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Sample records for neurons coding action

  1. Potential role of monkey inferior parietal neurons coding action semantic equivalences as precursors of parts of speech

    PubMed Central

    Yamazaki, Yumiko; Yokochi, Hiroko; Tanaka, Michio; Okanoya, Kazuo; Iriki, Atsushi

    2010-01-01

    The anterior portion of the inferior parietal cortex possesses comprehensive representations of actions embedded in behavioural contexts. Mirror neurons, which respond to both self-executed and observed actions, exist in this brain region in addition to those originally found in the premotor cortex. We found that parietal mirror neurons responded differentially to identical actions embedded in different contexts. Another type of parietal mirror neuron represents an inverse and complementary property of responding equally to dissimilar actions made by itself and others for an identical purpose. Here, we propose a hypothesis that these sets of inferior parietal neurons constitute a neural basis for encoding the semantic equivalence of various actions across different agents and contexts. The neurons have mirror neuron properties, and they encoded generalization of agents, differentiation of outcomes, and categorization of actions that led to common functions. By integrating the activities of these mirror neurons with various codings, we further suggest that in the ancestral primates' brains, these various representations of meaningful action led to the gradual establishment of equivalence relations among the different types of actions, by sharing common action semantics. Such differential codings of the components of actions might represent precursors to the parts of protolanguage, such as gestural communication, which are shared among various members of a society. Finally, we suggest that the inferior parietal cortex serves as an interface between this action semantics system and other higher semantic systems, through common structures of action representation that mimic language syntax. PMID:20119879

  2. Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding Auditory Neurons.

    PubMed

    Yang, Yang; Ramamurthy, Bina; Neef, Andreas; Xu-Friedman, Matthew A

    2016-11-23

    Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs. BCs play a central role in both relaying and refining precise timing information from the auditory nerve, whereas SCs discard precise timing information and encode the envelope of sound amplitude. Nucleated-patch recording at near-physiological temperature indicated that the Na current density was 62% lower in BCs, and the voltage dependence of gNa inactivation was 13 mV hyperpolarized compared with SCs. We endowed BCs with SC-like gNa using two-electrode dynamic clamp and found that synaptic activity at physiologically relevant rates elicited APs with significantly lower probability, through increased activation of delayed rectifier channels. In addition, for two near-simultaneous synaptic inputs, the window of coincidence detection widened significantly with increasing gNa, indicating that refinement of temporal information by BCs is degraded by gNa Thus, reduced somatic gNa appears to be an adaption for enhancing fidelity and precision in time-coding neurons.

  3. Substantia nigra pars reticulata neurons code initiation of a serial pattern: implications for natural action sequences and sequential disorders.

    PubMed

    Meyer-Luehmann, Melanie; Thompson, Jeffrey F; Berridge, Kent C; Aldridge, J Wayne

    2002-10-01

    Sequences of movements are initiated abnormally in neurological disorders involving basal ganglia dysfunction, such as Parkinson's disease or Tourette's syndrome. The substantia nigra pars reticulata (SNpr) is one of the two primary output structures of the basal ganglia. However, little is known about how substantia nigra mediates the initiation of normal movement sequences. We studied its role in coding initiation of a sequentially stereotyped but natural movement sequence by recording neuronal activity in SNpr during behavioural performance of 'syntactic grooming chains'. These are rule-governed sequences of up to 25 grooming movements emitted in four predictable (syntactic) phases, which occur spontaneously during grooming behaviour by rats and other rodents. Our results show that neuronal activation in central SNpr codes the onset of this entire rule-governed sequential pattern of grooming actions, not elemental grooming movements. We conclude that the context of sequential pattern may be more important than the elemental motor parameters in determining SNpr neuronal activation.

  4. The neuronal code(s) of the cerebellum.

    PubMed

    Heck, Detlef H; De Zeeuw, Chris I; Jaeger, Dieter; Khodakhah, Kamran; Person, Abigail L

    2013-11-06

    Understanding how neurons encode information in sequences of action potentials is of fundamental importance to neuroscience. The cerebellum is widely recognized for its involvement in the coordination of movements, which requires muscle activation patterns to be controlled with millisecond precision. Understanding how cerebellar neurons accomplish such high temporal precision is critical to understanding cerebellar function. Inhibitory Purkinje cells, the only output neurons of the cerebellar cortex, and their postsynaptic target neurons in the cerebellar nuclei, fire action potentials at high, sustained frequencies, suggesting spike rate modulation as a possible code. Yet, millisecond precise spatiotemporal spike activity patterns in Purkinje cells and inferior olivary neurons have also been observed. These results and ongoing studies suggest that the neuronal code used by cerebellar neurons may span a wide time scale from millisecond precision to slow rate modulations, likely depending on the behavioral context.

