHDA) rat model of PD. In order to further elucidate the modulatory effect of the PPTg on the STN we examined the effect of 25 Hz low frequency PPTg stimulation on neuronal single unit activity and oscillatory local field potentials (LFPs) of the STN, and on the electrocorticogram (ECoG) of the primary motor cortex region in rats with unilateral 6-OHDA induced nigrostriatal lesions. Stimulation of the PPTg reduced the enhanced firing rate in the STN, without affecting the firing pattern or approximate entropy (ApEn). It also reduced the activity in the beta band (15-30 Hz) of the STN, which is elevated in 6-OHDA lesioned rats, without affecting beta activity in the motor cortex. We showed a modulatory effect of PPTg stimulation on altered neuronal STN activity in the PD 6-OHDA rat model, indicating that PPTg DBS may alter activity of the basal ganglia circuitry at least partially. It remains unclear, however, how these changes are exactly mediated and whether they are relevant with regard to the descending PPTg projections in the lower brainstem.

  9. Thermally identified subgroups of marginal zone neurons project to distinct regions of the ventral posterior lateral nucleus in rats.

    PubMed

    Zhang, Xijing; Davidson, Steve; Giesler, Glenn J

    2006-05-10

    Spinal marginal zone (MZ) neurons play a crucial role in the transmission of nociceptive and thermoreceptive information to the brain. The precise areas to which physiologically characterized MZ neurons project in the ventral posterior lateral (VPL) nucleus of the thalamus have not been clearly established. Here, we examine this projection in rats using the method of antidromic activation to map the axon terminals of neurons recorded from the MZ. Thirty-three neurons were antidromically activated using pulses of < or =30 microA in the contralateral VPL. In every case, the most rostral point from which the MZ neuron could be antidromically activated was surrounded by stimulating tracks in which large-amplitude current pulses failed to activate the examined neuron, indicating the termination of the spinothalamic tract (STT) axon. Each of 30 examined neurons responded to noxious but not innocuous mechanical stimuli applied to their cutaneous receptive fields, which ranged in size from two digits to the entire limb. Of 17 thermally tested neurons, 16 responded to innocuous or noxious thermal stimuli. Among STT neurons that responded to thermal stimuli, 50% responded to innocuous cooling as well as noxious heat and cold, 31% responded to noxious heat and cold, and 19% responded only to noxious heat. Axons from cells responsive to innocuous cooling terminated in the core region of VPL, significantly dorsal and medial relative to other thermally responsive subgroups. In rats, thermally responsive subgroups of MZ neurons project directly to distinct regions of VPL.

  10. Mitochondrial Abnormality Associates with Type-Specific Neuronal Loss and Cell Morphology Changes in the Pedunculopontine Nucleus in Parkinson Disease

    PubMed Central

    Pienaar, Ilse S.; Elson, Joanna L.; Racca, Claudia; Nelson, Glyn; Turnbull, Douglass M.; Morris, Christopher M.

    2014-01-01

    Cholinergic neuronal loss in the pedunculopontine nucleus (PPN) associates with abnormal functions, including certain motor and nonmotor symptoms. This realization has led to low-frequency stimulation of the PPN for treating patients with Parkinson disease (PD) who are refractory to other treatment modalities. However, the molecular mechanisms underlying PPN neuronal loss and the therapeutic substrate for the clinical benefits following PPN stimulation remain poorly characterized, hampering progress toward designing more efficient therapies aimed at restoring the PPN's normal functions during progressive parkinsonism. Here, we investigated postmortem pathological changes in the PPN of PD cases. Our study detected a loss of neurons producing gamma-aminobutyric acid (GABA) as their output and glycinergic neurons, along with the pronounced loss of cholinergic neurons. These losses were accompanied by altered somatic cell size that affected the remaining neurons of all neuronal subtypes studied here. Because studies showed that mitochondrial dysfunction exists in sporadic PD and in PD animal models, we investigated whether altered mitochondrial composition exists in the PPN. A significant up-regulation of several mitochondrial proteins was seen in GABAergic and glycinergic neurons; however, cholinergic neurons indicated down-regulation of the same proteins. Our findings suggest an imbalance in the activity of key neuronal subgroups of the PPN in PD, potentially because of abnormal inhibitory activity and altered cholinergic outflow. PMID:24099985

  11. Interleukin-1 Inhibits Putative Cholinergic Neurons in Vitro and REM Sleep when Microinjected into the Rat Laterodorsal Tegmental Nucleus

    PubMed Central

    Brambilla, Dario; Barajon, Isabella; Bianchi, Susanna; Opp, Mark R.; Imeri, Luca

    2010-01-01

    Study Objectives: REM sleep is suppressed during infection, an effect mimicked by the administration of cytokines such as interleukin-1 (IL-1). In spite of this observation, brain sites and neurochemical systems mediating IL-1-induced suppression of REM sleep have not been identified. Cholinergic neurons in the brainstem laterodorsal tegmental nucleus (LDT) are part of the neuronal circuitry responsible for REM sleep generation. Since IL-1 inhibits acetylcholine synthesis and release, the aim of this study was to test the two different, but related hypotheses. We hypothesized that IL-1 inhibits LDT cholinergic neurons, and that, as a result of this inhibition, IL-1 suppresses REM sleep. Design, Measurement, and Results: To test these hypotheses, the electrophysiological activity of putative cholinergic LDT neurons was recorded in a rat brainstem slice preparation. Interleukin-1 significantly inhibited the firing rate of 76% of recorded putative cholinergic LDT neurons and reduced the amplitude of glutamatergic evoked potentials in 60% of recorded neurons. When IL-1 (1 ng) was microinjected into the LDT of freely behaving rats, REM sleep was reduced by about 50% (from 12.7% ± 1.5% of recording time [after vehicle] to 6.1% ± 1.4% following IL-1 administration) during post-injection hours 3-4. Conclusions: Results of this study support the hypothesis that IL-1 can suppress REM sleep by acting at the level of the LDT nucleus. Furthermore this effect may result from the inhibition of evoked glutamatergic responses and of spontaneous firing of putative cholinergic LDT neurons. Citation: Brambilla D; Barajon I; Bianchi S; Opp MR; Imeri L. Interleukin-1 inhibits putative cholinergic neurons in vitro and REM sleep when microinjected into the rat laterodorsal tegmental nucleus. SLEEP 2010;33(7):919-929. PMID:20614852

  12. Influence of the hypothalamic paraventricular nucleus on cardiovascular neurones in the rostral ventrolateral medulla of the rat.

    PubMed

    Yang, Z; Coote, J H

    1998-12-01

    1. The question of whether neurones in the paraventricular nucleus (PVN) of the hypothalamus have an excitatory influence on reticulo-spinal vasomotor neurones of the rostral ventrolateral medulla (RVL) has been addressed in this study using anaesthetized rats. 2. Extracellular microelectrode recordings were made from sixty vasomotor neurones in the RVL, identified by their cardiac cycle-related probability of discharge, by the decrease in activity in response to an increase in arterial blood pressure produced by intravenous phenylephrine and by the increase in activity in response to a decrease in blood pressure produced by intravenous nitroprusside. 3. More than 70 % of these RVL vasomotor neurones were identified as spinally projecting by antidromically activating their axons via a stimulating electrode in the lateral funiculus of the T2 or T10 segment of spinal cord. 4. Activation of neurones at different sites in the PVN with a microinjection of d,l-homocysteic acid (DLH) elicited either pressor or depressor responses. 5. At PVN pressor sites fifteen RVL vasomotor neurones were shown to be activated prior to the blood pressure change. A further twenty RVL vasomotor neurones were observed to decrease activity following the blood pressure rise. At PVN depressor sites twelve RVL neurones were inhibited prior to the blood pressure change whereas another thirteen identified RVL neurones increased their discharge following the fall in blood pressure. 6. In three rats single shock electrical stimulation at a PVN pressor site, first identified with DLH, elicited a single or double action potential in thirteen RVL neurones with a latency of 27 +/- 1 ms. 7. It is concluded that PVN neurones may elicit increases in blood pressure via excitatory connections with RVL-spinal vasomotor neurones, and that other PVN neurones may elicit decreases in blood pressure via inhibitory connections with these RVL neurones.

  13. Morphology, Classification, and Distribution of the Projection Neurons in the Dorsal Lateral Geniculate Nucleus of the Rat

    PubMed Central

    Ling, Changying; Hendrickson, Michael L.; Kalil, Ronald E.

    2012-01-01

    The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN) of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA) injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60–340 µm2. Labeled projection neurons supported 7–55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0×104 µm2. Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short “tufted” appendages arise mainly from the distal branches of dendrites; “spine-like” appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and “grape-like” appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole. PMID:23139837

  14. Effects of the murine mutation 'nervous' on neurons in cerebellum and dorsal cochlear nucleus.

    PubMed

    Berrebi, A S; Mugnaini, E

    1988-08-01

    'Nervous' mutant mice are presently available on two different genetic background strains which are derived from out-breeding of the original BALB/cGr mutant stock. Light and electron microscopic studies of these mutants demonstrate that cerebellar Purkinje cells and cartwheel neurons of the dorsal cochlear nucleus (DCoN) show similar, albeit not identical, cytoplasmic and mitochondrial alterations in both background strains. In the cerebellar cortex, all Purkinje cell perikarya developed a varying number of enlarged and rounded mitochondria, as previously described. Extensive changes were observed in various components of the mitochondrial matrix. As cellular degeneration proceeded, reduction, fragmentation and dilation of cisterns of endoplasmic reticulum and the Golgi apparatus were evident. Some of the mitochondria underwent a peculiar type of degeneration, i.e. the outer membrane partially or completely dissolved, occasionally accompanied by focal interruptions of the inner membrane. In older adult mutants only 10% of cerebellar Purkinje cells rehained. The few surviving cells displayed varying states, ranging from essentially normal ultrastructure to electron-dense condensation. Many of these cells, in both strains, continued to display greatly enlarged, rounded mitochondrial profiles, indicating a change in the expression of the gene defect resulting from genetic contamination. Criteria for the identification of neuronal cell classes in layers 1 and 2 of murine DCoN were established. Cartwheel neurons in the mutant DCoN presented alterations similar to those observed in cerebellar Purkinje cells. The characteristic mitochondrial anomaly developed and proceeded in cartwheel neurons within a comparable time frame. The vast majority of affected cartwheel cells did not undergo degeneration, however, but continued to possess altered mitochondria into adulthood. The differences between normal and mutant mitochondria in Purkinje and cartwheel were quantified by

  15. Passive cable properties and morphological correlates of neurones in the lateral geniculate nucleus of the cat.

    PubMed Central

    Bloomfield, S A; Hamos, J E; Sherman, S M

    1987-01-01

    1. We used an in vivo preparation of the cat to study the passive cable properties of sixteen X and twelve Y cells in the lateral geniculate nucleus. Cells were modelled as equivalent cylinders according to Rall's formulations (Rall, 1959a, 1969, 1977). We injected intracellular current pulses into these geniculate neurones, and we analysed the resulting voltage transients to obtain the cable parameters of these cells. In addition, fifty-four physiologically characterized neurones were labelled with horseradish peroxidase (HRP) and analysed morphologically. 2. Analysis of HRP-labelled geniculate neurones showed that the dendritic branching pattern of these cells adheres closely to the 3/2 power rule. That is, at each branch point, the diameter of the parent branch raised to the 3/2 power equals the sum of the diameters of the daughter dendrites after each is raised to the 3/2 power. Furthermore, preliminary data indicate that the dendritic terminations emanating from each primary dendrite occur at the same electrotonic distance from the soma. These observations suggest that both X and Y cells meet the geometric constraints necessary for reduction of their dendritic arbors into equivalent cylinders. 3. We found a strong linear relationship between the diameter of each primary dendrite and the membrane surface area of the arbor emanating from it. We used this relationship to derive an algorithm for determining the total somatic and dendritic membrane surface area of an X and Y cell simply from knowledge of the diameters of its soma and primary dendrites. 4. Both geniculate X and Y cells display current-voltage relationships that were linear within +/- 20 mV of the resting membrane potential. This meant that we could easily remain within the linear voltage range during the voltage transient analyses. 5. X and Y cells clearly differ in terms of many of their electrical properties, including input resistance, membrane time constant and electrotonic length. The

  16. Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive-compulsive disorder.

    PubMed

    Burbaud, Pierre; Clair, Anne-Hélène; Langbour, Nicolas; Fernandez-Vidal, Sara; Goillandeau, Michel; Michelet, Thomas; Bardinet, Eric; Chéreau, Isabelle; Durif, Franck; Polosan, Mircea; Chabardès, Stephan; Fontaine, Denys; Magnié-Mauro, Marie-Noelle; Houeto, Jean-Luc; Bataille, Benoît; Millet, Bruno; Vérin, Marc; Baup, Nicolas; Krebs, Marie-Odile; Cornu, Philippe; Pelissolo, Antoine; Arbus, Christophe; Simonetta-Moreau, Marion; Yelnik, Jérôme; Welter, Marie-Laure; Mallet, Luc

    2013-01-01

    Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.

  17. Ih Equalizes Membrane Input Resistance in a Heterogeneous Population of Fusiform Neurons in the Dorsal Cochlear Nucleus

    PubMed Central

    Ceballos, Cesar C.; Li, Shuang; Roque, Antonio C.; Tzounopoulos, Thanos; Leão, Ricardo M.

    2016-01-01

    In a neuronal population, several combinations of its ionic conductances are used to attain a specific firing phenotype. Some neurons present heterogeneity in their firing, generally produced by expression of a specific conductance, but how additional conductances vary along in order to homeostatically regulate membrane excitability is less known. Dorsal cochlear nucleus principal neurons, fusiform neurons, display heterogeneous spontaneous action potential activity and thus represent an appropriate model to study the role of different conductances in establishing firing heterogeneity. Particularly, fusiform neurons are divided into quiet, with no spontaneous firing, or active neurons, presenting spontaneous, regular firing. These modes are determined by the expression levels of an intrinsic membrane conductance, an inwardly rectifying potassium current (IKir). In this work, we tested whether other subthreshold conductances vary homeostatically to maintain membrane excitability constant across the two subtypes. We found that Ih expression covaries specifically with IKir in order to maintain membrane resistance constant. The impact of Ih on membrane resistance is dependent on the level of IKir expression, being much smaller in quiet neurons with bigger IKir, but Ih variations are not relevant for creating the quiet and active phenotypes. Finally, we demonstrate that the individual proportion of each conductance, and not their absolute conductance, is relevant for determining the neuronal firing mode. We conclude that in fusiform neurons the variations of their different subthreshold conductances are limited to specific conductances in order to create firing heterogeneity and maintain membrane homeostasis. PMID:27833532

  18. Distribution of Hypophysiotropic Thyrotropin-Releasing Hormone (TRH)-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus of the Mouse

    PubMed Central

    Kádár, Andrea; Sánchez, Edith; Wittmann, Gábor; Singru, Praful S.; Füzesi, Tamás; Marsili, Alessandro; Larsen, P. Reed; Liposits, Zsolt; Lechan, Ronald M.; Fekete, Csaba

    2010-01-01

    Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons, the central regulators of the hypothalamus-pituitary-thyroid axis, are located in the hypothalamic paraventricular nucleus (PVN) in a partly overlapping distribution with non-hypophysiotropic TRH neurons. The distribution of hypophysiotropic TRH neurons in the rat PVN is well understood, but the localization of these neurons is unknown in mice. To determine the distribution and phenotype of hypophysiotropic TRH neurons in mice, double- and triple-labeling experiments were performed on sections of intact mice, and mice treated intravenously and intraperitonially with the retrograde tracer Fluoro-Gold. TRH neurons were located in all parts of the PVN except the periventricular zone. Hypophysiotropic TRH neurons were observed only at the mid level of the PVN, primarily in the compact part. In the this part of the PVN, TRH-neurons were intermingled with oxytocin and vasopressin neurons, but based on their size, the TRH neurons were parvocellular and did not contain magnocellular neuropeptides. Co-localization of TRH and CART were observed only in areas where hypophysiotropic TRH neurons were located. In accordance with the morphological observations, hypothyroidism increased TRH mRNA content of neurons only at the mid level of the PVN. These data demonstrate that the distribution of hypophysiotropic TRH neurons in mice is vastly different from the pattern in rats, with a dominant occurrence of these neurosecretory cells in the compact part and adjacent regions at the mid level of the PVN. Furthermore, our data demonstrate that the organization of the PVN is markedly different in mice and rats. PMID:20737594

  19. Internal organization of medial rectus and inferior rectus muscle neurons in the C group of the oculomotor nucleus in monkey.

    PubMed

    Tang, Xiaofang; Büttner-Ennever, Jean A; Mustari, Michael J; Horn, Anja K E

    2015-08-15

    Mammalian extraocular muscles contain singly innervated twitch muscle fibers (SIF) and multiply innervated nontwitch muscle fibers (MIF). In monkey, MIF motoneurons lie around the periphery of oculomotor nuclei and have premotor inputs different from those of the motoneurons inside the nuclei. The most prominent MIF motoneuron group is the C group, which innervates the medial rectus (MR) and inferior rectus (IR) muscle. To explore the organization of both cell groups within the C group, we performed small injections of choleratoxin subunit B into the myotendinous junction of MR or IR in monkeys. In three animals the IR and MR myotendinous junction of one eye was injected simultaneously with different tracers (choleratoxin subunit B and wheat germ agglutinin). This revealed that both muscles were supplied by two different, nonoverlapping populations in the C group. The IR neurons lie adjacent to the dorsomedial border of the oculomotor nucleus, whereas MR neurons are located farther medially. A striking feature was the differing pattern of dendrite distribution of both cell groups. Whereas the dendrites of IR neurons spread into the supraoculomotor area bilaterally, those of the MR neurons were restricted to the ipsilateral side and sent a focused bundle dorsally to the preganglionic neurons of the Edinger-Westphal nucleus, which are involved in the "near response." In conclusion, MR and IR are innervated by independent neuron populations from the C group. Their dendritic branching pattern within the supraoculomotor area indicates a participation in the near response providing vergence but also reflects their differing functional roles.

  20. Peripheral chemoreceptors mediate training-induced plasticity in paraventricular nucleus pre-autonomic oxytocinergic neurons.

    PubMed

    Cruz, Josiane C; Cavalleri, Marina T; Ceroni, Alexandre; Michelini, Lisete C

    2013-02-01

    We showed previously that sino-aortic denervation prevented training-induced plasticity in pre-autonomic oxytocinergic neurons and blocked the beneficial effects of training. In this study, we investigate the combined effect of training and removal of specific chemoreceptor afferents on both cardiovascular parameters and oxytocin (OT) gene and protein expression within the hypothalamic paraventricular nucleus (PVN). Wistar rats and spontaneously hypertensive rats (SHRs) underwent carotid body denervation or sham surgery and were trained or kept sedentary for 3 months. After haemodynamic measurements at rest, rats were anaesthetized for brain perfusion. Fresh (perfused with PBS) and fixed brains (perfused with 4% paraformaldehyde) were processed for PVN OT mRNA (real-time PCR) and OT immunoreactivity within PVN subnuclei. In sham-operated rats, training improved treadmill performance and reduced resting heart rate (Wistar, -8%; SHRs, -10%), with a reduction in blood pressure only in SHRs (-8%). Training was accompanied by increased PVN OT mRNA expression (twofold increase in sham-operated SHRs) and peptide density in the posterior, ventromedial and dorsal cap PVN subnuclei (on average 70% increase in both strains), with significant correlations between OT content and training-induced resting bradycardia in sham-operated groups. Carotid body denervation did not interfere with the performance gain, abolished chemoreflex activation (without changing baroreflex control) and blocked training-induced cardiovascular adaptations and training-induced changes in PVN OT content in both strains. After carotid body denervation, there was no correlation between OT mRNA or OT immunoractivity and resting heart rate. The chronic absence of chemoreceptor inputs uncovers an unknown role of chemoreceptor signalling in driving the plasticity/activity of PVN oxytocinergic pre-autonomic neurons, thus mediating training-induced cardiovascular adaptive responses.

  1. The maintained discharge of neurons in the cat lateral geniculate nucleus: spectral analysis and computational modeling.

    PubMed

    Mukherjee, P; Kaplan, E

    1998-01-01

    The maintained discharge of neurons along the early visual pathway in mammals constitutes the "noise" from which the visual signal must be discriminated. The statistics of this background noise in cat retinal ganglion cells (RGCs) have been shown to conform to that of a gamma-distributed renewal process (Kuffler et al., 1957; Barlow & Levick, 1969), and power spectrum analysis reveals that this property allows for low noise levels at the temporal-frequency range (0-10 Hz) most important for visual performance (Troy & Robson, 1992). In this study, we compare the statistics of the maintained discharge of cat lateral geniculate neurons with those of its RGC input by simultaneous recordings of spikes and S-potentials in single relay cells of the cat lateral geniculate nucleus (LGN). We demonstrate that, during primarily tonic spiking activity, the LGN maintained discharge preserves the renewal process statistics of its RGC input and also generates relatively little noise at the temporal frequencies important for vision. However, during burst spiking activity, the renewal process model breaks down and increased noise is generated at 2-10 Hz. This suggests that optimization of the visual signal/noise ratio is not a prime consideration in the behavioral states associated with bursting activity in the LGN. The occurrence of burst spikes in LGN relay cells is dependent on the activity of T-type calcium channels in their plasma membranes (Jahnsen & Llinas, 1984a,b). We show that a computational model of LGN relay cells that incorporates T-channel kinetics (Mukherjee & Kaplan, 1995) can correctly simulate LGN maintained discharge statistics during both tonic and bursty firing conditions, and indicates an essential role for this ion channel in determining the dynamic noise properties of the LGN. We also use the computational model to predict how the burstiness of the LGN maintained discharge is affected by the statistics of its RGC input.

  2. New Rules Governing Synaptic Plasticity In Core Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Ji, Xincai; Martin, Gilles E.

    2012-01-01

    The nucleus accumbens is a forebrain region responsible for drug reward and goal directed behaviors. It has long been believed that drugs of abuse exert their addictive properties on behavior by altering the strength of synaptic communication over long periods of time. To date, attempts at understanding the relationship between drugs of abuse and synaptic plasticity have relied on the high-frequency long-term potentiation model of Bliss and LØmo (1973). We examined synaptic plasticity using spike-timing-dependent plasticity, a stimulation paradigm that reflects more closely in vivo firing patterns of core NAcc medium spiny neurons and their afferents. In contrast to other brain regions, the same stimulation paradigm evoked bidirectional long-term plasticity. Long-term potentiation (tLTP) magnitude changed with delay between action potentials (APs) and excitatory post-synaptic potentials (EPSPs), and frequency, while that of long-term depression (tLTD) remained unchanged. We showed that tLTP depended on NMDA receptors, whereas tLTD relied on action potentials. Importantly, intracellular calcium signaling pathways mobilized during tLTP and tLTD were different. Thus, calcium-induced calcium release underlies tLTD but not tLTP. Finally, we found that the firing pattern of a subset of MSNs was strongly inhibited by dopamine receptor agonists. Surprisingly, these neurons were exclusively associated with tLTP but not with tLTD. Taken together, these data point to the existence of two subgroups of MSNs with distinct properties, each displaying unique abilities to undergo synaptic plasticity. PMID:23013293

  3. A model of reverse spike frequency adaptation and repetitive firing of subthalamic nucleus neurons.

    PubMed

    Wilson, Charles J; Weyrick, Angela; Terman, David; Hallworth, Nicholas E; Bevan, Mark D

    2004-05-01

    Subthalamic nucleus neurons exhibit reverse spike-frequency adaptation. This occurs only at firing rates of 20-50 spikes/s and higher. Over this same frequency range, there is an increase in the steady-state frequency-intensity (F-I) curve's slope (the secondary range). Specific blockade of high-voltage activated calcium currents reduced the F-I curve slope and reverse adaptation. Blockade of calcium-dependent potassium current enhanced secondary range firing. A simple model that exhibited these properties used spike-triggered conductances similar to those in subthalamic neurons. It showed: 1) Nonaccumulating spike afterhyperpolarizations produce positively accelerating F-I curves and spike-frequency adaptation that is complete after the second spike. 2) Combinations of accumulating aftercurrents result in a linear F-I curve, whose slope depends on the relative contributions of inward and outward currents. Spike-frequency adaptation can be gradual. 3) With both accumulating and nonaccumulating aftercurrents, primary and secondary ranges will be present in the F-I curve. The slope of the primary range is determined by the nonaccumulating conductance; the accumulating conductances govern the secondary range. The transition is determined by the relative strengths of accumulating and nonaccumulating currents. 4) Spike-threshold accommodation contributes to the secondary range, reducing its slope at high firing rates. Threshold accommodation can stabilize firing when inward aftercurrents exceed outward ones. 5) Steady-state reverse adaptation results when accumulated inward aftercurrents exceed outward ones. This requires spike-threshold accommodation. Transient speedup arises when inward currents are smaller than outward ones at steady state, but accumulate more rapidly. 6) The same mechanisms alter firing in response to irregular patterns of synaptic conductances, as cell excitability fluctuates with changes in firing rate.

  4. Ionic basis of the caesium-induced depolarisation in rat supraoptic nucleus neurones

    PubMed Central

    Ghamari-Langroudi, Masoud; Bourque, Charles W

    2001-01-01

    The effects of external Cs+ on magnocellular neurosecretory cells were studied during intracellular recordings from 93 supraoptic nucleus neurones in superfused explants of rat hypothalamus.Bath application of 3–5 mm Cs+ provoked reversible membrane depolarisation and increased firing rate in all of the neurones tested. Voltage-current analysis revealed an increase in membrane resistance between −120 and −55 mV. The increase in resistance was greater below −85 mV than at more positive potentials.Voltage-clamp analysis showed that external Cs+ blocked the hyperpolarisation-activated inward current, IH. Under current clamp, application of ZD 7288, a selective blocker of IH, caused an increase in membrane resistance at voltages ≤−65 mV. Voltage-current analysis further revealed that blockade of IH caused hyperpolarisation when the initial voltage was < −60 mV but had no effect at more positive values.Current- and voltage-clamp analysis of the effects of Cs+ in the presence of ZD 7288, or ZD 7288 and tetraethyl ammonium (TEA), revealed an increase in membrane resistance throughout the range of voltages tested (−120 to −45 mV). The current blocked by Cs+ in the absence of IH was essentially voltage independent and reversed at −100 mV. The reversal potential shifted by +22.7 mV when external [K+] was increased from 3 to 9 mm. We conclude that, in addition to blocking IH, external Cs+ blocks a leakage K+ current that contributes significantly to the resting potential of rat magnocellular neurosecretory cells. PMID:11691873

  5. Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury.

    PubMed

    Li, Yafei; Li, Xihong; Qu, Yi; Huang, Jichong; Zhu, Tingting; Zhao, Fengyan; Li, Shiping; Mu, Dezhi

    2017-04-03

    High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining. Cortical levels of HMGB1, its receptor for advanced glycation end-products (RAGE), and downstream effecter, nuclear factor kappa-B (NF-κB) subunit p65, were detected via western blot.HMGB1was increased in the cytoplasm via translocation from the nucleus predominantly in neurons. Moreover, RAGE and NF-κB p65 were upregulated after septic brain injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of RAGE and NF-κB p65via inhibiting HMGB1 expression in the cytoplasm. Collectively, our findings suggest that HMGB1 and its signaling transduction have critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might be a potential new therapeutic target for septic brain injury.

  6. Medial parabrachial nucleus neurons modulate d-fenfluramine-induced anorexia through 5HT2C receptors.

    PubMed

    Trifunovic, Radmila; Reilly, Steve

    2006-01-05

    We previously reported that lesions of the medial parabrachial nucleus (PBN) enhanced d-fenfluramine (DFEN)-induced anorexia; a finding that suggests these lesions may potentiate the release of serotonin (5HT) or increase the postsynaptic action of 5HT. In the present study, we used SB 206553 (a 5HT2B/2C receptor antagonist) or m-CPP (a 5HT2C/1B receptor agonist) in a standard behavioral procedure (deprivation-induced feeding) to further explore the role of the medial PBN in drug-induced anorexia. In Experiment 1, DFEN (0 or 1.0 mg/kg) was given alone or in combination with SB 206553 (2.0 or 5.0 mg/kg). In Experiment 2, we investigated the food-suppressive effects of m-CPP (0.5, 1.0 or 2.0 mg/kg). The results of Experiment 1 show that SB 206553, while having no influence on the performance of control subjects, attenuated (2.0 mg/kg) or abolished (5 mg/kg) the potentiating effect of the lesions on DFEN-induced anorexia. In Experiment 2, m-CPP induced a suppression of food intake in nonlesioned animals that was significantly potentiated in rats with medial PBN lesions. These results are consistent with the hypothesis that medial PBN neurons mediate anorexia through 5HT2C receptors.

  7. Role of Per1-interacting protein of the suprachiasmatic nucleus in NGF mediated neuronal survival

    SciTech Connect

    Kiyama, Atsuko . E-mail: kiyama@pu-hiroshima.ac.jp; Isojima, Yasushi; Nagai, Katsuya

    2006-01-13

    We previously identified Per1-interacting protein of the suprachiasmatic nucleus (PIPS) in rats. To reveal its role, its tissue distribution was examined by immunoblotting. PIPS-like immunoreactive substance (PIPSLS) was observed in Brain, adrenal gland, and PC12 cells. Since PIPS, which has no nuclear localization signal (NLS), is translocated into nuclei of COS-7 cells in the presence of mPer1, the effect of NGF on nuclear localization of PIPS was examined using PC12 cells. NGF caused nuclear translocation of either PIPSLS or GFP-PIPS. NGF mediated nuclear translocation of PIPSLS was blocked by K252a, a TrkA-inhibitor, or wortmannin, a PI3K-inhibitor. Gab1, which is implicated in TrkA signaling and has NLS, co-immunoprecipitated with PIPSLS from PC12 cells using an anti-PIPS antibody. Inhibition of PIPS expression by RNAi increased levels of apoptosis in PC12 cells. These findings suggest that nuclear translocation of PIPS is involved in NGF mediated neuronal survival via TrkA, PI3K, and Gab1 signaling pathway.

  8. Analysis of distinct short and prolonged components in rebound spiking of deep cerebellar nucleus neurons

    PubMed Central

    Sangrey, Thomas; Jaeger, Dieter

    2010-01-01

    Deep cerebellar nucleus (DCN) neurons show pronounced post-hyperpolarization rebound burst behavior, which may contribute significantly to responses to strong inhibitory inputs from cerebellar cortical Purkinje cells. Thus, rebound behavior could importantly shape the output from the cerebellum. We used whole cell recordings in brain slices to characterize DCN rebound properties and their dependence on hyperpolarization duration and depth. We found that DCN rebounds showed distinct fast and prolonged components, with different stimulus dependence and different underlying currents. The initial depolarization leading into rebound spiking was carried by HCN current, and variable expression of this current could lead to a control of rebound latency. The ensuing fast rebound burst was due to T-type calcium current, as previously described. It was highly variable between cells in strength, and could be expressed fully after short periods of hyperpolarization. In contrast, a subsequent prolonged rebound component required longer and deeper periods of hyperpolarization before it was fully established. We found using voltage-clamp and dynamic clamp analyses that a slowly inactivating persistent sodium current fit the conductance underlying this prolonged rebound component resulting in spike rate increases over several seconds. Overall, our results demonstrate that multiphasic DCN rebound properties could be elicited differentially by different levels of Purkinje cell activation, and thus create a rich repertoire of potential rebound dynamics in the cerebellar control of motor timing. PMID:21039958

  9. Quantitative analysis of axon bouton distribution of subthalamic nucleus neurons in the rat by single neuron visualization with a viral vector.

    PubMed

    Koshimizu, Yoshinori; Fujiyama, Fumino; Nakamura, Kouichi C; Furuta, Takahiro; Kaneko, Takeshi

    2013-06-15

    The subthalamic nucleus (STN) of the basal ganglia plays a key role in motor control, and STN efferents are known to mainly target the external segment of the globus pallidus (GPe), entopeduncular nucleus (Ep), and substantia nigra (SN) with some axon collaterals to the other regions. However, it remains to be clarified how each STN neuron projects axon fibers and collaterals to those target nuclei of the STN. Here we visualized the whole axonal arborization of single STN neurons in the rat brain by using a viral vector expressing membrane-targeted green fluorescent protein, and examined the distribution of axon boutons in those target nuclei. The vast majority (8-9) of 10 reconstructed STN neurons projected to the GPe, SN, caudate-putamen (CPu), and Ep, which received, on average ± SD, 457 ± 425, 400 ± 347, 126 ± 143, and 106 ± 100 axon boutons per STN neuron, respectively. Furthermore, the density of axon boutons in the GPe was highest among these nuclei. Although these target nuclei were divided into calbindin-rich and -poor portions, STN projection showed no exclusive preference for those portions. Since STN neurons mainly projected not only to the GPe, SN, and Ep but also to the CPu, the subthalamostriatal projection might serve as a positive feedback path for the striato-GPe-subthalamic disinhibitory pathway, or work as another route of cortical inputs to the striatum through the corticosubthalamostriatal disynaptic excitatory pathway.

  10. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake

    PubMed Central

    Zhu, Xianglong; Ottenheimer, David; DiLeone, Ralph J.

    2016-01-01

    While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The nucleus accumbens (NAc) is one brain region that has received attention for its role in the regulation of energy balance; its D1 and D2 receptor containing neurons have distinct functions in regulating reward behavior and require further examination. The goal of the present study is to investigate how activation and inhibition of D1 and D2 neurons in the NAc influences behaviors related to energy intake and expenditure. Specific manipulation of D1 vs. D2 neurons was done in both low expenditure and high expenditure (wheel running) conditions to assess behavioral effects in these different states. Direct control of neural activity was achieved using a designer receptors exclusively activated by designer drugs (DREADD) strategy. Activation of NAc D1 neurons increased food intake, wheel running and locomotor activity. In contrast, activation of D2 neurons in the NAc reduced running and locomotion while D2 neuron inhibition had opposite effects. These results highlight the importance of considering both intake and expenditure in the analysis of D1 and D2 neuronal manipulations. Moreover, the behavioral outcomes from NAc D1 neuronal manipulations depend upon the activity state of the animals (wheel running vs. non-running). The data support and complement the hypothesis of specific NAc dopamine pathways facilitating energy expenditure and suggest a potential strategy for human weight control. PMID:27147989

  11. Visual Receptive Field Properties of Neurons in the Mouse Lateral Geniculate Nucleus

    PubMed Central

    Chakraborty, Subhojit; Schultz, Simon R.

    2016-01-01

    The lateral geniculate nucleus (LGN) is increasingly regarded as a “smart-gating” operator for processing visual information. Therefore, characterizing the response properties of LGN neurons will enable us to better understand how neurons encode and transfer visual signals. Efforts have been devoted to study its anatomical and functional features, and recent advances have highlighted the existence in rodents of complex features such as direction/orientation selectivity. However, unlike well-researched higher-order mammals such as primates, the full array of response characteristics vis-à-vis its morphological features have remained relatively unexplored in the mouse LGN. To address the issue, we recorded from mouse LGN neurons using multisite-electrode-arrays (MEAs) and analysed their discharge patterns in relation to their location under a series of visual stimulation paradigms. Several response properties paralleled results from earlier studies in the field and these include centre-surround organization, size of receptive field, spontaneous firing rate and linearity of spatial summation. However, our results also revealed “high-pass” and “low-pass” features in the temporal frequency tuning of some cells, and greater average contrast gain than reported by earlier studies. In addition, a small proportion of cells had direction/orientation selectivity. Both “high-pass” and “low-pass” cells, as well as direction and orientation selective cells, were found only in small numbers, supporting the notion that these properties emerge in the cortex. ON- and OFF-cells showed distinct contrast sensitivity and temporal frequency tuning properties, suggesting parallel projections from the retina. Incorporating a novel histological technique, we created a 3-D LGN volume model explicitly capturing the morphological features of mouse LGN and localising individual cells into anterior/middle/posterior LGN. Based on this categorization, we show that the ON

  12. The total number of neurons and calcium binding protein positive neurons during aging in the cochlear nucleus of CBA/CaJ mice: a quantitative study.

    PubMed

    Idrizbegovic, E; Canlon, B; Bross, L S; Willott, J F; Bogdanovic, N

    2001-08-01

    The quantitative stereological method, the optical fractionator, was used for determining the total number of neurons and the total number of neurons immunostained with parvalbumin, calbindin-D28k (calbindin), and calretinin in the dorsal and posteroventral cochlear nucleus (DCN and PVCN) in CBA/CaJ (CBA) mice during aging (1-39 months old). CBA mice have only a modest sensorineural pathology late in life. An age-related decrease of the total number of neurons was demonstrated in the DCN (r=-0.54, P<0.03), while the total number of neurons in the PVCN did not show any significant age-related differences (r=0.16, P=0.57). In the DCN 5.5% of neurons were parvalbumin positive in the very old (30-39 months) mice, vs. 2.2% in the 1 month old mice. In the DCN 3% of the neurons were calbindin immunopositive in the 30-39 months mice compared to 1.9% in the 1 month old group. In the PVCN, 20% of the neurons in the very old mice were parvalbumin immunopositive, compared to 12% in the young mice. Calbindin did not show any significant age-related differences in the PVCN. The total number of calretinin immunopositive neurons both in the DCN and PVCN did not show any significant change with increasing age. In conclusion, the total neuronal number in the DCN and PVCN was age-related and region-specific. While the neuronal number in the DCN and PVCN was decreased or unchanged, respectively, the calcium binding protein positive neuronal number showed a graded increase during aging in a region-specific and protein-specific manner.

  13. Extracellular K+ in the supraoptic nucleus of the rat during reflex bursting activity by oxytocin neurones.

    PubMed Central

    Coles, J A; Poulain, D A

    1991-01-01

    1. We have investigated changes in extracellular potassium concentration [K+]o in the supraoptic nucleus of lactating rats and in particular those that occur during the intense burst of firing by the oxytocin neurones involved in the milk ejection reflex. 2. Double-barrelled K(+)-selective microelectrodes containing a highly selective sensor based on valinomycin were lowered through the exposed cortex towards the supraoptic nucleus (SON) of female rats anaesthetized with urethane. The mean resting [K+]o in the hypothalami of five rats was 2.4 mM, S.D. = 0.3 mM. 3. Where the reference barrel recorded extracellular action potentials from an oxytocin cell, the reflex burst of firing (4 s, typical maximum 50 Hz) was accompanied by a mean increase in [K+]o (delta[K+]o) of 0.22 mM (S.E.M. = 0.02 mM, fifty-seven bursts in eight cells in seven rats). The rise in [K+]o did not begin more than 0.1 s before the onset of the burst, and began to fall from its maximum during the burst. Slow field potentials, indicative of spatial buffering of K+, were undetectable (less than 50 microV). When the electrode was advanced in steps, the amplitudes of both delta[K+]o and the action potential declined steeply to about 10% over a distance of 20 microns: K+ from oxytocin cells appears to be prevented from dispersing freely through the extracellular space of the SON. 4. When the electrode recorded action potentials from a vasopressin cell, delta[K+]o during an oxytocin cell burst was very small: 0.021 mM (S.E.M. = 0.005 mM). At other sites in the SON, where antidromic stimulation evoked a field potential but no action potential, delta[K+]o was 0.047 +/- 0.005 mM. We conclude that the reason oxytocin bursts do not affect vasopressin cells is that [K+]o rises very little around vasopressin cells. A fortiori, since the increases in [K+]o were very small except where action potentials from oxytocin cells were recorded, they can make no significant contribution to synchronizing the onsets of

  14. Morphological characterization of spinal cord dorsal horn lamina I neurons projecting to the parabrachial nucleus in the rat.

    PubMed

    Almarestani, L; Waters, S M; Krause, J E; Bennett, G J; Ribeiro-da-Silva, A

    2007-09-20

    Many Rexed's lamina I neurons are nociceptive and project to the brain. Lamina I projection neurons can be classified as multipolar, fusiform, or pyramidal, based on cell body shape and characteristics of their proximal dendrites in the horizontal plane. There is also evidence that both multipolar and fusiform cells are nociceptive and pyramidal neurons nonnociceptive. In this investigation we identified which types of lamina I neurons belong to the spinoparabrachial tract in the rat and characterized them regarding the presence or absence of neurokinin-1 receptor (NK-1r) immunoreactivity. For this, cholera toxin subunit B (CTb), conjugated to a fluorescent marker was injected unilaterally into the parabrachial nucleus. Sections were additionally stained for the detection of NK-1r immunoreactivity and were examined using fluorescence and confocal microscopy. Serial confocal optical sections and 3D reconstructions were obtained for a considerable number of neurons per animal. Using immunofluorescence, we assessed the proportion of lamina I neurons belonging to the spinoparabrachial (SPB) tract and/or expressing NK-1r. The relative distribution of neurons belonging to the SPB tract was: 38.7% multipolar, 36.8% fusiform, 22.7% pyramidal, and 1.9% unclassified. Most of the SPB neurons expressing NK-1r were either multipolar or fusiform. Pyramidal SPB neurons were seldom immunoreactive for NK-1r, an observation that provides further support to the concept that most lamina I projection neurons of the pyramidal type are nonnociceptive. In addition, our study provides further evidence that these distinct morphological types of neurons differ in their phenotypic properties, but not in their projection patterns.

  15. Muscarinic receptor subtypes differentially control synaptic input and excitability of cerebellum-projecting medial vestibular nucleus neurons.