  5. Prospective Coding by Spiking Neurons

    PubMed Central

    Brea, Johanni; Gaál, Alexisz Tamás; Senn, Walter

    2016-01-01

    Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron’s firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ). PMID:27341100

  6. Spike Code Flow in Cultured Neuronal Networks.

    PubMed

    Tamura, Shinichi; Nishitani, Yoshi; Hosokawa, Chie; Miyoshi, Tomomitsu; Sawai, Hajime; Kamimura, Takuya; Yagi, Yasushi; Mizuno-Matsumoto, Yuko; Chen, Yen-Wei

    2016-01-01

    We observed spike trains produced by one-shot electrical stimulation with 8 × 8 multielectrodes in cultured neuronal networks. Each electrode accepted spikes from several neurons. We extracted the short codes from spike trains and obtained a code spectrum with a nominal time accuracy of 1%. We then constructed code flow maps as movies of the electrode array to observe the code flow of "1101" and "1011," which are typical pseudorandom sequence such as that we often encountered in a literature and our experiments. They seemed to flow from one electrode to the neighboring one and maintained their shape to some extent. To quantify the flow, we calculated the "maximum cross-correlations" among neighboring electrodes, to find the direction of maximum flow of the codes with lengths less than 8. Normalized maximum cross-correlations were almost constant irrespective of code. Furthermore, if the spike trains were shuffled in interval orders or in electrodes, they became significantly small. Thus, the analysis suggested that local codes of approximately constant shape propagated and conveyed information across the network. Hence, the codes can serve as visible and trackable marks of propagating spike waves as well as evaluating information flow in the neuronal network.

  7. The Mirror Neuron System and Action Recognition

    ERIC Educational Resources Information Center

    Buccino, Giovanni; Binkofski, Ferdinand; Riggio, Lucia

    2004-01-01

    Mirror neurons, first described in the rostral part of monkey ventral premotor cortex (area F5), discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding to the observation of mouth actions have been…

  8. Do mirror neurons subserve action understanding?

    PubMed

    Hickok, Gregory

    2013-04-12

    Mirror neurons were once widely believed to support action understanding via motor simulation of the observed actions. Recent evidence regarding the functional properties of mirror neurons in monkeys as well as much neuropsychological evidence in humans has shown that this is not the case. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Functional differentiation of macaque visual temporal cortical neurons using a parametric action space.

    PubMed

    Vangeneugden, Joris; Pollick, Frank; Vogels, Rufin

    2009-03-01

    Neurons in the rostral superior temporal sulcus (STS) are responsive to displays of body movements. We employed a parametric action space to determine how similarities among actions are represented by visual temporal neurons and how form and motion information contributes to their responses. The stimulus space consisted of a stick-plus-point-light figure performing arm actions and their blends. Multidimensional scaling showed that the responses of temporal neurons represented the ordinal similarity between these actions. Further tests distinguished neurons responding equally strongly to static presentations and to actions ("snapshot" neurons), from those responding much less strongly to static presentations, but responding well when motion was present ("motion" neurons). The "motion" neurons were predominantly found in the upper bank/fundus of the STS, and "snapshot" neurons in the lower bank of the STS and inferior temporal convexity. Most "motion" neurons showed strong response modulation during the course of an action, thus responding to action kinematics. "Motion" neurons displayed a greater average selectivity for these simple arm actions than did "snapshot" neurons. We suggest that the "motion" neurons code for visual kinematics, whereas the "snapshot" neurons code for form/posture, and that both can contribute to action recognition, in agreement with computation models of action recognition.

  10. Nonspatial Sequence Coding in CA1 Neurons

    PubMed Central

    Allen, Timothy A.; Salz, Daniel M.; McKenzie, Sam

    2016-01-01

    The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequence-memory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as “in sequence” or “out of sequence”. We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items—in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe-specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20–40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4–12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus. SIGNIFICANCE STATEMENT The ability to remember the order of life events depends on the hippocampus, but the underlying neural mechanisms remain poorly understood. Here we addressed this issue by recording neural activity in hippocampal

  11. High-Fidelity Coding with Correlated Neurons

    PubMed Central

    da Silveira, Rava Azeredo; Berry, Michael J.

    2014-01-01

    Positive correlations in the activity of neurons are widely observed in the brain. Previous studies have shown these correlations to be detrimental to the fidelity of population codes, or at best marginally favorable compared to independent codes. Here, we show that positive correlations can enhance coding performance by astronomical factors. Specifically, the probability of discrimination error can be suppressed by many orders of magnitude. Likewise, the number of stimuli encoded—the capacity—can be enhanced more than tenfold. These effects do not necessitate unrealistic correlation values, and can occur for populations with a few tens of neurons. We further show that both effects benefit from heterogeneity commonly seen in population activity. Error suppression and capacity enhancement rest upon a pattern of correlation. Tuning of one or several effective parameters can yield a limit of perfect coding: the corresponding pattern of positive correlation leads to a ‘lock-in’ of response probabilities that eliminates variability in the subspace relevant for stimulus discrimination. We discuss the nature of this pattern and we suggest experimental tests to identify it. PMID:25412463

  12. Action Recognition Using Visual-Neuron Feature

    NASA Astrophysics Data System (ADS)

    Li, Ning; Xu, De

    This letter proposes a neurobiological approach for action recognition. In this approach, actions are represented by a visual-neuron feature (VNF) based on a quantitative model of object representation in the primate visual cortex. A supervised classification technique is then used to classify the actions. The proposed VNF is invariant to affine translation and scaling of moving objects while maintaining action specificity. Moreover, it is robust to the deformation of actors. Experiments on publicly available action datasets demonstrate the proposed approach outperforms conventional action recognition models based on computer-vision features.

  13. Action observation activates neurons of the monkey ventrolateral prefrontal cortex

    PubMed Central

    Simone, Luciano; Bimbi, Marco; Rodà, Francesca; Fogassi, Leonardo; Rozzi, Stefano

    2017-01-01

    Prefrontal cortex is crucial for exploiting contextual information for the planning and guidance of behavioral responses. Among contextual cues, those provided by others’ behavior are particularly important, in primates, for selecting appropriate reactions and suppressing the inappropriate ones. These latter functions deeply rely on the ability to understand others’ actions. However, it is largely unknown whether prefrontal neurons are activated by action observation. To address this issue, we recorded the activity of ventrolateral prefrontal (VLPF) neurons of macaque monkeys during the observation of videos depicting biological movements performed by a monkey or a human agent, and object motion. Our results show that a population of VLPF neurons respond to the observation of biological movements, in particular those representing goal directed actions. Many of these neurons also show a preference for the agent performing the action. The neural response is present also when part of the observed movement is obscured, suggesting that these VLPF neurons code a high order representation of the observed action rather than a simple visual description of it. PMID:28290511

  14. A memristive spiking neuron with firing rate coding

    PubMed Central

    Ignatov, Marina; Ziegler, Martin; Hansen, Mirko; Petraru, Adrian; Kohlstedt, Hermann

    2015-01-01

    Perception, decisions, and sensations are all encoded into trains of action potentials in the brain. The relation between stimulus strength and all-or-nothing spiking of neurons is widely believed to be the basis of this coding. This initiated the development of spiking neuron models; one of today's most powerful conceptual tool for the analysis and emulation of neural dynamics. The success of electronic circuit models and their physical realization within silicon field-effect transistor circuits lead to elegant technical approaches. Recently, the spectrum of electronic devices for neural computing has been extended by memristive devices, mainly used to emulate static synaptic functionality. Their capabilities for emulations of neural activity were recently demonstrated using a memristive neuristor circuit, while a memristive neuron circuit has so far been elusive. Here, a spiking neuron model is experimentally realized in a compact circuit comprising memristive and memcapacitive devices based on the strongly correlated electron material vanadium dioxide (VO2) and on the chemical electromigration cell Ag/TiO2−x/Al. The circuit can emulate dynamical spiking patterns in response to an external stimulus including adaptation, which is at the heart of firing rate coding as first observed by E.D. Adrian in 1926. PMID:26539074

  15. [Neuronal coding of spatial visual information].

    PubMed

    Eördegh, Gabriella

    2009-07-26

    The main differences between the geniculate and the ascending tectal/extrageniculate visual systems are the presence of multisensory units and the absence of the strict retinotopical organization in the tectal system. To investigate the coding of the visual and multisensory information in the tectal system, and to clarify the direction of visual information flow between the extrastriate cortex along the anterior ectosylvian sulcus and the lateral medialis-suprageniculate nucleus of the posterior thalamus. Extracellular single-cell recordings were carried out in anesthetized, immobilized cats to visual and multisensory stimulation. The thalamo-cortical route seems to have a dominant role in the bidirectional information flow between the LM-Sg and the AES cortex. The panoramic neurons in the AES cortex and the LM-Sg may code in their discharge rate the site of the spatial visual and multisensory information and exhibited multisensory cross-modal integration. Our results demonstrate the existence of a distributed population code of spatial multisensory information in the tectal visual system.