    PubMed

    Zhu, Yun; Chen, Shao-Rui; Pan, Hui-Lin

    2016-04-01

    Neurons in the vestibular nuclei have a vital function in balance maintenance, gaze stabilization, and posture. Although muscarinic acetylcholine receptors (mAChRs) are expressed and involved in regulating vestibular function, it remains unclear how individual mAChR subtypes regulate vestibular neuronal activity. In this study, we determined which specific subtypes of mAChRs control synaptic input and excitability of medial vestibular nucleus (MVN) neurons that project to the cerebellum. Cerebellum-projecting MVN neurons were labeled by a fluorescent retrograde tracer and then identified in rat brainstem slices. Quantitative PCR analysis suggested that M2 and M3 were the possible major mAChR subtypes expressed in the MVN. The mAChR agonist oxotremorine-M significantly reduced the amplitude of glutamatergic excitatory post-synaptic currents evoked by stimulation of vestibular primary afferents, and this effect was abolished by the M2-preferring antagonist AF-DX 116. However, oxotremorine-M had no effect on GABA-mediated spontaneous inhibitory post-synaptic currents of labeled MVN neurons. Furthermore, oxotremorine-M significantly increased the firing activity of labeled MVN neurons, and this effect was blocked by the M3-preferring antagonist J104129 in most neurons tested. In addition, AF-DX 116 reduced the onset latency and prolonged the excitatory effect of oxotremorine-M on the firing activity of labeled MVN neurons. Our findings suggest that M3 is the predominant post-synaptic mAChR involved in muscarinic excitation of cerebellum-projecting MVN neurons. Pre-synaptic M2 mAChR regulates excitatory glutamatergic input from vestibular primary afferents, which in turn influences the excitability of cerebellum-projecting MVN neurons. This new information has important therapeutic implications for treating vestibular disorders with mAChR subtype-selective agents. Medial vestibular nucleus (MVN) neurons projecting to the cerebellum are involved in balance control. We

  16. Ethanol inhibits histaminergic neurons in mouse tuberomammillary nucleus slices via potentiating GABAergic transmission onto the neurons at both pre- and postsynaptic sites

    PubMed Central

    Sun, Yu; Jiang, Shi-yu; Ni, Jian; Luo, Yan-jia; Chen, Chang-rui; Hong, Zong-yuan; Yanagawa, Yuchio; Qu, Wei-min; Wang, Lu; Huang, Zhi-li

    2016-01-01

    Aim: Ethanol, one of the most frequently used and abused substances in our society, has a profound impact on sedation. However, the neuronal mechanisms underlying its sedative effect remain unclear. In this study, we investigated the effects of ethanol on histaminergic neurons in the tuberomammillary nucleus (TMN), a brain region thought to be critical for wakefulness. Methods: Coronal brain slices (250 μm thick) containing the TMN were prepared from GAD67-GFP knock-in mice. GAD67-GFP was used to identify histaminergic neurons in the TMN. The spontaneous firing and membrane potential of histaminergic neurons, and GABAergic transmission onto these neurons were recorded using whole-cell patch-clamp recordings. Drugs were applied through superfusion. Results: Histaminergic and GAD67-expressing neurons in the TMN of GAD67-GFP mice were highly co-localized. TMN GFP-positive neurons exhibited a regular spontaneous discharge at a rate of 2–4 Hz without burst firing. Brief superfusion of ethanol (64, 190, and 560 mmol/L) dose-dependently and reversibly suppressed the spontaneous firing of the neurons in the TMN; when synaptic transmission was blocked by tetrodotoxin (1 μmol/L), ethanol caused hyperpolarization of the membrane potential. Furthermore, superfusion of ethanol markedly increased the frequency and amplitude of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs), which were abolished in the presence of the GABAA receptor antagonist bicuculline (20 μmol/L). Finally, ethanol-mediated enhancement of sIPSCs and mIPSCs was significantly attenuated when the slices were pretreated with the GABAB agonist baclofen (30 μmol/L). Conclusion: Ethanol inhibits the excitability of histaminergic neurons in mouse TMN slices, possibly via potentiating GABAergic transmission onto the neurons at both pre- and postsynaptic sites. PMID:27498778

  17. Selective Deletion of Cochlear Hair Cells Causes Rapid Age-Dependent Changes in Spiral Ganglion and Cochlear Nucleus Neurons

    PubMed Central

    Tong, Ling; Strong, Melissa K.; Kaur, Tejbeer; Juiz, Jose M.; Oesterle, Elizabeth C.; Hume, Clifford; Warchol, Mark E.; Palmiter, Richard D.

    2015-01-01

    During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN. Cochlear removal in older animals results in little or no neuron death. However, the extent to which hair-cell-specific afferent activity prevents neuronal death in the neonatal brain is unknown. We further explore this phenomenon using a new mouse model that allows temporal control of cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete loss of organ of Corti hair cells within 1 week of injection regardless of the age of injection. Injection of DT did not influence surrounding supporting cells directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of hair cells in neonates resulted in rapid and profound neuronal loss in the ventral CN, but not when hair cells were eliminated at a more mature age. In addition, normal survival of SGNs was dependent on hair cell integrity early in development and less so in mature animals. This defines a previously undocumented critical period for SGN survival. PMID:25995473

  18. Lack of response of serotonergic neurons in the dorsal raphe nucleus of freely moving cats to stressful stimuli.

    PubMed

    Wilkinson, L O; Jacobs, B L

    1988-09-01

    Changes in brain serotonin (5-HT) neurotransmission have been implicated in the mammalian response to stressful stimuli. The purpose of this study was to examine the extracellular single-unit activity of 5-HT neurons in cats exposed to three stressors: loud (100 dB) white noise, restraint, and confrontation with a dog. Serotonergic neurons were recorded in the dorsal raphe nucleus (DRN) and were identified by (i) slow and regular spontaneous activity, (ii) long duration (approximately 2 ms) waveform, (iii) complete suppression of activity during REM sleep and after systemic administration of 5-methoxy-N-N-dimethyltryptamine (250 micrograms/kg i.m.), and (iv) histological localization in the DRN. Despite behavioral and physiological evidence that all three manipulations induced a stress response, the maximal firing rate of 5-HT neurons was not significantly different from that observed under unstressed conditions. These data are consistent with previous studies from our laboratory which have indicated that very few manipulations are able to perturb the slow and regular activity of these neurons. In contrast, previous work has shown that the firing rate of noradrenergic neurons in the locus ceruleus is dramatically increased by these stressors. The relative imbalance in the activity of these two neuronal groups observed during stress may affect postsynaptic neuronal processing patterns and have adaptive significance during stressful conditions.

  19. Age-related changes in functional postsynaptic nicotinic acetylcholine receptor subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction.

    PubMed

    Christensen, Mark H; Kohlmeier, Kristi A

    2016-03-01

    The earlier an individual initiates cigarette smoking, the higher the likelihood of development of dependency to nicotine, the addictive ingredient in cigarettes. One possible mechanism underlying this higher addiction liability is an ontogenetically differential cellular response induced by nicotine in neurons mediating the reinforcing or euphoric effects of this drug, which could arise from age-related differences in the composition of nicotinic acetylcholine receptor (nAChR) subunits. In the current study, we examined whether the subunit composition of nAChRs differed between neurons within the laterodorsal tegmentum (LDT), a nucleus importantly involved in drug addiction associated behaviours, across two periods of ontogeny in which nicotine-mediated excitatory responses were shown to depend on age. To this end, whole-cell patch-clamp recordings in mouse brain slices from identified LDT neurons, in combination with nAChR subunit-specific receptor antagonists, were conducted. Comparison of the contribution of different nAChR subunits to acetylcholine (ACh)-induced inward currents indicated that the contributions of the β2 and/or β4 and α7 nAChR subunits alter across age. Taken together, we conclude that across a limited ontogenetic period, there is plasticity in the subunit composition of nAChRs in LDT neurons. In addition, our data indicate, for the first time, functional presence of α6 nAChR subunits in LDT neurons within the age ranges studied. Changes in subunit composition of nAChRs across ontogeny could contribute to the age-related differential excitability induced by nicotine. Differences in the subunit composition of nAChRs within the LDT would be expected to contribute to ontogenetic-dependent outflow from the LDT to target regions, which include reward-related circuitry.

  20. Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex

    PubMed Central

    Piché, Marilyse; Thomas, Sébastien

    2015-01-01

    The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex. PMID:26289469

  1. Muscarinic Receptor Subtypes Differentially Control Synaptic Input and Excitability of Cerebellum-Projecting Medial Vestibular Nucleus Neurons

    PubMed Central

    Zhu, Yun; Chen, Shao-Rui; Pan, Hui-Lin

    2016-01-01

    Neurons in the vestibular nuclei have a vital function in balance maintenance, gaze stabilization, and posture. Although muscarinic acetylcholine receptors (mAChRs) are expressed and involved in regulating vestibular function, it is unclear how individual mAChR subtypes regulate vestibular neuronal activity. In this study, we determined which specific subtypes of mAChRs control synaptic input and excitability of medial vestibular nucleus (MVN) neurons that project to the cerebellum. Cerebellum-projecting MVN neurons were labeled by a fluorescent retrograde tracer and then identified in rat brainstem slices. Quantitative PCR analysis suggested that M2 and M3 were the possible major mAChR subtypes expressed in the MVN. The mAChR agonist oxotremorine-M significantly reduced the amplitude of glutamatergic excitatory postsynaptic currents evoked by stimulation of vestibular primary afferents, and this effect was abolished by the M2-preferring antagonist AF-DX 116. However, oxotremorine-M had no effect on GABA-mediated spontaneous inhibitory postsynaptic currents of labeled MVN neurons. Furthermore, oxotremorine-M significantly increased the firing activity of labeled MVN neurons, and this effect was blocked by the M3-preferring antagonist J104129 in most neurons tested. In addition, AF-DX 116 reduced the onset latency and prolonged the excitatory effect of oxotremorine-M on the firing activity of labeled MVN neurons. Our findings suggest that M3 is the predominant postsynaptic mAChR involved in muscarinic excitation of cerebellum-projecting MVN neurons. Presynaptic M2 mAChR regulates excitatory glutamatergic input from vestibular primary afferents, which in turn influences the excitability of cerebellum-projecting MVN neurons. This new information has important therapeutic implications for treating vestibular disorders with mAChR subtype-selective agents. PMID:26823384

  2. Subpopulations of cholinergic, GABAergic and glutamatergic neurons in the pedunculopontine nucleus contain calcium-binding proteins and are heterogeneously distributed.

    PubMed

    Martinez-Gonzalez, Cristina; Wang, Hui-Ling; Micklem, Benjamin R; Bolam, J Paul; Mena-Segovia, Juan

    2012-03-01

    Neurons in the pedunculopontine nucleus (PPN) are highly heterogeneous in their discharge properties, their neurochemical markers, their pattern of connectivity and the behavioural processes in which they participate. Three main transmitter phenotypes have been described, cholinergic, GABAergic and glutamatergic, and yet electrophysiological evidence suggests heterogeneity within these subtypes. To gain further insight into the molecular composition of these three populations in the rat, we investigated the pattern of expression of calcium binding proteins (CBPs) across distinct regions of the PPN and in relation to the presence of other neurochemical markers. Calbindin- and calretinin-positive neurons are as abundant as cholinergic neurons, and their expression follows a rostro-caudal gradient, whereas parvalbumin is expressed by a low number of neurons. We observed a high degree of expression of CBPs by GABAergic and glutamatergic neurons, with a large majority of calbindin- and calretinin-positive neurons expressing GAD or VGluT2 mRNA. Notably, CBP-positive neurons expressing GAD mRNA were more concentrated in the rostral PPN, whereas the caudal PPN was characterized by a higher density of CBP-positive neurons expressing VGluT2 mRNA. In contrast to these two large populations, in cholinergic neurons expression of calretinin is observed only in low numbers and expression of calbindin is virtually non-existent. These findings thus identify novel subtypes of cholinergic, GABAergic and glutamatergic neurons based on their expression of CBPs, and further contribute to the notion of the PPN as a highly heterogeneous structure, an attribute that is likely to underlie its functional complexity.

  3. Neurokinin 3 Receptor-Expressing Neurons in the Median Preoptic Nucleus Modulate Heat-Dissipation Effectors in the Female Rat

    PubMed Central

    Mittelman-Smith, Melinda A.; Krajewski-Hall, Sally J.; McMullen, Nathaniel T.

    2015-01-01

    KNDy neurons facilitate tail skin vasodilation and modulate the effects of estradiol on thermoregulation. We hypothesize that KNDy neurons influence cutaneous vasodilation via projections to neurons in the median preoptic nucleus (MnPO) that express the neurokinin 3 receptor (NK3R). In support of this hypothesis, focal microinjections of senktide, an NK3R agonist, into the MnPO lowers core temperature (TCORE) in the female rat. To further study the role of MnPO NK3R neurons in thermoregulation, these neurons were specifically ablated using a conjugate of a selective NK3R agonist and saporin (NK3-SAP). NK3-SAP or blank-SAP (control) was injected into the MnPO/medial septum. Tail skin temperature (TSKIN) and TCORE were measured in ovariectomized rats exposed to 3 ambient temperatures (TAMBIENT) before and after estradiol-17β (E2) treatment. Before killing, we injected senktide (sc), monitored TCORE for 70 minutes, and harvested brains for Fos immunohistochemistry. Ablation of MnPO NK3R neurons lowered TSKIN at neutral and subneutral TAMBIENT regardless of E2 treatment. However, ablation did not prevent the effects of E2 on TCORE and TSKIN. In control rats, senktide injections induced hypothermia with numerous Fos-immunoreactive cells in the MnPO. In contrast, in NK3-SAP rats, senktide did not alter TCORE and minimal Fos-immunoreactive neurons were identified in the MnPO. These data show that NK3R neurons in the MnPO are required for the hypothermic effects of senktide but not for the E2 modulation of thermoregulation. The lower TSKIN in NK3-SAP–injected rats suggests that MnPO NK3R neurons, like KNDy neurons, facilitate cutaneous vasodilation, an important heat-dissipation effector. PMID:25825817

  4. Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.

    PubMed

    Carson, Dean S; Hunt, Glenn E; Guastella, Adam J; Barber, Lachlan; Cornish, Jennifer L; Arnold, Jonathon C; Boucher, Aurelie A; McGregor, Iain S

    2010-10-01

    Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.

  5. Development of action potentials and apamin-sensitive after-potentials in mouse vestibular nucleus neurones.

    PubMed

    Dutia, M B; Johnston, A R

    1998-01-01

    The postnatal maturation of medial vestibular nucleus (MVN) neurones was examined in slices of the dorsal brainstem prepared from balb/c mice at specific stages during the first postnatal month. Using spike-shape averaging to analyse the intracellularly recorded action potentials and after-hyperpolarizations (AHPs) in each cell, all the MVN neurones recorded in the young adult (postnatal day 30; P30) mouse were shown to have either a single deep AHP (type A cells), or an early fast and a delayed slow AHP (type B cells). The relative proportions of the two subtypes were similar to those in the young adult rat. At P5, all the MVN cells recorded showed immature forms of either the type A or the type B action potential shape. Immature type A cells had broad spontaneous spikes, and the characteristic single AHP was small in amplitude. Immature type B cells had somewhat narrower spontaneous spikes that were followed by a delayed, apamin-sensitive AHP. The delayed AHP was separated from the repolarisation phase of the spike by a period of isopotentiality. Over the period P10-P15, the mean resting potentials of the MVN cells became more negative, their action potential fall-times became shorter, the single AHP in type A cells became deeper, and the early fast AHP appeared in type B cells. Until P15 cells of varying degrees of electrophysiological maturity were found in the MVN but by P30 all MVN cells recorded were typical adult type A or type B cells. Exposure to the selective blocker of SK-type Ca-activated K channels, apamin (0.3 microM), induced depolarising plateaux and burst firing in immature type B cells at rest. The duration of the apamin-induced bursts and the spike frequency during the bursts were reduced but not abolished after blockade of Ca channels in Ca-free artificial cerebrospinal fluid containing Cd2+. By contrast, in mature type B cells at rest apamin selectively abolished the delayed slow AHP but did not induce bursting activity. Apamin had no effect

  6. Brain-derived neurotrophic factor is required for axonal growth of selective groups of neurons in the arcuate nucleus

    PubMed Central

    Liao, Guey-Ying; Bouyer, Karine; Kamitakahara, Anna; Sahibzada, Niaz; Wang, Chien-Hua; Rutlin, Michael; Simerly, Richard B.; Xu, Baoji

    2015-01-01

    Objective Brain-derived neurotrophic factor (BDNF) is a potent regulator of neuronal development, and the Bdnf gene produces two populations of transcripts with either a short or long 3′ untranslated region (3′ UTR). Deficiencies in BDNF signaling have been shown to cause severe obesity in humans; however, it remains unknown how BDNF signaling impacts the organization of neuronal circuits that control energy balance. Methods We examined the role of BDNF on survival, axonal projections, and synaptic inputs of neurons in the arcuate nucleus (ARH), a structure critical for the control of energy balance, using Bdnfklox/klox mice, which lack long 3′ UTR Bdnf mRNA and develop severe hyperphagic obesity. Results We found that a small fraction of neurons that express the receptor for BDNF, TrkB, also expressed proopiomelanocortin (POMC) or neuropeptide Y (NPY)/agouti-related protein (AgRP) in the ARH. Bdnfklox/klox mice had normal numbers of POMC, NPY, and TrkB neurons in the ARH; however, retrograde labeling revealed a drastic reduction in the number of ARH axons that project to the paraventricular hypothalamus (PVH) in these mice. In addition, fewer POMC and AgRP axons were found in the dorsomedial hypothalamic nucleus (DMH) and the lateral part of PVH, respectively, in Bdnfklox/klox mice. Using immunohistochemistry, we examined the impact of BDNF deficiency on inputs to ARH neurons. We found that excitatory inputs onto POMC and NPY neurons were increased and decreased, respectively, in Bdnfklox/klox mice, likely due to a compensatory response to marked hyperphagia displayed by the mutant mice. Conclusion This study shows that the majority of TrkB neurons in the ARH are distinct from known neuronal populations and that BDNF plays a critical role in directing projections from these neurons to the DMH and PVH. We propose that hyperphagic obesity due to BDNF deficiency is in part attributable to impaired axonal growth of TrkB-expressing ARH neurons. PMID:26042201

  7. Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence

    PubMed Central

    de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F.; Hope, Bruce T.; Brennan, Molly; Cole, Maury; Koob, George F.

    2016-01-01

    Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. SIGNIFICANCE STATEMENT Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These

  8. GAD67-GFP+ Neurons in the Nucleus of Roller. II. Subthreshold and Firing Resonance Properties

    PubMed Central

    Berger, A. J.

    2011-01-01

    In the companion paper we show that GAD67-GFP+ (GFP+) inhibitory neurons located in the Nucleus of Roller of the mouse brain stem can be classified into two main groups (tonic and phasic) based on their firing patterns in responses to injected depolarizing current steps. In this study we examined the responses of GFP+ cells to fluctuating sinusoidal (“chirp”) current stimuli. Membrane impedance profiles in response to chirp stimulation showed that nearly all phasic cells exhibited subthreshold resonance, whereas the majority of tonic GFP+ cells were nonresonant. In general, subthreshold resonance was associated with a relatively fast passive membrane time constant and low input resistance. In response to suprathreshold chirp current stimulation at a holding potential just below spike threshold the majority of tonic GFP+ cells fired multiple action potentials per cycle at low input frequencies (<5 Hz) and either stopped firing or were not entrained by the chirp at higher input frequencies (= tonic low-pass cells). A smaller group of phasic GFP+ cells did not fire at low input frequency but were able to phase-lock 1:1 at intermediate chirp frequencies (= band-pass cells). Spike timing reliability was tested with repeated chirp stimuli and our results show that phasic cells were able to reliably fire when they phase-locked 1:1 over a relatively broad range of input frequencies. Most tonic low-pass cells showed low reliability and poor phase-locking ability. Computer modeling suggested that these different firing resonance properties among GFP+ cells are due to differences in passive and active membrane properties and spiking mechanisms. This heterogeneity of resonance properties might serve to selectively activate subgroups of interneurons. PMID:21047931

  9. Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens.

    PubMed

    Zhou, Feng C; Anthony, Bruce; Dunn, Kenneth W; Lindquist, W Brent; Xu, Zao C; Deng, Ping

    2007-02-23

    Alcohol is known to affect glutamate transmission. However, how chronic alcohol affects the synaptic structure mediating glutamate transmission is unknown. Repeated alcohol exposure in a subject with familial alcoholic history often leads to alcohol addiction. The current study adopts alcohol-preferring rats, which are known to develop high drinking. Two-photon microscopy analysis indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C-Alc) or with repeated deprivation (RD-Alc), causes dysmorphology--thickened, beaded, and disoriented dendrites that are reminiscent of reactive astrocytes--in a subpopulation of medium spiny neurons. The density of dendritic spines was found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as compared with those of Water groups. Large-sized spines and multiple-headed spines were increased in the RD-Alc group. The NMDA receptor subunit NR1 proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD-Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a splice variant isoform with truncated exon 21, which is required for membrane-bound trafficking or anchoring into a spine synaptic site. These maladaptations may contribute to the transformation of spines. The changes, in density and head-size of spines and the corresponding NMDA receptors, demonstrated an alteration of microcircuitry for glutamate reception. The current study demonstrates for the first time that chronic alcohol exposure causes structural alteration of dendrites and their spines in the key reward brain region in animals that have a genetic background leading to alcohol addiction.

  10. Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease.

    PubMed

    Lim, Andrew S P; Ellison, Brian A; Wang, Joshua L; Yu, Lei; Schneider, Julie A; Buchman, Aron S; Bennett, David A; Saper, Clifford B

    2014-10-01

    Fragmented sleep is a common and troubling symptom in ageing and Alzheimer's disease; however, its neurobiological basis in many patients is unknown. In rodents, lesions of the hypothalamic ventrolateral preoptic nucleus cause fragmented sleep. We previously proposed that the intermediate nucleus in the human hypothalamus, which has a similar location and neurotransmitter profile, is the homologue of the ventrolateral preoptic nucleus, but physiological data in humans were lacking. We hypothesized that if the intermediate nucleus is important for human sleep, then intermediate nucleus cell loss may contribute to fragmentation and loss of sleep in ageing and Alzheimer's disease. We studied 45 older adults (mean age at death 89.2 years; 71% female; 12 with Alzheimer's disease) from the Rush Memory and Aging Project, a community-based study of ageing and dementia, who had at least 1 week of wrist actigraphy proximate to death. Upon death a median of 15.5 months later, we used immunohistochemistry and stereology to quantify the number of galanin-immunoreactive intermediate nucleus neurons in each individual, and related this to ante-mortem sleep fragmentation. Individuals with Alzheimer's disease had fewer galaninergic intermediate nucleus neurons than those without (estimate -2872, standard error = 829, P = 0.001). Individuals with more galanin-immunoreactive intermediate nucleus neurons had less fragmented sleep, after adjusting for age and sex, and this association was strongest in those for whom the lag between actigraphy and death was <1 year (estimate -0.0013, standard error = 0.0005, P = 0.023). This association did not differ between individuals with and without Alzheimer's disease, and similar associations were not seen for two other cell populations near the intermediate nucleus. These data are consistent with the intermediate nucleus being the human homologue of the ventrolateral preoptic nucleus. Moreover, they demonstrate that a paucity of galanin

  11. Morphological evidence for the existence of multiple neuronal classes in the cat lateral superior olivary nucleus.

    PubMed

    Helfert, R H; Schwartz, I R

    1986-02-22

    This study characterizes morphologically the neurons residing within the matrix of the cat lateral superior olive (LSO), excluding the hili and myelinated axon envelope. Several light microscopic techniques including Golgi impregnations, Nissl stains, and acetylcholinesterase histochemistry were used, as well as electron microscopy. Five distinct classes of neurons have been identified: principal neurons, multiplanar neurons, marginal neurons, small neurons, and class 5 neurons. These neuronal classes differ in regard to their size and shape, dendritic organization, perikaryal synaptic density, and their relative numbers. Principal neurons compose approximately three-quarters of the LSO neurons. They are multipolar and uniplanar in their dendritic arborization, radiating from the hili in rostrocaudal planes perpendicular to the curvatures of the LSO. In transverse sections the principal cell perikarya are fusiform and bipolar, with mean dimensions of 23 X 11 microns. More than 60% of the surface of these cells is contacted by synaptic terminals. Multiplanar neurons (averaging 23 X 19 microns) compose only 11% of the LSO neuronal population. Their dendritic arborization is not restricted to any particular plane, and their somal surface receives synaptic contacts similar, in number and type, to principal cells. Marginal neurons, although they are similar to principal neurons in shape and dendritic arborization, differ in that they are generally smaller (averaging 20 X 10.5 microns). They also possess fewer axosomatic synaptic contacts (approximately 33%), are oriented perpendicularly to principal neurons, are limited in distribution to the contours of the LSO immediately beneath the myelinated axon envelope, and constitute only 4% of the neuronal population. Small neurons (mean dimensions = 9 X 8 micron) compose 8% of the LSO neurons. They possess a multiplanar array of primary dendrites and have nuclei with multiple deep infoldings. Small neurons have the fewest

  12. Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats

    PubMed Central

    Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A.; Ulrich-Lai, Yvonne M.; Herman, James P.

    2015-01-01

    Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. Here, we tested the hypothesis that NTS noradrenergic A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n= 5; HPA study, n= 5], or vehicle [cardiovascular study, n= 6; HPA study, n= 4]. Rats were exposed to acute restraint stress followed by 14 days of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low frequency to high frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress. PMID:25765732

  13. Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats.

    PubMed

    Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A; Ulrich-Lai, Yvonne M; Herman, James P

    2015-01-01

    Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.

  14. Cue-Evoked Dopamine Release Rapidly Modulates D2 Neurons in the Nucleus Accumbens During Motivated Behavior

    PubMed Central

    Owesson-White, Catarina; Belle, Anna M.; Herr, Natalie R.; Peele, Jessica L.; Gowrishankar, Preethi; Carelli, Regina M.

    2016-01-01

    Dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) fire in response to unpredicted rewards or to cues that predict reward delivery. Although it is well established that reward-related events elicit dopamine release in the NAc, the role of rapid dopamine signaling in modulating NAc neurons that respond to these events remains unclear. Here, we examined dopamine's actions in the NAc in the rat brain during an intracranial self-stimulation task in which a cue predicted lever availability for electrical stimulation of the VTA. To distinguish actions of dopamine at select receptors on NAc neurons during the task, we used a multimodal sensor that probes three aspects of neuronal communication simultaneously: neurotransmitter release, cell firing, and identification of dopamine receptor type. Consistent with prior studies, we first show dopamine release events in the NAc both at cue presentation and after lever press (LP). Distinct populations of NAc neurons encode these behavioral events at these same locations selectively. Using our multimodal sensor, we found that dopamine-mediated responses after the cue involve exclusively a subset of D2-like receptors (D2Rs), whereas dopamine-mediated responses proximal to the LP are mediated by both D1-like receptors (D1R) and D2Rs. These results demonstrate for the first time that dopamine-mediated responses after cues that predict reward availability are specifically linked to its actions at a subset of neurons in the NAc containing D2Rs. SIGNIFICANCE STATEMENT Successful reward procurement typically involves the completion of a goal-directed behavior in response to appropriate environmental cues. Although numerous studies link the mesolimbic dopamine system with these processes, how dopamine's effects are mediated on the receptor level within a key neural substrate, the nucleus accumbens, remains elusive. Here, we used a unique multimodal sensor that reveals three aspects of

  15. Chronic alcoholics without Wernicke-Korsakoff syndrome or cirrhosis do not lose serotonergic neurons in the dorsal raphe nucleus.

    PubMed

    Baker, K G; Halliday, G M; Kril, J J; Harper, C G

    1996-02-01

    Despite the considerable evidence that alcoholics have perturbation of serotonergic function, there is little pathological evidence for alcohol directly affecting the nervous system. The present study aims to assess neuronal loss that occurs as a consequence of alcohol neurotoxicity in the serotonergic dorsal raphe nucleus (DRN). To that end, the brains of eight alcoholics and eight age-matched control cases were carefully screened to eliminate serious liver disease, the sequela of thiamine deficiency, Wernicke-Korsakoff syndrome (WKS), and other pathological abnormalities. Brains were formalin-fixed for 2 weeks, cut, and then immunohistochemically stained using a monoclonal PH8 antibody specific for the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. The morphology of the serotonin-synthesizing neurons and their average size was similar in all cases. However, there was a reduction in the staining intensity of the reaction product in the DRN serotonergic neurons of most alcoholics. Neuronal counts on spaced serial sections revealed that there were an estimated average total of 106,100 +/- 19,500 serotonergic neurons in the DRN of alcoholics and 108,300 +/- 11,800 in the DRN of controls, indicating that in most alcoholics there is no reduction in the number of these neurons. Therefore, the effect of chronic alcohol consumption on the serotonergic system, in the absence of WKS or liver disease, seems to be functional rather than neuropathological.

  16. Positive reinforcement mediated by midbrain dopamine neurons requires D1 and D2 receptor activation in the nucleus accumbens.

    PubMed

    Steinberg, Elizabeth E; Boivin, Josiah R; Saunders, Benjamin T; Witten, Ilana B; Deisseroth, Karl; Janak, Patricia H

    2014-01-01

    The neural basis of positive reinforcement is often studied in the laboratory using intracranial self-stimulation (ICSS), a simple behavioral model in which subjects perform an action in order to obtain exogenous stimulation of a specific brain area. Recently we showed that activation of ventral tegmental area (VTA) dopamine neurons supports ICSS behavior, consistent with proposed roles of this neural population in reinforcement learning. However, VTA dopamine neurons make connections with diverse brain regions, and the specific efferent target(s) that mediate the ability of dopamine neuron activation to support ICSS have not been definitively demonstrated. Here, we examine in transgenic rats whether dopamine neuron-specific ICSS relies on the connection between the VTA and the nucleus accumbens (NAc), a brain region also implicated in positive reinforcement. We find that optogenetic activation of dopaminergic terminals innervating the NAc is sufficient to drive ICSS, and that ICSS driven by optical activation of dopamine neuron somata in the VTA is significantly attenuated by intra-NAc injections of D1 or D2 receptor antagonists. These data demonstrate that the NAc is a critical efferent target sustaining dopamine neuron-specific ICSS, identify receptor subtypes through which dopamine acts to promote this behavior, and ultimately help to refine our understanding of the neural circuitry mediating positive reinforcement.

  17. Neurochemical characterization of body weight-regulating leptin receptor neurons in the nucleus of the solitary tract.

    PubMed

    Garfield, Alastair S; Patterson, Christa; Skora, Susanne; Gribble, Fiona M; Reimann, Frank; Evans, Mark L; Myers, Martin G; Heisler, Lora K

    2012-10-01

    The action of peripherally released leptin at long-form leptin receptors (LepRb) within the brain represents a fundamental axis in the regulation of energy homeostasis and body weight. Efforts to delineate the neuronal mediators of leptin action have recently focused on extrahypothalamic populations and have revealed that leptin action within the nucleus of the solitary tract (NTS) is critical for normal appetite and body weight regulation. To elucidate the neuronal circuits that mediate leptin action within the NTS, we employed multiple transgenic reporter lines to characterize the neurochemical identity of LepRb-expressing NTS neurons. LepRb expression was not detected in energy balance-associated NTS neurons that express cocaine- and amphetamine-regulated transcript, brain-derived neurotrophic factor, neuropeptide Y, nesfatin, catecholamines, γ-aminobutyric acid, prolactin-releasing peptide, or nitric oxide synthase. The population of LepRb-expressing NTS neurons was comprised of subpopulations marked by a proopiomelanocortin-enhanced green fluorescent protein (EGFP) transgene and distinct populations that express proglucagon and/or cholecystokinin. The significance of leptin action on these three populations of NTS neurons was assessed in leptin-deficient Ob/Ob mice, revealing increased NTS proglucagon and cholecystokinin, but not proopiomelanocortin, expression. These data provide new insight into the appetitive brainstem circuits engaged by leptin.

  18. [Single and Network Neuron Activity of Subthalamic Nucleus at Impulsive and Delayed (Self-Control) Reactions in Choice Behavior].

    PubMed

    Sidorina, V V; Gerasimova, Yu A; Kuleshova, E P; Merzhanova, G Kh

    2015-01-01

    During our experiments on cats was investigated the subthalamic neuron activity at different types of behavior in case of reinforcement choice depending on its value and availability. In chronic experiences the multiunit activity in subthalamic nucleus (STN) and orbitofrontal cortex (FC) has been recorded. Multiunit activity was analyzed over frequency and network properties of spikes. It was shown, that STN neurons reaction to different reinforcements and conditional stimulus at short- or long-delay reactions was represented by increasing or decreasing of frequency of single neurons. However the same STN neu- rons responded with increasing of frequency of single neuron during expectation of mix-bread-meat and decreasing--during the meat expectation. It has been revealed, that the number of STN interneuron interactions was authentic more at impulsive behavior than at self-control choice of behavior. The number of interactions between FC and STN neurons within intervals of 0-30 Ms was authentic more at display impulsive than during self-control behavior. These results suppose that FC and STN neurons participate in integration of reinforcement estimation; and distinctions in a choice of behavior are defined by the local and distributed interneuron interactions of STN and FC.

  19. Electrophysiological identification of the functional presynaptic nerve terminals on an isolated single vasopressin neurone of the rat supraoptic nucleus.

    PubMed

    Ohbuchi, T; Yokoyama, T; Fujihara, H; Suzuki, H; Ueta, Y

    2010-05-01

    Release of arginine vasopressin (AVP) and oxytocin from magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) is under the control of glutamate-dependent excitation and GABA-dependent inhibition. The possible role of the synaptic terminals attached to SON neurones has been investigated using whole-cell patch-clamp recording in in vitro rat brain slice preparations. Recent evidence has provided new insights into the repercussions of glial environment modifications on the physiology of MNCs at the synaptic level in the SON. In the present study, excitatory glutamatergic and inhibitory GABAergic synaptic inputs were recorded from an isolated single SON neurone cultured for 12 h, using the whole-cell patch clamp technique. Neurones expressed an AVP-enhanced green fluorescent protein (eGFP) fusion gene in MNCs. In addition, native synaptic terminals attached to a dissociated AVP-eGFP neurone were visualised with synaptic vesicle markers. These results suggest that the function of presynaptic nerve terminals may be evaluated directly in a single AVP-eGFP neurone. These preparations would be helpful in future studies aiming to electrophysiologically distinguish between the functions of synaptic terminals and glial modifications in the SON neurones.

  20. Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure.

    PubMed

    Pandit, Sudip; Jo, Ji Yoon; Lee, Sang Ung; Lee, Young Jae; Lee, So Yeong; Ryu, Pan Dong; Lee, Jung Un; Kim, Hyun-Woo; Jeon, Byeong Hwa; Park, Jin Bong

    2015-08-01

    γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal Itonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF Itonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure.

  1. CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery.

    PubMed

    Henckens, M J A G; Printz, Y; Shamgar, U; Dine, J; Lebow, M; Drori, Y; Kuehne, C; Kolarz, A; Eder, M; Deussing, J M; Justice, N J; Yizhar, O; Chen, A

    2016-08-23

    The bed nucleus of the stria terminalis (BNST) is critical in mediating states of anxiety, and its dysfunction has been linked to stress-related mental disease. Although the anxiety-related role of distinct subregions of the anterior BNST was recently reported, little is known about the contribution of the posterior BNST (pBNST) to the behavioral and neuroendocrine responses to stress. Previously, we observed abnormal expression of corticotropin-releasing factor receptor type 2 (CRFR2) to be associated with post-traumatic stress disorder (PTSD)-like symptoms. Here, we found that CRFR2-expressing neurons within the pBNST send dense inhibitory projections to other stress-related brain regions (for example, the locus coeruleus, medial amygdala and paraventricular nucleus), implicating a prominent role of these neurons in orchestrating the neuroendocrine, autonomic and behavioral response to stressful situations. Local CRFR2 activation by urocortin 3 depolarized the cells, increased the neuronal input resistance and increased firing of action potentials, indicating an enhanced excitability. Furthermore, we showed that CRFR2-expressing neurons within the pBNST are critically involved in the modulation of the behavioral and neuroendocrine response to stress. Optogenetic activation of CRFR2 neurons in the pBNST decreased anxiety, attenuated the neuroendocrine stress response, ameliorated stress-induced anxiety and impaired the fear memory for the stressful event. Moreover, activation following trauma exposure reduced the susceptibility for PTSD-like symptoms. Optogenetic inhibition of pBNST CRFR2 neurons yielded opposite effects. These data indicate the relevance of pBNST activity for adaptive stress recovery.Molecular Psychiatry advance online publication, 23 August 2016; doi:10.1038/mp.2016.133.

  2. Neurons identified by NeuN/Fox-3 immunoreactivity have a novel distribution in the hamster and mouse suprachiasmatic nucleus.

    PubMed

    Morin, Lawrence P; Hefton, Sara; Studholme, Keith M

    2011-11-03

    The suprachiasmatic nucleus (SCN) has several structural characteristics and cell phenotypes shared across species. Here, we describe a novel feature of SCN anatomy that is seen in both hamster and mouse. Frozen sections through the SCN were obtained from fixed brains and stained for the presence of immunoreactivity to neuronal nuclear protein (NeuN-IR) using a mouse monoclonal antibody which is known to exclusively identify neurons. NeuN-IR did not identify all SCN neurons as medial NeuN-IR neurons were generally not present. In the hamster, NeuN-IR cells are present rostrally, scattered in the dorsal half of the nucleus. More caudally, the NeuN-IR cells are largely, but not exclusively, scattered inside the lateral and dorsolateral border. At mid- to mid-caudal SCN levels, a dense group of NeuN-IR cells extends from the dorsolateral border ventromedially to encompass the central subnucleus of the SCN (SCNce). The pattern is similar in the mouse SCN. NeuN-IR does not co-localize with either cholecystokinin- or vasoactive intestinal polypeptide, but does with vasopressin-IR in the caudal SCN. In the hamster SCNce, numerous cells contain both calbindin- and NeuN-IR. The distribution of NeuN-IR cells in the SCN is unique, especially with regard to its generally lateral location through the length of the nucleus. The distribution of NeuN-IR cells is not consistent with most schemas representing SCN organization or with terminology referring to its widely accepted subdivisions. NeuN has recently been identified as Fox-3 protein. Its function in the SCN is not known, nor is it known why a large proportion of SCN cells do not contain NeuN-IR.

  3. Neurons Identified by NeuN/Fox-3 immunoreactivity have a Novel Distribution in the Hamster and Mouse Suprachiasmatic Nucleus

    PubMed Central

    Morin, Lawrence P.; Hefton, Sara; Studholme, Keith

    2011-01-01

    The suprachiasmatic nucleus (SCN) has several structural characteristics and cell phenotypes shared across species. Here, we describe a novel feature of SCN anatomy that is seen in both hamster and mouse. Frozen sections through the SCN were obtained from fixed brains and stained for the presence of immunoreactivity to neuronal nuclear protein (NeuN-IR) using a mouse monoclonal antibody which is known to exclusively identify neurons. NeuN-IR did not identify all SCN neurons as medial NeuNIR neurons were generally not present. In the hamster, NeuN-IR cells are present rostrally, scattered in the dorsal half of the nucleus. More caudally, the NeuN-IR cells are largely, but not exclusively, scattered inside the lateral and dorsolateral border. At mid- to mid-caudal SCN levels, a dense group of NeuN-IR cells extends from the dorsolateral border ventromedially to encompass the central subnucleus of the SCN (SCNce). The pattern is similar in the mouse SCN. NeuN-IR does not co-localize with either vasopressin-, cholecystokinin- or vasoactive intestinal polypeptide-IR. In the hamster SCNce, numerous cells contain both calbindin- and NeuN-IR. The distribution of NeuN-IR cells in the SCN is unique, especially with regard to its generally lateral location through the length of the nucleus. The distribution of NeuN-IR cells is not consistent with most schemas representing SCN organization or with terminology referring to its widely accepted subdivisions. NeuN has recently been identified as Fox-3 protein. Its function in the SCN is not known, nor is it known why a large proportion of SCN cells do not contain NeuN-IR. PMID:21981805

  4. Pre- and postnatal differences in membrane, action potential, and ion channel properties of rostral nucleus of the solitary tract neurons

    PubMed Central

    Suwabe, Takeshi; Mistretta, Charlotte M.; Krull, Catherine

    2011-01-01

    There is little known about the prenatal development of the rostral nucleus of the solitary tract (rNST) neurons in rodents or the factors that influence circuit formation. With morphological and electrophysiological techniques in vitro, we investigated differences in the biophysical properties of rNST neurons in pre- and postnatal rats from embryonic day 14 (E14) through postnatal day 20. Developmental changes in passive membrane and action potential (AP) properties and the emergence and maturation of ion channels important in neuron function were characterized. Morphological maturation of rNST neurons parallels changes in passive membrane properties. Mean soma size, dendritic branch points, neurite endings, and neurite length all increase prenatally. whereas neuron resting membrane potential, input resistance, and time constant decrease. Dendritic spines, on the other hand, develop after birth. AP discharge patterns alter in pre- and postnatal stages. At E14, neurons generated a single TTX-sensitive, voltage-gated Na+ AP when depolarized; a higher discharge rate appeared at older stages. AP amplitude, half-width, and rise and fall times all change during development. Responses to current injection revealed a number of voltage-gated conductances in embryonic rNST, including a hyperpolarization-activated inward current and a low-threshold Ca2+ current that initiated Ca2+ spikes. A hyperpolarization-activated, transient outward potassium current was also present in the developing neurons. Although the properties of these channels change during development, they are present before synapses form and therefore, can contribute to initial establishment of neural circuits, as well as to the changing electrophysiological properties in developing rNST neurons. PMID:21865434

  5. Midline thalamic paraventricular nucleus neurons display diurnal variation in resting membrane potentials, conductances, and firing patterns in vitro

    PubMed Central

    Kolaj, Miloslav; Zhang, Li; Rønnekleiv, Oline K.

    2012-01-01

    Neurons in the rodent midline thalamic paraventricular nucleus (PVT) receive inputs from brain stem and hypothalamic sites known to participate in sleep-wake and circadian rhythms. To evaluate possible diurnal changes in their excitability, we used patch-clamp techniques to record and examine the properties of neurons in anterior PVT (aPVT) in coronal rat brain slices prepared at zeitgeber time (ZT) 2–6 vs. ZT 14–18 and recorded at ZT 8.4 ± 0.2 (day) vs. ZT 21.2 ± 0.2 (night), the subjective quiet vs. aroused states, respectively. Compared with neurons recorded during the day, neurons from the night period were significantly more depolarized and exhibited a lower membrane conductance that in part reflected loss of a potassium-mediated conductance. Furthermore, these neurons were also significantly more active, with tonic and burst firing patterns. Neurons from each ZT period were assessed for amplitudes of two conductances known to contribute to bursting behavior, i.e., low-threshold-activated Ca2+ currents (IT) and hyperpolarization-activated cation currents (Ih). Data revealed that amplitudes of both IT and Ih were significantly larger during the night period. In addition, biopsy samples from the night period revealed a significant increase in mRNA for Cav3.1 and Cav3.3 low-threshold Ca2+ channel subtypes. Neurons recorded from the night period also displayed a comparative enhancement in spontaneous bursting at membrane potentials of approximately −60 mV and in burst firing consequent to hyperpolarization-induced low-threshold currents and depolarization-induced current pulses. These novel in vitro observations reveal that midline thalamic neurons undergo diurnal changes in their IT, Ih, and undefined potassium conductances. The underlying mechanisms remain to be characterized. PMID:22219029

  6. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates

    SciTech Connect

    Sekizawa, Shin-ichi; Joad, Jesse P.; Pinkerton, Kent E.; Bonham, Ann C.