  16. Computer Simulation of the Neuronal Action Potential.

    ERIC Educational Resources Information Center

    Solomon, Paul R.; And Others

    1988-01-01

    A series of computer simulations of the neuronal resting and action potentials are described. Discusses the use of simulations to overcome the difficulties of traditional instruction, such as blackboard illustration, which can only illustrate these events at one point in time. Describes systems requirements necessary to run the simulations.…

  17. Astrocytic Actions on Extrasynaptic Neuronal Currents

    PubMed Central

    Pál, Balázs

    2015-01-01

    In the last few decades, knowledge about astrocytic functions has significantly increased. It was demonstrated that astrocytes are not passive elements of the central nervous system (CNS), but active partners of neurons. There is a growing body of knowledge about the calcium excitability of astrocytes, the actions of different gliotransmitters and their release mechanisms, as well as the participation of astrocytes in the regulation of synaptic functions and their contribution to synaptic plasticity. However, astrocytic functions are even more complex than being a partner of the “tripartite synapse,” as they can influence extrasynaptic neuronal currents either by releasing substances or regulating ambient neurotransmitter levels. Several types of currents or changes of membrane potential with different kinetics and via different mechanisms can be elicited by astrocytic activity. Astrocyte-dependent phasic or tonic, inward or outward currents were described in several brain areas. Such currents, together with the synaptic actions of astrocytes, can contribute to neuromodulatory mechanisms, neurosensory and -secretory processes, cortical oscillatory activity, memory, and learning or overall neuronal excitability. This mini-review is an attempt to give a brief summary of astrocyte-dependent extrasynaptic neuronal currents and their possible functional significance. PMID:26696832

  18. Integration of visual and auditory information by superior temporal sulcus neurons responsive to the sight of actions.

    PubMed

    Barraclough, Nick E; Xiao, Dengke; Baker, Chris I; Oram, Mike W; Perrett, David I

    2005-03-01

    Processing of complex visual stimuli comprising facial movements, hand actions, and body movements is known to occur in the superior temporal sulcus (STS) of humans and nonhuman primates. The STS is also thought to play a role in the integration of multimodal sensory input. We investigated whether STS neurons coding the sight of actions also integrated the sound of those actions. For 23% of neurons responsive to the sight of an action, the sound of that action significantly modulated the visual response. The sound of the action increased or decreased the visually evoked response for an equal number of neurons. In the neurons whose visual response was increased by the addition of sound (but not those neurons whose responses were decreased), the audiovisual integration was dependent upon the sound of the action matching the sight of the action. These results suggest that neurons in the STS form multisensory representations of observed actions.

  19. Multisynaptic activity in a pyramidal neuron model and neural code.

    PubMed

    Ventriglia, Francesco; Di Maio, Vito

    2006-01-01

    The highly irregular firing of mammalian cortical pyramidal neurons is one of the most striking observation of the brain activity. This result affects greatly the discussion on the neural code, i.e. how the brain codes information transmitted along the different cortical stages. In fact it seems to be in favor of one of the two main hypotheses about this issue, named the rate code. But the supporters of the contrasting hypothesis, the temporal code, consider this evidence inconclusive. We discuss here a leaky integrate-and-fire model of a hippocampal pyramidal neuron intended to be biologically sound to investigate the genesis of the irregular pyramidal firing and to give useful information about the coding problem. To this aim, the complete set of excitatory and inhibitory synapses impinging on such a neuron has been taken into account. The firing activity of the neuron model has been studied by computer simulation both in basic conditions and allowing brief periods of over-stimulation in specific regions of its synaptic constellation. Our results show neuronal firing conditions similar to those observed in experimental investigations on pyramidal cortical neurons. In particular, the variation coefficient (CV) computed from the inter-spike intervals (ISIs) in our simulations for basic conditions is close to the unity as that computed from experimental data. Our simulation shows also different behaviors in firing sequences for different frequencies of stimulation.

  20. Simple models for reading neuronal population codes.

    PubMed Central

    Seung, H S; Sompolinsky, H

    1993-01-01

    In many neural systems, sensory information is distributed throughout a population of neurons. We study simple neural network models for extracting this information. The inputs to the networks are the stochastic responses of a population of sensory neurons tuned to directional stimuli. The performance of each network model in psychophysical tasks is compared with that of the optimal maximum likelihood procedure. As a model of direction estimation in two dimensions, we consider a linear network that computes a population vector. Its performance depends on the width of the population tuning curves and is maximal for width, which increases with the level of background activity. Although for narrowly tuned neurons the performance of the population vector is significantly inferior to that of maximum likelihood estimation, the difference between the two is small when the tuning is broad. For direction discrimination, we consider two models: a perceptron with fully adaptive weights and a network made by adding an adaptive second layer to the population vector network. We calculate the error rates of these networks after exhaustive training to a particular direction. By testing on the full range of possible directions, the extent of transfer of training to novel stimuli can be calculated. It is found that for threshold linear networks the transfer of perceptual learning is nonmonotonic. Although performance deteriorates away from the training stimulus, it peaks again at an intermediate angle. This nonmonotonicity provides an important psychophysical test of these models. PMID:8248166

  1. Chemical Coding for Cardiovascular Sympathetic Preganglionic Neurons in Rats

    PubMed Central

    Gonsalvez, DG; Kerman, IA; McAllen, RM; Anderson, CR

    2010-01-01

    Cocaine and amphetamine-regulated transcript peptide (CART) is present in a subset of sympathetic preganglionic neurons in the rat. We examined the distribution of CART-immunoreactive terminals in rat stellate and superior cervical ganglia and adrenal gland and found that they surround neuropeptide Y-immunoreactive postganglionic neurons and noradrenergic chromaffin cells. The targets of CART-immunoreactive preganglionic neurons in the stellate and superior cervical ganglia were shown to be vasoconstrictor neurons supplying muscle and skin and cardiac-projecting postganglionic neurons: they did not target non-vasoconstrictor neurons innervating salivary glands, piloerector muscle, brown fat or adrenergic chromaffin cells. Transneuronal tracing using pseudorabies virus demonstrated that many, but not all, preganglionic neurons in the vasoconstrictor pathway to forelimb skeletal muscle were CART-immunoreactive. Similarly, analysis with the confocal microscope confirmed that 70% of boutons in contact with vasoconstrictor ganglion cells contained CART, while 30% did not. Finally, we show that CART-immunoreactive cells represented 69% of the preganglionic neuron population expressing c-fos after systemic hypoxia. We conclude that CART is present in most, although not all, cardiovascular preganglionic neurons, but not thoracic preganglionic neurons with non-cardiovascular targets. We suggest that CART-immunoreactivity may identify the postulated “accessory” preganglionic neurons, whose actions may amplify vasomotor ganglionic transmission. PMID:20810898

  2. Distinct mechanisms for coding of visual actions in macaque temporal cortex.

    PubMed

    Vangeneugden, Joris; De Mazière, Patrick A; Van Hulle, Marc M; Jaeggli, Tobias; Van Gool, Luc; Vogels, Rufin

    2011-01-12

    Temporal cortical neurons are known to respond to visual dynamic-action displays. Many human psychophysical and functional imaging studies examining biological motion perception have used treadmill walking, in contrast to previous macaque single-cell studies. We assessed the coding of locomotion in rhesus monkey (Macaca mulatta) temporal cortex using movies of stationary walkers, varying both form and motion (i.e., different facing directions) or varying only the frame sequence (i.e., forward vs backward walking). The majority of superior temporal sulcus and inferior temporal neurons were selective for facing direction, whereas a minority distinguished forward from backward walking. Support vector machines using the temporal cortical population responses as input classified facing direction well, but forward and backward walking less so. Classification performance for the latter improved markedly when the within-action response modulation was considered, reflecting differences in momentary body poses within the locomotion sequences. Responses to static pose presentations predicted the responses during the course of the action. Analyses of the responses to walking sequences wherein the start frame was varied across trials showed that some neurons also carried a snapshot sequence signal. Such sequence information was present in neurons that responded to static snapshot presentations and in neurons that required motion. Our data suggest that actions are analyzed by temporal cortical neurons using distinct mechanisms. Most neurons predominantly signal momentary pose. In addition, temporal cortical neurons, including those responding to static pose, are sensitive to pose sequence, which can contribute to the signaling of learned action sequences.

  3. Simulation of Code Spectrum and Code Flow of Cultured Neuronal Networks.

    PubMed

    Tamura, Shinichi; Nishitani, Yoshi; Hosokawa, Chie; Miyoshi, Tomomitsu; Sawai, Hajime

    2016-01-01

    It has been shown that, in cultured neuronal networks on a multielectrode, pseudorandom-like sequences (codes) are detected, and they flow with some spatial decay constant. Each cultured neuronal network is characterized by a specific spectrum curve. That is, we may consider the spectrum curve as a "signature" of its associated neuronal network that is dependent on the characteristics of neurons and network configuration, including the weight distribution. In the present study, we used an integrate-and-fire model of neurons with intrinsic and instantaneous fluctuations of characteristics for performing a simulation of a code spectrum from multielectrodes on a 2D mesh neural network. We showed that it is possible to estimate the characteristics of neurons such as the distribution of number of neurons around each electrode and their refractory periods. Although this process is a reverse problem and theoretically the solutions are not sufficiently guaranteed, the parameters seem to be consistent with those of neurons. That is, the proposed neural network model may adequately reflect the behavior of a cultured neuronal network. Furthermore, such prospect is discussed that code analysis will provide a base of communication within a neural network that will also create a base of natural intelligence.