    2010-01-15

    Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3 or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS

  7. Modulation of motor cortex neuronal activity and motor behavior during subthalamic nucleus stimulation in the normal primate.

    PubMed

    Johnson, Luke A; Xu, Weidong; Baker, Kenneth B; Zhang, Jianyu; Vitek, Jerrold L

    2015-04-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical therapy for advanced Parkinson's disease (PD). An emerging hypothesis is that the therapeutic benefit of DBS is derived from direct modulation of primary motor cortex (M1), yet little is known about the influence of STN DBS on individual neurons in M1. We investigated the effect of STN DBS, delivered at discrete interval intensities (20, 40, 60, 80, and 100%) of corticospinal tract threshold (CSTT), on motor performance and M1 neuronal activity in a naive nonhuman primate. Motor performance during a food reach and retrieval task improved during low-intensity stimulation (20% CSTT) but worsened as intensity approached the threshold for activation of corticospinal fibers (80% and 100% CSTT). To assess cortical effects of STN DBS, spontaneous, extracellular neuronal activity was collected from M1 neurons before, during, and after DBS at the same CSTT stimulus intensities. STN DBS significantly modulated the firing of a majority of M1 neurons; however, the direction of effect varied with stimulus intensity such that, at 20% CSTT, most neurons were suppressed, whereas at the highest stimulus intensities the majority of neurons were activated. At a population level, firing rates increased as stimulus intensity increased. These results show that STN DBS influences both motor performance and M1 neuronal activity systematically according to stimulus intensity. In addition, the unanticipated reduction in reach times suggests that STN DBS, at stimulus intensities lower than typically used for treatment of PD motor signs, can enhance normal motor performance.

  8. The ionic dependence of the histamine-induced depolarization of vasopressin neurones in the rat supraoptic nucleus.

    PubMed Central

    Smith, B N; Armstrong, W E

    1996-01-01

    1. The ionic basis of the histamine-induced depolarization of immunohistochemically identified neurones in the supraoptic nucleus (SON) was investigated in the hypothalamo-neurohypophysial explant of male rats. Histamine (0.1-100 microM) caused an H1 receptor-mediated, dose-dependent depolarization of fifty of sixty-two vasopressin neurones in the SON. In contrast, twenty-three oxytocin neurones were either depolarized (n = 6), hyperpolarized (n = 4), or unaffected (n = 13) by histamine. Due to the low percentage of responding cells, oxytocin neurones were not further investigated. 2. Chelation of intracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA; 100-500 mM) blocked the depolarization, whereas blocking Ca2+ influx and synaptic transmission with equimolar Co2+ or elevated (5-20 mM) Mg2+ in nominally Ca(2+)-free solutions was without effect. 3. The amplitude of the histamine-induced depolarization was relatively independent of membrane potential. The input resistance was unaltered by histamine in nine neurones, but in nine other neurones it was decreased and in two neurones it was increased by more than 5%. Neither elevating extracellular K+ nor addition of the K+ channel blockers, apamin, d-tubocurarine, tetraethylammonium (TEA), or intracellular Cs+ decreased the histamine effect. Indeed, broadly blocking K+ currents with TEA and Cs+ significantly increased the depolarization to histamine. 4. Tetrodotoxin (2-3 microM) did not inhibit the histamine-induced depolarization. However, equimolar replacement of approximately 50% of extracellular Na+ with Tris+ or N-methyl-D-glucamine reduced or eliminated the response. 5. The depolarization of vasopressin neurones by histamine thus requires extracellular Na+ and intracellular Ca2+. Activation of a Ca(2+)-activated non-specific cation current or a Ca(2+)-Na+ pump are possible mechanisms for this effect. Images Figure 1 PMID:8887757

  9. Responses of the red nucleus neurons to stimulation of the paw pads of forelimbs before and after cerebellar lesions.

    PubMed

    Tarnecki, R; Lupa, K; Niechaj, A

    2001-09-01

    Cerebellar cortex ablation releases deep cerebellar nuclei of monosynaptic inhibition from Purkinje cells. Therefore, it strengthens excitatory influence from Interpositus Nucleus (IN) upon Red Nucleus (RN), which results in much higher facilitation of the rubro-spinal neurons. This causes a big increase of spontaneous discharge rate, and eliminates brakes of discharges from responses generated by somatosensory stimuli. These two changes destroy content and timing of feedback information flowing through the spino-cerebello-rubro-spinal loop. This false bias of the feedback information, very important for fast postural adjustment and coordination of ongoing movements executed by central motor program, may at least in part be responsible for abnormal motor behavior evoked by cerebellar damage. Hemicerebellectomy resulted in dramatically reduced spontaneous activity and responses to limb stimulation because of severing a major input to the red nucleus from deep cerebellar nuclei. Due to direct somatosensory input to magnocellular Red Nucleus (mcRN) from the spinal cord that bypassed the cerebellum, the latency of response to limb stimulation was not changed and the narrower receptive fields were still present.

  10. Nucleus Accumbens Dopamine D2-Receptor Expressing Neurons Control Behavioral Flexibility in a Place Discrimination Task in the IntelliCage

    ERIC Educational Resources Information Center

    Macpherson, Tom; Morita, Makiko; Wang, Yanyan; Sasaoka, Toshikuni; Sawa, Akira; Hikida, Takatoshi

    2016-01-01

    Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated…

  11. Role of GABAergic neurones in the nucleus tractus solitarii in modulation of cardiovascular activity.

    PubMed

    Zubcevic, Jasenka; Potts, Jeffrey T

    2010-09-01

    GABAergic neurones are interspersed throughout the nucleus tractus solitarii (NTS), and their tonic activity is crucial to the maintenance of cardiorespiratory homeostasis. However, the mechanisms that regulate the magnitude of GABAergic inhibition in the NTS remain unknown. We hypothesized that the level of GABAergic inhibition is proportionally regulated by the level of excitatory synaptic input to the NTS from baroreceptors. Using the in situ working heart-brainstem preparation in normotensive and spontaneously hypertensive rats, we blocked GABA(A) receptor-mediated neurotransmission in the NTS with gabazine (a specific GABA(A) receptor antagonist) at two levels of perfusion pressure (low PP, 60-70 mmHg; and high PP, 105-125 mmHg) while monitoring the immediate changes in cardiorespiratory variables. In normotensive rats, gabazine produced an immediate bradycardia consistent with disinhibition of NTS circuit neurones that regulate heart rate (HR) which was proportional to the level of arterial pressure (HR at low PP, 57 +/- 9 beats min(1); at high PP, 177 +/- 9 beats min(1); P < 0.001), suggesting that GABAergic circuitry in the NTS modulating heart rate was arterial pressure dependent. In contrast, there was no significant difference in the magnitude of gabazine-induced bradycardia in spontaneously hypertensive rats at low or high PP (HR at low PP, 45 +/- 10 beats min(1); at high PP, 58 +/- 7 beats min(1)). With regard to thoracic sympathetic nerve activity (tSNA), at high PP there was a significant reduction in tSNA during the inspiratory (I) phase of the respiratory cycle, but only in the normotensive rat (tSNA = 18.7 +/- 10%). At low PP, gabazine caused an elevation of the postinspiration phase of tSNA in both normotensive (tSNA = 23.7 +/- 2.9%) and hypertensive rats (tSNA = 44.2 +/- 14%). At low PP, gabazine produced no change in tSNA during the mid-expiration phase in either rat strain, but at high PP we observed a significant reduction in the mid

  12. Progression of tau pathology within cholinergic nucleus basalis neurons in chronic traumatic encephalopathy: A Chronic Effects of Neurotrauma Consortium Study

    PubMed Central

    Mufson, Elliott J.; Perez, Sylvia E.; Nadeem, Muhammad; Mahady, Laura; Kanaan, Nicholas M.; Abrahamson, Eric E.; Ikonomovic, Milos D.; Crawford, Fiona; Alvarez, Victor; Stein, Thor; McKee, Ann C.

    2017-01-01

    Objective To test the hypothesis that the nucleus basalis of Meynert (nbM), a cholinergic basal forebrain (CBF) cortical projection system, develops neurofibrillary tangles (NFTs) during the progressive pathological stages of chronic traumatic encephalopathy (CTE) in the brain of athletes. Method To characterize NFT pathology we used tau- antibodies marking early, intermediate, and late stages of NFT development in cholinergic basal forebrain tissue obtained at autopsy from eighteen former athletes and veterans with a history of repetitive mild traumatic brain injury (TBI). Results We found evidence that cholinergic nbM neurons develop intracellular tau-immunoreactive changes progressively across the pathological stages of CTE. In particular, there was an increase in pretangle (phosphorylated pS422) and oligomeric (TOC1 and TNT1) forms of tau in stage IV compared to stage II CTE cases. The nbM neurons also displayed pathologic TDP-43 inclusions and diffuse extracellular and vascular amyloid-β (Aβ) deposits in CTE. A higher percent of pS422/p75NTR, pS422 and TNT1 labeled neurons were significantly correlated with age at symptom onset, interval between symptom onset and death and age at death. Conclusion The development of NFTs within the nbM neurons could contribute to the basal forebrain cortical cholinergic disconnection in CTE. Further studies are needed to determine the mechanism driving NFT formation in the nbM neurons and its relation to chronic cognitive dysfunction in CTE. PMID:27834536

  13. Two opposite effects of Delta(9)-tetrahydrocannabinol on subthalamic nucleus neuron activity: involvement of GABAergic and glutamatergic neurotransmission.

    PubMed

    Morera-Herreras, Teresa; Ruiz-Ortega, Jose Angel; Ugedo, Luisa

    2010-01-01

    Activation of CB1 cannabinoid receptors in the basal ganglia interferes with movement regulation. The aim of this study was to characterize the effect of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) on neurons in the subthalamic nucleus (STN) and to elucidate the mechanisms involved in this effect using single-unit extracellular recordings in anesthetized rats. Administration of Delta(9)-THC (0.25-2 mg/kg, i.v.) stimulated (by 107% +/- 32%) neurons mainly recorded in the ventromedial portion of the caudal STN, whereas it inhibited (by 65% +/- 4%) neurons recorded in the dorsolateral portion of the rostral STN. The CB1 receptor antagonist rimonabant (1 mg/kg, i.v.) completely reverted these effects. The excitatory effect of Delta(9)-THC on STN neurons was not observed after antagonism of GABA(A) receptors by bicuculline administration (10 ng, icv.) or after chemical lesion of the globus pallidus with ibotenic acid. The inhibitory effect was abolished when excitatory amino acid receptors were blocked by kynurenic acid (0.5 mumol, icv.). These results indicate that CB1 receptor activation modulates STN neuron activity by indirect mechanisms involving glutamatergic and GABAergic neurotransmission.

  14. Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice.

    PubMed

    Kroeger, Daniel; Ferrari, Loris L; Petit, Gaetan; Mahoney, Carrie E; Fuller, Patrick M; Arrigoni, Elda; Scammell, Thomas E

    2017-02-01

    The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states.

  15. Activation of glycine receptor phase-shifts the circadian rhythm in neuronal activity in the mouse suprachiasmatic nucleus

    PubMed Central

    Mordel, Jérôme; Karnas, Diana; Inyushkin, Alexey; Challet, Etienne; Pévet, Paul; Meissl, Hilmar

    2011-01-01

    Abstract In mammals, the master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is composed of numerous synchronized oscillating cells that drive daily behavioural and physiological processes. Several entrainment pathways, afferent inputs to the SCN with their neurotransmitter and neuromodulator systems, can reset the circadian system regularly and also modulate neuronal activity within the SCN. In the present study, we investigated the function of the inhibitory neurotransmitter glycine on neuronal activity in the mouse SCN and on resetting of the circadian clock. The effects of glycine on the electrical activity of SCN cells from C57Bl/6 mice were studied either by patch-clamp recordings from acute brain slices or by long-term recordings from organotypic brain slices using multi-microelectrode arrays (MEA). Voltage-clamp recordings confirmed the existence of glycine-induced, chloride-selective currents in SCN neurons. These currents were reversibly suppressed by strychnine, phenylbenzene ω-phosphono-α-amino acid (PMBA) or ginkgolide B, selective blockers of glycine receptors (GlyRs). Long-term recordings of the spontaneous activity of SCN neurons revealed that glycine application induces a phase advance during the subjective day and a phase delay during the early subjective night. Both effects were suppressed by strychnine or by PMBA. These results suggest that glycine is able to modulate circadian activity by acting directly on its specific receptors in SCN neurons. PMID:21486797

  16. Genetic cell targeting uncovers specific neuronal types and distinct subregions in the bed nucleus of the stria terminalis

    PubMed Central

    Nguyen, Amanda Q.; Cruz, Julie A.D. Dela; Sun, Yanjun; Holmes, Todd C.; Xu, Xiangmin

    2017-01-01

    The bed nucleus of the stria terminalis (BNST) plays an important role in fear, stress, and anxiety. It contains a collection of sub-nuclei delineated by gross cytoarchitecture features; however, there has yet to be a systematic examination of specific BNST neuronal types and their associated neurochemical makeup. The present study focuses on improved characterization of the anterior BNST based on differing molecular and chemical expression aided by mouse genetics. Specific Cre driver lines crossed with a fluorescent reporter line were used for genetic cell targeting and immunochemical staining. Using this new approach, we were able to robustly identify specific excitatory and inhibitory cell types in the BNST. The presence and distribution of excitatory neurons were firmly established; glutamatergic neurons in the anterior BNST accounted for about 14% and 31% of dorsal and ventral BNST cells, respectively. GABAergic neurons expressing different isoforms of glutamic acid decarboxylase were found to have differential sub-regional distributions. Almost no parvalbumin-expressing cells were found in the BNST, while somatostatin-expressing cells and calretinin-expressing cells account for modest proportions of BNST cells. In addition, vasoactive intestinal peptide-expressing axonal plexuses were prominent in the oval and juxtacapsular (jc) subregions. In addition, we discovered that corticotropin-releasing hormone (CRH) expressing cells contain GABAergic and glutamatergic subpopulations. Together, this study reveals new information on excitatory and inhibitory neurons in the BNST, which will facilitate genetic dissection and functional studies of BNST subregions. PMID:26718312

  17. Neuronal Expression and Cell-Type-Specific Gene-Silencing of Best1 in Thalamic Reticular Nucleus Neurons Using pSico-Red System

    PubMed Central

    Jung, Jae-Young; Lee, Seung Eun; Hwang, Eun Mi

    2016-01-01

    Assessing the cell-type expression pattern of a certain gene can be achieved by using cell-type-specific gene manipulation. Recently, cre-recombinase-dependent gene-silencing tool, pSico has become popular in neuroscientific research. However, pSico has a critical limitation that gene-silenced cell cannot be identified by fluorescence, due to an excision of the reporter gene for green fluorescence protein (GFP). To overcome this limitation, we newly developed pSico-Red, with mCherry gene as a reporter outside two loxP sites, so that red mCherry signal is detected in all transfected cells. When a cell expresses cre, GFP is excised and shRNA is enabled, resulting in disappearance of GFP. This feature of pSico-Red provides not only cell-type-specific gene-silencing but also identification of cre expressing cells. Using this system, we demonstrated for the first time the neuronal expression of the Bestrophin-1 (Best1) in thalamic reticular nucleus (TRN) and TRN-neuron-specific gene-silencing of Best1. We combined adeno-associated virus (AAV) carrying Best1-shRNA in pSico-Red vector and transgenic mouse expressing cre under the promoter of distal-less homeobox 5/6 (DLX5/6), a marker for inhibitory neurons. Firstly, we found that almost all of inhibitory neurons in TRN express Best1 by immunohistochemistry. Using pSico-Red virus, we found that 80% of infected TRN neurons were DLX5/6-cre positive but parvalbumin negative. Finally, we found that Best1 in DLX5/6-cre positive neurons were significantly reduced by Best1-shRNA. Our study demonstrates that TRN neurons strongly express Best1 and that pSico-Red is a valuable tool for cell-type-specific gene manipulation and identification of specific cell population. PMID:27358580

  18. [Convergence and interaction of reticulofugal and afferent impulses on caudate nucleus neurons in the cat].

    PubMed

    Litvinova, A N; Verba, V G

    1987-01-01

    In chronic experiments on cats the activity of 269 striatal neurons was investigated extracellularly under direct electrical stimulation of the midbrain reticular formation and using different sensory stimuli: auditory, mechanical, visual. The same striatal neuron responded to reticular and peripheral stimulations. The responses to reticular stimulation recorded in 53% of striatal neurons were orthodromic with high probability of appearance. 23% of striatal neurons responded to reticular stimulation and to stimuli of a single modality. 14% of neurons exhibited polymodal responses. Under all kinds of stimulation excitatory reactions prevailed. Interaction between reticular and acoustic inputs was revealed with paired stimulation in 100 striatal neurons. The reticular formation stimulation caused both facilitatory (predominantly) and inhibitory influences on striatal neurons.

  19. The anterior and posterior pedunculopontine tegmental nucleus are involved in behavior and neuronal activity of the cuneiform and entopeduncular nuclei.

    PubMed

    Jin, X; Schwabe, K; Krauss, J K; Alam, M

    2016-05-13

    Loss of cholinergic neurons in the mesencephalic locomotor region, comprising the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CnF), is related to gait disturbances in late stage Parkinson's disease (PD). We investigate the effect of anterior or posterior cholinergic lesions of the PPN on gait-related motor behavior, and on neuronal network activity of the PPN area and basal ganglia (BG) motor loop in rats. Anterior PPN lesions, posterior PPN lesions or sham lesions were induced by stereotaxic microinjection of the cholinergic toxin AF64-A or vehicle in male Sprague-Dawley rats. First, locomotor activity (open field), postural disturbances (Rotarod) and gait asymmetry (treadmill test) were assessed. Thereafter, single-unit and oscillatory activities were measured in the non-lesioned area of the PPN, the CnF and the entopeduncular nucleus (EPN), the BG output region, with microelectrodes under urethane anesthesia. Additionally, ECoG was recorded in the motor cortex. Injection of AF64-A into the anterior and posterior PPN decreased cholinergic cell counts as compared to naive controls (P<0.001) but also destroyed non-cholinergic cells. Only anterior PPN lesions decreased the front limb swing time of gait in the treadmill test, while not affecting other gait-related parameters tested. Main electrophysiological findings were that anterior PPN lesions increased the firing activity in the CnF (P<0.001). Further, lesions of either PPN region decreased the coherence of alpha (8-12 Hz) band between CnF and motor cortex (MCx), and increased the beta (12-30 Hz) oscillatory synchronization between EPN and the MCx. Lesions of the PPN in rats had complex effects on oscillatory neuronal activity of the CnF and the BG network, which may contribute to the understanding of the pathophysiology of gait disturbance in PD.

  20. Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

    PubMed Central

    Xu, Yuanzhong; Shu, Gang; Wang, Chunmei; Yang, Yongjie; Saito, Kenji; Xu, Pingwen; Hinton, Antentor Othrell; Yan, Xiaofeng; Yu, Likai; Wu, Qi; Tso, Patrick; Tong, Qingchun; Xu, Yong

    2015-01-01

    Background/Aims Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. Methods We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) and in neurons that express pro-opiomelanocortin (POMC). We then compared anorexigenic effects of apoA-IV in wild type mice and in mutant mice lacking melanocortin 4 receptors (MC4Rs, the receptors of AgRP and the POMC gene product). Finally, we examined expression of apoA-IV in mouse hypothalamus and quantified its protein levels at fed vs. fasted states. Results We demonstrate that apoA-IV inhibited the firing rate of AgRP/NPY neurons. The decreased firing was associated with hyperpolarized membrane potential and decreased miniature excitatory postsynaptic current. We further used c-fos immunoreactivity to show that intracerebroventricular (i.c.v.) injections of apoA-IV abolished the fasting-induced activation of AgRP/NPY neurons in mice. Further, we found that apoA-IV depolarized POMC neurons and increased their firing rate. In addition, genetic deletion of MC4Rs blocked anorexigenic effects of i.c.v. apoA-IV. Finally, we detected endogenous apoA-IV in multiple neural populations in mouse hypothalamus, including AgRP/NPY neurons, and food deprivation suppresses hypothalamic apoA-IV protein levels. Conclusion Our findings support a model where central apoA-IV inhibits AgRP/NPY neurons and activates POMC neurons to activate MC4Rs, which in turn suppresses food intake. PMID:26337236

  1. Competitor suppresses neuronal representation of food reward in the nucleus accumbens/medial striatum of domestic chicks.

    PubMed

    Amita, Hidetoshi; Matsushima, Toshiya

    2014-07-15

    To investigate the role of social contexts in controlling the neuronal representation of food reward, we recorded single neuron activity in the medial striatum/nucleus accumbens of domestic chicks and examined whether activities differed between two blocks with different contexts. Chicks were trained in an operant task to associate light-emitting diode color cues with three trial types that differed in the type of food reward: no reward (S-), a small reward/short-delay option (SS), and a large reward/long-delay alternative (LL). Amount and duration of reward were set such that both of SS and LL were chosen roughly equally. Neurons showing distinct cue-period activity in rewarding trials (SS and LL) were identified during an isolation block, and activity patterns were compared with those recorded from the same neuron during a subsequent pseudo-competition block in which another chick was allowed to forage in the same area, but was separated by a transparent window. In some neurons, cue-period activity was lower in the pseudo-competition block, and the difference was not ascribed to the number of repeated trials. Comparison at neuronal population level revealed statistically significant suppression in the pseudo-competition block in both SS and LL trials, suggesting that perceived competition generally suppressed the representation of cue-associated food reward. The delay- and reward-period activities, however, did not significantly different between blocks. These results demonstrate that visual perception of a competitive forager per se weakens the neuronal representation of predicted food reward. Possible functional links to impulse control are discussed.

  2. The human neurosecretory neurones under perinatal hypoxia: a quantitative immunohistochemical study of the supraoptic nucleus in autopsy material.

    PubMed

    Pagida, M A; Konstantinidou, A E; Malidelis, Y I; Ganou, V; Tsekoura, E; Patsouris, E; Panayotacopoulou, M T

    2013-12-01

    In the rat, experimental manipulations that cause activation of the magnocellular neurosecretory neurones result in the synthesis, in addition to vasopressin (AVP) and oxytocin (OXY), of other neurotransmitters or peptides, including tyrosine hydroxylase (TH), the first and rate limiting enzyme for catecholamine biosynthesis. In the human neonate, our previous study showed that TH was selectively increased in AVP neurones of subjects that died from prolonged perinatal hypoxia. The purpose of the present study was to quantitatively investigate the expression of TH, AVP, OXY and neurophysin in magnocellular neurones of the human neonate in relation to the severity/duration of perinatal hypoxia, as estimated by neuropathological criteria. Autopsy was performed after obtaining parental written consent for diagnostic and research purposes. The intensity of the immunohistochemical reactions and the cellular/nuclear size were measured in the dorsolateral supraoptic nucleus using a computerised image analysis system. We showed that prolonged perinatal hypoxia resulted in the activation of the magnocellular neuroendocrine neurones of the human neonate, as indicated by their increased neuronal and nuclear size. OXY neurones appeared larger than the AVP ones at birth, possibly indicating an active role of foetal OXY during labour or even earlier. The gradual increase in the duration of the insult resulted in the reduction of intracellular AVP content, in parallel with a dramatic increase in the expression of TH, indicating a functional interaction of these peptides under neuronal activation. Ιsolated evidence in our series, obtained from an infant of a diabetic mother, raises the probability that in the case of hyperglycaemia the above pathogenetic mechanisms are diversified.

  3. Phenotype-dependent inhibition of glutamatergic transmission on nucleus accumbens medium spiny neurons by the abused inhalant toluene.

    PubMed

    Beckley, Jacob T; Randall, Patrick K; Smith, Rachel J; Hughes, Benjamin A; Kalivas, Peter W; Woodward, John J

    2016-05-01

    Abused inhalants are voluntarily inhaled at high concentrations to produce intoxicating effects. Results from animal studies show that the abused inhalant toluene triggers behaviors, such as self-administration and conditioned place preference, which are commonly associated with addictive drugs. However, little is known about how toluene affects neurons within the nucleus accumbens (NAc), a brain region within the basal ganglia that mediates goal-directed behaviors and is implicated in the development and maintenance of addictive behaviors. Here we report that toluene inhibits a component of the after-hyperpolarization potential, and dose-dependently inhibits N-methyl-D-aspartate (NMDA)-mediated currents in rat NAc medium spiny neurons (MSN). Moreover, using the multivariate statistical technique, partial least squares discriminative analysis to analyze electrophysiological measures from rat NAc MSNs, we show that toluene induces a persistent depression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated currents in one subtype of NAc MSNs, and that the electrophysiological features of MSN neurons predicts their sensitivity to toluene. The CB1 receptor antagonist AM281 blocked the toluene-induced long-term depression of AMPA currents, indicating that this process is dependent on endocannabinoid signaling. The neuronal identity of recorded cells was examined using dual histochemistry and shows that toluene-sensitive NAc neurons are dopamine D2 MSNs that express preproenkephalin mRNA. Overall, the results from these studies indicate that physiological characteristics obtained from NAc MSNs during whole-cell patch-clamp recordings reliably predict neuronal phenotype, and that the abused inhalant toluene differentially depresses excitatory neurotransmission in NAc neuronal subtypes.

  4. Neuromedin B and gastrin releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong renilla GFP in NPY neurons

    PubMed Central

    van den Pol, Anthony N.; Yao, Yang; Fu, Li-Ying; Foo, Kylie; Huang, Hao; Coppari, Roberto; Lowell, Brad; Broberger, Christian

    2009-01-01

    Neuropeptide Y (NPY) is one of the most widespread neuropeptides in the brain. Transgenic mice were generated that expressed bright renilla GFP in most or all of the known NPY cells in the brain, which otherwise were not identifiable. GFP expression in NPY cells was confirmed with immunocytochemistry and single cell RT-PCR. NPY neurons in the hypothalamic arcuate nucleus play an important role in energy homeostasis and endocrine control. Whole cell patch clamp recording was used to study identified arcuate NPY cells. Primary agents that regulate energy balance include melanocortin receptor agonists, AgRP, and cannabinoids; none of these substances substantially influenced electrical properties of NPY neurons. In striking contrast, neuropeptides of the bombesin family, including gastrin releasing peptide and neuromedin B which are found in axons in the arcuate nucleus and may also be released from the gut to signal the brain, showed strong direct excitatory actions at nanomolar levels on the NPY neurons, stronger than the actions of ghrelin and hypocretin/orexin. Bombesin-related peptides reduced input resistance and depolarized the membrane potential. The depolarization was attenuated by several factors: substitution of choline for sodium, extracellular Ni2+, inclusion of BAPTA in the pipette, KB-R7943 and SKF96365. Reduced extracellular calcium enhanced the current, which reversed around − 20 mV. Together, these data suggest two mechanisms, activation of non-selective cation channels and the sodium/calcium exchanger. Since both NPY and POMC neurons, which we also studied, are similarly directly excited by bombesin-like peptides, the peptides may function to initiate broad activation, rather than the cell-type selective activation or inhibition reported for many other compounds that modulate energy homeostasis. PMID:19357287

  5. Excitotoxicity by kainate-induced seizure causes diacylglycerol kinase ζ to shuttle from the nucleus to the cytoplasm in hippocampal neurons.

    PubMed

    Saino-Saito, Sachiko; Hozumi, Yasukazu; Goto, Kaoru

    2011-05-02

    Diacylglycerol kinase (DGK), which consists of several isozymes, plays a pivotal role in lipid second-messenger diacylglycerol metabolism. A nuclear isozyme, DGKζ, which is translocated from the nucleus to the cytoplasm in hippocampal neurons under transient ischemic stress, is implicated in nuclear events of delayed neuronal death. Kainate (KA)-induced seizure is another model used to study excitotoxic stress. Therefore, we examined whether DGKζ is implicated in a different type of degenerative excitotoxicity in hippocampal neurons. We conducted immunohistochemical analysis of rat hippocampi after KA-induced seizures. DGKζ in hippocampal neurons shuttles from the nucleus to the cytoplasm. It never relocates to the nucleus during KA-induced seizures. Marked change in the immunoreactivity is first observed in CA1 pyramidal neurons 2h after injection during stage 3 seizures. Immunoreactivity for DGKι remains unchanged in the cytoplasm. That for NeuN remains mostly unchanged in the nucleus. Results show that nucleocytoplasmic translocation of DGKζ also occurs in a different model of excitotoxicity that results in apoptotic neuronal death. Cytoplasmic translocation of DGKζ might be involved in early events of the apoptotic cell death pathway in hippocampal neurons under stressed conditions.

  6. Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions.

    PubMed

    Wahle, Petra; Di Cristo, Graziella; Schwerdtfeger, Gudrun; Engelhardt, Maren; Berardi, Nicoletta; Maffei, Lamberto

    2003-02-01

    Neurotrophins strongly affect visual system development and plasticity. However, the mode of delivery and targets of neurotrophin action are still under debate. For instance, cortical NT-4/5 (neurotrophin 4/5; Ntf4/5) was shown to rescue lateral geniculate nucleus (LGN) neurons from monocular deprivation-induced atrophy suggesting a retrograde action on thalamic afferents. It is still unclear whether LGN neurons respond to NT-4/5 and other neurotrophins during development in animals with normal vision. We now show that infusions of NT-4/5 and NGF (nerve growth factor) into visual cortex at the onset and the peak of the critical period accelerated LGN neuron growth. BDNF (brain-derived neurotrophic factor) was ineffective. The effects of neurotrophin on LGN development were clearly dissociated from the effects at cortical level because soma growth of cortical layer IV and VI neurons was strongly promoted by BDNF. NT-4/5 was only effective at the onset, but no longer at the peak of the critical period suggesting a switch in neurotrophin dependency for these cortical cell classes. To dissociate retrograde and anterograde effects of the TrkB ligands, we analyzed the stratum griseum superficiale (SGS) of the superior colliculus, a target of visual cortical efferents. Indeed, TrkB-expressing inhibitory SGS neurons responded to cortical NT-4/5 infusion with somatic growth. Strikingly, the TrkB-expressing excitatory tectothalamic calbindin neurons in the SGS did not respond. This demonstrated for the first time a selective cell type-specific anterograde action of NT-4/5 and suggested for the LGN that anterograde as well as retrograde effects contribute to soma size regulation. Strikingly, cortical infusion of the cytokine LIF, which affects development of visual cortex neurochemical architecture, transiently inhibited growth of neurons in LGN, cortical layer IV and VI and SGS. In summary, the study presents three important results. First, central neurons regulate soma size

  7. Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal column lesions: a pathway that could contribute to recovery after spinal cord injury

    PubMed Central

    Liao, Chia-Chi; DiCarlo, Gabriella E.; Gharbawie, Omar A.; Qi, Hui-Xin; Kaas, Jon H.

    2015-01-01

    Dorsal column lesions at a high cervical level deprive the cuneate nucleus and much of the somatosensory system of its major cutaneous inputs. Over weeks of recovery, much of the hand representations in the contralateral cortex are reactivated. One possibility for such cortical reactivation by hand afferents is that preserved second-order spinal cord neurons reach the cuneate nucleus through pathways that circumvent the dorsal column lesions, contributing to cortical reactivation in an increasingly effective manner over time. To evaluate this possibility, we first injected anatomical tracers into the cuneate nucleus and plotted the distributions of labeled spinal cord neurons and fibers in control monkeys. Large numbers of neurons in the dorsal horn of the cervical spinal cord were labeled, especially unilaterally in lamina IV. Labeled fibers were distributed in the cuneate fasciculus and lateral funiculus. In three other squirrel monkeys, unilateral dorsal column lesions were placed at the cervical segment 4 (C4) level and tracers were injected into the ipsilateral cuneate nucleus. Two weeks later, a largely unresponsive hand representation in contralateral somatosensory cortex confirmed the effectiveness of the dorsal column lesion. However, tracer injections in the cuneate nucleus labeled only about 5% of the normal number of dorsal horn neurons, mainly in lamina IV, below the level of lesions. Our results revealed a small second-order pathway to the cuneate nucleus that survives high cervical dorsal column lesions by traveling in the lateral funiculus. This could be important for cortical reactivation by hand afferents, and recovery of hand use. PMID:25845707

  8. Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal column lesions: A pathway that could contribute to recovery after spinal cord injury.

    PubMed

    Liao, Chia-Chi; DiCarlo, Gabriella E; Gharbawie, Omar A; Qi, Hui-Xin; Kaas, Jon H

    2015-10-01

    Dorsal column lesions at a high cervical level deprive the cuneate nucleus and much of the somatosensory system of its major cutaneous inputs. Over weeks of recovery, much of the hand representations in the contralateral cortex are reactivated. One possibility for such cortical reactivation by hand afferents is that preserved second-order spinal cord neurons reach the cuneate nucleus through pathways that circumvent the dorsal column lesions, contributing to cortical reactivation in an increasingly effective manner over time. To evaluate this possibility, we first injected anatomical tracers into the cuneate nucleus and plotted the distributions of labeled spinal cord neurons and fibers in control monkeys. Large numbers of neurons in the dorsal horn of the cervical spinal cord were labeled, especially ipsilaterally in lamina IV. Labeled fibers were distributed in the cuneate fasciculus and lateral funiculus. In three other squirrel monkeys, unilateral dorsal column lesions were placed at the cervical segment 4 level and tracers were injected into the ipsilateral cuneate nucleus. Two weeks later, a largely unresponsive hand representation in contralateral somatosensory cortex confirmed the effectiveness of the dorsal column lesion. However, tracer injections in the cuneate nucleus labeled only about 5% of the normal number of dorsal horn neurons, mainly in lamina IV, below the level of lesions. Our results revealed a small second-order pathway to the cuneate nucleus that survives high cervical dorsal column lesions by traveling in the lateral funiculus. This could be important for cortical reactivation by hand afferents, and recovery of hand use.

  9. Sleep deprivation reduces the citalopram-induced inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis of the rat.

    PubMed

    Prévot, E; Maudhuit, C; Le Poul, E; Hamon, M; Adrien, J

    1996-12-01

    Sleep deprivation (SD) for one night induces mood improvement in depressed patients. However, relapse often occurs on the day after deprivation subsequently to a sleep episode. In light of the possible involvement of central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission in both depression and sleep mechanisms, we presently investigated, in the rat, the effects of SD and recovery sleep on the electrophysiological response of 5-HT neurons in the nucleus raphe dorsalis (NRD) to an acute challenge with the 5-HT reuptake blocker citalopram. In all rats, citalopram induced a dose-dependent inhibition of the firing of NRD neurons recorded under chloral hydrate anaesthesia. After SD, achieved by placing rats in a slowly rotating cylinder for 24 h, the inhibitory action of citalopram was significantly reduced (with a concomitant 53% increase in its ED50 value). After a recovery period of 4 h, a normal susceptibility of the firing to citalopram was restored. The decreased sensitivity of 5-HT neuronal firing to the inhibitory effect of citalopram after SD probably results in an enhancement of 5-HT neurotransmission. Such an adaptive phenomenon (similar to that reported after chronic antidepressant treatment), and its normalization after recovery sleep, parallel the mood improvement effect of SD and the subsequent relapse observed in depressed patients. These data suggest that the associated changes in 5-HT autocontrol of the firing of NRD serotoninergic neurons are relevant to the antidepressant action of SD.

  10. Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala.

    PubMed

    Adams, Thomas; Rosenkranz, J Amiel

    2016-06-01

    Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus-specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders.

  11. Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairment in Rats

    PubMed Central

    De Melo, Vitor U.; Saldanha, Rayssa R. M.; Dos Santos, Carla R.; De Campos Cruz, Josiane; Lira, Vitor A.; Santana-Filho, Valter J.; Michelini, Lisete C.

    2016-01-01

    The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic) neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN). Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry) within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation. PMID:27790154

  12. Cervical Stimulation Activates A1 and Locus Coeruleus Neurons that Project to the Paraventricular Nucleus of the Hypothalamus

    PubMed Central

    Poletini, Maristela O.; McKee, De’Nise T.; Szawka, Raphael E.; Bertram, Richard; Helena, Cleyde V. V.; Freeman, Marc E.

    2012-01-01

    In female rats, stimulation of the uterine cervix during mating induces two daily surges of prolactin. Inhibition of hypothalamic dopamine release and stimulation of oxytocin neurons in the paraventricular nucleus (PVN) are required for prolactin secretion. We aim to better understand how stimulation of the uterine cervix is translated into two daily prolactin surges. We hypothesize that noradrenergic neurons in the A1, A2, and locus coeruleus (LC) are responsible for conveying the peripheral stimulus to the PVN. In order to determine whether projections from these neurons to the PVN are activated by cervical stimulation (CS), we injected a retrograde tracer, Fluoro-Gold (FG), into the PVN of ovariectomized rats. Fourteen days after injection, animals were submitted to artificial CS or handling and perfused with a fixative solution. Brains were removed and sectioned from the A1, A2, and LC for c-Fos, tyrosine hydroxylase (TH), and FG triple-labeling using immunohistochemistry. CS increased the percentage of TH/FG+ double-labeled neurons expressing c-Fos in the A1 and LC. CS also increased the percentage of TH+ neurons expressing c-Fos within the A1 and A2, independent of their projections to the PVN. Our data reinforce the significant contributions of the A1 and A2 to carry sensory information during mating, and provide evidence of a functional pathway in which CS activates A1 and LC neurons projecting to the PVN, which is potentially involved in the translation of CS into two daily prolactin surges. PMID:22732530

  13. Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats

    PubMed Central

    Zheng, H.; Stornetta, R. L.; Agassandian, K.

    2017-01-01

    The expression of a vesicular glutamate transporter (VGLUT) suffices to assign a glutamatergic phenotype to neurons and other secretory cells. For example, intestinal L cells express VGLUT2 and secrete glutamate along with glucagon-like peptide 1 (GLP1). We hypothesized that GLP1-positive neurons within the caudal (visceral) nucleus of the solitary tract (cNST) also are glutamatergic. To test this, the axonal projections of GLP1 and other neurons within the cNST were labeled in rats via iontophoretic delivery of anterograde tracer. Dual immunofluorescence and confocal microscopy was used to visualize tracer-, GLP1-, and VGLUT2-positive fibers within brainstem, hypothalamic, and limbic forebrain nuclei that receive input from the cNST. Electron microscopy was used to confirm GLP1 and VGLUT2 immunolabeling within the same axon varicosities, and fluorescent in situ hybridization was used to examine VGLUT2 mRNA expression by GLP1-positive neurons. Most anterograde tracer-labeled fibers displayed VGLUT2-positive varicosities, providing new evidence that ascending axonal projections from the cNST are primarily glutamatergic. Virtually all GLP1-positive varicosities also were VGLUT2-positive. Electron microscopy confirmed the colocalization of GLP1 and VGLUT2 immunolabeling in axon terminals that formed asymmetric (excitatory-type) synapses with unlabeled dendrites in the hypothalamus. Finally, in situ hybridization confirmed that GLP1-positive cNST neurons express VGLUT2 mRNA. Thus, hindbrain GLP1 neurons in rats are equipped to store glutamate in synaptic vesicles, and likely co-release both glutamate and GLP1 from axon varicosities and terminals in the hypothalamus and other brain regions. PMID:25012114

  14. Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats.

    PubMed

    Zheng, H; Stornetta, R L; Agassandian, K; Rinaman, Linda

    2015-09-01

    The expression of a vesicular glutamate transporter (VGLUT) suffices to assign a glutamatergic phenotype to neurons and other secretory cells. For example, intestinal L cells express VGLUT2 and secrete glutamate along with glucagon-like peptide 1 (GLP1). We hypothesized that GLP1-positive neurons within the caudal (visceral) nucleus of the solitary tract (cNST) also are glutamatergic. To test this, the axonal projections of GLP1 and other neurons within the cNST were labeled in rats via iontophoretic delivery of anterograde tracer. Dual immunofluorescence and confocal microscopy was used to visualize tracer-, GLP1-, and VGLUT2-positive fibers within brainstem, hypothalamic, and limbic forebrain nuclei that receive input from the cNST. Electron microscopy was used to confirm GLP1 and VGLUT2 immunolabeling within the same axon varicosities, and fluorescent in situ hybridization was used to examine VGLUT2 mRNA expression by GLP1-positive neurons. Most anterograde tracer-labeled fibers displayed VGLUT2-positive varicosities, providing new evidence that ascending axonal projections from the cNST are primarily glutamatergic. Virtually all GLP1-positive varicosities also were VGLUT2-positive. Electron microscopy confirmed the colocalization of GLP1 and VGLUT2 immunolabeling in axon terminals that formed asymmetric (excitatory-type) synapses with unlabeled dendrites in the hypothalamus. Finally, in situ hybridization confirmed that GLP1-positive cNST neurons express VGLUT2 mRNA. Thus, hindbrain GLP1 neurons in rats are equipped to store glutamate in synaptic vesicles, and likely co-release both glutamate and GLP1 from axon varicosities and terminals in the hypothalamus and other brain regions.

  15. BDNF contributes to both rapid and homeostatic alterations in AMPA receptor surface expression in nucleus accumbens medium spiny neurons

    PubMed Central

    Reimers, Jeremy M.; Loweth, Jessica A.; Wolf, Marina E.