  4. Do spinocerebellar neurones forward information on spinal actions of neurones in the feline red nucleus?

    PubMed

    Jankowska, E; Nilsson, E; Hammar, I

    2011-12-01

    We recently demonstrated that feline ventral spinocerebellar tract (VSCT) neurones monitor descending commands for voluntary movements initiated by pyramidal tract (PT) neurones as well as locomotor movements relayed by reticulospinal (RS) neurones. The aim of the present study was to examine whether VSCT neurones likewise monitor descending commands from the red nucleus (RN). Extracellular records from the spinal border (SB) subpopulation of VSCT neurons revealed that a third (31%) of SB neurones may be discharged by trains of stimuli applied in the RN. Moreover, when RN stimuli failed to discharge SB neurones they facilitated activation of some of these neurones by RS and/or PT neurones, while activation of other SB neurones was depressed. We propose that the facilitation and depression of actions of RS neurones by RN neurones might serve to reflect a higher or lower excitability of motoneurones and therefore a likely higher or lower efficacy of the RS descending commands, prompting the cerebellum to adjust the activation of reticulospinal neurones. Activation of SB neurones by RN stimuli alone would also allow monitoring and adjusting the RN descending commands. Intracellular records from SB neurones revealed both monosynaptic and disynaptic EPSPs and disynaptic IPSPs evoked by RN stimuli. The disynaptic actions remained following transection of axons of reticulospinal neurones within the medullary longitudinal fascicle (MLF) and were therefore taken to be relayed primarily by spinal neurones, in contrast to EPSPs and IPSPs evoked by PT stimuli found to be relayed by reticulospinal rather than spinal neurones.

  5. Do spinocerebellar neurones forward information on spinal actions of neurones in the feline red nucleus?

    PubMed Central

    Jankowska, E; Nilsson, E; Hammar, I

    2011-01-01

    Abstract We recently demonstrated that feline ventral spinocerebellar tract (VSCT) neurones monitor descending commands for voluntary movements initiated by pyramidal tract (PT) neurones as well as locomotor movements relayed by reticulospinal (RS) neurones. The aim of the present study was to examine whether VSCT neurones likewise monitor descending commands from the red nucleus (RN). Extracellular records from the spinal border (SB) subpopulation of VSCT neurons revealed that a third (31%) of SB neurones may be discharged by trains of stimuli applied in the RN. Moreover, when RN stimuli failed to discharge SB neurones they facilitated activation of some of these neurones by RS and/or PT neurones, while activation of other SB neurones was depressed. We propose that the facilitation and depression of actions of RS neurones by RN neurones might serve to reflect a higher or lower excitability of motoneurones and therefore a likely higher or lower efficacy of the RS descending commands, prompting the cerebellum to adjust the activation of reticulospinal neurones. Activation of SB neurones by RN stimuli alone would also allow monitoring and adjusting the RN descending commands. Intracellular records from SB neurones revealed both monosynaptic and disynaptic EPSPs and disynaptic IPSPs evoked by RN stimuli. The disynaptic actions remained following transection of axons of reticulospinal neurones within the medullary longitudinal fascicle (MLF) and were therefore taken to be relayed primarily by spinal neurones, in contrast to EPSPs and IPSPs evoked by PT stimuli found to be relayed by reticulospinal rather than spinal neurones. PMID:21986203

  6. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.

    PubMed

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-12-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.

  7. Neural coding of cooperative vs. affective human interactions: 150 ms to code the action's purpose.

    PubMed

    Proverbio, Alice Mado; Riva, Federica; Paganelli, Laura; Cappa, Stefano F; Canessa, Nicola; Perani, Daniela; Zani, Alberto

    2011-01-01

    The timing and neural processing of the understanding of social interactions was investigated by presenting scenes in which 2 people performed cooperative or affective actions. While the role of the human mirror neuron system (MNS) in understanding actions and intentions is widely accepted, little is known about the time course within which these aspects of visual information are automatically extracted. Event-Related Potentials were recorded in 35 university students perceiving 260 pictures of cooperative (e.g., 2 people dragging a box) or affective (e.g., 2 people smiling and holding hands) interactions. The action's goal was automatically discriminated at about 150-170 ms, as reflected by occipito/temporal N170 response. The swLORETA inverse solution revealed the strongest sources in the right posterior cingulate cortex (CC) for affective actions and in the right pSTS for cooperative actions. It was found a right hemispheric asymmetry that involved the fusiform gyrus (BA37), the posterior CC, and the medial frontal gyrus (BA10/11) for the processing of affective interactions, particularly in the 155-175 ms time window. In a later time window (200-250 ms) the processing of cooperative interactions activated the left post-central gyrus (BA3), the left parahippocampal gyrus, the left superior frontal gyrus (BA10), as well as the right premotor cortex (BA6). Women showed a greater response discriminative of the action's goal compared to men at P300 and anterior negativity level (220-500 ms). These findings might be related to a greater responsiveness of the female vs. male MNS. In addition, the discriminative effect was bilateral in women and was smaller and left-sided in men. Evidence was provided that perceptually similar social interactions are discriminated on the basis of the agents' intentions quite early in neural processing, differentially activating regions devoted to face/body/action coding, the limbic system and the MNS.

  8. Unique features of action potential initiation in cortical neurons.

    PubMed

    Naundorf, Björn; Wolf, Fred; Volgushev, Maxim

    2006-04-20

    Neurons process and encode information by generating sequences of action potentials. For all spiking neurons, the encoding of single-neuron computations into sequences of spikes is biophysically determined by the cell's action-potential-generating mechanism. It has recently been discovered that apparently minor modifications of this mechanism can qualitatively change the nature of neuronal encoding. Here we quantitatively analyse the dynamics of action potential initiation in cortical neurons in vivo, in vitro and in computational models. Unexpectedly, key features of the initiation dynamics of cortical neuron action potentials--their rapid initiation and variable onset potential--are outside the range of behaviours described by the classical Hodgkin-Huxley theory. We propose a new model based on the cooperative activation of sodium channels that reproduces the observed dynamics of action potential initiation. This new model predicts that Hodgkin-Huxley-type dynamics of action potential initiation can be induced by artificially decreasing the effective density of sodium channels. In vitro experiments confirm this prediction, supporting the hypothesis that cooperative sodium channel activation underlies the dynamics of action potential initiation in cortical neurons.

  9. Neurons in Primary Motor Cortex Engaged During Action Observation

    PubMed Central

    Dushanova, Juliana; Donoghue, John

    2010-01-01

    Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in primary motor cortex (MI) responding to viewed actions, an area generally considered to initiate and guide movement performance. Multielectrode recordings in monkeys performing or observing a well-learned step tracking task showed that approximately half of MI neurons, active when monkeys performed the task, were also active when they observed the action being performed by a human. These ‘view’ neurons were spatially intermingled with ‘do’ neurons, active only during movement performance. Simultaneously recorded, ‘view’ neurons comprised two groups: ∼38% retained the same preferred direction (PD) and timing during performance and viewing, while the remainder (62%) changed their PDs and time lag during viewing compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. ‘View’ neurons became less active and contained poorer representations of action when viewing only sub-components of the task. MI ‘view’ neurons thus appear to reflect the aspects of a learned movement when observed in others and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of MI activity needed to perform the observed action and could additionally reflect processing related to understanding, learning or mentally rehearsing action. PMID:20074212

  10. Cracking Taste Codes by Tapping into Sensory Neuron Impulse Traffic

    PubMed Central

    Frank, Marion E.; Lundy, Robert F.; Contreras, Robert J.

    2008-01-01

    Insights into the biological basis for mammalian taste quality coding began with electrophysiological recordings from “taste” nerves and this technique continues to produce essential information today. Chorda tympani (geniculate ganglion) neurons, which are particularly involved in taste quality discrimination, are specialists or generalists. Specialists respond to stimuli characterized by a single taste quality as defined by behavioral cross-generalization in conditioned taste tests. Generalists respond to electrolytes that elicit multiple aversive qualities. Na+-salt (N) specialists in rodents and sweet-stimulus (S) specialists in multiple orders of mammals are well-characterized. Specialists are associated with species’ nutritional needs and their activation is known to be malleable by internal physiological conditions and contaminated external caloric sources. S specialists, associated with the heterodimeric G-protein coupled receptor: T1R, and N specialists, associated with the epithelial sodium channel: ENaC, are consistent with labeled line coding from taste bud to afferent neuron. Yet, S-specialist neurons and behavior are less specific thanT1R2-3 in encompassing glutamate and E generalist neurons are much less specific than a candidate, PDK TRP channel, sour receptor in encompassing salts and bitter stimuli. Specialist labeled lines for nutrients and generalist patterns for aversive electrolytes may be transmitting taste information to the brain side by side. However, specific roles of generalists in taste quality coding may be resolved by selecting stimuli and stimulus levels found in natural situations. T2Rs, participating in reflexes via the glossopharynygeal nerve, became highly diversified in mammalian phylogenesis as they evolved to deal with dangerous substances within specific environmental niches. Establishing the information afferent neurons traffic to the brain about natural taste stimuli imbedded in dynamic complex mixtures will

  11. Extra-coding RNAs regulate neuronal DNA methylation dynamics

    PubMed Central

    Savell, Katherine E.; Gallus, Nancy V. N.; Simon, Rhiana C.; Brown, Jordan A.; Revanna, Jasmin S.; Osborn, Mary Katherine; Song, Esther Y.; O'Malley, John J.; Stackhouse, Christian T.; Norvil, Allison; Gowher, Humaira; Sweatt, J. David; Day, Jeremy J.