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in plasticity at glutamate synapses and the effects of repeated cocaine exposure. We recently showed that intracranial injection of BDNF into the rat nucleus accumbens (NAc), a key region for cocaine addiction, rapidly increases AMPA receptor (AMPAR) surface expression. To further characterize BDNF’s role in both rapid AMPAR trafficking and slower, homeostatic changes in AMPAR surface expression, we investigated the effects of acute (30 min) and long-term (24 h) treatment with BDNF on AMPAR distribution in NAc medium spiny neurons from postnatal rats co-cultured with mouse prefrontal cortex (PFC) neurons to restore excitatory inputs. Immunocytochemical studies showed that acute BDNF treatment increased cell surface GluA1 and GluA2 levels, as well as their co-localization, on NAc neurons. This effect of BDNF, confirmed using a protein crosslinking assay, was dependent on ERK but not AKT signaling. In contrast, long-term BDNF treatment decreased AMPAR surface expression on NAc neurons. Based on this latter result, we tested the hypothesis that BDNF plays a role in AMPAR “scaling down” in response to a prolonged increase in neuronal activity produced by bicuculline (24 h). Supporting this hypothesis, decreasing BDNF signaling with the extracellular BDNF scavenger TrkB-Fc prevented the scaling down of GluA1 and GluA2 surface levels in NAc neurons normally produced by bicuculline. In conclusion, BDNF exerts bidirectional effects on NAc AMPAR surface expression, depending on duration of exposure. Furthermore, BDNF’s involvement in synaptic scaling in the NAc differs from its previously described role in the visual cortex. PMID:24712995

  16. Repeated cocaine administration suppresses HVA-Ca2+ potentials and enhances activity of K+ channels in rat nucleus accumbens neurons.

    PubMed

    Hu, Xiu-Ti; Basu, Somnath; White, Francis J

    2004-09-01

    The nucleus accumbens (NAc) is an important forebrain area involved in sensitization, withdrawal effects, and self-administration of cocaine. However, little is known about cocaine-induced alterations in the neuronal excitability and whole cell neuroplasticity in this region that may affect behaviors. Our recent investigations have demonstrated that repeated cocaine administration decreases voltage-sensitive sodium and calcium currents (VSSCs and VSCCs, respectively) in freshly dissociated NAc neurons of rats. In this study, current-clamp recordings were performed in slice preparations to determine the effects of chronic cocaine on evoked Ca(2+) potentials and voltage-sensitive K(+) currents in NAc neurons. Repeated cocaine administration with 3-4 days of withdrawal caused significant alterations in Ca(2+) potentials, including suppression of Ca(2+)-mediated spikes, increase in the intracellular injected current intensity required for generation of Ca(2+) potentials (rheobase), reduced duration of Ca(2+) plateau potentials, and abolishment of secondary Ca(2+) potentials associated with the primary Ca(2+) plateau potential. Application of nickel (Ni(2+)), which blocks low-voltage activated T-type Ca(2+) channels, had no impact on evoked Ca(2+) plateau potentials in NAc neurons, indicating that these Ca(2+) potentials are high-voltage activated (HVA). In addition, repeated cocaine pretreatment also hyperpolarized the resting membrane potential, increased the amplitude of afterhyperpolarization in Ca(2+) spikes, and enhanced the outward rectification observed during membrane depolarization. These findings indicate that repeated cocaine administration not only suppressed HVA-Ca(2+) potentials but also significantly enhanced the activity of various K(+) channels in NAc neurons. They also demonstrate an integrative role of whole cell neuroplasticity during cocaine withdrawal, by which the subthreshold membrane excitability of NAc neurons is significantly decreased.

  17. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain

    PubMed Central

    Lake, Blue B.; Ai, Rizi; Kaeser, Gwendolyn E.; Salathia, Neeraj S.; Yung, Yun C.; Liu, Rui; Wildberg, Andre; Gao, Derek; Fung, Ho-Lim; Chen, Song; Vijayaraghavan, Raakhee; Wong, Julian; Chen, Allison; Sheng, Xiaoyan; Kaper, Fiona; Shen, Richard; Ronaghi, Mostafa; Fan, Jian-Bing; Wang, Wei; Chun, Jerold; Zhang, Kun

    2016-01-01

    The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from post-mortem brain, generating 3,227 sets of single neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish novel and orthologous neuronal subtypes as well as regional identity within the human brain. PMID:27339989

  18. Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and ne...

  19. Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons

    PubMed Central

    Han, Jin-Eon; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon

    2017-01-01

    The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K+ and Ca2+ channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K+ currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K+ currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs+ (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca2+ channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions. PMID:28280415

  20. Histaminergic H1 and H2 Receptors Mediate the Effects of Propofol on the Noradrenalin-Inhibited Neurons in Rat Ventrolateral Preoptic Nucleus.

    PubMed

    Liu, Yang; Zhang, Yu; Qian, Kun; Zhang, Lin; Yu, Tian

    2017-02-09

    The ventrolateral preoptic nucleus is a sleep-promoting nucleus located in the basal forebrain. A commonly used intravenous anesthetic, propofol, had been reported to induce sleep spindles and augment the firing rate of neurons in ventrolateral preoptic nucleus, but the underlining mechanism is yet to be known. By using patch clamp recording on neuron in acute brain slice, present study tested if histaminergic H1 and H2 receptors play a role in the effect of propofol on the noradrenalin-inhibited neurons in ventrolateral preoptic nucleus. We found that the firing rate of noradrenalin-inhibited neurons were significantly augmented by propofol; the frequency of inhibitory postsynaptic currents of noradrenalin-inhibited neuron were evidently attenuated by propofol; such inhibition effect was suppressed by histamine; and both triprolidine (antagonist for H1 histamine receptor) and ranitidine (antagonist for H2 histamine receptor) were able to increase the inhibition rate of propofol in presence of histamine. Present study demonstrated that propofol-induced inhibition of inhibitory postsynaptic currents on noradrenalin-inhibited neurons were mediated by histaminergic H1 and H2 receptors.

  1. Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents.

    PubMed

    Gittis, Aryn H; Moghadam, Setareh H; du Lac, Sascha

    2010-09-01

    To fire at high rates, neurons express ionic currents that work together to minimize refractory periods by ensuring that sodium channels are available for activation shortly after each action potential. Vestibular nucleus neurons operate around high baseline firing rates and encode information with bidirectional modulation of firing rates up to several hundred Hz. To determine the mechanisms that enable these neurons to sustain firing at high rates, ionic currents were measured during firing by using the action potential clamp technique in vestibular nucleus neurons acutely dissociated from transgenic mice. Although neurons from the YFP-16 line fire at rates higher than those from the GIN line, both classes of neurons express Kv3 and BK currents as well as both transient and resurgent Na currents. In the fastest firing neurons, Kv3 currents dominated repolarization at all firing rates and minimized Na channel inactivation by rapidly transitioning Na channels from the open to the closed state. In slower firing neurons, BK currents dominated repolarization at the highest firing rates and sodium channel availability was protected by a resurgent blocking mechanism. Quantitative differences in Kv3 current density across neurons and qualitative differences in immunohistochemically detected expression of Kv3 subunits could account for the difference in firing range within and across cell classes. These results demonstrate how divergent firing properties of two neuronal populations arise through the interplay of at least three ionic currents.

  2. Electrophysiological and morphological properties of neurons in the prepositus hypoglossi nucleus that express both ChAT and VGAT in a double-transgenic rat model.

    PubMed

    Saito, Yasuhiko; Zhang, Yue; Yanagawa, Yuchio

    2015-04-01

    Although it has been proposed that neurons that contain both acetylcholine (ACh) and γ-aminobutyric acid (GABA) are present in the prepositus hypoglossi nucleus (PHN), these neurons have not been characterized because of the difficulty in identifying them. In the present study, PHN neurons that express both choline acetyltransferase and the vesicular GABA transporter (VGAT) were identified using double-transgenic rats, in which the cholinergic and inhibitory neurons express the fluorescent proteins tdTomato and Venus, respectively. To characterize the neurons that express both tdTomato and Venus (D+ neurons), the afterhyperpolarization (AHP) profiles and firing patterns of these neurons were investigated via whole-cell recordings of brainstem slice preparations. Regarding the three AHP profiles and four firing patterns that the D+ neurons exhibited, an AHP with an afterdepolarization and a firing pattern that exhibited a delay in the generation of the first spike were the preferential properties of these neurons. In the three morphological types classified, the multipolar type that exhibited radiating dendrites was predominant among the D+ neurons. Immunocytochemical analysis revealed that the VGAT-immunopositive axonal boutons that expressed tdTomato were primarily located in the dorsal cap of inferior olive (IO) and the PHN. Although the PHN receives cholinergic inputs from the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus, D+ neurons were absent from these brain areas. Together, these results suggest that PHN neurons that co-express ACh and GABA exhibit specific electrophysiological and morphological properties, and innervate the dorsal cap of the IO and the PHN.

  3. Neuronal Correlates of Fear Conditioning in the Bed Nucleus of the Stria Terminalis

    ERIC Educational Resources Information Center

    Haufler, Darrell; Nagy, Frank Z.; Pare, Denis

    2013-01-01

    Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and…

  4. Central ghrelin increases food foraging/hoarding that is blocked by GHSR antagonism and attenuates hypothalamic paraventricular nucleus neuronal activation.

    PubMed

    Thomas, Michael A; Ryu, Vitaly; Bartness, Timothy J

    2016-02-01

    The stomach-derived "hunger hormone" ghrelin increases in the circulation in direct response to time since the last meal, increasing preprandially and falling immediately following food consumption. We found previously that peripheral injection of ghrelin potently stimulates food foraging (FF), food hoarding (FH), and food intake (FI) in Siberian hamsters. It remains, however, largely unknown if central ghrelin stimulation is necessary/sufficient to increase these behaviors regardless of peripheral stimulation of the ghrelin receptor [growth hormone secretagogue receptor (GHSR)]. We injected three doses (0.01, 0.1, and 1.0 μg) of ghrelin into the third ventricle (3V) of Siberian hamsters and measured changes in FF, FH, and FI. To test the effects of 3V ghrelin receptor blockade, we used the potent GHSR antagonist JMV2959 to block these behaviors in response to food deprivation or a peripheral ghrelin challenge. Finally, we examined neuronal activation in the arcuate nucleus and paraventricular hypothalamic nucleus in response to peripheral ghrelin administration and 3V GHSR antagonism. Third ventricular ghrelin injection significantly increased FI through 24 h and FH through day 4. Pretreatment with 3V JMV2959 successfully blocked peripheral ghrelin-induced increases in FF, FH, and FI at all time points and food deprivation-induced increases in FF, FH, and FI up to 4 h. c-Fos immunoreactivity was significantly reduced in the paraventricular hypothalamic nucleus, but not in the arcuate nucleus, following pretreatment with intraperitoneal JMV2959 and ghrelin. Collectively, these data suggest that central GHSR activation is both necessary and sufficient to increase appetitive and consummatory behaviors in Siberian hamsters.

  5. The response of neurons in the bed nucleus of the stria terminalis to serotonin: Implications for anxiety

    PubMed Central

    Hammack, Sayamwong E.; Guo, JiDong; Hazra, Rimi; Dabrowska, Joanna; Myers, Karyn M.; Rainnie, Donald G.

    2009-01-01

    Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT1A, 5-HT2A, 5-HT2C and 5-HT7 receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increase anxiety. PMID:19467288

  6. Reward and Behavioral Factors Contributing to the Tonic Activity of Monkey Pedunculopontine Tegmental Nucleus Neurons during Saccade Tasks

    PubMed Central

    Okada, Ken-ichi; Kobayashi, Yasushi

    2016-01-01

    The pedunculopontine tegmental nucleus (PPTg) in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined the activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our normal visually guided saccade task, the monkey initially fixated on the central fixation target (FT), then made saccades to the peripheral saccade target and received a juice reward after the saccade target disappeared. Most of the tonic activity terminated shortly after the reward delivery, when the monkey broke fixation. To distinguish between reward and behavioral epochs, we then changed the task sequence for a block of trials, such that the saccade target remained visible after the reward delivery. Under these visible conditions, the monkeys tended to continue fixating on the saccade target even after the reward delivery. Therefore, the prediction of the upcoming reward and the end of an individual trial were separated in time. Regardless of the task conditions, half of the tonically active PPTg neurons terminated their activity around the time of the reward delivery, consistent with the view that PPTg neurons might send reward prediction signals until the time of reward delivery, which is essential for computing reward prediction error in reinforcement learning. On the other hand, the other half of the tonically active PPTg neurons changed their activity dependent on the task condition. In the normal condition, the tonic responses terminated around the time of the reward delivery, while in the visible condition, the activity continued

  7. Enhanced Endocannabinoid-Mediated Modulation of Rostromedial Tegmental Nucleus Drive onto Dopamine Neurons in Sardinian Alcohol-Preferring Rats

    PubMed Central

    Sagheddu, Claudia; De Felice, Marta; Casti, Alberto; Madeddu, Camilla; Spiga, Saturnino; Muntoni, Anna Lisa; Mackie, Kenneth; Marsicano, Giovanni; Colombo, Giancarlo; Castelli, Maria Paola; Pistis, Marco

    2014-01-01

    The progressive predominance of rewarding effects of addictive drugs over their aversive properties likely contributes to the transition from drug use to drug dependence. By inhibiting the activity of DA neurons in the VTA, GABA projections from the rostromedial tegmental nucleus (RMTg) are well suited to shift the balance between drug-induced reward and aversion. Since cannabinoids suppress RMTg inputs to DA cells and CB1 receptors affect alcohol intake in rodents, we hypothesized that the endocannabinoid system, by modulating this pathway, might contribute to alcohol preference. Here we found that RMTg afferents onto VTA DA neurons express CB1 receptors and display a 2-arachidonoylglycerol (2-AG)-dependent form of short-term plasticity, that is, depolarization-induced suppression of inhibition (DSI). Next, we compared rodents with innate opposite alcohol preference, the Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. We found that DA cells from alcohol-naive sP rats displayed a decreased probability of GABA release and a larger DSI. This difference was due to the rate of 2-AG degradation. In vivo, we found a reduced RMTg-induced inhibition of putative DA neurons in sP rats that negatively correlated with an increased firing. Finally, alcohol failed to enhance RMTg spontaneous activity and to prolong RMTg-induced silencing of putative DA neurons in sP rats. Our results indicate functional modifications of RMTg projections to DA neurons that might impact the reward/aversion balance of alcohol attributes, which may contribute to the innate preference observed in sP rats and to their elevated alcohol intake. PMID:25232109

  8. Enhanced endocannabinoid-mediated modulation of rostromedial tegmental nucleus drive onto dopamine neurons in Sardinian alcohol-preferring rats.

    PubMed

    Melis, Miriam; Sagheddu, Claudia; De Felice, Marta; Casti, Alberto; Madeddu, Camilla; Spiga, Saturnino; Muntoni, Anna Lisa; Mackie, Kenneth; Marsicano, Giovanni; Colombo, Giancarlo; Castelli, Maria Paola; Pistis, Marco

    2014-09-17

    The progressive predominance of rewarding effects of addictive drugs over their aversive properties likely contributes to the transition from drug use to drug dependence. By inhibiting the activity of DA neurons in the VTA, GABA projections from the rostromedial tegmental nucleus (RMTg) are well suited to shift the balance between drug-induced reward and aversion. Since cannabinoids suppress RMTg inputs to DA cells and CB1 receptors affect alcohol intake in rodents, we hypothesized that the endocannabinoid system, by modulating this pathway, might contribute to alcohol preference. Here we found that RMTg afferents onto VTA DA neurons express CB1 receptors and display a 2-arachidonoylglycerol (2-AG)-dependent form of short-term plasticity, that is, depolarization-induced suppression of inhibition (DSI). Next, we compared rodents with innate opposite alcohol preference, the Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. We found that DA cells from alcohol-naive sP rats displayed a decreased probability of GABA release and a larger DSI. This difference was due to the rate of 2-AG degradation. In vivo, we found a reduced RMTg-induced inhibition of putative DA neurons in sP rats that negatively correlated with an increased firing. Finally, alcohol failed to enhance RMTg spontaneous activity and to prolong RMTg-induced silencing of putative DA neurons in sP rats. Our results indicate functional modifications of RMTg projections to DA neurons that might impact the reward/aversion balance of alcohol attributes, which may contribute to the innate preference observed in sP rats and to their elevated alcohol intake.

  9. Effects of morphine withdrawal on the membrane properties of medium spiny neurons in the nucleus accumbens shell.

    PubMed

    Wu, Xiaobo; Shi, Meimei; Ling, Hengli; Wei, Chunling; Liu, Yihui; Liu, Zhiqiang; Ren, Wei

    2013-01-01

    Medium spiny neurons (MSNs) in the nucleus accumbens (NAc) undergo persistent alterations in their biological and physiological characteristics upon exposure to drugs of abuse. Previous studies demonstrated that the biochemical, morphological, and intrinsic physiological properties of MSNs are heterogeneous and provided new insights into the physiological and molecular roles of individual MSNs in addictive behaviors. However, it remains unclear whether MSNs in the NAc shell (NAcSh), an important region for mediating behavioral sensitization, are electrophysiologically heterogeneous and how such heterogeneity is relevant to neuroadaptation associated with drug addiction. Here, the membrane properties, i.e., the intrinsic excitability and spike adaptation, of MSNs in the NAcSh from saline- or morphine-treated rats were investigated in vitro by whole-cell recording. In saline-treated rats, three distinct cell types were identified by their membrane properties: type I neurons showed high levels of intrinsic excitability and rapid spike adaptation; type II neurons showed moderate levels of intrinsic excitability and relatively slow spike frequency adaptation; type III neurons showed low levels of intrinsic excitability and putative strong spike adaptation. MSNs in rats undergoing withdrawal from chronic morphine treatment (10-14 days after the last injection) also exhibited the typical firing behaviors of these three types of neurons. However, the membrane properties of the MSNs were differentially altered after withdrawal. There was an enhancement in intrinsic excitability in type II MSNs and a promotion of spike adaptation in type I MSNs. The apamin-sensitive afterhyperpolarization current (I(AHP)) and the apamin-insensitive I(AHP) of the NAcSh MSNs were attenuated after chronic morphine withdrawal. These findings suggest that individual MSNs in the NAcSh manifest unique electrophysiological properties, which might contribute to psychostimulant-induced neuroadaptation.

  10. D2 dopamine receptors modulate neuronal resonance in subthalamic nucleus and cortical high-voltage spindles through HCN channels.

    PubMed

    Yang, Chen; Yan, Zhiqiang; Zhao, Bo; Wang, Julei; Gao, Guodong; Zhu, Junling; Wang, Wenting

    2016-06-01

    The high-voltage spindles (HVSs), one of the characteristic oscillations that include theta frequencies in the basal ganglia (BG)-cortical system, are involved in immobile behavior and show increasing power in Parkinson's disease (PD). Our previous results suggested that the D2 dopamine receptor might be involved in HVSs modulations in a rat model of PD. Membrane resonance is one of the cellular mechanisms of network oscillation; therefore, we investigated how dopamine modulates the theta frequency membrane resonance of neurons in the subthalamic nucleus (STN), a central pacemaker of BG, and whether such changes in STN neurons subsequently alter HVSs in the BG-cortical system. In particular, we tested whether dopamine modulates HVSs through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-dependent membrane resonance in STN neurons. We found that an antagonist of D2 receptors, but not of D1 receptors, inhibited membrane resonance and HCN currents of STN neurons through a G-protein activity in acute brain slices. Our further in vivo experiments using local injection of a D2 receptor antagonist or an HCN blocker in STNs of free-moving rats showed an increase in HVSs power and correlation in the BG-cortical system. Local injection of lamotrigine, an HCN agonist, counteracted the effect induced by the D2 antagonist. Taken together, our results revealed a potential cellular mechanism underlying HVSs activity modulation in the BG-cortical system, i.e. tuning HCN activities in STN neurons through dopamine D2 receptors. Our findings might lead to a new direction in PD treatment by providing promising new drug targets for HVSs activity modulation.

  11. A comparison of the postnatal development of muscle-spindle and periodontal-ligament neurons in the mesencephalic trigeminal nucleus of the rat.

    PubMed

    Umemura, Tetsuhiro; Yasuda, Kouichi; Ishihama, Kohji; Yamada, Hidefumi; Okayama, Masaki; Hasumi-Nakayama, Yoko; Furusawa, Kiyofumi

    2010-04-05

    The trigeminal mesencephalic nucleus (Vmes) is known to include primary afferent neurons of jaw muscle spindles (MS neurons) and periodontal ligament receptors (PL neurons). The aim of this study was to clarify the postnatal development of Vmes neurons by comparing MS neurons with PL neurons using horseradish peroxidase labeling. We measured somal diameter and somal shape of MS and PL neurons in rats from postnatal day (P)7 to P70. No significant changes were seen between postnatal day P7 and P70 in somal diameter or somal shape of MS neurons. Conversely, PL neurons showed a larger somal diameter at P7 than at P14, and in terms of somal profile, multipolar neurons comprised 0% at P7, but 4.8% at P14 and 16.9% at P70. These findings suggest that PL neurons develop with the eruption of teeth, taking into account the fact that tooth eruption occurs from around P14 in rats. Conversely, the lack of postnatal changes in MS neurons is due to the fact that these neurons have been active since the embryonic period, as swallowing starts in utero.

  12. The synchronization of neuronal oscillators determined by the directed network structure of the suprachiasmatic nucleus under different photoperiods.

    PubMed

    Gu, Changgui; Tang, Ming; Yang, Huijie

    2016-06-30

    The main function of the principal clock located in the suprachiasmatic nucleus (SCN) of mammals is synchronizing the body rhythms to the 24 h light-dark cycle. Additionally, the SCN is able to adapt to the photoperiod of the cycle which varies among seasons. Under the long photoperiod (LP), the synchronization degree of the SCN neurons is lower than that under the photoperiod (SP). In the present study, a potential explanation is given for this phenomenon. We propose that the asymmetrical coupling between the light-signal-sensitive part (the ventralateral part, abbreviation: VL) and the light-signal-insensitive part (the dorsalmedial part, abbreviation: DM) of the SCN plays a role in the synchronization degree, which is reflected by the ratio of the number of the directed links from the VL neurons to the DM neurons to the total links of both directions between the VL and the DM. The ratio is assumed to characterize the directed network structure under different photoperiods, which is larger under the SP and smaller under the LP. We found that with the larger ratio in the situation of the SP, the synchronization degree is higher. Our finding may shed new light on the asymmetrical coupling between the VL and the DM, and the network structure of the SCN.

  13. The synchronization of neuronal oscillators determined by the directed network structure of the suprachiasmatic nucleus under different photoperiods

    NASA Astrophysics Data System (ADS)

    Gu, Changgui; Tang, Ming; Yang, Huijie

    2016-06-01

    The main function of the principal clock located in the suprachiasmatic nucleus (SCN) of mammals is synchronizing the body rhythms to the 24 h light-dark cycle. Additionally, the SCN is able to adapt to the photoperiod of the cycle which varies among seasons. Under the long photoperiod (LP), the synchronization degree of the SCN neurons is lower than that under the photoperiod (SP). In the present study, a potential explanation is given for this phenomenon. We propose that the asymmetrical coupling between the light-signal-sensitive part (the ventralateral part, abbreviation: VL) and the light-signal-insensitive part (the dorsalmedial part, abbreviation: DM) of the SCN plays a role in the synchronization degree, which is reflected by the ratio of the number of the directed links from the VL neurons to the DM neurons to the total links of both directions between the VL and the DM. The ratio is assumed to characterize the directed network structure under different photoperiods, which is larger under the SP and smaller under the LP. We found that with the larger ratio in the situation of the SP, the synchronization degree is higher. Our finding may shed new light on the asymmetrical coupling between the VL and the DM, and the network structure of the SCN.

  14. Selective activation of dorsal raphe nucleus-projecting neurons in the ventral medial prefrontal cortex by controllable stress

    PubMed Central

    Baratta, Michael V.; Zarza, Christina M.; Gomez, Devan M.; Campeau, Serge; Watkins, Linda R.; Maier, Steven F.

    2009-01-01

    Exposure to uncontrollable stressors produces a variety of behavioral consequences (e.g. exaggerated fear, reduced social exploration) that do not occur if the stressor is controllable. In addition, an initial experience with a controllable stressor can block the behavioral and neural responses to a later uncontrollable stressor. The serotonergic (5-HT) dorsal raphe nucleus (DRN) has come to be viewed as a critical structure in mediating the behavioral effects of uncontrollable stress. Recent work suggests that the buffering effects of behavioral control on the DRN-dependent behavioral outcomes of uncontrollable stress require ventral medial prefrontal cortex (mPFCv) activation at the time of behavioral control. The present studies were conducted to directly determine whether or not controllable stress selectively activates DRN-projecting neurons within the mPFCv. To examine this possibility in the rat, we combined retrograde tracing (fluorogold iontophoresed into the DRN) with Fos immunohistochemistry, a marker for neural activation. Exposure to controllable, relative to uncontrollable, stress increased Fos expression in fluorogold-labeled neurons in the prelimbic region (PL) of the mPFCv. Furthermore, in a separate experiment, a prior experience with controllable stress led to potentiation of Fos expression in retrogradely labeled PL neurons in response to an uncontrollable stressor one week later. These results suggest that the PL selectively responds to behavioral control and utilizes such information to regulate the brainstem response to ongoing and subsequent stressors. PMID:19686468

  15. Electrophysiological characterization of synaptic connections between layer VI cortical cells and neurons of the nucleus reticularis thalami in juvenile rats.

    PubMed

    Gentet, Luc J; Ulrich, Daniel

    2004-02-01

    Corticothalamic (CT) feedback projections to the thalamus outnumber sensory inputs from the periphery by orders of magnitude. However, their functional role remains elusive. CT projections may directly excite thalamic relay cells or indirectly inhibit them via excitation of the nucleus reticularis thalami (nRT), a nuclear formation composed entirely of gamma-aminobutyric acidergic neurons. The relative strengths of these two pathways will ultimately control the effects of CT projections on the output of thalamic relay cells. However, corticoreticular synapses have not yet been fully physiologically characterized. Here, local stimulation of layer VI cells by focal application of K+ or AMPA elicited excitatory postsynaptic potentials in nRT neurons with a mean peak amplitude of 2.4 +/- 0.1 mV (n = 75, mean +/- SEM), a mean rise time (10-90%) of 0.74 +/- 0.03 ms and a weighted decay time constant of 11 +/- 0.3 ms. A pharmacological profile of responses was drawn in both current-clamp and voltage-clamp modes, showing the presence of a small N-methyl-d-aspartate receptor-dependent component at depolarized potentials. In two pairs of synaptically coupled layer VI cell-nRT neuron, moderate rates of transmission failures were observed while the latencies were above 5 ms in both cases. Our results indicate that the corticoreticular pathway fulfills the criteria for 'modulatory' inputs and is temporally restricted. We suggest that it may be involved in coincidence detection of convergent corticoreticular signals.

  16. Intracellular calcium signalling in magnocellular neurones of the rat supraoptic nucleus: understanding the autoregulatory mechanisms.

    PubMed

    Dayanithi, G; Sabatier, N; Widmer, H

    2000-03-01

    Oxytocin and vasopressin, released at the soma and dendrites of neurones, bind to specific autoreceptors and induce an increase in [Ca2+]i. In oxytocin cells, the increase results from a mobilisation of Ca2+ from intracellular stores, whereas in vasopressin cells, it results mainly from an influx of Ca2+ through voltage-dependent channels. The response to vasopressin is coupled to phospholipase C and adenylyl-cyclase pathways which are activated by V1 (V1a and V1b)- and V2-type receptors respectively. Measurements of [Ca2+]i in response to V1a and V2 agonists and antagonists suggest the functional expression of these two types of receptors in vasopressin neurones. The intracellular mechanisms involved are similar to those observed for the action of the pituitary adenylyl-cyclase-activating peptide (PACAP). Isolated vasopressin neurones exhibit spontaneous [Ca2+]i oscillations and these are synchronised with phasic bursts of electrical activity. Vasopressin modulates these spontaneous [Ca2+]i oscillations in a manner that depends on the initial state of the neurone, and such varied effects of vasopressin may be related to those observed on the electrical activity of vasopressin neurones in vivo.

  17. Nutritional Programming of Accelerated Puberty in Heifers: Involvement of Pro-Opiomelanocortin Neurones in the Arcuate Nucleus.

    PubMed

    Cardoso, R C; Alves, B R C; Sharpton, S M; Williams, G L; Amstalden, M

    2015-08-01

    The timing of puberty and subsequent fertility in female mammals are dependent on the integration of metabolic signals by the hypothalamus. Pro-opiomelanocortin (POMC) neurones in the arcuate nucleus (ARC) comprise a critical metabolic-sensing pathway controlling the reproductive neuroendocrine axis. α-Melanocyte-stimulating hormone (αMSH), a product of the POMC gene, has excitatory effects on gonadotrophin-releasing hormone (GnRH) neurones and fibres containing αMSH project to GnRH and kisspeptin neurones. Because kisspeptin is a potent stimulator of GnRH release, αMSH may also stimulate GnRH secretion indirectly via kisspeptin neurones. In the present work, we report studies conducted in young female cattle (heifers) aiming to determine whether increased nutrient intake during the juvenile period (4-8 months of age), a strategy previously shown to advance puberty, alters POMC and KISS1 mRNA expression, as well as αMSH close contacts on GnRH and kisspeptin neurones. In Experiment 1, POMC mRNA expression, detected by in situ hybridisation, was greater (P < 0.05) in the ARC in heifers that gained 1 kg/day of body weight (high-gain, HG; n = 6) compared to heifers that gained 0.5 kg/day (low-gain, LG; n = 5). The number of KISS1-expressing cells in the middle ARC was reduced (P < 0.05) in HG compared to LG heifers. In Experiment 2, double-immunofluorescence showed limited αMSH-positive close contacts on GnRH neurones, and the magnitude of these inputs was not influenced by nutritional status. Conversely, a large number of kisspeptin-immunoreactive cells in the ARC were observed in close proximity to αMSH-containing varicosities. Furthermore, HG heifers (n = 5) exhibited a greater (P < 0.05) percentage of kisspeptin neurones in direct apposition to αMSH fibres and an increased (P < 0.05) number of αMSH close contacts per kisspeptin cell compared to LG heifers (n = 6). These results indicate that the POMC-kisspeptin pathway may be important

  18. Enhancement of calcium-dependent afterpotentials in oxytocin neurons of the rat supraoptic nucleus during lactation

    PubMed Central

    Teruyama, Ryoichi; Armstrong, William E

    2005-01-01

    The firing pattern of oxytocin (OT) hormone synthesizing neurons changes dramatically immediately before each milk ejection, when a brief burst of action potentials is discharged. OT neurons possess intrinsic currents that would modulate this burst. Our previous studies showed the amplitude of the Ca2+-dependent afterhyperpolarization (AHP) following spike trains is significantly larger during lactation. In the present study we sought to determine which component of the AHP is enhanced, and whether the enhancement could be related to changes in whole-cell Ca2+ current or the Ca2+ transient in identified OT or vasopressin (VP) neurons during lactation. We confirmed, with whole-cell current-clamp recordings, our previous finding from sharp electrodes that the size of the AHP following spike trains increased in OT, but not VP neurons during lactation. We then determined that an apamin-sensitive medium-duration AHP (mAHP) and an apamin-insensitive slow AHP (sAHP) were specifically increased in OT neurons. Simultaneous Ca2+ imaging revealed that the peak change in somatic [Ca2+]i was not altered in either cell type, but the slow decay of the Ca2+ transient was faster in both cell types during lactation. In voltage clamp, the whole-cell, Ca2+ current was slightly larger during lactation in OT cells only, but current density was unchanged when corrected for somatic hypertrophy. The currents, ImAHP and IsAHP, also were increased in OT neurons only, but only the apamin-sensitive ImAHP showed an increase in current density after adjusting for somatic hypertrophy. These findings suggest a specific modulation (e.g. increased number) of the small-conductance Ca2+-dependent K+ (SK) channels, or their interaction with Ca2+, underlies the increased mAHP/ImAHP during lactation. This larger mAHP may be necessary to limit the explosive bursts during milk ejection. PMID:15878948

  19. Neurokinin-1 Receptor-Immunopositive Neurons in the Medullary Dorsal Horn Provide Collateral Axons to both the Thalamus and Parabrachial Nucleus in Rats.

    PubMed

    Li, Xu; Ge, Shun-Nan; Li, Yang; Wang, Han-Tao

    2017-01-17

    It has been suggested that the trigemino-thalamic and trigemino-parabrachial projection neurons in the medullary dorsal horn (MDH) are highly implicated in the sensory-discriminative and emotional/affective aspects of orofacial pain, respectively. In previous studies, some neurons were reported to send projections to both the thalamus and parabrachial nucleus by way of collaterals in the MDH. However, little is known about the chemoarchitecture of this group of neurons. Thus, in the present study, we determined whether the neurokinin-1 (NK-1) receptor, which is crucial for primary orofacial pain signaling, was expressed in MDH neurons co-innervating the thalamus and parabrachial nucleus. Vesicular glutamate transporter 2 (VGLUT2) mRNA, a biomarker for the subgroup of glutamatergic neurons closely related to pain sensation, was assessed in trigemino-parabrachial projection neurons in the MDH. After stereotactic injection of fluorogold (FG) and cholera toxin subunit B (CTB) into the ventral posteromedial thalamic nucleus (VPM) and parabrachial nucleus (PBN), respectively, triple labeling with fluorescence dyes for FG, CTB and NK-1 receptor (NK-1R) revealed that approximately 76 % of the total FG/CTB dually labeled neurons were detected as NK-1R-immunopositive, and more than 94 % of the triple-labeled neurons were distributed in lamina I. In addition, by FG retrograde tract-tracing combined with fluorescence in situ hybridization (FISH) for VGLUT2 mRNA, 54, 48 and 70 % of FG-labeled neurons in laminae I, II and III, respectively, of the MDH co-expressed FG and VGLUT2 mRNA. Thus, most of the MDH neurons co-innervating the thalamus and PBN were glutamatergic. Most MDH neurons providing the collateral axons to both the thalamus and parabrachial nucleus in rats were NK-1R-immunopositive and expressed VGLUT2 mRNA. NK-1R and VGLUT2 in MDH neurons may be involved in both sensory-discriminative and emotional/affective aspects of orofacial pain processing.

  20. Projections of the nucleus of the basal optic root in pigeons (Columba livia): a comparison of the morphology and distribution of neurons with different efferent projections.

    PubMed

    Wylie, Douglas R W; Pakan, Janelle M P; Elliott, Cameron A; Graham, David J; Iwaniuk, Andrew N

    2007-01-01

    The avian nucleus of the basal optic root (nBOR) is a visual structure involved in the optokinetic response. nBOR consists of several morphologically distinct cell types, and in the present study, we sought to determine if these different cell types had differential projections. Using retrograde tracers, we examined the morphology and distribution of nBOR neurons projecting to the vestibulocerebellum (VbC), inferior olive (IO), dorsal thalamus, the pretectal nucleus lentiformis mesencephali (LM), the contralateral nBOR, the oculomotor complex (OMC) and a group of structures along the midline of the mesencephalon. The retrogradely labeled neurons fell into two broad categories: large neurons, most of which were multipolar rather than fusiform and small neurons, which were either fusiform or multipolar. From injections into the IO, LM, contralateral nBOR, and structures along the midline-mesencephalon small nBOR neurons were labeled. Although there were no differences with respect to the size of the labeled neurons from these injections, there were some differences with the respect to the distribution of labeled neurons and the proportion of multipolar vs. fusiform neurons. From injections into the VbC, the large multipolar cells were labeled throughout nBOR. The only other cases in which these large neurons were labeled were contralateral OMC injections. To investigate if single neurons project to multiple targets we used paired injections of red and green fluorescent retrograde tracers into different targets. Double-labeled neurons were never observed indicating that nBOR neurons do not project to multiple targets. We conclude that individual nBOR neurons have unique projections, which may have differential roles in processing optic flow and controlling the optokinetic response.

  1. Heterogeneous responses of nucleus incertus neurons to corticotrophin-releasing factor and coherent activity with hippocampal theta rhythm in the rat

    PubMed Central

    Ma, Sherie; Blasiak, Anna; Olucha-Bordonau, Francisco E; Verberne, Anthony J M; Gundlach, Andrew L

    2013-01-01

    The nucleus incertus (NI) of the rat hindbrain is a putative node in the ascending control of the septohippocampal system and hippocampal theta rhythm and is stress and arousal responsive. NI contains GABA neurons that express multiple neuropeptides, including relaxin-3 (RLN3) and neuropeptide receptors, including corticotrophin-releasing factor receptor-1 (CRF-R1), but the precise anatomical and physiological characteristics of NI neurons are unclear. Therefore, we examined the firing properties of NI neurons and their responses to CRF, the correlation of these responses with occurrence of relaxin-3, and NI neuron morphology in the rat. Most NI neurons excited by intracerebroventricular CRF infusion were RLN3-positive (9 of 10), whereas all inhibited cells were RLN3-negative (8 of 8). The spontaneous firing of RLN3 (n= 6) but not non-RLN3 neurons (n= 6) was strongly modulated and phase-locked with the initial ascending phase of hippocampal theta oscillations. In brain slices, the majority of recorded NI neurons (15 of 19) displayed excitatory responses to CRF, which uniformly increased action potential frequency and membrane potential depolarization in the presence of tetrodotoxin, indicating a direct, postsynaptic action of CRF on NI neurons. This excitation was associated with reduction in the slow component of afterhyperpolarization and a strong depolarization. Quantitative analysis in naïve rats of validated CRF-R1, RLN3 and neuronal nuclear antigen (NeuN) immunoreactivity revealed 52% of NI neurons as CRF-R1 positive, of which 53% were RLN3 positive, while 48% of NI neurons lacked CRF-R1 and RLN3. All RLN3 neurons expressed CRF-R1. CRF neurons that projected to the NI were identified in lateral preoptic hypothalamus, but not in paraventricular hypothalamus, bed nucleus of stria terminalis or central amygdala. Our findings suggest NI is an important site for CRF modulation of hippocampal theta rhythm via effects on GABA/RLN3 transmission. PMID:23671163

  2. Release of Norepinephrine in the Preoptic Area Activates Anteroventral Periventricular Nucleus Neurons and Stimulates the Surge of Luteinizing Hormone

    PubMed Central

    Poletini, Maristela O.; Leite, Cristiane M.; Bernuci, Marcelo P.; Kalil, Bruna; Mendonça, Leonardo B.D.; Carolino, Ruither O. G.; Helena, Cleyde V. V.; Bertram, Richard; Franci, Celso R.; Anselmo-Franci, Janete A.

    2013-01-01

    The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids. PMID:23150494

  3. The Sodium Channel β4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Ji, Xincai; Saha, Sucharita; Gao, Guangping; Lasek, Amy W.; Homanics, Gregg E.; Guildford, Melissa; Tapper, Andrew R.; Martin, Gilles E.

    2017-01-01

    Voltage-gated sodium channels are essential for generating the initial rapid depolarization of neuronal membrane potential during action potentials (APs) that enable cell-to-cell communication, the propagation of signals throughout the brain, and the induction of synaptic plasticity. Although all brain neurons express one or several variants coding for the core pore-forming sodium channel α subunit, the expression of the β (β1–4) auxiliary subunits varies greatly. Of particular interest is the β4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i.e., nucleus accumbens – NAc) striata compared to other brain regions, and that endows sodium channels with unique gating properties. However, its role on neuronal activity, synaptic plasticity, and behaviors related to drugs of abuse remains poorly understood. Combining whole-cell patch-clamp recordings with two-photon calcium imaging in Scn4b knockout (KO) and knockdown mice, we found that Scn4b altered the properties of APs in core accumbens medium spiny neurons (MSNs). These alterations are associated with a reduction of the probability of MSNs to evoke spike-timing-dependent long-term depression (tLTD) and a reduced ability of backpropagating APs to evoke dendritic calcium transients. In contrast, long-term potentiation (tLTP) remained unaffected. Interestingly, we also showed that amphetamine-induced locomotor activity was significantly reduced in male Scn4b KO mice compared to wild-type controls. Taken together, these data indicate that the Scn4b subunit selectively controls tLTD by modulating dendritic calcium transients evoked by backpropagating APs. PMID:28243192

  4. NAD+ Attenuates Bilirubin-Induced Hyperexcitation in the Ventral Cochlear Nucleus by Inhibiting Excitatory Neurotransmission and Neuronal Excitability

    PubMed Central

    Liang, Min; Yin, Xin-Lu; Wang, Lu-Yang; Yin, Wei-Hai; Song, Ning-Ying; Shi, Hai-Bo; Li, Chun-Yan; Yin, Shan-Kai

    2017-01-01

    Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the ventral cochlear nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity. We found that NAD+ effectively decreased the size of evoked excitatory postsynaptic currents (eEPSCs), increased paired-pulse ratio (PPR) and reversed the effect of bilirubin on eEPSCs, implicating its inhibitory effects on the presynaptic release probability (Pr). Moreover, NAD+ not only decreased the basal frequency of miniature EPSCs (mEPSCs), but also reversed bilirubin-induced increases in the frequency of mEPSCs without affecting their amplitude under either condition. Furthermore, we found that NAD+ decreased the frequency of spontaneous firing of VCN neurons as well as bilirubin-induced increases in firing frequency. Whole-cell current-clamp recordings showed that NAD+ could directly decrease the intrinsic excitability of VCN neurons in the presence of synaptic blockers, suggesting NAD+ exerts its actions in both presynaptic and postsynaptic loci. Consistent with these observations, we found that the latency of the first postsynaptic spike triggered by high-frequency train stimulation of presynaptic afferents (i.e., the auditory nerve) was prolonged by NAD+. These results collectively indicate that NAD+ suppresses presynaptic transmitter release and postsynaptic excitability, jointly weakening excitatory neurotransmission. Our findings provide a basis for the exploration of NAD+ for the prevention and treatment of bilirubin encephalopathy and excitotoxicity associated with other neurological disorders. PMID:28217084

  5. T-type calcium channels promote predictive homeostasis of input-output relations in thalamocortical neurons of lateral geniculate nucleus

    PubMed Central

    Hong, Su Z.; Kim, Haram R.; Fiorillo, Christopher D.

    2014-01-01

    A general theory views the function of all neurons as prediction, and one component of this theory is that of “predictive homeostasis” or “prediction error.” It is well established that sensory systems adapt so that neuronal output maintains sensitivity to sensory input, in accord with information theory. Predictive homeostasis applies the same principle at the cellular level, where the challenge is to maintain membrane excitability at the optimal homeostatic level so that spike generation is maximally sensitive to small gradations in synaptic drive. Negative feedback is a hallmark of homeostatic mechanisms, as exemplified by depolarization-activated potassium channels. In contrast, T-type calcium channels exhibit positive feedback that appears at odds with the theory. In thalamocortical neurons of lateral geniculate nucleus (LGN), T-type channels are capable of causing bursts of spikes with an all-or-none character in response to excitation from a hyperpolarized potential. This “burst mode” would partially uncouple visual input from spike output and reduce the information spikes convey about gradations in visual input. However, past observations of T-type-driven bursts may have resulted from unnaturally high membrane excitability. Here we have mimicked within rat brain slices the patterns of synaptic conductance that occur naturally during vision. In support of the theory of predictive homeostasis, we found that T-type channels restored excitability toward its homeostatic level during periods of hyperpolarization. Thus, activation of T-type channels allowed two retinal input spikes to cause one output spike on average, and we observed almost no instances in which output count exceeded input count (a “burst”). T-type calcium channels therefore help to maintain a single optimal mode of transmission rather than creating a second mode. More fundamentally our results support the general theory, which seeks to predict the properties of a neuron's ion

  6. Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons.

    PubMed

    Wang, Yi-Chi; Yang, Jyh-Jeen; Huang, Rong-Chi

    2012-10-01

    Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na(+) and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K(+) to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K(+) to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K(+)-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na(+) imaging with a Na(+)-sensitive fluorescent dye indicated saturating accumulation of intracellular Na(+) in response to pump blockade with zero K(+). The Na(+) ionophore monensin also induced Na(+) loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na(+) or by pump blockade. Conversely, Na(+) depletion with Na(+)-free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na(+) levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na(+) and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons.

  7. Chronic intermittent hypoxia increases sympathetic control of blood pressure: role of neuronal activity in the hypothalamic paraventricular nucleus.

    PubMed

    Sharpe, Amanda L; Calderon, Alfredo S; Andrade, Mary Ann; Cunningham, J Thomas; Mifflin, Steven W; Toney, Glenn M

    2013-12-01

    Like humans with sleep apnea, rats exposed to chronic intermittent hypoxia (CIH) experience arterial hypoxemias and develop hypertension characterized by exaggerated sympathetic nerve activity (SNA). To gain insights into the poorly understood mechanisms that initiate sleep apnea/CIH-associated hypertension, experiments were performed in rats exposed to CIH for only 7 days. Compared with sham-treated normoxic control rats, CIH-exposed rats (n = 8 rats/group) had significantly increased hematocrit (P < 0.001) and mean arterial pressure (MAP; P < 0.05). Blockade of ganglionic transmission caused a significantly (P < 0.05) greater reduction of MAP in rats exposed to CIH than control rats (n = 8 rats/group), indicating a greater contribution of SNA in the support of MAP even at this early stage of CIH hypertension. Chemical inhibition of neuronal discharge in the hypothalamic paraventricular nucleus (PVN) (100 pmol muscimol) had no effect on renal SNA but reduced lumbar SNA (P < 0.005) and MAP (P < 0.05) more in CIH-exposed rats (n = 8) than control rats (n = 7), indicating that CIH increased the contribution of PVN neuronal activity in the support of lumbar SNA and MAP. Because CIH activates brain regions controlling body fluid homeostasis, the effects of internal carotid artery injection of hypertonic saline were tested and determined to increase lumbar SNA more (P < 0.05) in CIH-exposed rats than in control rats (n = 9 rats/group). We conclude that neurogenic mechanisms are activated early in the development of CIH hypertension such that elevated MAP relies on increased sympathetic tonus and ongoing PVN neuronal activity. The increased sensitivity of Na(+)/osmosensitive circuitry in CIH-exposed rats suggests that early neuroadaptive responses among body fluid regulatory neurons could contribute to the initiation of CIH hypertension.

  8. BK Channels Mediate Dopamine Inhibition of Firing in a Subpopulation of Core Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Ji, Xincai; Martin, Gilles E.

    2014-01-01

    Dopamine, a key neurotransmitter mediating the rewarding properties of drugs of abuse, is widely believed to exert some of its effects by modulating neuronal activity of nucleus accumbens (NAcc) medium spiny neurons (MSNs). Although its effects on synaptic transmission have been well documented, its regulation of intrinsic neuronal excitability is less understood. In this study, we examined the cellular mechanisms of acute dopamine effects on core accumbens MSNs evoked firing. We found that 0.5 μM A-77636 and 10 μM quinpirole, dopamine D1 (DR1s) and D2 receptor (D2Rs) agonists, respectively, markedly inhibited MSN evoked action potentials. This effect, observed only in about 25% of all neurons, was associated with spike-timing-dependent (STDP) long-term potentiation (tLTP), but not long-term depression (tLTD). Dopamine inhibited evoked firing by compromising subthreshold depolarization, not by altering action potentials themselves. Recordings in voltage-clamp mode revealed that all MSNs expressed fast (IA), slowly inactivating delayed rectifier (Idr), and large conductance voltage- and calcium-activated potassium (BKs) channels . Although A-77636 and quinpirole enhanced IA, its selective blockade by 0.5 μM phrixotoxin-1 had no effect on evoked firing. In contrast, exposing tissue to low TEA concentrations and to 10 μM paxilline, a selective BK channel blocker, prevented D1R agonist from inhibiting MSN firing. This result indicates that dopamine inhibits MSN firing through BK channels in a subpopulation of core accumbens MSNs exclusively associated with spike-timing-dependent long-term potentiation. PMID:25219484

  9. NMDA Receptors Containing the GluN2D Subunit Control Neuronal Function in the Subthalamic Nucleus

    PubMed Central

    Swanger, Sharon A.; Vance, Katie M.; Pare, Jean-François; Sotty, Florence; Fog, Karina; Smith, Yoland

    2015-01-01

    The GluN2D subunit of the NMDA receptor is prominently expressed in the basal ganglia and associated brainstem nuclei, including the subthalamic nucleus (STN), globus pallidus, striatum, and substantia nigra. However, little is known about how GluN2D-containing NMDA receptors contribute to synaptic activity in these regions. Using Western blotting of STN tissue punches, we demonstrated that GluN2D is expressed in the rat STN throughout development [age postnatal day 7 (P7)–P60] and in the adult (age P120). Immunoelectron microscopy of the adult rat brain showed that GluN2D is predominantly expressed in dendrites, unmyelinated axons, and axon terminals within the STN. Using subunit-selective allosteric modulators of NMDA receptors (TCN-201, ifenprodil, CIQ, and DQP-1105), we provide evidence that receptors containing the GluN2B and GluN2D subunits mediate responses to exogenously applied NMDA and glycine, as well as synaptic NMDA receptor activation in the STN of rat brain slices. EPSCs in the STN were mediated primarily by AMPA and NMDA receptors and GluN2D-containing NMDA receptors controlled the slow deactivation time course of EPSCs in the STN. In vivo recordings from the STN of anesthetized adult rats demonstrated that the spike firing rate was increased by the GluN2C/D potentiator CIQ and decreased by the GluN2C/D antagonist DQP-1105, suggesting that NMDA receptor activity can influence STN output. These data indicate that the GluN2B and GluN2D NMDA receptor subunits contribute to synaptic activity in the STN and may represent potential therapeutic targets for modulating subthalamic neuron activity in neurological disorders such as Parkinson's disease. SIGNIFICANCE STATEMENT The subthalamic nucleus (STN) is a key component of the basal ganglia, a group of subcortical nuclei that control movement and are dysregulated in movement disorders such as Parkinson's disease. Subthalamic neurons receive direct excitatory input, but the pharmacology of excitatory

  10. In situ hybridization of nucleus basalis neurons shows increased. beta. -amyloid mRNA in Alzheimer disease

    SciTech Connect

    Cohen, M.L.; Golde, T.E.; Usiak, M.F.; Younkin, L.H.; Younkin, S.G.

    1988-02-01

    To determine which cells within the brain produce ..beta..-amyloid mRNA and to assess expression of the ..beta..-amyloid gene in Alzheimer disease, the authors analyzed brain tissue from Alzheimer and control patients by in situ hybridization. The results demonstrate that ..beta..-amyloid mRNA is produced by neurons in the nucleus basalis of Meynert and cerebral cortex and that nuclues basalis perikarya from Alzheimer patients consistently hybridize more ..beta..-amyloid probe than those from controls. These observations support the hypothesis that increased expression of the ..beta..-amyloid gene plays an important role in the deposition of amyloid in the brains of patients with Alzheimer disease.

  11. Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbens

    PubMed Central

    Marty, Vincent N.; Spigelman, Igor

    2013-01-01

    Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal. PMID:22445807

  12. Neurochemical properties of the synapses between the parabrachial nucleus-derived CGRP-positive axonal terminals and the GABAergic neurons in the lateral capsular division of central nucleus of amygdala.

    PubMed

    Lu, Ya-Cheng; Chen, Yan-Zhou; Wei, Yan-Yan; He, Xiao-Tao; Li, Xia; Hu, Wei; Yanagawa, Yuchio; Wang, Wen; Wu, Sheng-Xi; Dong, Yu-Lin

    2015-02-01

    The lateral capsular division of central nucleus of amygdala (CeC) contains neurons using γ-amino butyric acid (GABA) as the predominant neurotransmitter and expresses abundant calcitonin gene-related peptide (CGRP)-positive terminals. However, the relationship between them has not been revealed yet. Using GAD67-green fluorescent protein (GFP) knock-in mouse, we investigated the neurochemical features of synapses between CGRP-positive terminals and GABAergic neurons within CeC and the potential involvement of CGRP1 receptor by combining fluorescent in situ hybridization for CGRP1 receptor mRNA with immunofluorescent histochemistry for GFP and CGRP. The ultrastructures of these synapses were investigated with pre-embedding electron microscopy for GFP and CGRP. We found that some GABAergic neurons in the CeC received parabrachial nucleus (PBN) derived CGRP innervations and some of these GABAergic neurons can be activated by subcutaneous injection of formalin. Moreover, more than 90 % GABAergic neurons innervated by CGRP-positive terminal also express CGRP1 receptor mRNA. The CGRP-positive fibers made symmetric synapses onto the GABAergic somata, and asymmetric synapses onto the GABA-LI dendritic shafts and spines. This study provides direct ultrastructural evidences for the synaptic contacts between CGRP-positive terminals and GABAergic neurons within the CeC, which may underlie the pain-related neural pathway from PBN to CeC and be involved in the chronic pain modulation.

  13. Lipopolysaccharide inhibits ghrelin-excited neurons of the arcuate nucleus and reduces food intake via central nitric oxide signaling.

    PubMed

    Borner, Tito; Pinkernell, Sarah; Lutz, Thomas A; Riediger, Thomas

    2012-08-01

    Lipopolysaccharide (LPS) induces anorexia and expression of inducible nitric oxide synthase (iNOS) in the hypothalamic arcuate nucleus (Arc). Peripheral administration of the iNOS inhibitor 1400 W counteracts the anorectic effects of LPS. Here we investigated the role of central NO signaling in LPS anorexia. In electrophysiological studies we tested whether 1400 W counteracts the iNOS-dependent inhibition of Arc neurons triggered by in vivo or in vitro stimulation with LPS. We used the hormone ghrelin as a functional reference stimulus because ghrelin is known to activate orexigenic Arc neurons. Further, we investigated whether in vitro LPS stimulation induces an iNOS-mediated formation of the second messenger cGMP. Since the STAT1 pathway contributes to the regulation of iNOS expression we investigated whether LPS treatment induces STAT1 phosphorylation in the Arc. Finally we tested the effect of intracerebroventricular injection of 1400 W on LPS-induced anorexia. Superfusion with 1400 W (10(-4) M) increased neuronal activity in 37% of neurons in Arc slices from LPS treated (100 μg/kg ip) but not from saline treated rats. Similarly, 1400 W excited 45% of Arc neurons after in vitro stimulation with LPS (100 ng/ml). In both approaches, a considerable percentage of 1400 W sensitive neurons were excited by ghrelin (10(-8)M; 50% and 75%, respectively). In vitro stimulation with LPS induced cGMP formation in the Arc, which was blocked by co-incubation with 1400 W. LPS treatment elicited a pSTAT1 response in the Arc of mice. Central 1400 W injection (4 μg/rat) attenuated LPS-induced anorexia and counteracted the LPS-dependent decrease in respiratory quotient and energy expenditure. In conclusion, the current findings substantiate a role of central iNOS dependent NO formation in LPS-induced effects on eating and energy homeostasis. A pharmacological blockade of NO formation might be a therapeutic approach to ameliorate disease-related anorexia.

  14. An ionic current model for neurons in the rat medial nucleus tractus solitarii receiving sensory afferent input.

    PubMed Central

    Schild, J H; Khushalani, S; Clark, J W; Andresen, M C; Kunze, D L; Yang, M

    1993-01-01

    1. Neurons from a horizontal slice of adult rat brainstem were examined using intracellular recording techniques. Investigations were restricted to a region within the nucleus tractus solitarii, medial to the solitary tract and centred on the obex (mNTS). Previous work has shown this restricted area of the NTS to contain the greatest concentration of aortic afferent baroreceptor terminal fields. Electrical stimulation of the tract elicited short-latency excitatory postsynaptic potentials in all neurons. 2. mNTS neurons were spontaneously active with firing frequencies ranging between 1 and 10 Hz, at resting potentials of -65 to -45 mV. These neurons did not exhibit spontaneous bursting activity. 3. Depolarizing current injection immediately evoked a finite, high-frequency spike discharge which rapidly declined to a lower steady-state level (i.e. spike frequency adaptation, SFA). Increasing depolarizations produced a marked increase in the peak instantaneous frequency but a much smaller increase in the steady-state firing level. 4. Conditioning with a hyperpolarizing prepulse resulted in a prolonged delay of up to 600 ms before the first action potential (i.e. delayed excitation, DE) with an attendant decrease in peak discharge rates. DE was modulated by both the magnitude and duration of the prestimulus hyperpolarization, as well as the magnitude of the depolarizing stimulus. Tetrodotoxin (TTX) eliminated spike discharge but had little effect on the ramp-like membrane depolarization characteristic of DE. 5. We have developed a mathematical model for mNTS neurons to facilitate our understanding of the interplay between the underlying ionic currents. It consists of a comprehensive membrane model of the Hodgkin-Huxley type coupled with a fluid compartment model describing cytoplasmic [Ca2+]i homeostasis. 6. The model suggests that (a) SFA is caused by an increase in [Ca2+]i which activates the outward K+ current, IK,Ca, and (b) DE results from the competitive

  15. Topographic relationship between anteromedial thalamic nucleus neurons and their cortical terminal fields in the rat.

    PubMed

    Shibata, H; Kato, A

    1993-06-01

    The present study has examined the topographic relationship between cells in the anteromedial thalamic nucleus (AM) and their cortical terminal fields, with retrograde transport of Fluoro Gold in the rat. Projections to the frontal area 2 originate from the ventrolateral part of the AM and the entire interanteromedial nucleus (IAM). Projections to the anterior cingulate area originate from the peripheral part of the rostral AM and the entire IAM. Fibers to the rostral retrosplenial area arise from the caudodorsal part of the AM, whereas those to the caudal retrosplenial area arise from the rostralmost and the rostrodorsomedial parts. Fibers to the rostral area 29D originate from the rostrocentral part of the AM, whereas those to the caudal area 29D originate from the rostroventrolateral and the ventromedial parts. Projections to the medial half of the entorhinal area originate from the rostrodorsomedial part of the AM. In contrast, projections to the lateral half of the entorhinal area originate from the IAM and the central part of the AM. The results show a complex topographic relationship between cells of origin of the AM and their cortical terminal fields, suggesting complex functional roles played by the AM in learning behavior such as discriminative avoidance behavior.

  16. Inhibition of monocarboxylate transporter 2 in the retrotrapezoid nucleus in rats: a test of the astrocyte-neuron lactate-shuttle hypothesis.

    PubMed

    Erlichman, Joseph S; Hewitt, Amy; Damon, Tracey L; Hart, Michael; Kurascz, Jennifer; Li, Aihua; Leiter, James C

    2008-05-07

    The astrocyte-neuronal lactate-shuttle hypothesis posits that lactate released from astrocytes into the extracellular space is metabolized by neurons. The lactate released should alter extracellular pH (pHe), and changes in pH in central chemosensory regions of the brainstem stimulate ventilation. Therefore, we assessed the impact of disrupting the lactate shuttle by administering 100 microM alpha-cyano-4-hydroxy-cinnamate (4-CIN), a dose that blocks the neuronal monocarboxylate transporter (MCT) 2 but not the astrocytic MCTs (MCT1 and MCT4). Administration of 4-CIN focally in the retrotrapezoid nucleus (RTN), a medullary central chemosensory nucleus, increased ventilation and decreased pHe in intact animals. In medullary brain slices, 4-CIN reduced astrocytic intracellular pH (pHi) slightly but alkalinized neuronal pHi. Nonetheless, pHi fell significantly in both cell types when they were treated with exogenous lactate, although 100 microM 4-CIN significantly reduced the magnitude of the acidosis in neurons but not astrocytes. Finally, 4-CIN treatment increased the uptake of a fluorescent 2-deoxy-D-glucose analog in neurons but did not alter the uptake rate of this 2-deoxy-D-glucose analog in astrocytes. These data confirm the existence of an astrocyte to neuron lactate shuttle in intact animals in the RTN, and lactate derived from astrocytes forms part of the central chemosensory stimulus for ventilation in this nucleus. When the lactate shuttle was disrupted by treatment with 4-CIN, neurons increased the uptake of glucose. Therefore, neurons seem to metabolize a combination of glucose and lactate (and other substances such as pyruvate) depending, in part, on the availability of each of these particular substrates.

  17. Effects of ventro-medial mesencephalic tegmentum (VMT) stimulation on the spontaneous activity of nucleus accumbens neurones: influence of the dopamine system.

    PubMed

    Le Douarin, C; Penit, J; Glowinski, J; Thierry, A M

    1986-01-22

    The effects of VMT-stimulation (100-500 microA, 0.6 ms; 1 Hz) on the spontaneous activity of neurones in the nucleus accumbens were analyzed in ketamine-anaesthetized rats. On spontaneously active cells (firing greater than 0.5 spikes/s), 3 types of responses were observed: either inhibition (36%), excitation (5%) or a composite sequence of excitation followed by inhibition (12%). Moreover, 14% of silent nucleus accumbens neurones were excited by single pulse VMT-stimulation. Finally, 3% of nucleus accumbens neurones recorded were driven antidromically by VMT-stimulation. Destruction of dopamine (DA) projections by 6-hydroxydopamine prevented the inhibitory responses to VMT stimulation in the great majority of cells studied, without affecting the excitatory responses. After systemic administration of haloperidol or sulpiride, the inhibitory responses to VMT stimulation were attenuated markedly, whilst the excitatory responses were, however, maintained. These results suggest that the inhibitory, but not the excitatory, effects of VMT-stimulation on nucleus accumbens neurones may be mediated by an activation of the mesolimbic DA system.

  18. A Kv3-like persistent, outwardly rectifying, Cs+-permeable, K+ current in rat subthalamic nucleus neurones

    PubMed Central

    Wigmore, Mark A; Lacey, Michael G

    2000-01-01

    A persistent outward K+ current (IPO), activated by depolarization from resting potential, has been identified and characterized in rat subthalamic nucleus (SThN) neurones using whole-cell voltage-clamp recording in brain slices.IPO both rapidly activated (τ= 8 ms at +5 mV) and deactivated (τ= 2 ms at −68 mV), while showing little inactivation. Tail current reversal potentials varied with extracellular K+ concentration in a Nernstian manner.Intracellular Cs+ did not alter either IPO amplitude or the voltage dependence of activation, but blocked transient (A-like) outward currents activated by depolarization. When extracellular K+ was replaced with Cs+, IPO tail current reversal potentials were dependent upon the extracellular Cs+ concentration, indicating an ability to conduct Cs+, as well as K+.IPO was blocked by Ba2+ (1 mm), 4-aminopyridine (1 mm) and tetraethylammonium (TEA; 20 mm), with an IC50 for TEA of 0.39 mm.The IPO conductance appeared maximal (38 nS) at around +27 mV, half-maximal at −13 mV, with the threshold for activation at around −38 mV.TEA (1 mm) blocked the action potential after-hyperpolarization and permitted accommodation of action potential firing at frequencies greater than around 200 Hz.We conclude that IPO, which shares many characteristics of currents attributable to Kv3.1 K+ channels, enables high-frequency spike trains in SThN neurones. PMID:10990536

  19. Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder

    PubMed Central

    D'Onofrio, Stasia; Kezunovic, Nebojsa; Hyde, James R.; Luster, Brennon; Messias, Erick; Urbano, Francisco J.

    2014-01-01

    Reduced levels of gamma-band activity are present in schizophrenia and bipolar disorder patients. In the same disorders, increased neuronal calcium sensor protein-1 (NCS-1) expression was reported in a series of postmortem studies. These disorders are also characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). The discovery of gamma-band activity in the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, revealed that such activity was mediated by high-threshold calcium channels that are regulated by NCS-1. We hypothesized that NCS-1 normally regulates gamma-band oscillations through these calcium channels and that excessive levels of NCS-1, such as would be expected with overexpression, decrease gamma-band activity. We found that PPN neurons in rat brain slices manifested gamma-band oscillations that were increased by low levels of NCS-1 but suppressed by high levels of NCS-1. Our results suggest that NCS-1 overexpression may be responsible for the decrease in gamma-band activity present in at least some schizophrenia and bipolar disorder patients. PMID:25376789

  20. Cellular prion protein localizes to the nucleus of endocrine and neuronal cells and interacts with structural chromatin components.

    PubMed

    Strom, Alexander; Wang, Gen-Sheng; Picketts, David J; Reimer, Rudolph; Stuke, Andreas W; Scott, Fraser W

    2011-05-01

    Several physiological processes have been purported for cellular prion protein (PrP(C)). However, the physiological function of PrP(C) is still unclear and the cellular localization of PrP(C) remains a subject of debate. PrP(C) is expressed in a wide range of tissues including islets of Langerhans. We previously demonstrated that the function of PrP(C) is associated with blood glucose regulation. Little is known of the function of PrP(C) in islet cells and specifically in β-cells. To get first insight into the putative role of PrP(C) in β-cells, we used far-Western immunoblotting and MS to identify candidate PrP(C)-interacting proteins. We also used Western blot, immunofluorescence (IF) and protein overlay IF to characterize the sub-cellular localization of PrP(C). Here we demonstrate in vivo that PrP(C) is abundant in the nuclear lamina of endocrine and neuronal cells and interacts with histone H1(0), histone H3 and lamin B1. The interaction of PrP(C) with histone H3 suggests that it is involved in transcriptional regulation in the nucleus. This study reveals new avenues for the elucidation of the physiological function of PrP(C) in endocrine and neuronal cells as well as the molecular mechanisms leading to prion diseases.

  1. Cocaine and Amphetamine Induce Overlapping but Distinct Patterns of AMPAR Plasticity in Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Jedynak, Jakub; Hearing, Matthew; Ingebretson, Anna; Ebner, Stephanie R; Kelly, Matthew; Fischer, Rachel A; Kourrich, Saïd; Thomas, Mark J

    2016-01-01

    Repeated exposure to psychostimulant drugs such as cocaine or amphetamine can promote drug-seeking and -taking behavior. In rodent addiction models, persistent changes in excitatory glutamatergic neurotransmission in the nucleus accumbens (NAc) appear to drive this drug-induced behavioral plasticity. To study whether changes in glutamatergic signaling are shared between or exclusive to specific psychostimulant drugs, we examined synaptic transmission from mice following repeated amphetamine or cocaine administration. Synaptic transmission mediated by AMPA-type glutamate receptors was potentiated in the NAc shell 10–14 days following repeated amphetamine or cocaine treatment. This synaptic enhancement was depotentiated by re-exposure to amphetamine or cocaine. By contrast, in the NAc core only repeated cocaine exposure enhanced synaptic transmission, which was subsequently depotentiated by an additional cocaine but not amphetamine injection during drug abstinence. To better understand the drug-induced depotentiation, we replicated these in vivo findings using an ex vivo model termed ‘challenge in the bath,' and showed that drug-induced decreases in synaptic strength occur rapidly (within 30 min) and require activation of metabotropic glutamate receptor 5 (mGluR5) and protein synthesis in the NAc shell, but not NAc core. Overall, these data demonstrate the specificity of neuronal circuit changes induced by amphetamine, introduce a novel method for studying drug challenge-induced plasticity, and define NAc shell medium spiny neurons as a primary site of persistent AMPA-type glutamate receptor plasticity by two widely used psychostimulant drugs. PMID:26068728

  2. Cocaine and Amphetamine Induce Overlapping but Distinct Patterns of AMPAR Plasticity in Nucleus Accumbens Medium Spiny Neurons.

    PubMed

    Jedynak, Jakub; Hearing, Matthew; Ingebretson, Anna; Ebner, Stephanie R; Kelly, Matthew; Fischer, Rachel A; Kourrich, Saïd; Thomas, Mark J

    2016-01-01

    Repeated exposure to psychostimulant drugs such as cocaine or amphetamine can promote drug-seeking and -taking behavior. In rodent addiction models, persistent changes in excitatory glutamatergic neurotransmission in the nucleus accumbens (NAc) appear to drive this drug-induced behavioral plasticity. To study whether changes in glutamatergic signaling are shared between or exclusive to specific psychostimulant drugs, we examined synaptic transmission from mice following repeated amphetamine or cocaine administration. Synaptic transmission mediated by AMPA-type glutamate receptors was potentiated in the NAc shell 10-14 days following repeated amphetamine or cocaine treatment. This synaptic enhancement was depotentiated by re-exposure to amphetamine or cocaine. By contrast, in the NAc core only repeated cocaine exposure enhanced synaptic transmission, which was subsequently depotentiated by an additional cocaine but not amphetamine injection during drug abstinence. To better understand the drug-induced depotentiation, we replicated these in vivo findings using an ex vivo model termed 'challenge in the bath,' and showed that drug-induced decreases in synaptic strength occur rapidly (within 30 min) and require activation of metabotropic glutamate receptor 5 (mGluR5) and protein synthesis in the NAc shell, but not NAc core. Overall, these data demonstrate the specificity of neuronal circuit changes induced by amphetamine, introduce a novel method for studying drug challenge-induced plasticity, and define NAc shell medium spiny neurons as a primary site of persistent AMPA-type glutamate receptor plasticity by two widely used psychostimulant drugs.

  3. SELECTIVE REDUCTION OF NEURON NUMBER AND VOLUME OF THE MEDIODORSAL NUCLEUS OF THE THALAMUS IN MACAQUES FOLLOWING IRRADIATION AT EARLY GESTATIONAL AGES

    PubMed Central

    Selemon, Lynn D.; Begović, Anita; Rakic, Pasko

    2009-01-01

    Neurons in the macaque brain arise from progenitors located near the cerebral ventricles in a temporally segregated manner such that lethal doses of ionizing irradiation, if administered over a discrete time interval, can deplete individual nuclei selectively. A previous study showed that neuron number in the dorsal lateral geniculate nucleus is reduced following early gestational exposure to x- irradiation (Algan and Rakic, 1997). Here we examine whether similarly timed irradiation decreases neuron number in three associational thalamic nuclei: mediodorsal (MD), anterior, and pulvinar. Ten macaques were exposed to multiple doses of x-rays (total exposure: 175–350cGy) in early (E33-E42) or midgestation (E70-E90); 8 non-irradiated macaques were controls. Only the early irradiated monkeys, not the midgestationally irradiated animals, exhibited deficits in whole thalamic neuron (−15%) and glia numbers (−21%) compared to controls. Reduction of neuron number (−26%) and volume (−29%) was particularly pronounced in MD. In contrast, cell number and volume were not significantly decreased in the anterior or pulvinar nuclei following early gestational irradiation. Thus, reduced thalamic neuron number was associated specifically with irradiation in early gestation. Persistence of the thalamic neuronal deficit in adult animals indicates that prenatally deleted neurons had not been replenished during maturation or in adulthood. The selective reduction of MD neuron number also supports the protomap hypothesis that neurons of each thalamic nucleus originate sequentially from separate lines of neuronal stem cells (Rakic, 1977a). The early gestationally irradiated macaque is discussed as a potentially useful model for studying the neurodevelopmental pathogenesis of schizophrenia. PMID:19459221

  4. Automatic subthalamic nucleus detection from microelectrode recordings based on noise level and neuronal activity

    NASA Astrophysics Data System (ADS)

    Cagnan, Hayriye; Dolan, Kevin; He, Xuan; Fiorella Contarino, Maria; Schuurman, Richard; van den Munckhof, Pepijn; Wadman, Wytse J.; Bour, Lo; Martens, Hubert C. F.

    2011-08-01

    Microelectrode recording (MER) along surgical trajectories is commonly applied for refinement of the target location during deep brain stimulation (DBS) surgery. In this study, we utilize automatically detected MER features in order to locate the subthalamic nucleus (STN) employing an unsupervised algorithm. The automated algorithm makes use of background noise level, compound firing rate and power spectral density along the trajectory and applies a threshold-based method to detect the dorsal and the ventral borders of the STN. Depending on the combination of measures used for detection of the borders, the algorithm allocates confidence levels for the annotation made (i.e. high, medium and low). The algorithm has been applied to 258 trajectories obtained from 84 STN DBS implantations. MERs used in this study have not been pre-selected or pre-processed and include all the viable measurements made. Out of 258 trajectories, 239 trajectories were annotated by the surgical team as containing the STN versus 238 trajectories by the automated algorithm. The agreement level between the automatic annotations and the surgical annotations is 88%. Taking the surgical annotations as the golden standard, across all trajectories, the algorithm made true positive annotations in 231 trajectories, true negative annotations in 12 trajectories, false positive annotations in 7 trajectories and false negative annotations in 8 trajectories. We conclude that our algorithm is accurate and reliable in automatically identifying the STN and locating the dorsal and ventral borders of the nucleus, and in a near future could be implemented for on-line intra-operative use.

  5. Taurine activates strychnine-sensitive glycine receptors in neurons freshly isolated from nucleus accumbens of young rats.

    PubMed

    Jiang, Zhenglin; Krnjević, Kresimir; Wang, Fushun; Ye, Jiang Hong

    2004-01-01

    Although functional glycine receptors (GlyRs) are present in the mature nucleus accumbens (NAcc), an important area of the mesolimbic dopamine system involved in drug addiction, their role has been unclear because the NAcc contains little glycine. However, taurine, an agonist of GlyRs, is abundant throughout the brain, especially during early development. In the present study on freshly dissociated NAcc neurons from young Sprague-Dawley rats (12- to 21-day old), we found that both glycine and taurine can strongly depolarize NAcc neurons and modulate their excitability. In voltage-clamped NAcc neurons, glycine and taurine elicited chloride currents (IGly and ITau) with an EC50 of 0.12 and 1.25 mM, respectively. The reversal potential of IGly or ITau was 0 mV in conventional whole cell mode and -30 mV in gramicidin-perforated mode. At concentrations <1 mM, both glycine and taurine were very effectively antagonized by strychnine and by picrotoxin (with an IC50 of 60 nM and 36.5 microM for IGly, and 40 nM and 42.2 microM for ITau) but were insensitive to 10 microM bicuculline. The currents elicited by taurine (< or =1 mM) showed complete cross-desensitization with IGly, but none with gamma-aminobutyric acid (GABA)-induced currents (IGABA). However, ITau elicited by very concentrated taurine (10 mM) showed partial cross-desensitization with IGABA, and it was substantially antagonized by 10 microM bicuculline. These results indicate that taurine binds mainly to GlyRs in NAcc, but it could be a partial agonist of GABAA receptors. By activating GlyRs, taurine may play an important physiological role in the control of NAcc function, especially during development.

  6. D1 and D2 specific dopamine antagonist modulate the caudate nucleus neuronal responses to chronic methylphenidate exposure.

    PubMed

    Venkataraman, Sidish; Claussen, Catherine; Dafny, Nachum

    2017-02-01

    The psychostimulant, methylphenidate (MPD), is the first line treatment as a pharmacotherapy to treat behavioral disorders such as attention deficit hyperactivity disorder (ADHD). MPD is commonly misused in non-ADHD (normal) youth and young adults both as a recreational drug and for cognitive enhancing effects to improve their grades. MPD is known to act on the reward circuit; including the caudate nucleus (CN). The CN is comprised of medium spiny neurons containing largely dopamine (DA) D1 and D2 receptors. It has been widely shown that the DA system plays an important role in the response to MPD exposure. We investigated the role of both D1 and D2 DA receptors in the CN response to chronic MPD administration using specific D1 and D2 DA antagonist. Four groups of young adult, male SD rats were used: a saline (control) and three MPD dose groups (0.6, 2.5, and 10.0 mg/kg). The experiment lasted 11 consecutive days. Each MPD dose group was randomly divided into two subgroups to receive either a 0.4 mg/kg SCH-23390 selective D1 DA antagonist or a 0.3 mg/kg raclopride selective D2 DA antagonist prior to their final (repetitive) MPD rechallenge administration. It was observed that selective D1 DA antagonist (SCH-23390) given 30 min prior to the last MPD exposure at ED11 partially reduced or prevented the effect induced by MPD exposure in CN neuronal firing rates across all MPD doses. Selective D2 DA antagonist (raclopride) resulted in less obvious trends; some CN neuronal firing rates exhibited a slight increase in all MPD doses.

  7. Presynaptic α4β2 nicotinic acetylcholine receptors increase glutamate release and serotonin neuron excitability in the dorsal raphe nucleus.

    PubMed

    Garduño, Julieta; Galindo-Charles, Luis; Jiménez-Rodríguez, Javier; Galarraga, Elvira; Tapia, Dagoberto; Mihailescu, Stefan; Hernandez-Lopez, Salvador

    2012-10-24

    Several behavioral effects of nicotine are mediated by changes in serotonin (5-HT) release in brain areas that receive serotonergic afferents from the dorsal raphe nucleus (DRN). In vitro experiments have demonstrated that nicotine increases the firing activity in the majority of DRN 5-HT neurons and that DRN contains nicotinic acetylcholine receptors (nAChRs) located at both somata and presynaptic elements. One of the most common presynaptic effects of nicotine is to increase glutamate release. Although DRN receives profuse glutamatergic afferents, the effect of nicotine on glutamate release in the DRN has not been studied in detail. Using whole-cell recording techniques, we investigated the effects of nicotine on the glutamatergic input to 5-HT DRN neurons in rat midbrain slices. Low nicotine concentrations, in the presence of bicuculline and tetrodotoxin (TTX), increased the frequency but did not change the amplitude of glutamate-induced EPSCs, recorded from identified 5-HT neurons. Nicotine-induced increase of glutamatergic EPSC frequency persisted 10-20 min after drug withdrawal. This nicotinic effect was mimicked by exogenous administration of acetylcholine (ACh) or inhibition of ACh metabolism. In addition, the nicotine-induced increase in EPSC frequency was abolished by blockade of α4β2 nAChRs, voltage-gated calcium channels, or intracellular calcium signaling but not by α7 nAChR antagonists. These data suggest that both nicotine and endogenous ACh can increase glutamate release through activation of presynaptic α4β2 but not α7 nAChRs in the DRN. The effect involves long-term changes in synaptic function, and it is dependent on voltage-gated calcium channels and presynaptic calcium stores.

  8. [Some Features of Sound Signal Envelope by the Frog's Cochlear Nucleus Neurons].

    PubMed

    Bibikov, N G

    2015-01-01

    The responses of single neurons in the medullar auditory center of the grass frog were recorded extracellularly under the action of long tonal signals of the characteristic frequency modulated by repeating fragments of low-frequency (0-15 Hz, 0-50 Hz or 0-150 Hz) noise. Correlation method was used for evaluating the efficacy of different envelope fragments to ensure generation of a neuron pulse discharge. Carrying out these evaluations at different time intervals between a signal and a response the maximum delays were assessed. Two important envelope fragments were revealed. In majority of units the most effective was the time interval of the amplitude rise from mean value to maximum, and the fragment where the amplitude fall from maximum to mean value was the second by the efficacy. This type of response was observed in the vast majority of cells in the range of the envelope frequency bands 0-150 and 0-50 Hz. These cells performed half-wave rectification of such type of the envelope. However, in some neurons we observed more strong preference toward a time interval with growing amplitude, including even those where the amplitude value was smaller than the mean one. These properties were observed mainly for low-frequency (0-15 Hz) modulated signals at high modulation depth. The data show that even in medulla oblongata specialization of neural elements of the auditory pathway occurs with respect to time interval features of sound stimulus. This diversity is most evident for signals with a relatively slowly varying amplitude.

  9. GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nucleus neurones [correction of nuclei] of a hypothalamic slice preparation in vitro.

    PubMed

    Hewson, A K; Viltart, O; McKenzie, D N; Dyball, R E; Dickson, S L

    1999-12-01

    unresponsive and the remaining three cells (15.8%) were significantly inhibited. Of 19 cells recorded in the periventricular nucleus, 13 (68.4%) were unresponsive to GHRP-6 and six (31.6%) were significantly inhibited. Thus, electrophysiological studies in vitro suggest that: (1) neurones in the hypothalamic arcuate nucleus, ventromedial nucleus and periventricular nucleus show changes in electrical activity in response to GHRP-6; and (2) the arcuate nucleus cells excited by GHRP-6 are also subject to inhibitory control by somatostatin.

  10. Projections of the nucleus lentiformis mesencephali in pigeons (Columba livia): a comparison of the morphology and distribution of neurons with different efferent projections.

    PubMed

    Pakan, Janelle M P; Krueger, Kimberly; Kelcher, Erin; Cooper, Sarah; Todd, Kathryn G; Wylie, Douglas R W

    2006-03-01

    The avian nucleus lentiformis mesencephali (LM) is a visual structure involved in the optokinetic response. The LM consists of several morphologically distinct cell types. In the present study we sought to determine if different cell types had differential projections. Using retrograde tracers, we examined the morphology and distribution of LM neurons projecting to the vestibulocerebellum (VbC), inferior olive (IO), dorsal thalamus, nucleus of the basal optic root (nBOR), and midline mesencephalon. From injections into the latter two structures, small LM cells were labeled. More were localized to the lateral LM as opposed to medial LM. From injections into the dorsal thalamus, small neurons were found throughout LM. From injections into the VbC, large multipolar cells were found throughout LM. From injections into IO, a strip of medium-sized fusiform neurons along the border of the medial and lateral subnuclei was labeled. To investigate if neurons project to multiple targets we used fluorescent retrograde tracers. After injections into IO and VbC, double-labeled neurons were not observed in LM. Likewise, after injections into nBOR and IO, double-labeled neurons were not observed. Finally, we processed sections through LM for glutamic acid decarboxylase (GAD). Small neurons, mostly in the lateral LM, were labeled, suggesting that projections from LM to nBOR and midline mesencephalon are GABAergic. We conclude that two efferents of LM, VbC and IO, receive input from morphologically distinct neurons: large multipolar and medium-sized fusiform neurons, respectively. The dorsal thalamus, nBOR, and midline mesencephalon receive input from small neurons, some of which are likely GABAergic.

  11. Chronic intermittent hypoxia affects integration of sensory input by neurons in the nucleus tractus solitarii.

    PubMed

    Kline, David D

    2010-11-30

    The autonomic nervous and respiratory systems, as well as their coupling, adapt over a wide range of conditions. Chronic intermittent hypoxia (CIH) is a model for recurrent apneas and induces alterations in breathing and increases in sympathetic nerve activity which may ultimately result in hypertension if left untreated. These alterations are believed to be due to increases in the carotid body chemoreflex pathway. Here we present evidence that the nucleus tractus solitarii (nTS), the central brainstem termination site of chemoreceptor afferents, expresses a form of synaptic plasticity that increases overall nTS activity following intermittent hypoxia. Following CIH, an increase in presynaptic spontaneous neurotransmitter release occurs under baseline conditions. Furthermore, during and following afferent stimulation there is an augmentation of spontaneous transmitter release that occurs out of synchrony with sensory stimulation. On the other hand, afferent evoked synchronous transmitter release is attenuated. Overall, this shift from synchronous to asynchronous transmitter release enhances nTS cellular discharge. The role of the neurotransmitter dopamine in CIH-induced plasticity is also discussed. Dopamine attenuates synaptic transmission in nTS cells by blockade of N-type calcium channels, and this mechanism occurs tonically following normoxia and CIH. This dopaminergic pathway, however, is not altered in CIH. Taken together, alterations in nTS synaptic activity may play a role in the changes of chemoreflex function and cardiorespiratory activity in the CIH apnea model.

  12. Glial regulation of extrasynaptic NMDA receptor-mediated excitation of supraoptic nucleus neurones during dehydration.

    PubMed

    Joe, N; Scott, V; Brown, C H

    2014-01-01

    Magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) project to the posterior pituitary gland where they release the hormones, vasopressin and oxytocin into the circulation to maintain plasma osmolality. Hormone release is proportionate to SON MNC action potential (spike) firing rate. When activated by ambient extracellular glutamate, extrasynaptic NMDA receptors (eNMDARs) mediate a tonic (persistent) depolarisation to increase the probability of action potential firing. In the present study, in vivo single-unit electrophysiological recordings were made from urethane-anaesthetised female Sprague-Dawley rats to investigate the impact of tonic eNMDAR activation on MNC activity. Water deprivation (for up to 48 h) caused an increase in the firing rate of SON MNCs that was associated with a general increase in post-spike excitability. To determine whether eNMDAR activation contributes to the increased MNC excitability during water deprivation, memantine, which preferentially blocks eNMDARs, was administered locally into the SON by microdialysis. Memantine significantly decreased the firing rate of MNCs recorded from 48-h water-deprived rats but had no effect on MNCs recorded from euhydrated rats. In the presence of the glial glutamate transporter-1 (GLT-1) blocker, dihydrokainate, memantine also reduced the MNC firing rate in euhydrated rats. Taken together, these observations suggest that GLT-1 clears extracellular glutamate to prevent the activation of eNDMARs under basal conditions and that, during dehydration, eNMDAR activation contributes to the increased firing rate of MNCs.

  13. Netrin-1 rescues neuron loss by attenuating secondary apoptosis in ipsilateral thalamic nucleus following focal cerebral infarction in hypertensive rats.

    PubMed

    Liao, S-J; Gong, Q; Chen, X-R; Ye, L-X; Ding, Q; Zeng, J-S; Yu, J

    2013-02-12

    Neurological deficit following cerebral infarction correlates with not only primary injury, but also secondary neuronal apoptosis in remote loci connected to the infarction. Netrin-1 is crucial for axonal guidance by interacting with its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H (UNC5H). DCC and UNC5H are also dependence receptors inducing cell apoptosis when unbound by netrin-1. The present study is to investigate the role of netrin-1 and its receptors in ipsilateral ventroposterior thalamic nucleus (VPN) injury secondary to stroke in hypertensive rats. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO). Continuous intracerebroventricular infusion of netrin-1 (600 ng/d for 7 days) or vehicle (IgG/Fc) was given 24h after MCAO. Neurological function was evaluated by postural reflex 8 and 14 days after MCAO. Then, immunoreactivity was determined in the ipsilateral VPN for NeuN, glial fibrillary acidic protein, netrin-1 and its receptors (DCC and UNC5H2), apoptosis was detected with Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay, and the expressions of caspase-3, netrin-1, DCC, and UNC5H2 were quantified by western blot analysis. MCAO resulted in the impaired postural reflex after 8 and 14 days, with decreased NeuN marked neurons and increased TUNEL-positive cells, as well as an up-regulation in the levels of cleaved caspase-3 and UNC5H2 protein in the ipsilateral VPN, without significant change in DCC or netrin-1 expression. By exogenous netrin-1 infusion, the number of neurons was increased in the ipsilateral VPN, and both TUNEL-positive cell number and caspase-3 protein level were reduced, while UNC5H2 expression remained unaffected, simultaneously, the impairment of postural reflex was improved. Taken together, the present study indicates that exogenous netrin-1 could rescue neuron loss by attenuating secondary apoptosis in the

  14. Application of nucleus pulposus to L5 dorsal root ganglion in rats enhances nociceptive dorsal horn neuronal windup.

    PubMed

    Cuellar, J M; Montesano, P X; Antognini, J F; Carstens, E

    2005-07-01

    Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain possibly through a neuroinflammatory response. NP sensitizes dorsal horn neuronal responses, but it is unknown whether this reflects a central or peripheral sensitization. To study central sensitization, we tested if NP enhances windup--the progressive increase in the response of a nociceptive spinal neuron to repeated electrical C-fiber stimulation--a phenomenon that may partly account for temporal summation of pain. Single-unit recordings were made from wide dynamic range (WDR; n = 36) or nociceptive-specific (NS; n = 8) L5 dorsal horn neurons in 44 isoflurane-anesthetized rats. Subcutaneous electrodes delivered electrical stimuli (20 pulses, 3 times the C-fiber threshold, 0.5 ms) to the receptive field on the hindpaw. Autologous NP was harvested from a tail disc and placed onto the L5 dorsal root ganglion after recording of baseline responses (n = 22). Controls had saline applied similarly (n = 22). Electrical stimulus trains (0.1, 0.3, and 1 Hz; 5-min interstimulus interval) were repeated every 30 min for 3-6 h after each treatment. The total number of evoked spikes (summed across all 20 stimuli) to 0.1 Hz was enhanced 3 h after NP, mainly in the after-discharge (AD) period (latency > 400 ms). Total responses to 0.3 and 1.0 Hz were also enhanced at > or = 60 min after NP in both the C-fiber (100- to 400-ms latency) and AD periods, whereas the absolute windup (C-fiber + AD - 20 times the initial response) increased at > or = 90 min after treatment. In saline controls, windup was not enhanced at any time after treatment for any stimulus frequency, although there was a trend toward enhancement at 0.3 Hz. These results are consistent with NP-induced central sensitization. Mechanical responses were not significantly enhanced after saline or NP treatment. We speculate that inflammatory agents released from (or recruited by) NP affect the dorsal root

  15. Regulation of Kv channel expression and neuronal excitability in rat medial nucleus of the trapezoid body maintained in organotypic culture

    PubMed Central

    Tong, Huaxia; Steinert, Joern R; Robinson, Susan W; Chernova, Tatyana; Read, David J; Oliver, Douglas L; Forsythe, Ian D

    2010-01-01

    Principal neurons of the medial nucleus of the trapezoid body (MNTB) express a spectrum of voltage-dependent K+ conductances mediated by Kv1–Kv4 channels, which shape action potential (AP) firing and regulate intrinsic excitability. Postsynaptic factors influencing expression of Kv channels were explored using organotypic cultures of brainstem prepared from P9–P12 rats and maintained in either low (5 mm, low-K) or high (25 mm, high-K) [K+]o medium. Whole cell patch-clamp recordings were made after 7–28 days in vitro. MNTB neurons cultured in high-K medium maintained a single AP firing phenotype, while low-K cultures had smaller K+ currents, enhanced excitability and fired multiple APs. The calyx of Held inputs degenerated within 3 days in culture, having lost their major afferent input; this preparation of calyx-free MNTB neurons allowed the effects of postsynaptic depolarisation to be studied with minimal synaptic activity. The depolarization caused by the high-K aCSF only transiently increased spontaneous AP firing (<2 min) and did not measurably increase synaptic activity. Chronic depolarization in high-K cultures raised basal levels of [Ca2+]i, increased Kv3 currents and shortened AP half-widths. These events relied on raised [Ca2+]i, mediated by influx through voltage-gated calcium channels (VGCCs) and release from intracellular stores, causing an increase in cAMP-response element binding protein (CREB) phosphorylation. Block of VGCCs or of CREB function suppressed Kv3 currents, increased AP duration, and reduced Kv3.3 and c-fos expression. Real-time PCR revealed higher Kv3.3 and Kv1.1 mRNA in high-K compared to low-K cultures, although the increased Kv1.1 mRNA was mediated by a CREB-independent mechanism. We conclude that Kv channel expression and hence the intrinsic membrane properties of MNTB neurons are homeostatically regulated by [Ca2+]i-dependent mechanisms and influenced by sustained depolarization of the resting membrane potential. PMID:20211981

  16. Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse ventral tegmental area that project to nucleus accumbens and other mesolimbic targets.

    PubMed

    Peris, Joanna; MacFadyen, Kaley; Smith, Justin A; de Kloet, Annette D; Wang, Lei; Krause, Eric G

    2017-04-01

    The mesolimbic dopamine (DA) circuitry determines which behaviors are positively reinforcing and therefore should be encoded in the memory to become a part of the behavioral repertoire. Natural reinforcers, like food and sex, activate this pathway, thereby increasing the likelihood of further consummatory, social, and sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward and OT-synthesizing neurons project to the ventral tegmental area (VTA) and nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT regulation of DA neurons within the VTA is sparse. To phenotype OT-receptor (OTR) expressing neurons originating within the VTA, we delivered Cre-inducible adeno-associated virus that drives the expression of fluorescent marker into the VTA of male mice that had Cre-recombinase driven by OTR gene expression. OTR-expressing VTA neurons project to NAc, prefrontal cortex, the extended amygdala, and other forebrain regions but less than 10% of these OTR-expressing neurons were identified as DA neurons (defined by tyrosine hydroxylase colocalization). Instead, almost 50% of OTR-expressing cells in the VTA were glutamate (GLU) neurons, as indicated by expression of mRNA for the vesicular GLU transporter (vGluT). About one-third of OTR-expressing VTA neurons did not colocalize with either DA or GLU phenotypic markers. Thus, OTR expression by VTA neurons implicates that OT regulation of reward circuitry is more complex than a direct action on DA neurotransmission. J. Comp. Neurol. 525:1094-1108, 2017. © 2016 Wiley Periodicals, Inc.

  17. The neuronal structure of the dorsal nucleus of the lateral geniculate body in the common shrew (Sorex araneus) and the bank vole (Clethrionomys glareolus): Golgi and Nissl studies.

    PubMed

    Najdzion, J; Wasilewska, B; Szteyn, S; Robak, A; Bogus-Nowakowska, K; Równiak, M

    2006-11-01

    The topography and neuronal structure of the dorsal nucleus of the lateral geniculate body (GLd) of the common shrew and the bank vole are similar. The lateral geniculate body of both the species examined has a homogeneous structure and no observable cytoarchitectonic lamination. On the basis of the shape of the dendritic arbours as well as the pattern of dendritic arborisations the following two types of neurons were distinguished. Type I "bushy" neurons that have multipolar or round perikarya (common shrew perikarya 9-12 microm, bank vole perikarya 10-13 microm), with 4-6 short thick dendritic trunks that subdivide into many bush-like branches. The dendritic trunks are smooth, in contrast to the distal branches, which are covered with numerous spine-like protrusions of different lengths and forms. An axon emerges from the soma, sometimes very close to one of the primary dendrites. The type I neurons are typically projection cells that send their axons to the primary visual cortex. These neurons predominate in the GLd of both species. Type II neurons, which have an elongated soma with primary dendrites arising from opposite poles of the perikaryon (common shrew perikarya 8-10 microm, bank vole perikarya 9-11 microm). The dendritic arbours of these cells are less extensive and their dendrites have fewer spines than those of the type I neurons. Axons were seldom observed. The type II neurons are presumably interneurons and are definitely less numerous than the type I neurons.

  18. Fasted/fed states regulate postsynaptic hub protein DYNLL2 and glutamatergic transmission in oxytocin neurons in the hypothalamic paraventricular nucleus.

    PubMed

    Suyama, Shigetomo; Kodaira-Hirano, Misato; Otgon-Uul, Zesemdorj; Ueta, Yoichi; Nakata, Masanori; Yada, Toshihiko

    2016-04-01

    The neurons in the hypothalamus regulate food intake and energy metabolism on reception of systemic energy states. Accumulating evidences have indicated that synaptic transmission on the hypothalamic neurons is modulated by the metabolic condition related to fasted/fed states, and that this modulation of synaptic plasticity plays a role in regulation of feeding. It has been shown that oxytocin (Oxt) neurons in the paraventricular nucleus (PVN) of the hypothalamus sense and integrate various peripheral and central signals and thereby induce satiety. However, whether metabolic conditions regulate the synaptic transmission on Oxt neurons in PVN remains unclear. The present study examined whether the fasted/fed states regulate synaptic transmission on Oxt neurons in PVN. The miniature excitatory postsynaptic currents (mEPSCs) onto Oxt neurons in PVN were increased under ad lib fed condition compared to 24h fasted condition. Furthermore, the NMDA receptor-mediated EPSC on Oxt neurons was increased under fed, compared to fasted, condition. In Oxt neurons, dynein light chain 2 (DYNLL2), a protein suggested to be implicated in the NMDA receptor trafficking to the postsynaptic site, was increased under fed, compared to fasted, condition. The present results suggest that feeding increases excitatory synaptic input on PVN Oxt neurons via mechanisms involving DYNLL2 upregulation and NMDA receptor-mediated synaptic reorganization.

  19. Interplay between low threshold voltage-gated K(+) channels and synaptic inhibition in neurons of the chicken nucleus laminaris along its frequency axis.

    PubMed

    Hamlet, William R; Liu, Yu-Wei; Tang, Zheng-Quan; Lu, Yong

    2014-01-01

    Central auditory neurons that localize sound in horizontal space have specialized intrinsic and synaptic cellular mechanisms to tightly control the threshold and timing for action potential generation. However, the critical interplay between intrinsic voltage-gated conductances and extrinsic synaptic conductances in determining neuronal output are not well understood. In chicken, neurons in the nucleus laminaris (NL) encode sound location using interaural time difference (ITD) as a cue. Along the tonotopic axis of NL, there exist robust differences among low, middle, and high frequency (LF, MF, and HF, respectively) neurons in a variety of neuronal properties such as low threshold voltage-gated K(+) (LTK) channels and depolarizing inhibition. This establishes NL as an ideal model to examine the interactions between LTK currents and synaptic inhibition across the tonotopic axis. Using whole-cell patch clamp recordings prepared from chicken embryos (E17-E18), we found that LTK currents were larger in MF and HF neurons than in LF neurons. Kinetic analysis revealed that LTK currents in MF neurons activated at lower voltages than in LF and HF neurons, whereas the inactivation of the currents was similar across the tonotopic axis. Surprisingly, blockade of LTK currents using dendrotoxin-I (DTX) tended to broaden the duration and increase the amplitude of the depolarizing inhibitory postsynaptic potentials (IPSPs) in NL neurons without dependence on coding frequency regions. Analyses of the effects of DTX on inhibitory postsynaptic currents led us to interpret this unexpected observation as a result of primarily postsynaptic effects of LTK currents on MF and HF neurons, and combined presynaptic and postsynaptic effects in LF neurons. Furthermore, DTX transferred subthreshold IPSPs to spikes. Taken together, the results suggest a critical role for LTK currents in regulating inhibitory synaptic strength in ITD-coding neurons at various frequencies.

  20. Response of neurons in the thalamic nucleus submedius (Sm) to noxious stimulation and electrophysiological identification of on- and off-cells in rats.

    PubMed

    Fu, Jian-Jun; Tang, Jing-Shi; Yuan, Bin; Jia, Hong

    2002-09-01

    Previous studies have indicated that thalamic nucleus submedius (Sm) is involved in nociceptive modulation and plays an important role in an endogenous analgesic system (a feedback loop) consisting of spinal cord (Sc)-Sm-ventrolateral orbital cortex-periaqueductal gray-Sc. However, the function of different types of Sm neurons in nociceptive modulation is unclear. For this reason, on the basis of further studies of properties of the Sm neurons responding to noxious stimuli, the different effects of systemic morphine on the Sm neurons were examined and two classes of nociceptive modulatory neurons, named as off- and on-cells, in this region were identified in lightly anesthetized rats. The results showed that (1) most (84%, 132/157) of the Sm neurons responded to peripheral noxious stimuli. Of these neurons, 66% (n = 87) were inhibited, 34% (n = 45) excited. All neurons had very large and bilateral, even all body receptive fields. No neuron was found to be responsive to innocuous stimulation; (2) systemic morphine increased the firing rate of neurons inhibited by noxious stimulation, but decreased that of neurons excited by the same stimulation. Furthermore, the effects of morphine could be reversed by systemic naloxone; (3) 45 of Sm neurons examined could be divided into three different classes: off-cells that decreased the firing rate from tail heating just prior to occurrence of the tail-flick (TF) reflex (3140 +/- 167 ms, n = 27), on-cells that increased the firing rate just before the TF reflex (1720 +/- 240 ms, n = 8), and neutral-cells that did not respond to any stimuli and neuronal activities were not related to the TF reflex (n = 10). Findings of this study provided electrophysiological evidence for involvement of Sm neurons, as those in the rostral ventromedial medulla, in the opioid-receptor-mediated descending nociceptive modulation.

  1. [Characteristic of serotoninergic neurons of medullary nucleus raphe obscurus in norm and in serotoninergic system deficiency during the prenatal period of development in rats].

    PubMed

    Khozhaĭ, L I

    2013-01-01

    Morphological characteristics of the serotoninergic neurons forming nucleus raphe obscurus (NRO), were studied in rats at the early stages (days 5, 10, 12 and 14) of the postnatal period in normal rats and in animals whose prenatal development took place under the conditions of serotonin deficiency. NRO was found to contain three subpopulations serotonin-producing neurons (large, medium and small), which had different sensitivity to serotonin level during development. The results have shown that serotoninergic system deficiency during the prenatal period resulted in the changes of NRO structural organization and in the decrease of the rate of this nucleus formation, serotonin-producing neurons differentiation and the reduction of their total number by approximately a factor of 1.6. At the same time, the significant changes of the dimensions of serotoninergic neurons of all types took place. In control animals, the size of large, medium and small neurons was 1.8, 1.4 and 1.5 times greater than that in experimental animals, respectively. Reduction of the neuron dimensions was associated with the changes of a nucleo-cytoplasmic ratio. The volume of the cytoplasm and of Nissl bodies was significantly decreased. Along with it, the cell destruction was noted that increased with age. Synchronously with it, the marked astrocytic reaction developed, which could further lead to gliosis.

  2. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity.

    PubMed

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P M; Swaab, Dick F

    2011-10-15

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir) neurons in relation to sex, age, and gender identity in the postmortem brain of 77 subjects. First we compared the InM volume and number of Gal-Ir neurons of 22 males and 22 females in the course of aging. In a second experiment, we compared for the first time the InM volume and the total and Gal-Ir neuron number in 43 subjects with different gender identities: 14 control males (M), 11 control females (F), 10 male-to-female (MtF) transsexual people, and 5 men who were castrated because of prostate cancer (CAS). In the first experiment we found a sex difference in the younger age group (<45 years of age), i.e., a larger volume and Gal-Ir neuron number in males and an age difference, with a decrease in volume and Gal-Ir neuron number in males > 45 years. In the second experiment the MtF transsexual group presented an intermediate value for the total InM neuron number and volume that did not seem different in males and females. Because the CAS group did not have total neuron numbers that were different from the intact males, the change in adult circulating testosterone levels does not seem to explain the intermediate values in the MtF group. Organizational and activational hormone effects on the InM are discussed.

  3. Evolutionary and functional perspectives on signaling from neuronal surface to nucleus

    SciTech Connect

    Cohen, Samuel M.; Li, Boxing; Tsien, Richard W. Ma, Huan

    2015-04-24

    Reliance on Ca{sup 2+} signaling has been well-preserved through the course of evolution. While the complexity of Ca{sup 2+} signaling pathways has increased, activation of transcription factors including CREB by Ca{sup 2+}/CaM-dependent kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans, the CaMK family is made up of only three members, and CREB phosphorylation is mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly regulates adaptation of thermotaxis behavior in response to changes in the environment. In mammals, the CaMK family has been expanded from three to ten members, enabling specialization of individual elements of a signal transduction pathway and increased reliance on the CaMKII subfamily. This increased complexity enables private line communication between Ca{sup 2+} sources at the cell surface and specific cellular targets. Using both new and previously published data, we review the mechanism of a γCaMKII-CaM nuclear translocation. This intricate pathway depends on a specific role for multiple Ca{sup 2+}/CaM-dependent kinases and phosphatases: α/βCaMKII phosphorylates γCaMKII to trap CaM; CaN dephosphorylates γCaMKII to dispatch it to the nucleus; and PP2A induces CaM release from γCaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C. elegans, evolutionary modifications offer opportunities for targeted communication, regulation of key nodes and checkpoints, and greater specificity and flexibility in signaling.

  4. Efferent projection from the bed nucleus of the stria terminalis suppresses activity of taste-responsive neurons in the hamster parabrachial nuclei.

    PubMed

    Li, Cheng-Shu; Cho, Young K

    2006-10-01

    Although the reciprocal projections between the bed nucleus of the stria terminalis (BNST) and the gustatory parabrachial nuclei (PbN) have been demonstrated neuroanatomically, there is no direct evidence showing that the projections from the PbN to the BNST carry taste information or that descending inputs from the BNST to the PbN modulate the activity of PbN gustatory neurons. A recent electrophysiological study has demonstrated that the BNST exerts modulatory influence on taste neurons in the nucleus of the solitary tract (NST), suggesting that the BNST may also modulate the activity of taste neurons in the PbN. In the present study, we recorded from 117 taste-responsive neurons in the PbN and examined their responsiveness to electrical stimulation of the BNST bilaterally. Thirteen neurons (11.1%) were antidromically invaded from the BNST, mostly from the ipsilateral side (12 cells), indicating that a subset of taste neurons in the PbN project their axons to the BNST. The BNST stimulation induced orthodromic responses on most of the PbN neurons: 115 out of 117 (98.3%), including all BNST projection units. This descending modulation on the PbN gustatory neurons was exclusively inhibitory. We also confirmed that activation of this efferent inhibitory projection from the BNST reduces taste responses of PbN neurons in all units tested. The BNST is part of the neural circuits that involve stress-associated feeding behavior. It is also known that brain stem gustatory nuclei, including the PbN, are associated with feeding behavior. Therefore, this neural substrate may be important in the stress-elicited alteration in ingestive behavior.

  5. Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis

    PubMed Central

    Sharko, Amanda C.; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

    2016-01-01

    High rates of comorbidity for anxiety and alcohol-use disorders suggest a causal relationship between these conditions. Previous work demonstrates basal anxiety levels in outbred Long-Evans rats correlate with differences in voluntary ethanol consumption and that amygdalar Neuropeptide Y (NPY) systems may play a role in this relationship. The present work explores the possibility that differences in sensitivity to ethanol’s anxiolytic effects contribute to differential ethanol self-administration in these animals and examines the potential role of central and peripheral NPY in mediating this relationship. Animals were first exposed to the elevated plus maze (EPM) to assess individual differences in anxiety-like behaviors and levels of circulating NPY and corticosterone (CORT). Rats were then tested for anxiety-like behavior in the light-dark box (LD box) following acute ethanol treatment (1 g/kg; intraperitoneally [i.p.]), and neuronal activation in the amygdala and bed nucleus of the stria terminalis (BNST) was assessed using Fos immunohistochemistry. EPM exposure increased plasma CORT levels without altering plasma NPY levels. Acute ethanol treatment significantly increased light-dark transitions and latency to re-enter the light arena, but no differences were seen between high- and low-anxiety groups and no correlations were found between anxiety-like behaviors in the EPM and LD box. Acute ethanol treatment significantly increased Fos immunoreactivity in the BNST and the central amygdala. Although NPY neurons were not significantly activated following ethanol exposure, in saline-treated animals lower levels of anxiety-like behavior in the LD box (more time in the light arena and more transitions) were correlated with higher NPY-positive cell density in the central amygdala. Our results suggest that activation of the CeA and BNST are involved in the behavioral expression of ethanol-induced anxiolysis, and that differences in basal anxiety state may be

  6. Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis.

    PubMed

    Sharko, Amanda C; Kaigler, Kris F; Fadel, Jim R; Wilson, Marlene A

    2016-02-01

    High rates of comorbidity for anxiety and alcohol-use disorders suggest a causal relationship between these conditions. Previous work demonstrates basal anxiety levels in outbred Long-Evans rats correlate with differences in voluntary ethanol consumption and that amygdalar Neuropeptide Y (NPY) systems may play a role in this relationship. The present work explores the possibility that differences in sensitivity to ethanol's anxiolytic effects contribute to differential ethanol self-administration in these animals and examines the potential role of central and peripheral NPY in mediating this relationship. Animals were first exposed to the elevated plus maze (EPM) to assess individual differences in anxiety-like behaviors and levels of circulating NPY and corticosterone (CORT). Rats were then tested for anxiety-like behavior in the light-dark box (LD box) following acute ethanol treatment (1 g/kg; intraperitoneally [i.p.]), and neuronal activation in the amygdala and bed nucleus of the stria terminalis (BNST) was assessed using Fos immunohistochemistry. EPM exposure increased plasma CORT levels without altering plasma NPY levels. Acute ethanol treatment significantly increased light-dark transitions and latency to re-enter the light arena, but no differences were seen between high- and low-anxiety groups and no correlations were found between anxiety-like behaviors in the EPM and LD box. Acute ethanol treatment significantly increased Fos immunoreactivity in the BNST and the central amygdala. Although NPY neurons were not significantly activated following ethanol exposure, in saline-treated animals lower levels of anxiety-like behavior in the LD box (more time in the light arena and more transitions) were correlated with higher NPY-positive cell density in the central amygdala. Our results suggest that activation of the CeA and BNST are involved in the behavioral expression of ethanol-induced anxiolysis, and that differences in basal anxiety state may be correlated

  7. Melanocortin 4 receptor ligands modulate energy homeostasis through urocortin 1 neurons of the centrally projecting Edinger-Westphal nucleus.

    PubMed

    Füredi, Nóra; Nagy, Ákos; Mikó, Alexandra; Berta, Gergely; Kozicz, Tamás; Pétervári, Erika; Balaskó, Márta; Gaszner, Balázs

    2017-03-03

    The role of the urocortin 1 (Ucn1) expressing centrally projecting Edinger-Westphal (EWcp) nucleus in energy homeostasis and stress adaptation response has previously been investigated. Morphological and functional studies have proven that orexigenic and anorexigenic peptidergic afferents and receptors for endocrine messengers involved in the energy homeostasis are found in the EWcp. The central role of the hypothalamic melanocortin system in energy homeostasis is well known, however, no data have been published so far on possible crosstalk between melanocortins and EWcp-Ucn1. First, we hypothesized that members of the melanocortin system [i.e. alpha-melanocyte stimulating hormone (alpha-MSH), agouti-related peptide (AgRP), melanocortin 4 receptor (MC4R)] would be expressed in the EWcp. Second, we put forward, that alpha-MSH and AgRP contents as well as neuronal activity and Ucn1 peptide content of the EWcp would be affected by fasting. Third, we assumed that the intra-EWcp injections of exogenous MC4R agonists and antagonist would cause food intake-related and metabolic changes. Ucn1 neurons were found to carry MC4Rs, and they were contacted both by alpha-MSH and AgRP immunoreactive nerve fibers in the rat. The alpha-MSH immunosignal was reduced, while that of AgRP was increased upon starvation. These were associated with the elevation of FosB and Ucn1 expression. The intra-EWcp administration of MC4R blocker (i.e. HS024) had a similar, but enhanced effect on FosB and Ucn1. Furthermore, alpha-MSH injected into the EWcp had anorexigenic effect, increased oxygen consumption and caused peripheral vasodilation. We conclude that the melanocortin system influences the EWcp that contributes to energy-homeostasis.

  8. Linear coding of complex sound spectra by discharge rate in neurons of the medial nucleus of the trapezoid body (MNTB) and its inputs

    PubMed Central

    Koka, Kanthaiah; Tollin, Daniel J.

    2014-01-01

    The interaural level difference (ILD) cue to sound location is first encoded in the lateral superior olive (LSO). ILD sensitivity results because the LSO receives excitatory input from the ipsilateral cochlear nucleus and inhibitory input indirectly from the contralateral cochlear nucleus via glycinergic neurons of the ipsilateral medial nucleus of the trapezoid body (MNTB). It is hypothesized that in order for LSO neurons to encode ILDs, the sound spectra at both ears must be accurately encoded via spike rate by their afferents. This spectral-coding hypothesis has not been directly tested in MNTB, likely because MNTB neurons have been mostly described and studied recently in regards to their abilities to encode temporal aspects of sounds, not spectral. Here, we test the hypothesis that MNTB neurons and their inputs from the cochlear nucleus and auditory nerve code sound spectra via discharge rate. The Random Spectral Shape (RSS) method was used to estimate how the levels of 100-ms duration spectrally stationary stimuli were weighted, both linearly and non-linearly, across a wide band of frequencies. In general, MNTB neurons, and their globular bushy cell inputs, were found to be well-modeled by a linear weighting of spectra demonstrating that the pathways through the MNTB can accurately encode sound spectra including those resulting from the acoustical cues to sound location provided by head-related directional transfer functions (DTFs). Together with the anatomical and biophysical specializations for timing in the MNTB-LSO complex, these mechanisms may allow ILDs to be computed for complex stimuli with rapid spectrotemporally-modulated envelopes such as speech and animal vocalizations and moving sound sources. PMID:25565971

  9. Chronic oestradiol reduces the dendritic spine density of KNDy (kisspeptin/neurokinin B/dynorphin) neurones in the arcuate nucleus of ovariectomised Tac2-enhanced green fluorescent protein transgenic mice.

    PubMed

    Cholanian, M; Krajewski-Hall, S J; McMullen, N T; Rance, N E

    2015-04-01

    Neurones in the arcuate nucleus that express neurokinin B (NKB), kisspeptin and dynorphin (KNDy) play an important role in the reproductive axis. Oestradiol modulates the gene expression and somatic size of these neurones, although there is limited information available about whether their dendritic structure, a correlate of cellular plasticity, is altered by oestrogens. In the present study, we investigated the morphology of KNDy neurones by filling fluorescent neurones in the arcuate nucleus of Tac2-enhanced green fluorescent protein (EGFP) transgenic mice with biocytin. Filled neurones from ovariectomised (OVX) or OVX plus 17β-oestradiol (E2)-treated mice were visualised with anti-biotin immunohistochemistry and reconstructed in three dimensions with computer-assisted microscopy. KNDy neurones exhibited two primary dendrites, each with a few branches confined to the arcuate nucleus. Quantitative analysis revealed that E2 treatment of OVX mice decreased the cell size and dendritic spine density of KNDy neurones. The axons of KNDy neurones originated from the cell body or proximal dendrite and gave rise to local branches that appeared to terminate within the arcuate nucleus. Numerous terminal boutons were also visualised within the ependymal layer of the third ventricle adjacent to the arcuate nucleus. Axonal branches also projected to the adjacent median eminence and exited the arcuate nucleus. Confocal microscopy revealed close apposition of EGFP and gonadotrophin-releasing hormone-immunoreactive fibres within the median eminence and confirmed the presence of KNDy axon terminals in the ependymal layer of the third ventricle. The axonal branching pattern of KNDy neurones suggests that a single KNDy neurone could influence multiple arcuate neurones, tanycytes in the wall of the third ventricle, axon terminals in the median eminence and numerous areas outside of the arcuate nucleus. In parallel with its inhibitory effects on electrical excitability, E2 treatment

  10. Chronic oestradiol reduces the dendritic spine density of KNDy (kisspeptin/neurokinin B/dynorphin) neurones in the arcuate nucleus of ovariectomised Tac2-enhanced green fluorescent protein transgenic mice

    PubMed Central

    Cholanian, Marina; Krajewski-Hall, Sally J.; McMullen, Nathaniel T.; Rance, Naomi E.

    2016-01-01

    Neurones in the arcuate nucleus that express neurokinin B (NKB), kisspeptin and dynorphin (KNDy) play an important role in the reproductive axis. Oestradiol modulates the gene expression and somatic size of these neurones but there is limited information whether their dendritic structure, a correlate of cellular plasticity, is altered by oestrogens. Here we study the morphology of KNDy neurones by filling fluorescent neurones in the arcuate nucleus of Tac2-EGFP transgenic mice with biocytin. Filled neurones from ovariectomized (OVX) or OVX plus 17β-oestradiol (E2)-treated mice were visualized with anti-biotin immunohistochemistry and reconstructed in three dimensions with computer-assisted microscopy. KNDy neurones exhibited two primary dendrites, each with a few branches confined to the arcuate nucleus. Quantitative analysis revealed that E2 treatment of OVX mice decreased the cell size and dendritic spine density of KNDy neurones. The axons of KNDy neurones originated from the cell body or proximal dendrite and gave rise to local branches that appeared to terminate within the arcuate nucleus. Numerous terminal boutons were also visualized within the ependymal layer of the third ventricle adjacent to the arcuate nucleus. Axonal branches also projected to the adjacent median eminence and exited the arcuate nucleus. Confocal microscopy revealed close apposition of EGFP and GnRH-immunoreactive fibers within the median eminence and confirmed the presence of KNDy axon terminals in the ependymal layer of the third ventricle. The axonal branching pattern of KNDy neurones suggests that a single KNDy neurone could influence multiple arcuate neurones, tanycytes in the wall of the third ventricle, axon terminals in the median eminence and numerous areas outside of the arcuate nucleus. In parallel with its inhibitory effects on electrical excitability, E2 treatment of OVX Tac2-EGFP mice induces structural changes in the somata and dendrites of KNDy neurones. PMID:25659412

  11. Heterogeneity of Intrinsic and Synaptic Properties of Neurons in the Ventral and Dorsal Parts of the Ventral Nucleus of the Lateral Lemniscus.

    PubMed

    Caspari, Franziska; Baumann, Veronika J; Garcia-Pino, Elisabet; Koch, Ursula

    2015-01-01

    The ventral nucleus of the lateral lemniscus (VNLL) provides a major inhibitory projection to the inferior colliculus (IC). Neurons in the VNLL respond with various firing patterns and different temporal precision to acoustic stimulation. The present study investigates the underlying intrinsic and synaptic properties of various cell types in different regions of the VNLL, using in vitro electrophysiological recordings from acute brain slices of mice and immunohistochemistry. We show that the biophysical membrane properties and excitatory input characteristics differed between dorsal and ventral VNLL neurons. Neurons in the ventral VNLL displayed an onset-type firing pattern and little hyperpolarization-activated current (Ih). Stimulation of lemniscal inputs evoked a large all-or-none excitatory response similar to Calyx of Held synapses in neurons in the lateral part of the ventral VNLL. Neurons that were located within the fiber tract of the lateral lemniscus, received several and weak excitatory input fibers. In the dorsal VNLL onset-type and sustained firing neurons were intermingled. These neurons showed large Ih and were strongly immunopositive for the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) subunit. Both neuron types received several excitatory inputs that were weaker and slower compared to ventrolateral VNLL neurons. Using a mouse model that expresses channelrhodopsin under the promotor of the vesicular GABA transporter (VGAT) suggests that dorsal and ventral neurons were inhibitory since they were all depolarized by light stimulation. The diverse membrane and input properties in dorsal and ventral VNLL neurons suggest differential roles of these neurons for sound processing.

  12. Interaction between taurine and GABA(A)/glycine receptors in neurons of the rat anteroventral cochlear nucleus.

    PubMed

    Song, Ning-Ying; Shi, Hai-Bo; Li, Chun-Yan; Yin, Shan-Kai

    2012-09-07

    Taurine, one of the most abundant endogenous amino acids in the mammalian central nervous system (CNS), is involved in neural development and many physiological functions. In this study, the interaction between taurine and GABA(A)/glycine receptors was investigated in young rat (P13-P15) anteroventral cochlear nucleus (AVCN) neurons using the whole-cell patch-clamp method. We found that taurine at low (0.1mM) and high (1mM) concentrations activated both GABA(A) and glycine receptors, but not AMPA and NMDA receptors. The reversal potentials of taurine-, GABA- or glycine-evoked currents were close to the expected chloride equilibrium potential, indicating that receptors activated by these agonists were mediating chloride conductance. Moreover, our results showed that the currents activated by co-application of GABA and glycine were cross-inhibitive. Sequential application of GABA and glycine or vice versa also reduced the glycine or GABA evoked currents. There was no cross-inhibition when taurine and GABA or taurine and glycine were applied simultaneously, but the response was larger than that evoked by GABA or glycine alone. These results suggest that taurine can serve as a neuromodulator to strengthen GABAergic and glycinergic neurotransmission in the rat AVCN.

  13. Estrogen evokes a rapid effect on intracellular calcium in neurons characterized by calcium oscillations in the arcuate nucleus.

    PubMed

    Fricke, Oliver; Kow, Lee-Ming; Bogun, Magda; Pfaff, Donald W

    2007-06-01

    Rapid estrogen effects became an interesting topic to explain estrogen effects not associated with the classical nuclear pathway. The rapid estrogen effect on intracellular calcium oscillations was characterized in neurons of the arcuate nucleus. Ratiometric calcium imaging (fura-2AM) was used to measure intracellular calcium in brain slices of female Swiss Webster mice (median of age 27 days p.n.). Calcium oscillations were dependent on intracellular calcium and also on calcium influx from the extracellular space. The perfusion of slices with calcium-free solution inhibited spontaneous calcium oscillations. The metabotropic glutamate receptor agonist t-ACPD (5 microM) and low concentrated ryanodine (100 nM) induced intracellular calcium release when slices were perfused with calcium-free solution. 17beta-estradiol (10 nM) also induced intracellular calcium release in calcium-free ACSF. This effect was inhibited by the preceding administration of thapsigargin (2 microM) indicating the association of the rapid estrogen effect with intracellular calcium stores. The administration of the non-selective phospholipase C-inhibitor ET-18 (30 microM), but not U73122 (10 microM), and the inhibition of protein kinase A by H-89 (0.25 microM) suppressed the rapid estrogen effect. Analyses indicated a qualitative, but not quantitatively significant effect of 17beta-estradiol on calcium oscillations.

  14. Effects of general anaesthetics on 5-HT neuronal activity in the dorsal raphe nucleus.

    PubMed

    McCardle, Caroline E; Gartside, Sarah E

    2012-03-01

    The ascending 5-HT system has been and continues to be the subject of much research. The majority of in vivo electrophysiological and neurochemical studies of 5-HT function in rodents have been conducted in animals under anaesthesia - usually chloral hydrate or urethane. However, the effects of anaesthetics, on 5-HT function have not been systematically investigated. Here we used in vitro electrophysiology in dorsal raphe slices, to determine the effects of anaesthetically relevant concentrations of chloral hydrate (100 μM and 1 mM), urethane (10 and 30 mM), pentobarbitone (10 and 100 μM) and ketamine (10, 100 and 300 μM) on regulators of 5-HT firing activity. We examined i) basal firing (driven by α(1) adrenoceptors), ii) the excitatory response to N-methyl-d-aspartate (NMDA), iii) the 5-HT(1A) autoreceptor-mediated inhibitory response to 5-HT and iv) the GABA(A) receptor-mediated inhibitory response to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridinyl-3-ol (THIP, gaboxadol). Pentobarbitone selectively enhanced the response to THIP. Ketamine decreased basal firing, attenuated the response to NMDA, and enhanced responses to both 5-HT and THIP. Chloral hydrate had marginal effects on basal firing, slightly attenuated the NMDA response, and enhanced both the 5-HT and THIP responses. Urethane increased basal firing, decreased the NMDA response, increased the response to THIP, but had no effect on the 5-HT response. Our data indicate that all anaesthetics tested significantly affect the regulators of 5-HT neuronal function. These findings will aid in the interpretation of previous reports of in vivo studies of the 5-HT system and will allow researchers to make a rational selection of anaesthetic for future studies.

  15. Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp.

    PubMed

    Zhang, S; Chiang, C Y; Xie, Y F; Park, S J; Lu, Y; Hu, J W; Dostrovsky, J O; Sessle, B J

    2006-10-27

    We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.

  16. Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior.

    PubMed

    Kamii, Hironori; Kurosawa, Ryo; Taoka, Naofumi; Shinohara, Fumiya; Minami, Masabumi; Kaneda, Katsuyuki

    2015-05-01

    The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus implicated in reward processing and is one of the main sources of cholinergic afferents to the ventral tegmental area (VTA). Neuroplasticity in this structure may affect the excitability of VTA dopamine neurons and mesocorticolimbic circuitry. Here, we provide evidence that cocaine-induced intrinsic membrane plasticity in LDT cholinergic neurons is involved in addictive behaviors. After repeated experimenter-delivered cocaine exposure, ex vivo whole-cell recordings obtained from LDT cholinergic neurons revealed an induction of intrinsic membrane plasticity in regular- but not burst-type neurons, resulting in increased firing activity. Pharmacological examinations showed that increased riluzole-sensitive persistent sodium currents, but not changes in Ca(2+) -activated BK, SK or voltage-dependent A-type potassium conductance, mediated this plasticity. In addition, bilateral microinjection of riluzole into the LDT immediately before the test session in a cocaine-induced conditioned place preference (CPP) paradigm inhibited the expression of cocaine-induced CPP. These findings suggest that intrinsic membrane plasticity in LDT cholinergic neurons is causally involved in the development of cocaine-induced addictive behaviors.

  17. Inhibition by 5-hydroxytryptamine and noradrenaline in substantia gelatinosa of guinea-pig spinal trigeminal nucleus.

    PubMed

    Grudt, T J; Williams, J T; Travagli, R A

    1995-05-15

    1. Whole-cell and intracellular recordings were made from neurons in slices of guinea-pig spinal trigeminal nucleus pars caudalis. 2. 5-Hydroxytryptamine (5-HT) hyperpolarized 70% of neurons by activating 5-HT1A receptors. The effect was mimicked by 5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronapthalene hydrobromide (8-OH-DPAT) and antagonized by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-butyl]-piperazine hydrobromide (NAN 190) and pindobind-5-HT1A. Nine per cent of the neurons were depolarized by 5-HT. 3. In about 20% of recordings, 5-HT also evoked repetitive inhibitory postsynaptic potentials that were mediated by glycine. 4. Noradrenaline (NA) hyperpolarized 71% of neurons. This effect was mediated by activation of alpha 2-adrenoceptors, since 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) also caused a hyperpolarization and idazoxan (1 microM) blocked the hyperpolarization to both NA and UK14304. Phenylephrine depolarized a subset of neurons and this depolarization was blocked by prazosin, suggesting an action mediated by activation of alpha 1-adrenoceptors. 5. NA also evoked repetitive GABAA-mediated inhibitory postsynaptic potentials in about 20% of recordings. The increase in synaptic activity was mimicked by phenylephrine and blocked by prazosin. 6. These results indicate that there are at least two mechanisms through which 5-HT and NA inhibit neurons: (i) in many cells both 5-HT and NA mediate a hyperpolarization through an increase of a potassium conductance; (ii) 5-HT and NA also activated GABA- and glycine-containing interneurons to cause IPSPs in separate groups of cells.

  18. No Evidence for Sex Differences in the Electrophysiological Properties and Excitatory Synaptic Input onto Nucleus Accumbens Shell Medium Spiny Neurons123

    PubMed Central

    Will, Tyler; Hauser, Caitlin A.; Cao, Jinyan

    2016-01-01

    Sex differences exist in how the brain regulates motivated behavior and reward, both in normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the dorsal striatum and nucleus accumbens core and shell. These investigations yield accumulating evidence of sexually different electrophysiological properties, excitatory synaptic input, and sensitivity to neuromodulator/hormone action in select striatal regions both before and after puberty. It is unknown whether the electrical properties of neurons in the nucleus accumbens shell differ by sex, and whether sex differences in excitatory synaptic input are present before puberty. To test the hypothesis that these properties differ by sex, we performed whole-cell patch-clamp recordings on male and female medium spiny neurons (MSNs) in acute brain slices obtained from prepubertal rat nucleus accumbens shell. We analyzed passive and active electrophysiological properties, and miniature EPSCs (mEPSCs). No sex differences were detected; this includes those properties, such as intrinsic excitability, action potential afterhyperpolarization, threshold, and mEPSC frequency, that have been found to differ by sex in other striatal regions and/or developmental periods. These findings indicate that, unlike other striatal brain regions, the electrophysiological properties of nucleus accumbens shell MSNs do not differ by sex. Overall, it appears that sex differences in striatal function, including motivated behavior and reward, are likely mediated by other factors and striatal regions. PMID:27022621

  19. Neuronal composition of the magnocellular division of the medial preoptic nucleus (MPN mag) is sex specific in the Syrian hamster (Mesocricetus auratus).

    PubMed

    Richendrfer, Holly A; Swann, Jennifer M

    2010-09-10

    The magnocellular division of the medial Preoptic nucleus (MPN mag) plays a critical role in the regulation of male sexual behavior in the hamster. Results from previous studies indicated that the number of neurons in the MPN mag is greater in males than females but failed to find significant differences in the volume of the nucleus suggesting that other elements in the nucleus may be greater in the female. The results of the present study, using NeuN to identify neurons, are in line with this hypothesis. The data show that (1) neurons in the MPN mag display two distinct phenotypes, those with a single nucleolus and those with multiple nucleoli; (2) the percentage of each phenotype is sex specific, differing over the course of development and (3) there is no sex difference in the number of glial cells at any age. Sex differences in the numbers of each type are correlated with developmental milestones and suggest that morphological changes are influenced by changes in circulating gonadal steroids during development.

  20. Enhanced dendritic spine number of neurons of the prefrontal cortex, hippocampus and nucleus accumbens in old rats after chronic donepezil administration

    PubMed Central

    Alcantara-Gonzalez, Faviola; Juarez, Ismael; Solis, Oscar; Martinez-Tellez, Isaura; Camacho-Abrego, Israel; Masliah, Eliezer; Mena, Raul; Flores, Gonzalo

    2010-01-01

    In Alzheimer's disease brains morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect of oral administration of this drug on the morphology of neuronal cells from the brain of aged rats. We examined dendrites of pyramidal neurons of the PFC, dorsal or ventral hippocampus and medium spiny neurons of the nucleus accumbens (NAcc). Donepezil (1 mg/Kg, vo) was administrated every day for 60 days to rats aged 10 and 18 months. Dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at 12 and 20 months ages, respectively. In all Donepezil treated-rats a significant increment of the dendritic spines number in pyramidal neurons of the PFC, dorsal hippocampus was observed. However, pyramidal neurons of the ventral hippocampus and medium spiny cells of the NAcc only showed an increase in the number of their spines in 12 months old-rats. Our results suggest that Donepezil prevents the alterations of the neuronal dendrite morphology caused by aging. PMID:20336627

  1. Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by hypotension and hypertension in conscious rats

    PubMed Central

    Miller, Rebecca L.; Knuepfer, Mark M.; Wang, Michelle H.; Denny, George O.; Gray, Paul A.; Loewy, Arthur D.

    2012-01-01

    The parabrachial nucleus (PB) is a brainstem cell group that receives a strong input from the nucleus tractus solitarius regarding the physiological status of the internal organs and sends efferent projections throughout the forebrain. Since the neuroanatomical organization of the PB remains unclear, our first step was to use specific antibodies against two neural lineage transcription factors: Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta (Lmx1b) to define the PB in adult rats. This allowed us to construct a cytoarchitectonic PB map based on the distribution of neurons that constitutively express these two transcription factors. Second, the in situ hybridization method combined with immunohistochemistry demonstrated that mRNA for glutamate vesicular transporter Vglut2 (Slc17a6) was present in most of the Lmx1b+ and FoxP2+ parabrachial neurons, indicating these neurons use glutamate as a transmitter. Third, conscious rats were maintained in a hypotensive or hypertensive state for two hours, and then, their brainstems were prepared by the standard c-Fos method which is a measure of neuronal activity. Both hypotension and hypertension resulted in c-Fos activation of Lmx1b+ neurons in the external lateral-outer subdivision of the PB (PBel-outer). Hypotension, but not hypertension, caused c-Fos activity in the FoxP2+ neurons of the central lateral PB (PBcl) subnucleus. The Kölliker-Fuse nucleus as well as the lateral crescent PB and rostralmost part of the PBcl contain neurons that co-express FoxP2+ and Lmx1b+, but none of these were activated after blood pressure changes. Salt-sensitive FoxP2 neurons in the pre-locus coeruleus and PBel-inner were not c-Fos activated following blood pressure changes. In summary, the present study shows that the PBel-outer and PBcl subnuclei originate from two different neural progenitors, contain glutamatergic neurons, and are affected by blood pressure changes, with the PBel-outer reacting to both hypo

  2. Sodium MRI in a rat migraine model and a NEURON simulation study support a role for sodium in migraine

    PubMed Central

    Harrington, Michael G; Chekmenev, Eduard Y; Schepkin, Victor; Fonteh, Alfred N; Arakaki, Xianghong

    2012-01-01

    Introduction Increased lumbar cerebrospinal fluid (CSF) sodium has been reported during migraine. We used ultra-high field MRI to investigate cranial sodium in a rat migraine model, and simulated the effects of extracellular sodium on neuronal excitability. Methods Behavioral changes in the nitroglycerin (NTG) rat migraine model were determined from von Frey hair withdrawal response and photography. Central sensitization was measured by counting cFos-immunoreactive cells in the trigeminal nucleus caudalis (TNC). Sodium was quantified in vivo by ultra-high field sodium MRI at 21 Tesla. Effects of extracellular sodium on neuronal excitability were modeled using NEURON software. Results NTG decreased von Frey withdrawal threshold (p=0.0003), decreased eyelid vertical height:width ratio (p<0.0001), increased TNC cFos stain (p<0.0001), and increased sodium between 7.5 and 17% in brain, intracranial CSF, and vitreous humor (p<0.05). Simulated neurons exposed to higher sodium have more frequent and earlier spontaneous action potentials, and corresponding earlier sodium and potassium currents. Conclusions In the rat migraine model, sodium rises to levels that increase neuronal excitability. We propose that rising sodium in CSF surrounding trigeminal nociceptors increases their excitability and causes pain and that rising sodium in vitreous humor increases retinal neuronal excitability and causes photosensitivity. PMID:21816771

  3. Increased responsiveness and failure of habituation in neurons of the external nucleus of inferior colliculus associated with audiogenic seizures of the genetically epilepsy-prone rat.

    PubMed

    Chakravarty, D N; Faingold, C L

    1996-10-01

    Initiation of audiogenic seizures (AGS) emanates from the inferior colliculus (IC) to other IC subnuclei in the genetically epilepsy-prone rat (GEPR). The external nucleus of IC (ICx) is a suggested site of convergence of the auditory output onto the sensorimotor integration network components for AGS in the brainstem. Neuronal firing was recorded from the ICx of the awake, freely moving GEPR and normal Sprague-Dawley rats using microwire electrodes in the present study. Auditory stimuli consisted of 12-kHz tones (100 ms, 5-ms rise-fall at rates of 1/4s, 1/2s, and 1/s). AGS incidence in the GEPR is highest at 12 kHz. In the GEPR, ICx neuronal responses to acoustic stimuli were significantly greater than those seen in normal rats. This increased ICx firing was observed at relatively high acoustic intensities (> 80 dB SPL), which are near the threshold for AGS induction. Repetition-induced response attenuation (habituation) is commonly observed in ICx neurons, which appears to be overcome in the GEPR during AGS initiation. Tonic, acoustically evoked ICx neuronal firing was observed just prior to wild running. ICx firing was suppressed during the tonic and postictal phases of AGS. Recovery of ICx responses occurred when the animal regained postural control. Abnormal, intense output has previously been observed in the GEPR IC central nucleus (ICc) neurons. The neuronal firing pattern changes observed in the ICx in the present study may result from this intense ICc output. Diminished efficacy of GABA, which has been observed in several regions of the GEPR brain, including the IC, in a number of previous studies, may be involved in the exaggerated ICx responses to acoustic stimuli in the GEPR. Participation of the ICx in the AGS neuronal network may be subserved by this acoustic hyperresponsiveness.

  4. Ca(2+)-activated ion currents triggered by ryanodine receptor-mediated Ca(2+) release control firing of inhibitory neurons in the prepositus hypoglossi nucleus.

    PubMed

    Saito, Yasuhiko; Yanagawa, Yuchio

    2013-01-01

    Spontaneous miniature outward currents (SMOCs) are known to exist in smooth muscles and peripheral neurons, and evidence for the presence of SMOCs in central neurons has been accumulating. SMOCs in central neurons are induced through Ca(2+)-activated K(+) (K(Ca)) channels, which are activated through Ca(2+)-induced Ca(2+) release from the endoplasmic reticulum via ryanodine receptors (RyRs). Previously, we found that some neurons in the prepositus hypoglossi nucleus (PHN) showed spontaneous outward currents (SOCs). In the present study, we used whole cell recordings in slice preparations of the rat brain stem to investigate the following: 1) the ionic mechanisms of SOCs, 2) the types of neurons exhibiting frequent SOCs, and 3) the effect of Ca(2+)-activated conductance on neuronal firing. Pharmacological analyses revealed that SOCs were induced via the activation of small-conductance-type K(Ca) (SK) channels and RyRs, indicating that SOCs correspond to SMOCs. An analysis of the voltage responses to current pulses of the fluorescence-expressing inhibitory neurons of transgenic rats revealed that inhibitory neurons frequently exhibited SOCs. Abolition of SOCs via blockade of SK channels enhanced the frequency of spontaneous firing of inhibitory PHN neurons. However, abolition of SOCs via blockade of RyRs reduced the firing frequency and hyperpolarized the membrane potential. Similar reductions in firing frequency and hyperpolarization were also observed when Ca(2+)-activated nonselective cation (CAN) channels were blocked. These results suggest that, in inhibitory neurons in the PHN, Ca(2+) release via RyRs activates SK and CAN channels, and these channels regulate spontaneous firing in a complementary manner.

  5. Intracellular postsynaptic cannabinoid receptors link thyrotropin-releasing hormone receptors to TRPC-like channels in thalamic paraventricular nucleus neurons.

    PubMed

    Zhang, L; Kolaj, M; Renaud, L P

    2015-12-17

    In rat thalamic paraventricular nucleus of thalamus (PVT) neurons, activation of thyrotropin-releasing hormone (TRH) receptors enhances excitability via concurrent decrease in G protein-coupled inwardly-rectifying potassium (GIRK)-like and activation of transient receptor potential cation (TRPC)4/5-like cationic conductances. An exploration of intracellular signaling pathways revealed the TRH-induced current to be insensitive to phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitors, but reduced by D609, an inhibitor of phosphatidylcholine-specific PLC (PC-PLC). A corresponding change in the I-V relationship implied suppression of the cationic component of the TRH-induced current. Diacylglycerol (DAG) is a product of the hydrolysis of PC. Studies focused on the isolated cationic component of the TRH-induced response revealed a reduction by RHC80267, an inhibitor of DAG lipase, the enzyme involved in the hydrolysis of DAG to the endocannabinoid 2-arachidonoylglycerol (2-AG). Further investigation revealed enhancement of the cationic component in the presence of either JZL184 or WWL70, inhibitors of enzymes involved in the hydrolysis of 2-AG. A decrease in the TRH-induced response was noted in the presence of rimonabant or SR144528, membrane permeable CB1 and CB2 receptor antagonists, respectively. A decrease in the TRH-induced current by intracellular, but not by bath application of the membrane impermeable peptide hemopressin, selective for CB1 receptors, suggests a postsynaptic intracellular localization of these receptors. The TRH-induced current was increased in the presence of arachidonyl-2'-chloroethylamide (ACEA) or JWH133, CB1 and CB2 receptor agonists, respectively. The PI3-kinase inhibitor LY294002, known to inhibit TRPC translocation, decreased the response to TRH. In addition, a TRH-induced enhancement of the low-threshold spike was prevented by both rimonabant, and SR144528. TRH had no influence on excitatory or inhibitory miniature

  6. Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression.

    PubMed

    Riediger, Thomas; Bothe, Christine; Becskei, Csilla; Lutz, Thomas A

    2004-01-01

    The hypothalamic arcuate nucleus (Arc) monitors and integrates hormonal and metabolic signals involved in the maintenance of energy homeostasis. The orexigenic peptide ghrelin is secreted from the stomach during negative status of energy intake and directly activates neurons of the medial arcuate nucleus (ArcM) in rats. In contrast to ghrelin, peptide YY (PYY) is released postprandially from the gut and reduces food intake when applied peripherally. Neurons in the ArcM express ghrelin receptors and neuropeptide Y receptors. Thus, PYY may inhibit feeding by acting on ghrelin-sensitive Arc neurons. Using extracellular recordings, we (1) characterized the effects of PYY on the electrical activity of ghrelin-sensitive neurons in the ArcM of rats. In order to correlate the effect of PYY on neuronal activity with the energy status, we (2) investigated the ability of PYY to reverse fasting-induced c-Fos expression in Arc neurons of mice. In addition, we (3) sought to confirm that PYY reduces food intake under our experimental conditions. Superfusion of PYY reversibly inhibited 94% of all ArcM neurons by a direct postsynaptic mechanism. The PYY-induced inhibition was dose-dependent and occurred at a threshold concentration of 10(-8)M. Consistent with the opposite effects of ghrelin and PYY on food intake, a high percentage (50%) of Arc neurons was activated by ghrelin and inhibited by PYY. In line with this inhibitory action, peripherally injected PYY partly reversed the fasting-induced c-Fos expression in Arc neurons of mice. Similarly, refeeding of food-deprived mice reversed the fasting-induced activation in the Arc. Furthermore, peripherally injected PYY reduced food intake in 12-hour fasted mice. Thus the activity of Arc neurons correlated with the feeding status and was not only reduced by feeding but also by administration of PYY in non-refed mice. In conclusion, our current observations suggest that PYY may contribute to signaling a positive status of energy intake

  7. Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

    PubMed Central

    Coldren, K. Max; Brown, Randall; Hasser, Eileen M.

    2015-01-01

    Pregnancy is characterized by increased blood volume and baseline sympathetic nerve activity (SNA), vasodilation, and tachycardia. Relaxin (RLX), an ovarian hormone elevated in pregnancy, activates forebrain sites involved in control of blood volume and SNA through ANG II-dependent mechanisms and contributes to adaptations during pregnancy. In anesthetized, arterial baroreceptor-denervated nonpregnant (NP) rats, RLX microinjected into the subfornical organ (SFO; 0.77 pmol in 50 nl) produced sustained increases in lumbar SNA (8 ± 3%) and mean arterial pressure (MAP; 26 ± 4 mmHg). Low-dose intracarotid artery infusion of RLX (155 pmol·ml−1·h−1; 1.5 h) had minor transient effects on AP and activated neurons [increased Fos-immunoreactivity (IR)] in the SFO and in spinally projecting (19 ± 2%) and arginine-vasopressin (AVP)-IR (21 ± 5%) cells in the paraventricular nucleus of the hypothalamus of NP, but not pregnant (P), rats. However, mRNA for RLX and ANG II type 1a receptors in the SFO was preserved in pregnancy. RLX receptor-IR is present in the region of the SFO in NP and P rats and is localized in astrocytes, the major source of angiotensinogen in the SFO. These data provide an anatomical substrate for a role of RLX in the resetting of AVP secretion and increased baseline SNA in pregnancy. Since RLX and ANG II receptor expression was preserved in the SFO of P rats, we speculate that the lack of response to exogenous RLX may be due to maximal activation by elevated endogenous levels of RLX in near-term pregnancy. PMID:26400184

  8. Repeated Cocaine Exposure Decreases Dopamine D2-Like Receptor Modulation of Ca2+ Homeostasis in Rat Nucleus Accumbens Neurons

    PubMed Central

    PEREZ, MARIELA F.; FORD, KERSTIN A.; GOUSSAKOV, IVAN; STUTZMANN, GRACE E.; HU, XIU-TI

    2013-01-01

    The nucleus accumbens (NAc) is a limbic structure in the forebrain that plays a critical role in cognitive function and addiction. Dopamine modulates activity of medium spiny neurons (MSNs) in the NAc. Both dopamine D1-like and D2-like receptors (including D1R or D1,5R and D2R or D2,3,4R, respectively) are thought to play critical roles in cocaine addiction. Our previous studies demonstrated that repeated cocaine exposure (which alters dopamine transmission) decreases excitability of NAc MSNs in cocaine-sensitized, withdrawn rats. This decrease is characterized by a reduction in voltage-sensitive Na+ currents and high voltage-activated Ca2+ currents, along with increased voltage-gated K+ currents. These changes are associated with enhanced activity in the D1R/cAMP/PKA/protein phosphatase 1 pathway and diminished calcineurin function. Although D1R-mediated signaling is enhanced by repeated cocaine exposure, little is known whether and how the D2R is implicated in the cocaine-induced NAc dysfunction. Here, we performed a combined electrophysiological, biochemical, and neuroimaging study that reveals the cocaine-induced dysregulation of Ca2+ homeostasis with involvement of D2R. Our novel findings reveal that D2R stimulation reduced Ca2+ influx preferentially via the L-type Ca2+ channels and evoked intracellular Ca2+ release, likely via inhibiting the cAMP/PKA cascade, in the NAc MSNs of drug-free rats. However, repeated cocaine exposure abolished the D2R effects on modulating Ca2+ homeostasis with enhanced PKA activity and led to a decrease in whole-cell Ca2+ influx. These adaptations, which persisted for 21 days during cocaine abstinence, may contribute to the mechanism of cocaine withdrawal. PMID:20665696

  9. Neuronal and Endothelial Nitric Oxide Synthases in the Paraventricular Nucleus Modulate Sympathetic Overdrive in Insulin-Resistant Rats

    PubMed Central

    Lu, Qing-Bo; Feng, Xue-Mei; Tong, Ning; Sun, Hai-Jian; Ding, Lei; Wang, Yu-Jiao; Wang, Xuan; Zhou, Ye-Bo

    2015-01-01

    A central mechanism participates in sympathetic overdrive during insulin resistance (IR). Nitric oxide synthase (NOS) and nitric oxide (NO) modulate sympathetic nerve activity (SNA) in the paraventricular nucleus (PVN), which influences the autonomic regulation of cardiovascular responses. The aim of this study was to explore whether the NO system in the PVN is involved in the modulation of SNA in fructose-induced IR rats. Control rats received ordinary drinking water, whereas IR rats received 12.5% fructose-containing drinking water for 12 wks to induce IR. Basal SNA was assessed based on the changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to chemicals administered to the PVN. We found an increased plasma norepinephrine level but significantly reduced NO content and neuronal NOS (nNOS) and endothelial NOS (eNOS) protein expression levels in the PVN of IR rats compared to Control rats. No difference in inducible NOS (iNOS) protein expression was observed between the two groups. In anesthetized rats, the microinjection of sodium nitroprusside (SNP), an NO donor, or Nω-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of NOS, into the PVN significantly decreased and increased basal SNA, respectively, in both normal and IR rats, but these responses to SNP and L-NAME in IR rats were smaller than those in normal rats. The administration of selective inhibitors of nNOS or eNOS, but not iNOS, to the PVN significantly increased basal SNA in both groups, but these responses were also smaller in IR rats. Moreover, IR rats exhibited reduced nNOS and eNOS activity in the PVN. In conclusion, these data indicate that the decreased protein expression and activity levels of nNOS and eNOS in the PVN lead to a reduction in the NO content in the PVN, thereby contributing to a subsequent enhancement in sympathoexcitation during IR. PMID:26485682

  10. Gamma Aminobutyric Acidergic and Neuronal Structural Markers in the Nucleus Accumbens Core Underlie Trait-like Impulsive Behavior

    PubMed Central

    Caprioli, Daniele; Sawiak, Stephen J.; Merlo, Emiliano; Theobald, David E.H.; Spoelder, Marcia; Jupp, Bianca; Voon, Valerie; Carpenter, T. Adrian; Everitt, Barry J.; Robbins, Trevor W.; Dalley, Jeffrey W.

    2014-01-01

    Background Pathological forms of impulsivity are manifest in a number of psychiatric disorders listed in DSM-5, including attention-deficit/hyperactivity disorder and substance use disorder. However, the molecular and cellular substrates of impulsivity are poorly understood. Here, we investigated a specific form of motor impulsivity in rats, namely premature responding, on a five-choice serial reaction time task. Methods We used in vivo voxel-based magnetic resonance imaging and ex vivo Western blot analyses to investigate putative structural, neuronal, and glial protein markers in low-impulsive (LI) and high-impulsive rats. We also investigated whether messenger RNA interference targeting glutamate decarboxylase 65/67 (GAD65/67) gene expression in the nucleus accumbens core (NAcbC) is sufficient to increase impulsivity in LI rats. Results We identified structural and molecular abnormalities in the NAcbC associated with motor impulsivity in rats. We report a reduction in gray matter density in the left NAcbC of high-impulsive rats, with corresponding reductions in this region of glutamate decarboxylase (GAD65/67) and markers of dendritic spines and microtubules. We further demonstrate that the experimental reduction of de novo of GAD65/67 expression bilaterally in the NAcbC is sufficient to increase impulsivity in LI rats. Conclusions These results reveal a novel mechanism of impulsivity in rats involving gamma aminobutyric acidergic and structural abnormalities in the NAcbC with potential relevance to the etiology and treatment of attention-deficit/hyperactivity disorder and related disorders. PMID:23973096

  11. Substance P presynaptically depresses the transmission of sensory input to bronchopulmonary neurons in the guinea pig nucleus tractus solitarii

    PubMed Central

    Sekizawa, Shin-ichi; Joad, Jesse P; Bonham, Ann C

    2003-01-01

    Substance P modulates the reflex regulation of respiratory function by its actions both peripherally and in the CNS, particularly in the nucleus tractus solitarii (NTS), the first central site for synaptic contact of the lung and airway afferent fibres. There is considerable evidence that the actions of substance P in the NTS augment respiratory reflex output, but the precise effects on synaptic transmission have not yet been determined. Therefore, we determined the effects of substance P on synaptic transmission at the first central synapses by using whole-cell voltage clamping in an NTS slice preparation. Studies were performed on second-order neurons in the slice anatomically identified as receiving monosynaptic input from sensory nerves in the lungs and airways. This was done by the fluorescent labelling of terminal boutons after 1,1′-dioctadecyl-3,3,3′,3′-tetra-methylindocarbo-cyanine perchlorate (DiI) was applied via tracheal instillation. Substance P (1.0, 0.3 and 0.1 μM) significantly decreased the amplitude of excitatory postsynaptic currents (eEPSCs) evoked by stimulation of the tractus solitarius, in a concentration-dependent manner. The decrease was accompanied by an increase in the paired-pulse ratio of two consecutive eEPSCs, and a decrease in the frequency, but not the amplitude, of spontaneous EPSCs and miniature EPSCs, findings consistent with a presynaptic site of action. The effects were consistently and significantly attenuated by a neurokinin-1 (NK1) receptor antagonist (SR140333, 3 μM). The data suggest a new site of action for substance P in the NTS (NK1 receptors on the central terminals of sensory fibres) and a new mechanism (depression of synaptic transmission) for regulating respiratory reflex function. PMID:14561836

  12. The neuronal architecture of the anteroventral cochlear nucleus of the cat in the region of the cochlear nerve root: Golgi and Nissl methods.

    PubMed

    Tolbert, L P; Morest, D K

    1982-01-01

    This report characterizes the cells and fibers in one part of the cochlear nucleus, the posterior division of the anteroventral cochlear nucleus. This includes the region where the cochlear nerve root enters the brain and begins to form endings. Nissl stains reveal the somata of globular cells with dispersed Nissl substance and those of multipolar cells with coarse, clumped Nissl bodies. Both parts of the posterior division contain cells with each Nissl pattern, but in different relative numbers and locations. Golgi impregnations demonstrate two types of neurons: bushy cells, with short bush-like dendrites, and stellate and elongate cells, with long tapered dendrites. Several varieties of bushy cells, differing in the morphology of the cell body and in the size and extent of the dendritic field, can be distinguished. Comparison of the distributions of these cell types, as well as cellular morphology, suggest that the globular cells recognized in Nissl stains correspond to bushy neurons, while the multipolar cells correspond to stellate and elongate neurons. Golgi impregnations reveal large end-bulbs and smaller boutons from cochlear nerve fibers, as well as boutons from other, unidentified sources, ending in this region. The particular arrangements of the dendritic fields of the different cell types and the axonal endings associated with them indicate that these neurons must have different physiological properties, since they define different domains with respect to the cochlear and non-cochlear inputs.

  13. Central action of ELABELA reduces food intake and activates arginine vasopressin and corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus.

    PubMed

    Santoso, Putra; Maejima, Yuko; Kumamoto, Kensuke; Takenoshita, Seiichi; Shimomura, Kenju

    2015-09-30

    ELABELA (ELA) is a novel hormone consisting of 32 amino acid peptides found in humans as well as other vertebrates and is considered to play an important role in the circulatory system through the apelin receptor (APJ). However, whether ELA also acts in the central nervous system remains unknown. Here, we show that ELA functions as an anorexigenic hormone in adult mouse brain. An intracerebroventricular injection of ELA reduces food intake and activates arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN), a hypothalamic region that regulates food intake. Cytosolic calcium ([Ca]i) measurement shows that ELA dose dependently increases [Ca]i in single AVP and CRH-immunoreactive neurons isolated from the PVN. Our data suggest that ELA functions as an anorexigenic hormone through activation of AVP and CRH neurons in the PVN.

  14. A distinct group of non-cholinergic neurons along the mid-line of the septum and within the rat medial septal nucleus.

    PubMed

    Tsurusaki, Massashi; Gallagher, Joel P

    2006-12-13

    The septum is a critical and integral component of the limbic brain that serves as a link between diverse brain structures while being necessary for human cognition and emotionality. A major anatomical component of the septum is designated as the medial septum/diagonal band of Broca complex (MS/DB). A primary focus of much research has been to investigate cholinergic neurons within the MS/DB, as these are the rodent brain's main source of acetylcholine to the cortex and hippocampus. On the other hand, we have chosen to investigate a specific group of neurons that lie on the midline of the MS/DB in an area distinguished anatomically as the medial septal nucleus (MSN). Based on somatic morphology and electrophysiological characteristics we conclude that these neurons, characterized into three different types, are non-cholinergic.

  15. The neuronal structure of the dorsal lateral geniculate nucleus in the guinea pig: Golgi and Klüver-Barrera studies.

    PubMed

    Szteyn, S; Bogus-Nowakowska, K; Robak, A; Najdzion, J

    2001-01-01

    On the basis of Golgi and Klüver-Barrera preparations we have distinguished four types of neurons in the dorsal lateral geniculate nucleus of the guinea pig: 1. Fusiform neurons with 1-3 thick dendritic trunks arising from each pole of the soma. The dendritic trunks branch twice dichotomically. The branches sometimes show varicosities. 2. Pear-shaped cells. From one pole of the perikaryon one or two thick dendritic trunks arise, from the opposite pole an axon emerges. The ends of the dendritic branches divide in a tuft-like manner (a characteristic feature of the interneurons). 3. Rounded neurons with 4-7 dendritic trunks without cones. The dendritic trunks branch once or twice dichotomically and give finally 2-3 thin ramifications which show a varicose course and knob-like protuberances. 4. Triangular cells with 3 thick, chronically arising dendritic trunks. They bifurcate dichotomically. The surface of the dendritic trunks and of their branches is smooth.

  16. Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

    PubMed Central

    Kohno, Daisuke; Koike, Miho; Ninomiya, Yuzo; Kojima, Itaru; Kitamura, Tadahiro; Yada, Toshihiko

    2016-01-01

    The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10−5–10−2 M dose dependently increased [Ca2+]i in 12–16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation mainly

  17. The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

    PubMed

    Clément, Olivier; Valencia Garcia, Sara; Libourel, Paul-Antoine; Arthaud, Sébastien; Fort, Patrice; Luppi, Pierre-Hervé

    2014-01-01

    GABAergic neurons specifically active during paradoxical sleep (PS) localized in the dorsal paragigantocellular reticular nucleus (DPGi) are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

  18. Phase-dependent activity of neurons in the rostral part of the thalamic reticular nucleus with saccharin intake in a cue-guided lever-manipulation task.

    PubMed

    Aoki, Ryuhei; Kato, Risako; Fujita, Satoshi; Shimada, Jun; Koshikawa, Noriaki; Kobayashi, Masayuki

    2017-03-01

    Neurons in the rostral part of the thalamic reticular nucleus (rTRN) receive somatosensory and motor information and regulate neural activities of the thalamic nuclei. Previous studies showed that when activity in visual TRN neurons is suppressed prior to the visual stimuli in a visual detection task, the performance of the task improves. However, little is known about such changes in the rTRN preceding certain events. In the present study, we performed unit recordings in the rTRN in alert rats during a cue-guided lever-manipulation task in which saccharin was provided as a reward. Changes in neural activity during saccharin intake were observed in 56% (51 of 91) of the recorded neurons; the firing rates increased in 21 neurons and decreased in 23 neurons. Seven neurons both increased and decreased their firing rates during saccharin intake. Changes in firing rates during the reward-waiting stage between task termination and saccharin intake were also observed in 73% (37 of 51) of the neurons that responded to saccharin intake. Increased activity during saccharin intake did not correlate with increased activity during lever-manipulation or activity during the reward-waiting stage. However, decreased activity during saccharin intake was correlated with activity during the reward-waiting stage. These results suggest that rTRN neurons have phase-dependent changes in their activity and regulate the thalamic activities. Furthermore, the decreased activity of rTRN neurons before reward may contribute to refine somatosensory and motor information processing in the thalamic nuclei depending on the status of mind such as expectation and attention.

  19. Is state-dependent alternation of slow dynamics in central single neurons during sleep present in the rat ventroposterior thalamic nucleus?

    PubMed

    Takahashi, Kazumi; Koyama, Yoshimasa; Kayama, Yukihiko; Nakamura, Kazuhiro; Yamamoto, Mitsuaki

    2004-02-01

    Based upon our previous results in cats, we hypothesized that neurons in the central processor systems of the brain generally exhibit state-dependent dynamics alternation of slow fluctuations in spontaneous activity during sleep. To test the validity of this hypothesis across species, we recorded single neuronal activity during sleep from the ventroposterior (VP) thalamic nucleus in unanesthetized, head-restrained rats. Spectral analysis was performed on successive spike-counts of neuronal activity recorded during three stages of the sleep-wakefulness cycle: wakefulness (W, n=6), slow-wave sleep (SWS, n=20), and paradoxical sleep (PS, n=32). We found that firing of VP neurons displayed white-noise-like dynamics over the range of 0.04-1.0 Hz during SWS and 1/f-noise-like dynamics over the same range during PS. We also demonstrated for the first time that the slow dynamics of neuronal activity during quiet wakefulness (but not drowsiness) are white-noise-like. These results suggest that our hypothesis is true across species. During W and SWS, the brain may be considered as under global inhibition. Conversely, PS may represent a state of global disinhibition in the brain, where neuronal activity exhibits 1/f-noise-like dynamics. Fluctuations observed in living organisms may be involved in essential processes in generation and function of sleep states.

  20. Orexinergic innervation of urocortin1 and cocaine and amphetamine regulated transcript neurons in the midbrain centrally projecting Edinger-Westphal nucleus.

    PubMed

    Emmerzaal, T L; vd Doelen, R H A; Roubos, E W; Kozicz, T

    2013-12-01

    Orexin is a neuropeptide that has been implicated in several processes, such as induction of appetite, arousal and alertness and sleep/wake regulation. Multiple lines of evidence also suggest that orexin is involved in the stress response. When orexin is administered intracerebroventricular it activates the hypothalamic pituitary adrenal (HPA)-axis, which is the main regulator of the stress response. The HPA-axis is not the only player in the stress response evidence suggests that urocortin 1 (Ucn1), a member of the corticotropin releasing factor (CRF) neuropeptide family, also plays an important role in the stress response adaptation. Ucn1 is primarily synthetized in the centrally projecting Edinger-Westphal nucleus (EWcp), which also receives dense innervation by orexin terminals. In this study we tested the hypothesis that orexin would directly shape the response of EWcp-Ucn1 neurons to acute cold stress. To test this hypothesis, we first assessed whether orexinergic axon terminals would innervate EWcp-Ucn1/CART neurons, and next we exposed orexin deficient (orexin-KO) male mice and their male wild-type (WT) littermates to acute cold stress for 2h. We also assessed stress-associated changes in plasma corticosterone (CORT), as well as the activation of Ucn1/CART neurons in the EWcp nucleus. We found that orexin immunoreactive axon terminals were juxtaposed to EWcp-Ucn1/CART neurons, which also expressed orexin receptor 1 mRNA. Furthermore, acute stress strongly activated the EWcp-Ucn1/CART neurons and increased plasma CORT in both WT littermates and orexin-KO mice, however no genotype effect was found on these indices. Taken together our data show that orexin in general is not involved in the animal's acute stress response (plasma CORT) and it does not play a direct role in shaping the response of EWcp-Ucn1 neurons to acute stress either.

  1. Expression of ankyrin repeat and suppressor of cytokine signaling box protein 4 (Asb-4) in proopiomelanocortin neurons of the arcuate nucleus of mice produces a hyperphagic, lean phenotype.

    PubMed

    Li, Ji-Yao; Chai, Biao-Xin; Zhang, Weizhen; Wang, Hui; Mulholland, Michael W

    2010-01-01

    Ankyrin repeat and suppressor of cytokine signaling box-containing protein 4 (Asb-4) is specifically expressed in the energy homeostasis-related brain areas and colocalizes with proopiomelanocortin (POMC) neurons of the arcuate nucleus (ARC). Injection of insulin into the third ventricle of the rat brain increased Asb-4 mRNA expression in the paraventricular nucleus but not in the ARC of the hypothalamus, whereas injection of leptin (ip) increased Asb-4 expression in both mouse paraventricular nucleus and ARC. A transgenic mouse in which Myc-tagged Asb-4 is specifically expressed in POMC neurons of the ARC was made and used to study the effects of Asb-4 on ingestive behavior and metabolic rate. Animals with overexpression of Asb-4 in POMC neurons demonstrated an increase in food intake. However, POMC-Asb-4 transgenic animals gained significantly less weight from 6-30 wk of age. The POMC-Asb-4 mice had reduced fat mass and increased lean mass and lower levels of blood leptin. The transgenic animals were resistant to high-fat diet-induced obesity. Transgenic mice had significantly higher rates of oxygen consumption and carbon dioxide production than wild-type mice during both light and dark periods. The locomotive activity of transgenic mice was increased. The overexpression of Asb-4 in POMC neurons increased POMC mRNA expression in the ARC. The transgenic animals had no observed effect on peripheral glucose metabolism and the activity of the autonomic nervous system. These results indicate that Asb-4 is a key regulatory protein in the central nervous system, involved in the control of feeding behavior and metabolic rate.

  2. Repeated social defeat increases reactive emotional coping behavior and alters functional responses in serotonergic neurons in the rat dorsal raphe nucleus.

    PubMed

    Paul, Evan D; Hale, Matthew W; Lukkes, Jodi L; Valentine, McKenzie J; Sarchet, Derek M; Lowry, Christopher A

    2011-08-03

    Chronic stress is a vulnerability factor for a number of psychiatric disorders, including anxiety and affective disorders. Social defeat in rats has proven to be a useful paradigm to investigate the neural mechanisms underlying physiologic and behavioral adaptation to acute and chronic stress. Previous studies suggest that serotonergic systems may contribute to the physiologic and behavioral adaptation to chronic stress, including social defeat in rodent models. In order to test the hypothesis that repeated social defeat alters the emotional behavior and the excitability of brainstem serotonergic systems implicated in control of emotional behavior, we exposed adult male rats either to home cage control conditions, acute social defeat, or social defeat followed 24h later by a second social defeat encounter. We then assessed behavioral responses during social defeat as well as the excitability of serotonergic neurons within the dorsal raphe nucleus using immunohistochemical staining of tryptophan hydroxylase, a marker of serotonergic neurons, and the protein product of the immediate-early gene, c-fos. Repeated social defeat resulted in a shift away from proactive emotional coping behaviors, such as rearing (explorative escape behavior), and toward reactive emotional coping behaviors such as freezing. Both acute and repeated defeat led to widespread increases in c-Fos expression in serotonergic neurons in the dorsal raphe nucleus. Changes in behavior following a second exposure to social defeat, relative to acute defeat, were associated with decreased c-Fos expression in serotonergic neurons within the dorsal and ventral parts of the mid-rostrocaudal dorsal raphe nucleus, regions that have been implicated in 1) serotonergic modulation of fear- and anxiety-related behavior and 2) defensive behavior in conspecific aggressive encounters, respectively. These data support the hypothesis that serotonergic systems play a role in physiologic and behavioral responses to both

  3. Topographic organizations of taste-responsive neurons in the parabrachial nucleus of C57BL/6J mice: An electrophysiological mapping study.

    PubMed

    Tokita, K; Boughter, J D

    2016-03-01

    The activities of 178 taste-responsive neurons were recorded extracellularly from the parabrachial nucleus (PbN) in the anesthetized C57BL/6J mouse. Taste stimuli included those representative of five basic taste qualities, sweet, salty, sour, bitter and umami. Umami synergism was represented by all sucrose-best and sweet-sensitive sodium chloride-best neurons. Mediolaterally the PbN was divided into medial, brachium conjunctivum (BC) and lateral subdivisions while rostrocaudally the PbN was divided into rostral and caudal subdivisions for mapping and reconstruction of recording sites. Neurons in the medial and BC subdivisions had a significantly greater magnitude of response to sucrose and to the mixture of monopotassium glutamate and inosine monophosphate than those found in the lateral subdivision. In contrast, neurons in the lateral subdivision possessed a more robust response to quinine hydrochloride. Rostrocaudally no difference was found in the mean magnitude of response. Analysis on the distribution pattern of neuron types classified by their best stimulus revealed that the proportion of neuron types in the medial vs. lateral and BC vs. lateral subdivisions was significantly different, with a greater amount of sucrose-best neurons found medially and within the BC, and a greater amount of sodium chloride-, citric acid- and quinine hydrochloride-best neurons found laterally. There was no significant difference in the neuron-type distribution between rostral and caudal PbN. We also assessed breadth of tuning in these neurons by calculating entropy (H) and noise-to-signal (N/S) ratio. The mean N/S ratio of all neurons (0.43) was significantly lower than that of H value (0.64). Neurons in the caudal PbN had a significantly higher H value than in the rostral PbN. In contrast, mean N/S ratios were not different both mediolaterally and rostrocaudally. These results suggest that although there is overlap in taste quality representation in the mouse PbN, taste

  4. Behavioral Flexibility Is Increased by Optogenetic Inhibition of Neurons in the Nucleus Accumbens Shell during Specific Time Segments

    ERIC Educational Resources Information Center

    Aquili, Luca; Liu, Andrew W.; Shindou, Mayumi; Shindou, Tomomi; Wickens, Jeffery R.

    2014-01-01

    Behavioral flexibility is vital for survival in an environment of changing contingencies. The nucleus accumbens may play an important role in behavioral flexibility, representing learned stimulus-reward associations in neural activity during response selection and learning from results. To investigate the role of nucleus accumbens neural activity…

  5. The human thalamic somatic sensory nucleus [ventral caudal (Vc)] shows neuronal mechanoreceptor-like responses to optimal stimuli for peripheral mechanoreceptors.

    PubMed

    Weiss, N; Ohara, S; Johnson, K O; Lenz, F A

    2009-02-01

    Although the response of human cutaneous mechanoreceptors to controlled stimuli is well studied, it is not clear how these peripheral signals may be reflected in neuronal activity of the human CNS. We now test the hypothesis that individual neurons in the human thalamic principal somatic sensory nucleus [ventral caudal (Vc)] respond selectively to the optimal stimulus for one of the four mechanoreceptors. The optimal stimuli for particular mechanoreceptors were defined as follows: Pacinian corpuscles (PC), vibration at 128 Hz; rapidly adapting (RA), vibration at 32 or 64 Hz; slowly adapting type 1 (SA1), edge; slowly adapting type 2 (SA2), skin stretch. Nineteen neurons had a significant response to at least one optimal stimulus, and 17 had a significantly greater response to one stimulus than to the other three, including 7 PC-related, 7 RA-like, 3 SA1-like, and 2 SA2-like neurons. One of each of the SA1- and SA2-like thalamic neurons responded to vibration with firing rates that were lower than those to edge or stretch but not significantly. Except in the case of PC-related neurons, the receptive field (RF) sizes were larger for these thalamic neurons than for the corresponding mechanoreceptor. Von Frey thresholds were higher than those for the corresponding human RA and SA1 mechanoreceptors. These results suggest that there is a convergence of pathways transmitting input from multiple mechanoreceptors of one type on single thalamic neurons via the dorsal columns. They are also consistent with the presence of primate thalamic elements of modality and somatotopic isorepresentation.

  6. Aggressive Encounters Alter the Activation of Serotonergic Neurons and the Expression of 5-HT1A mRNA in the Hamster Dorsal Raphe Nucleus

    PubMed Central

    Cooper, Matthew A.; Grober, Matthew S.; Nicholas, Christopher; Huhman, Kim L.

    2009-01-01

    Serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN) have been implicated in stress-induced changes in behavior. Previous research indicates that stressful stimuli activate 5-HT neurons in select subregions of the DRN. Uncontrollable stress is thought to sensitize 5-HT neurons in the DRN and allow for an exaggerated 5-HT response to future stimuli. In the current study, we tested the hypothesis that following aggressive encounters, losing male Syrian hamsters would exhibit increased c-Fos immunoreactivity in 5-HT DRN neurons compared to winners or controls. In addition, we tested the hypothesis that losers would have decreased 5-HT1A mRNA levels in the DRN compared to winners or controls. We found that a single 15-min aggressive encounter increased c-Fos expression in 5-HT and non-5-HT neurons in losers compared to winners and controls. The increased c-Fos expression in losers was restricted to ventral regions of the rostral DRN. We also found that four 5-min aggressive encounters reduced total 5-HT1A mRNA levels in the DRN in losers compared to winners and controls, and that differences in mRNA levels were not restricted to specific DRN subregions. These results suggest that social defeat activates neurons in select subregions of the DRN and reduces message for DRN 5-HT1A autoreceptors. Our results support the hypothesis that social stress can activate 5-HT neurons in the DRN, reduce 5-HT1A autoreceptor-mediated inhibition, and lead to hyperactivity of 5-HT neurons. PMID:19362123

  7. Differential regulation of parvocellular neuronal activity in the paraventricular nucleus of the hypothalamus following single vs. repeated episodes of water restriction-induced drinking.

    PubMed

    Arnhold, Michelle M; Wotus, Cheryl; Engeland, William C

    2007-07-01

    Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated glucocorticoids has deleterious effects. Due to the potential benefits of limiting stress-induced glucocorticoid secretion, the present study uses drinking in dehydrated rats as a model to delineate mechanisms mobilized to rapidly inhibit HPA activity during stress. Using Fos expression as an indicator of neuronal activation, the effect of a single or repeated episode of dehydration-induced drinking on the activity of magnocellular and parvocellular neurons in the paraventricular nucleus (PVN) of the hypothalamus was examined. Adult male rats underwent a single episode or repeated (six) episodes of water restriction and were sacrificed before or after drinking water in the AM. Plasma osmolality, vasopressin (AVP), adrenocorticotropic hormone (ACTH) and corticosterone were elevated by water restriction and reduced after drinking in both models. Fos expression was elevated in AVP-positive magnocellular PVN neurons and AVP- and corticotropin releasing hormone (CRH)-positive parvocellular PVN neurons after water restriction. Fos expression was reduced in magnocellular AVP neurons after both models of restriction-induced drinking. In contrast, Fos expression did not change in AVP and CRH parvocellular neurons after a single episode of restriction-induced drinking, but was reduced after repeated episodes of restriction-induced drinking. These data indicate that drinking-induced decreases in glucocorticoids in dehydrated rats involve multiple factors including reduction in magnocellular release of vasopressin and reduction in parvocellular neuronal activity. The differential inhibition of PVN parvocellular neurons after repeated rehydration may reflect a conditioned response to repeated stress reduction.

  8. Postnatal Excitability Development and Innervation by Functional Transient Receptor Potential Vanilloid 1 (TRPV1) Terminals in Neurons of the Rat Spinal Sacral Dorsal Commissural Nucleus: an Electrophysiological Study.

    PubMed

    Yang, Kun

    2016-11-01

    The sacral dorsal commissural nucleus (SDCN) in the spinal cord receives both somatic and visceral primary afferents. Transient receptor potential vanilloid 1 (TRPV1) channels are preferentially expressed in certain fine primary afferents. However, knowledge of the SDCN neurons postnatal excitability development and their contacts with TRPV1 fibers remains elusive. Here, whole-cell recordings were conducted in spinal cord slices to evaluate the postnatal development of SDCN neurons and their possible contacts with functional TRPV1-expressing terminals. SDCN neurons in neonatal (postnatal day (P) 1-2), young (P8-10), and adult rats (P35-40) have different electrophysiological properties. SDCN neurons in neonatal rats have higher frequency of spontaneous firing, higher resting membrane potential, and lower presynaptic glutamate release probability. However, no difference in quantal release was found. At all developmental stages, TRPV1 activation with the selective agonist capsaicin increases glutamate release in the presence of tetrodotoxin, which blocks action potential-dependent and polysynaptic neurotransmission, indicating that functional TRPV1 fibers innervate SDCN neurons directly. Capsaicin-induced presynaptic glutamate release onto SDCN neurons depends on external Ca(2+) influx through TRPV1 channels; voltage-dependent calcium channels had a slighter impact. In contrast, capsaicin blocked C fiber-evoked synaptic transmission, indicating that TRPV1 activation has opposite effects on spontaneous asynchronous and action potential-dependent synchronous glutamate release. These data indicate that excitability of SDCN neurons undergoes a developmental shift, and these neurons receive functional TRPV1 terminals from early postnatal stage. The opposite action of capsaicin on asynchronous and synchronous glutamate release should be taken into account when TRPV1 channels are considered as therapeutic targets.

  9. Properties of native P2X receptors in large multipolar neurons dissociated from rat hypothalamic arcuate nucleus.

    PubMed

    Wakamori, Minoru; Sorimachi, Masaru

    2004-04-16

    ATP, the ligand of P2X receptors, is a candidate of neurotransmitter or co-transmitter in the peripheral and the central nervous systems. Anatomical studies have revealed the wide distribution of P2X receptors in the brain. So far, P2X-mediated small synaptic responses have been recorded in some brain regions. To determine the physiological significance of postsynaptic ATP receptors in the brain, we have investigated the P2X responses in rat dissociated hypothalamic arcuate neurons by using the patch-clamp technique. ATP evoked inward currents in a concentration-dependent manner (EC(50)=42 microM) at a holding potential of -70 mV. The current-voltage relationship showed a marked inward rectification starting around -10 mV. Although neither 300 microM alphabeta-methylene-ATP nor 300 microM betagamma-methylene-ATP induced any currents, 100 microM ATPgammaS and 100 microM 2-methylthio-ATP evoked inward currents of which amplitude was about 60% of the control currents evoked by 100 microM ATP. PPADS, one of P2 receptor antagonists, inhibited the ATP-evoked currents in a time- and a concentration-dependent manners (IC(50)=19 microM at 2 min). Permeant Ca(2+) inhibited the ATP-evoked currents in the range of millimolars (IC(50)=7 mM); however, Cd(2+) (1-300 microM), a broad cation channel blocker, facilitated the currents with slow off-response. Zn(2+) in the range of 1-100 microM facilitated the currents whereas Zn(2+) at the concentrations over 100 microM inhibited the currents. These observations suggest that functional P2X receptors are expressed in the hypothalamic arcuate nucleus. The most likely subunit combinations of the P2X receptors are P2X(2)-homomultimer and P2X(2)/P2X(6)-heteromultimer.

  10. D5 (not D1) dopamine receptors potentiate burst-firing in neurons of the subthalamic nucleus by modulating an L-type calcium conductance.

    PubMed

    Baufreton, Jérôme; Garret, Maurice; Rivera, Alicia; de la Calle, Adélaïda; Gonon, François; Dufy, Bernard; Bioulac, Bernard; Taupignon, Anne

    2003-02-01

    Dopamine is a crucial factor in basal ganglia functioning. In current models of basal ganglia, dopamine is postulated to act on striatal neurons. However, it may also act on the subthalamic nucleus (STN), a key nucleus in the basal ganglia circuit. The data presented here were obtained in brain slices using whole-cell patch clamp. They reveal that D5 dopamine receptors strengthen electrical activity in the subset of subthalamic neurons endowed with burst-firing capacity, resulting in longer discharges of spontaneous or evoked bursts. To distinguish between D1 and D5 subtypes, the action of agonists in the D1/D5 receptor family was first investigated on rat subthalamic neurons. Single-cell reverse transcription-PCR profiling showed that burst-competent neurons only expressed D5 receptors. Accordingly, receptors localized in postsynaptic membranes within the STN were labeled by a D5-specific antibody. Second, agonists in the D1/D5 family were tested in mouse brain slices. It was found that these agonists were active in D1 receptor knock-out mice in a similar way to wild-type mice or rats. This proved that D5 rather than D1 receptors were involved. Pharmacological tools (dihydropyridines, omega-conotoxins, and calciseptine) were used to identify the target of D5 receptors as an L-type channel. This was reached via G-protein and protein kinase A. The action of dopamine on D5 receptors therefore shapes neuronal activity. It contributes to normal information processing in basal ganglia outside striatum. This finding may be useful in drug therapy for various disorders involving changes in STN activity, such as Parkinson's disease and related disorders.

  11. Estrogen in cycling rats alters gene expression in the temporomandibular joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper cervical cord junction.

    PubMed

    Puri, Jyoti; Bellinger, Larry L; Kramer, Phillip R

    2011-12-01

    Females report temporomandibular joint (TMJ) pain more than men and studies suggest estrogen modulates this pain response. Our goal in this study was to determine genes that are modulated by physiological levels of 17β-estradiol that could have a role in TMJ pain. To complete this goal, saline or complete Freund's adjuvant was injected in the TMJ when plasma 17β-estradiol was low or when it was at a high proestrus level. TMJ, trigeminal ganglion, and trigeminal subnucleus caudalis/upper cervical cord junction (Vc/C(1-2) ) tissues were isolated from the treated rats and expression of 184 genes was quantitated in each tissue using real-time PCR. Significant changes in the amount of specific transcripts were observed in the TMJ tissues, trigeminal ganglia, and Vc/C(1-2) region when comparing rats with high and low estrogen. GABA A receptor subunit α6 (Gabra6) and the glycine receptor α2 (Glra2) were two genes of interest because of their direct function in neuronal activity and a >29-fold increase in the trigeminal ganglia was observed in proestrus rats with TMJ inflammation. Immunohistochemical studies showed that Gabrα6 and Glrα2 neuronal and not glial expression increased when comparing rats with high and low estrogen. Estrogen receptors α and β are present in neurons of the trigeminal ganglia, whereby 17β-estradiol can alter expression of Gabrα6 and Glrα2. Also, estrogen receptor α (ERα) but not ERβ was observed in satellite glial cells of the trigeminal ganglia. These results demonstrate that genes associated with neurogenic inflammation or neuronal excitability were altered by changes in the concentration of 17β-estradiol.

  12. IL-1beta in the trigeminal subnucleus caudalis contributes to extra-territorial allodynia/hyperalgesia following a trigeminal nerve injury.

    PubMed

    Takahashi, Kouji; Watanabe, Mineo; Suekawa, Yohei; Ito, Goshi; Inubushi, Toshihiro; Hirose, Naoto; Murasaki, Kyoko; Hiyama, Shinji; Uchida, Takashi; Tanne, Kazuo

    2011-05-01

    It has been reported that the whisker pad (WP) area, which is innervated by the second branch of the trigeminal nerve, shows allodynia/hyperalgesia following transection of the mental nerve (MN: the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain induction still remain unclear. Glia and cytokines are known to facilitate perception of noxious input, raising a possibility that these non-neuronal elements are involved in the induction and spread of allodynia/hyperalgesia at non-injured skin territory. One day after MN transection, tactile allodynia/hyperalgesia developed on the ipsilateral WP area, which is in the non-injured skin territory. The tactile allodynia/hyperalgesia lasted for more than 56 days. In response to MN transection, astrocytes and microglia appeared to be in an activated state, and interleukin (IL)-1beta was up-regulated in astrocytes in the trigeminal subnucleus caudalis (Vc). Allodynia/hyperalgesia at WP area induced by MN transection was attenuated dose-dependently by IL-1 receptor antagonist IL-1ra (i.t., 0.05, 0.5, and 5 pg/rat). Fos-like immunoreactive (Fos-Li) neurons were observed in the Vc after non-noxious mechanical stimulation of the WP area in the rats with MN transection. Administration of IL-1ra also attenuated the number of Fos-Li neurons dose-dependently. Administration of a noncompetitive antagonist of NMDA receptors MK-801 (i.t., 5 μg/rat) reversed allodynia/hyperalgesia. IL-1 receptor type I (IL-1RI) was localized in Fos- and phospho NR1-immunoreactive neurons. These results suggest that IL-1beta in the Vc plays an important role in the development of extra-territorial tactile allodynia/hyperalgesia after MN transection.

  13. [Neuronal activity of the head of the caudate nucleus during formation of positive and inhibitory motor alimentary conditioned reflexes in cats].

    PubMed

    Driagin, Iu M

    1977-01-01

    Cellular activity of the caudate nucleus head was studied on 15 cats during motor alimentary conditioning, extinction and elaboration of differentiation response. Analysis of the dynamics of the appearance and stabilization of neuronal conditioned responses attests that the caudate nuclei are a part of the morpho-functional structure of the given conditioned reflex. A functional heterogeneity within the nuclels head has been shown on the basis of responses of the cells during conditioned and unconditioned behaviour. It has been assumed that cellular populations of the ventral segment of the caudate nucleus head are predominantly involved in providing for a normal course of the processes of extinction and detection of significant signals in this form of conditioned alimentary behaviour in cats.

  14. Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

    PubMed Central

    Yasrebi, Ali; Hsieh, Anna; Mamounis, Kyle J.; Krumm, Elizabeth A.; Yang, Jennifer A.; Magby, Jason; Hu, Pu; Roepke, Troy A.

    2015-01-01

    Ghrelin’s receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner. PMID:26577678

  15. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse

    PubMed Central

    Navarro, VM; Gottsch, ML; Chavkin, C; Okamura, H; Clifton, DK; Steiner, RA

    2009-01-01

    Kisspeptin is encoded by the Kiss1 gene and kisspeptin signaling plays a critical role in reproduction. In rodents, kisspeptin neurons in the arcuate nucleus (Arc) provide tonic drive to GnRH neurons, which in turn supports basal LH secretion. Our objectives were to determine whether preprodynorphin (Dyn) and neurokinin B (NKB) are coexpressed in Kiss1 neurons in the mouse and to evaluate its physiological significance. Using in situ hybridization, we found that Kiss1 neurons in the Arc of female mice not only express the Dyn and NKB genes, but also the NKB receptor gene (NK3) and the Dyn receptor (the kappa opioid receptor, KOR) gene. We also found that expression of the Dyn, NKB, KOR, and NK3 in the Arc are inhibited by estradiol (E2), as has been established for Kiss1, and confirmed that Dyn and NKB inhibit LH secretion. Moreover, using Dyn and KOR knockout mice, we found that long-term disruption of Dyn/KOR signaling compromises the rise of LH after ovariectomy. We propose a model whereby NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in the median eminence. PMID:19776272

  16. A painful cutaneous laser stimulus evokes responses from single neurons in the human thalamic principal somatic sensory nucleus ventral caudal (Vc).

    PubMed

    Kobayashi, K; Winberry, J; Liu, C C; Treede, R D; Lenz, F A

    2009-05-01

    Cutaneous application of painful radiant heat laser pulses evokes potentials (laser-evoked potentials) that can be recorded from scalp or intracranial electrodes. We have now tested the hypothesis that the response of thalamic neurons to a cutaneous laser stimulus occurs at latencies predicted by the conduction delay between the periphery and the thalamus. We have carried out recordings from human thalamic neurons in the principal sensory nucleus (ventral caudal) in patients undergoing awake surgery for the treatment of tremor. The results demonstrate that many neurons respond to the laser with early and/or late latency peaks of activity, consistent with conduction of the response to the laser stimulus through pathways from Adelta and C fibers to the thalamus. These peaks were of short duration, perhaps due to the somatotopic- and modality-specific arrangements of afferent pathways to the thalamus. The responses of these thalamic neurons to the laser stimulus sometimes included low-threshold spike (LTS) bursts of action potentials, consistent with previous studies of different painful stimuli. A prior study has demonstrated that spike trains characterized by common LTS bursts such as the intermediate (I) category spontaneously change their category more commonly than do those without LTS bursts (NG: nongrouped category) during changes in the cognitive task. Spike trains of laser-responsive neurons were more common in the I category, whereas those of laser nonresponsive neurons were more common in the NG category. Therefore neuronal spike trains in the I category may mediate shifts in endogenous or cognitive pain-related behavior.

  17. Expression of doublecortin, a neuronal migration protein, in unipolar brush cells of the vestibulocerebellum and dorsal cochlear nucleus of the adult rat

    PubMed Central

    Manohar, Senthilvelan; Paolone, Nicholas A.; Bleichfeld, Marni; Hayes, Sarah; Salvi, Richard J.; Baizer, Joan S.

    2011-01-01

    Doublecortin (DCX) is a microtubule associated protein that is critical for neuronal migration and the development of the cerebral cortex. In the adult, it is expressed in newborn neurons in the subventricular and subgranular zones but not in the mature neurons of the cerebral cortex. By contrast, neurogenesis and neuronal migration of cells in the cerebellum continue into early postnatal life; migration of one class of cerebellar interneuron, unipolar brush cells (UBCs), may continue into adulthood. To explore the possibility of continued neuronal migration in the adult cerebellum, closely spaced sections through the brainstem and cerebellum of adult (3–16 months old) Sprague Dawley rats were immunolabeled for DCX. Neurons immunoreactive (ir) to DCX were present in the granular cell layer of the vestibulocerebellum, most densely in the transition zone (tz), the region between the flocculus (FL) and ventral paraflocculus (PFL), as well as in the dorsal cochlear nucleus (DCN). These DCX-ir cells had the morphological appearance of unipolar brush cells (UBCs) with oval somata and a single dendrite ending in a “brush.” There were many examples of colocalization of DCX with Eps8 or calretinin, UBC markers. We also identified DCX-ir elements along the fourth ventricle and its lateral recess that had labeled somata but lacked the dendritic structure characteristic of UBCs. Labeled UBCs were seen in nearby white matter. These results suggest that there may be continued neurogenesis and/or migration of UBCs in the adult. Another possibility is that UBCs maintain DCX expression even after migration and maturation, reflecting a role of DCX in adult neuronal plasticity in addition to a developmental role in migration. PMID:22198017

  18. SDF-1α/CXCL12 enhances GABA and glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus

    PubMed Central

    Heinisch, Silke; Kirby, Lynn G.

    2009-01-01

    Summary The serotonin (5-hydroxytryptamine; 5-HT) system has a well-characterized role in depression. Recent reports describe comorbidities of mood-immune disorders, suggesting an immunological component may contribute to the pathogenesis of depression as well. Chemokines, immune proteins which mediate leukocyte trafficking, and their receptors are widely distributed in the brain, mediate neuronal patterning, and modulate various neuropathologies. The purpose of this study was to investigate the neuroanatomical relationship and functional impact of the chemokine stromal cell-derived factor-1α/CXCL12 and its receptor, CXCR4, on the serotonin dorsal raphe nucleus (DRN) system in the rat using anatomical and electrophysiological techniques. Immunohistochemical analysis indicates that over 70% of 5-HT neurons colocalize with CXCL12 and CXCR4. At a subcellular level, CXCL12 localizes throughout the cytoplasm whereas CXCR4 concentrates to the outer membrane and processes of 5-HT neurons. CXCL12 and CXCR4 also colocalize on individual DRN cells. Furthermore, electrophysiological studies demonstrate CXCL12 depolarization of 5-HT neurons indirectly via glutamate synaptic inputs. CXCL12 also enhances the frequency of spontaneous inhibitory and excitatory postsynaptic currents (sIPSC and sEPSC). CXCL12 concentration-dependently increases evoked IPSC amplitude and decreases evoked IPSC paired-pulse ratio selectively in 5-HT neurons, effects blocked by the CXCR4 antagonist AMD3100. These data indicate presynaptic enhancement of GABA and glutamate release at 5-HT DRN neurons by CXCL12. Immunohistochemical analysis further shows CXCR4 localization to DRN GABA neurons, providing an anatomical basis for CXCL12 effects on GABA release. Thus, CXCL12 indirectly modulates 5-HT neurotransmission via GABA and glutamate synaptic afferents. Future therapies targeting CXCL12 and other chemokines may treat serotonin related mood disorders, particularly depression experienced by immune

  19. Transplants of cells genetically modified to express neurotrophin-3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats.

    PubMed

    Himes, B T; Liu, Y; Solowska, J M; Snyder, E Y; Fischer, I; Tessler, A

    2001-09-15

    To test the idea that genetically engineered cells can rescue axotomized neurons, we transplanted fibroblasts and immortalized neural stem cells (NSCs) modified to express neurotrophic factors into the injured spinal cord. The neurotrophin-3 (NT-3) or nerve growth factor (NGF) transgene was introduced into these cells using recombinant retroviral vectors containing an internal ribosome entry site (IRES) sequence and the beta-galactosidase or alkaline phosphatase reporter gene. Bioassay confirmed biological activity of the secreted neurotrophic factors. Clarke's nucleus (CN) axons, which project to the rostral spinal cord and cerebellum, were cut unilaterally in adult rats by T8 hemisection. Rats received transplants of fibroblasts or NSCs genetically modified to express NT-3 or NGF and a reporter gene, only a reporter gene, or no transplant. Two months postoperatively, grafted cells survived at the hemisection site. Grafted fibroblasts and NSCs expressed a reporter gene and immunoreactivity for the NGF or NT-3 transgene. Rats receiving no transplant or a transplant expressing only a reporter gene showed a 30% loss of CN neurons in the L1 segment on the lesioned side. NGF-expressing transplants produced partial rescue compared with hemisection alone. There was no significant neuron loss in rats receiving grafts of either fibroblasts or NSCs engineered to express NT-3. We postulate that NT-3 mediates survival of CN neurons through interaction with trkC receptors, which are expressed on CN neurons. These results support the idea that NT-3 contributes to long-term survival of axotomized CN neurons and show that genetically modified cells rescue axotomized neurons as efficiently as fetal CNS transplants.

  20. Connections between EM2-containing terminals and GABA/μ-opioid receptor co-expressing neurons in the rat spinal trigeminal caudal nucleus

    PubMed Central

    Li, Meng-Ying; Wu, Zhen-Yu; Lu, Ya-Cheng; Yin, Jun-Bin; Wang, Jian; Zhang, Ting; Dong, Yu-Lin; Wang, Feng

    2014-01-01

    Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect via the μ-opioid receptor (MOR). To provide morphological evidence for the pain control effect of EM2, the synaptic connections between EM2-immunoreactive (IR) axonal terminals and γ-amino butyric acid (GABA)/MOR co-expressing neurons in lamina II of the spinal trigeminal caudal nucleus (Vc) were investigated in the rat. Dense EM2-, MOR- and GABA-IR fibers and terminals were mainly observed in lamina II of the Vc. Within lamina II, GABA- and MOR-neuronal cell bodies were also encountered. The results of immunofluorescent histochemical triple-staining showed that approximately 14.2 or 18.9% of GABA-IR or MOR-IR neurons also showed MOR- or GABA-immunopositive staining in lamina II; approximately 45.2 and 36.1% of the GABA-IR and MOR-IR neurons, respectively, expressed FOS protein in their nuclei induced by injecting formalin into the left lower lip of the mouth. Most of the GABA/MOR, GABA/FOS, and MOR/FOS double-labeled neurons made close contacts with EM2-IR fibers and terminals. Immuno-electron microscopy confirmed that the EM2-IR terminals formed synapses with GABA-IR or MOR-IR dendritic processes and neuronal cell bodies in lamina II of the Vc. These results suggest that EM2 might participate in pain transmission and modulation by binding to MOR-IR and GABAergic inhibitory interneuron in lamina II of the Vc to exert inhibitory effect on the excitatory interneuron in lamina II and projection neurons in laminae I and III. PMID:25386121

  1. Serotonin modifies the spontaneous spiking activity of gracile nucleus neurons in rats: role of 5-HT1A and 5-HT2 receptors.

    PubMed

    Grasso, C; Li Volsi, G; Barresi, M

    2016-06-01

    We tested the effects of microiontophoretic application of serotonin (5-HT) on the firing rate of neurons located in the gracile nucleus (GN) of rats. Application of 5-HT1A and 5-HT2 agonists and antagonists respectively mimicked/ modulated and blocked the effects produced by the amine, respectively. Among the tested neurons, 88.2% modified their background firing activity in the presence of 5-HT. Responsive neurons decreased their mean firing activity (MFA) in 56.7% of cases and increased it in the remaining 43.3%. To ascertain the specificity of the effects induced by 5-HT, we utilized 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and alpha-methyl-5-hydroxytryptamine (α-MET-5-HT), agonists for 5-HT1A and 5-HT2 receptors, respectively. The microiontophoresis of 8-OH-DPAT modified the background firing rate of all GN neurons (100% of tested neurons) mimicking the decrease of MFA evoked by 5-HT. The application of a-MET-5-HT modified the MFA in 76.9% of tested neurons, decreasing it in 61.5% of cases and increasing in the remaining 23.1%. The decrease of MFA induced by 8-OH-DPAT was antagonized by application of the 5-HT1A receptor antagonist N-[2-[-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635), while application of 5-HT2 receptor antagonist ketanserine tartrate (KET) antagonized only the increase of MFA induced by a-MET-5-HT. These results indicate that 5-HT is able to modulate the background firing activity of GN neurons by 5-HT1A and 5-HT2 receptors.

  2. Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract.

    PubMed

    Mimee, Andrea; Ferguson, Alastair V

    2015-04-15

    The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis.

  3. NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21).

    PubMed

    Zhang, Xin; Cheng, Bin; Jing, Xianghong; Qiao, Yongfa; Gao, Xinyan; Yu, Huijuan; Zhu, Bing; Qiao, Haifa

    2012-01-01

    A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

  4. Altered Neuronal Firing Pattern of the Basal Ganglia Nucleus Plays a Role in Levodopa-Induced Dyskinesia in Patients with Parkinson’s Disease

    PubMed Central

    Li, Xiaoyu; Zhuang, Ping; Li, Yongjie

    2015-01-01

    Background: Levodopa therapy alleviates the symptoms of Parkinson’s disease (PD), but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID). Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1 ± 11.0 years; disease duration, 8.7 ± 5.6 years) were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr (1967) scores ranged from 2–4 and their UPDRS III scores were 28.5 ± 5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7 ± 1.6). Microelectrode recording was performed in the globus pallidus internus (GPi) and subthalamic nucleus (STN) during pallidotomy (n = 12) or STN deep brain stimulation (DBS; bilateral, n = 12; unilateral, n = 6). The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs) and the corresponding coefficient of variation (CV). Results: A total of 295 neurons were identified from the GPi (n = 12) and STN (n = 18). These included 26 (8.8%) highly grouped discharge, 30 (10.2%) low frequency firing, 78 (26.4%) rapid tonic discharge, 103 (34.9%) irregular activity, and 58 (19.7%) tremor-related activity. There were significant differences between the two groups (p < 0.05) for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID. PMID:26635583

  5. Pick's disease with Pick bodies: an unusual autopsy case showing degeneration of the pontine nucleus, dentate nucleus, Clarke's column, and lower motor neuron.

    PubMed

    Oda, Tatsuro; Tsuchiya, Kuniaki; Arai, Tetsuaki; Togo, Takashi; Uchikado, Hirotake; de Silva, Rohan; Lees, Andrew; Akiyama, Haruhiko; Haga, Chie; Ikeda, Kenji; Kato, Motoichiro; Kato, Yuji; Hara, Tsunekatsu; Onaya, Mitsumoto; Hori, Koji; Teramoto, Hiroshi; Tominaga, Itaru

    2007-02-01

    We report a 51-year-old female with Pick's disease with Pick bodies (PDPB) showing a brainweight of 530 g. This case was considered to be a very rare case of PDPB, in which the lesion developed in the temporal and frontal lobes and later spread to the parietal lobe, occipital lobe, brainstem, cerebellum and spinal cord. This case showed very atypical clinicopathological findings. Clinically, bulging eyes and myoclonus were observed. Neuropathologically, Pick bodies were widely distributed beyond the usual distribution areas to the parietal cortices, occipital cortices, dentate nuclei, motor neuron nuclei in the brain stem, and spinal cord. The atypical clinical symptoms and the widespread neuropathological abnormalities observed in this case seem to represent an extremely extended form of PDPB.

  6. Extrasynaptic localization of glycine receptors in the rat supraoptic nucleus: further evidence for their involvement in glia-to-neuron communication.

    PubMed

    Deleuze, C; Alonso, G; Lefevre, I A; Duvoid-Guillou, A; Hussy, N

    2005-01-01

    Neurons of the rat supraoptic nucleus (SON) express glycine receptors (GlyRs), which are implicated in the osmoregulation of neuronal activity. The endogenous agonist of the receptors has been postulated to be taurine, shown to be released from astrocytes. We here provide additional pieces of evidence supporting the absence of functional glycinergic synapses in the SON. First, we show that blockade of GlyRs with strychnine has no effect on either the amplitude or frequency of miniature inhibitory postsynaptic currents recorded in SON neurons, whereas they were all suppressed by the GABA(A) antagonist gabazine. Then, double immunostaining of sections with presynaptic markers and either GlyR or GABA(A) receptor (GABA(A)R) antibodies indicates that, in contrast with GABA(A)Rs, most GlyR membrane clusters are not localized facing presynaptic terminals, indicative of their extrasynaptic localization. Moreover, we found a striking anatomical association between SON GlyR clusters and glial fibrillary acidic protein (GFAP)-positive astroglial processes, which contain high levels of taurine. This type of correlation is specific to GlyRs, since GABA(A)R clusters show no association with GFAP-positive structures. These results substantiate and strengthen the concept of extrasynaptic GlyRs mediating a paracrine communication between astrocytes and neurons in the SON.

  7. Prolonged Consumption of Sucrose in a Binge-Like Manner, Alters the Morphology of Medium Spiny Neurons in the Nucleus Accumbens Shell

    PubMed Central

    Klenowski, Paul M.; Shariff, Masroor R.; Belmer, Arnauld; Fogarty, Matthew J.; Mu, Erica W. H.; Bellingham, Mark C.; Bartlett, Selena E.

    2016-01-01

    The modern diet has become highly sweetened, resulting in unprecedented levels of sugar consumption, particularly among adolescents. While chronic long-term sugar intake is known to contribute to the development of metabolic disorders including obesity and type II diabetes, little is known regarding the direct consequences of long-term, binge-like sugar consumption on the brain. Because sugar can cause the release of dopamine in the nucleus accumbens (NAc) similarly to drugs of abuse, we investigated changes in the morphology of neurons in this brain region following short- (4 weeks) and long-term (12 weeks) binge-like sucrose consumption using an intermittent two-bottle choice paradigm. We used Golgi-Cox staining to impregnate medium spiny neurons (MSNs) from the NAc core and shell of short- and long-term sucrose consuming rats and compared these to age-matched water controls. We show that prolonged binge-like sucrose consumption significantly decreased the total dendritic length of NAc shell MSNs compared to age-matched control rats. We also found that the restructuring of these neurons resulted primarily from reduced distal dendritic complexity. Conversely, we observed increased spine densities at the distal branch orders of NAc shell MSNs from long-term sucrose consuming rats. Combined, these results highlight the neuronal effects of prolonged binge-like intake of sucrose on NAc shell MSN morphology. PMID:27047355

  8. Chronic alcoholism in the absence of Wernicke-Korsakoff syndrome and cirrhosis does not result in the loss of serotonergic neurons from the median raphe nucleus.

    PubMed

    Baker, K G; Halliday, G M; Kril, J J; Harper, C G

    1996-09-01

    Previous studies have identified alcohol, thiamine deficiency and liver disease as contributing to the neuropathology of alcohol-related brain damage. In order to examine the effects of alcohol toxicity and thiamine deficiency on serotonergic neurons in the median raphe nucleus (MnR), alcoholic and previously published Wernicke-Korsakoff syndrome (WKS) cases without liver disease, were compared with age-matched non-alcoholic controls. While there was no difference between the estimated number of serotonergic neurons in either controls or alcoholics without WKS (means of 63,010 +/- 8,900 and 59,560 +/- 8,010 respectively), a substantial loss of serotonergic neurons was previously found in WKS cases (mean of 19,050 +/- 13,140). Further analysis revealed a significant difference in the maximum daily alcohol consumption between these groups. However, analysis of covariance showed that the number or serotonergic neurons in the MnR did not correlate with the amount of alcohol consumed. Therefore, our results suggest that cell loss in the MnR can be attributed to thiamine deficiency rather than alcohol per se.

  9. Cell bodies of the trigeminal proprioceptive neurons that transmit reflex contraction of the levator muscle are located in the mesencephalic trigeminal nucleus in rats.

    PubMed

    Fujita, Kenya; Matsuo, Kiyoshi; Yuzuriha, Shunsuke; Kawagishi, Kyutaro; Moriizumi, Tetsuji

    2012-12-01

    Since the levator and frontalis muscles lack interior muscle spindles despite being antigravity mixed muscles to involuntarily sustain eyelid opening and eyebrow lifting, this study has proposed a hypothetical mechanism to compensate for this anatomical defect. The voluntary contraction of fast-twitch fibres of the levator muscle stretches the mechanoreceptors in Müller's muscle to evoke proprioception, which continuously induces reflex contraction of slow-twitch fibres of the levator and frontalis muscles. This study confirmed the presence of cell bodies of the trigeminal proprioceptive neurons that transmit reflex contraction of the levator and frontalis muscles. After confirming that severing the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle induced ipsilateral eyelid ptosis, Fluorogold was applied as a tracer to the proximal stump of the trigeminal proprioceptive nerve in rats. Fluorogold labelled the cell bodies of the trigeminal proprioceptive neurons, not in any regions of the rat brain including the trigeminal ganglion, but in the ipsilateral mesencephalic trigeminal nucleus neighbouring the locus ceruleus. Some Fluorogold particles accumulated in the area of the locus ceruleus. The trigeminal proprioceptive neurons could be considered centrally displaced ganglion cells to transmit afferent signal from the mechanoreceptors in Müller's muscle to the mesencephalon, where they may be able to make excitatory synaptic connections with both the oculomotor neurons and the frontalis muscle motoneurons for the involuntary coordination of the eyelid and eyebrow activities, and potentially to the locus ceruleus.

  10. Fibroblast growth factor 21, assisted by elevated glucose, activates paraventricular nucleus NUCB2/Nesfatin-1 neurons to produce satiety under fed states

    PubMed Central

    Santoso, Putra; Nakata, Masanori; Shiizaki, Kazuhiro; Boyang, Zhang; Parmila, Kumari; Otgon-Uul, Zesemdorj; Hashimoto, Koshi; Satoh, Tetsurou; Mori, Masatomo; Kuro-o, Makoto; Yada, Toshihiko

    2017-01-01

    Fibroblast growth factor 21 (FGF21), liver-derived hormone, exerts diverse metabolic effects, being considered for clinical application to treat obesity and diabetes. However, its anorexigenic effect is debatable and whether it involves the central mechanism remains unclarified. Moreover, the neuron mediating FGF21’s anorexigenic effect and the systemic energy state supporting it are unclear. We explored the target neuron and fed/fasted state dependence of FGF21’s anorexigenic action. Intracerebroventricular (ICV) injection of FGF21 markedly suppressed food intake in fed mice with elevated blood glucose. FGF21 induced c-Fos expression preferentially in hypothalamic paraventricular nucleus (PVN), and increased mRNA expression selectively for nucleobindin 2/nesfatin-1 (NUCB2/Nesf-1). FGF21 at elevated glucose increased [Ca2+]i in PVN NUCB2/Nesf-1 neurons. FGF21 failed to suppress food intake in PVN-preferential Sim1-Nucb2-KO mice. These findings reveal that FGF21, assisted by elevated glucose, activates PVN NUCB2/Nesf-1 neurons to suppress feeding under fed states, serving as the glycemia-monitoring messenger of liver-hypothalamic network for integrative regulation of energy and glucose metabolism. PMID:28374855

  11. Neurons in monkey dorsal raphe nucleus code beginning and progress of step-by-step schedule, reward expectation, and amount of reward outcome in the reward schedule task.

    PubMed

    Inaba, Kiyonori; Mizuhiki, Takashi; Setogawa, Tsuyoshi; Toda, Koji; Richmond, Barry J; Shidara, Munetaka

    2013-02-20

    The dorsal raphe nucleus is the major source of serotonin in the brain. It is connected to brain regions related to reward processing, and the neurons show activity related to predicted reward outcome. Clinical observations also suggest that it is important in maintaining alertness and its apparent role in addiction seems to be related to reward processing. Here, we examined whether the neurons in dorsal raphe carry signals about reward outcome and task progress during multitrial schedules. We recorded from 98 single neurons in dorsal raphe of two monkeys. The monkeys perform one, two, or three visual discrimination trials (schedule), obtaining one, two, or three drops of liquid. In the valid cue condition, the length and brightness of a visual cue indicated schedule progress and reward amount, respectively. In the random cue condition, the visual cue was randomly presented with respect to schedule length and reward amount. We found information encoded about (1) schedule onset, (2) reward expectation, (3) reward outcome, and (4) reward amount in the mean firing rates. Information theoretic analysis showed that the temporal variation of the neuronal responses contained additional information related to the progress of the schedule toward the reward rather than only discriminating schedule onset or reward/no reward. When considered in light of all that is known about the raphe in anatomy, physiology, and behavior, the rich encoding about both task progress and predicted reward outcome makes the raphe a strong candidate for providing signals throughout the brain to coordinate persistent goal-seeking behavior.

  12. Serotonin, via HTR2 receptors, excites neurons in a cortical-like pre-motor nucleus necessary for song learning and production

    PubMed Central

    Wood, William E.; Lovell, Peter V.; Mello, Claudio V.; Perkel, David J.

    2011-01-01

    Serotonin (5-HT) is a neuromodulator that is important for neural development, learning and memory, mood, and perception. Dysfunction of the serotonin system is central to depression and other clinically important mood disorders and has been linked with learning deficits. In mammals, 5-HT release from the raphe nuclei in the brainstem can modulate the functional properties of cortical neurons, influencing sensory and motor processing. Birds also have serotonergic neurons in the dorsal raphe, suggesting that 5-HT plays similar roles in sensory and motor processing, perhaps modulating brain circuitry underlying birdsong. To investigate this possibility we measured the effects of 5-HT on spontaneous firing of projection neurons in the premotor robust nucleus of the arcopallium in brain slices from male zebra finches. These neurons are thought be akin to cortical layer V pyramidal neurons. 5-HT dramatically and reversibly enhanced the endogenous firing of RA neurons. Using pharmacological agonists and antagonists in vitro, we determined this action is mediated via HTR2 receptors, which we verified are expressed by in situ hybridization. Finally, focal administration of the serotonin selective reuptake inhibitor (SSRI) fluvoxamine revealed that endogenous 5-HT is sufficient to mediate this effect in vivo. These findings reveal a modulatory action of serotonin on the physiology of the song system circuitry and suggest a novel role of serotonin in regulating song production and/or learning; further understanding of the role of 5-HT in this system may help illuminate the complex role of this neuromodulator in social interactions and motor plasticity in humans. PMID:21957243

  13. Collapsin response mediator protein 4 affects the number of tyrosine hydroxylase-immunoreactive neurons in the sexually dimorphic nucleus in female mice.

    PubMed

    Iwakura, Takashi; Sakoh, Miyuki; Tsutiya, Atsuhiro; Yamashita, Naoya; Ohtani, Akiko; Tsuda, Mumeko C; Ogawa, Sonoko; Tsukahara, Shinji; Nishihara, Masugi; Shiga, Takashi; Goshima, Yoshio; Kato, Tomohiro; Ohtani-Kaneko, Ritsuko

    2013-07-01

    In the sexually dimorphic anteroventral periventricular nucleus (AVPV) of the hypothalamus, females have a greater number of tyrosine hydroxylase-immunoreactive (TH-ir) and kisspeptin-immunoreactive (kisspeptin-ir) neurons than males. In this study, we used proteomics analysis and gene-deficient mice to identify proteins that regulate the number of TH-ir and kisspeptin-ir neurons in the AVPV. Analysis of protein expressions in the rat AVPV on postnatal day 1 (PD1; the early phase of sex differentiation) using two-dimensional fluorescence difference gel electrophoresis followed by MALDI-TOF-MS identified collapsin response mediator protein 4 (CRMP4) as a protein exhibiting sexually dimorphic expression. Interestingly, this sexually differential expressions of CRMP4 protein and mRNA in the AVPV was not detected on PD6. Prenatal testosterone exposure canceled the sexual difference in the expression of Crmp4 mRNA in the rat AVPV. Next, we used CRMP4-knockout (CRMP4-KO) mice to determine the in vivo function of CRMP4 in the AVPV. Crmp4 knockout did not change the number of kisspeptin-ir neurons in the adult AVPV in either sex. However, the number of TH-ir neurons was increased in the AVPV of adult female CRMP4-KO mice as compared with the adult female wild-type mice. During development, no significant difference in the number of TH-ir neurons was detected between sexes or genotypes on embryonic day 15, but a female-specific increase in TH-ir neurons was observed in CRMP4-KO mice on PD1, when the sex difference was not yet apparent in wild-type mice. These results indicate that CRMP4 regulates the number of TH-ir cell number in the female AVPV.

  14. Neuronal development in the trigeminal mesencephalic nucleus of the duck under normal and hypothyroid states: I. A light microscopic morphometric analysis.

    PubMed

    Narayanan, Y; Narayanan, C H

    1987-01-01

    Light microscopic morphometric procedures were used in order to examine the effects of propylthiouracil (PTU) on the development of the mesencephalic nucleus of the trigeminal nerve in the duck. A single vascular injection of a 0.2% solution of PTU was administered at a dosage of 2 microliter/gm embryo weight on embryonic day nine (E9). Control embryos received a similar dose of Ringer's solution. The following parameters of cytodifferentiation of cells of the mesencephalic nucleus of V were studied: somal area profiles, nuclear area, and nuclear cytoplasmic ratios. In addition, the frequency of beak clapping was recorded from E16. Significant differences were observed in somal area profiles in the experimental group at E16 and E18 and in nuclear area profiles from E16 through hatching. Beak activity in the experimental embryos was drastically reduced. It is concluded that PTU induces a retardation in the differentiation of cells of the mesencephalic nucleus of V which may lead to behavior deficits as evidenced by reduction of beak activity. These observations provide a basis for the study of interactions between thyroid hormone and specific neuronal systems in the emergence of an adaptive function.

  15. Vasoactive Intestinal Polypeptide (VIP)-Expressing Neurons in the Suprachiasmatic Nucleus Provide Sparse GABAergic Outputs to Local Neurons with Circadian Regulation Occurring Distal to the Opening of Postsynaptic GABAA Ionotropic Receptors

    PubMed Central

    Fan, Junmei; Zeng, Hongkui; Olson, David P.; Huber, Kimberly M.

    2015-01-01

    GABAergic synaptic transmission plays an important role in resetting and synchronizing circadian rhythms in the suprachiasmatic nucleus (SCN). Although the circadian modulation of intrinsic membrane currents and biochemical signaling have been examined in the SCN, the modulation of specific synaptic pathways within the SCN is unexplored. In addition, little is known about the functional properties of these pathways, including which ones involve GABAA receptors (GABAA-Rs). In brain slices obtained from mice, we examined synaptic responses originating from the SCN neurons expressing vasoactive intestinal peptide (VIP+ neurons). Focusing on the local projection within the ventromedial SCN, we found that VIP+ afferents provided input onto 49% of neurons with a preference for VIP-negative (VIP−) neurons. Responses were mediated by GABAA-Rs. The projection was sparsely connected and preferentially targeted a subset of SCN neurons unrelated to postsynaptic VIP expression. For most aspects of VIP+ network output, there was no circadian regulation. Excitability and spontaneous firing of the presynaptic VIP+ neurons were unchanged between day and night, and their network connectivity and synaptic function up through the evoked synaptic conductance were also unchanged. On the other hand, VIP+ input onto VIP− neurons became less inhibitory at night suggesting a postsynaptic alteration in the coupling of GABAA-R conductances to action potential firing. These data suggest that components of the VIP network and its synaptic output up through GABAA-R opening are invariant during the circadian cycle, but the effect on action potential firing is modulated by postsynaptic processes occurring after GABAA-R channel opening. PMID:25653351

  16. Effects of bilateral vestibular deafferentation in rat on hippocampal theta response to somatosensory stimulation, acetylcholine release, and cholinergic neurons in the pedunculopontine tegmental nucleus.

    PubMed

    Aitken, Phillip; Zheng, Yiwen; Smith, Paul F

    2017-03-27

    Vestibular dysfunction has been shown to cause spatial memory impairment. Neurophysiological studies indicate that bilateral vestibular loss (BVL), in particular, is associated with an impairment of the response of hippocampal place cells and theta rhythm. However, the specific neural pathways through which vestibular information reaches the hippocampus are yet to be fully elucidated. The aim of the present study was to further investigate the hypothesised 'theta-generating pathway' from the brainstem vestibular nucleus to