    2016-01-01

    Epigenetic mechanisms such as DNA methylation are essential regulators of the function and information storage capacity of neurons. DNA methylation is highly dynamic in the developing and adult brain, and is actively regulated by neuronal activity and behavioural experiences. However, it is presently unclear how methylation status at individual genes is targeted for modification. Here, we report that extra-coding RNAs (ecRNAs) interact with DNA methyltransferases and regulate neuronal DNA methylation. Expression of ecRNA species is associated with gene promoter hypomethylation, is altered by neuronal activity, and is overrepresented at genes involved in neuronal function. Knockdown of the Fos ecRNA locus results in gene hypermethylation and mRNA silencing, and hippocampal expression of Fos ecRNA is required for long-term fear memory formation in rats. These results suggest that ecRNAs are fundamental regulators of DNA methylation patterns in neuronal systems, and reveal a promising avenue for therapeutic targeting in neuropsychiatric disease states. PMID:27384705

  12. A neuronal learning rule for sub-millisecond temporal coding.

    PubMed

    Gerstner, W; Kempter, R; van Hemmen, J L; Wagner, H

    1996-09-05

    A paradox that exists in auditory and electrosensory neural systems is that they encode behaviorally relevant signals in the range of a few microseconds with neurons that are at least one order of magnitude slower. The importance of temporal coding in neural information processing is not clear yet. A central question is whether neuronal firing can be more precise than the time constants of the neuronal processes involved. Here we address this problem using the auditory system of the barn owl as an example. We present a modelling study based on computer simulations of a neuron in the laminar nucleus. Three observations explain the paradox. First, spiking of an 'integrate-and-fire' neuron driven by excitatory postsynaptic potentials with a width at half-maximum height of 250 micros, has an accuracy of 25 micros if the presynaptic signals arrive coherently. Second, the necessary degree of coherence in the signal arrival times can be attained during ontogenetic development by virtue of an unsupervised hebbian learning rule. Learning selects connections with matching delays from a broad distribution of axons with random delays. Third, the learning rule also selects the correct delays from two independent groups of inputs, for example, from the left and right ear.

  13. A neuronal learning rule for sub-millisecond temporal coding

    NASA Astrophysics Data System (ADS)

    Gerstner, Wulfram; Kempter, Richard; van Hemmen, J. Leo; Wagner, Hermann

    1996-09-01

    A PARADOX that exists in auditory and electrosensory neural systems1,2 is that they encode behaviourally relevant signals in the range of a few microseconds with neurons that are at least one order of magnitude slower. The importance of temporal coding in neural information processing is not clear yet3-8. A central question is whether neuronal firing can be more precise than the time constants of the neuronal processes involved9. Here we address this problem using the auditory system of the barn owl as an example. We present a modelling study based on computer simulations of a neuron in the laminar nucleus. Three observations explain the paradox. First, spiking of an 'integrate-and-fire' neuron driven by excitatory postsynaptic potentials with a width at half-maximum height of 250 μs, has an accuracy of 25 μs if the presynaptic signals arrive coherently. Second, the necessary degree of coherence in the signal arrival times can be attained during ontogenetic development by virtue of an unsupervised hebbian learning rule. Learning selects connections with matching delays from a broad distribution of axons with random delays. Third, the learning rule also selects the correct delays from two independent groups of inputs, for example, from the left and right ear.

  14. Action-space coding in social contexts

    PubMed Central

    Ciardo, Francesca; Lugli, Luisa; Nicoletti, Roberto; Rubichi, Sandro; Iani, Cristina

    2016-01-01

    In two behavioural experiments we tested whether performing a spatial task along with another agent changes space representation by rendering some reference frames more/less salient than others. To this end, we used a Simon task in which stimuli were presented in four horizontal locations thus allowing for spatial coding according to multiple frames of reference. In Experiment 1 participants performed a go/no-go Simon task along another agent, each being in charge of one response. In Experiment 2 they performed a two-choice Simon task along another agent, each being in charge of two responses. Results showed that when participants were in charge of only one response, stimulus position was coded only with reference to the centre of the screen hence suggesting that the co-actor’s response, or the position of the co-actor, was represented and used as a reference for spatial coding. Differently, when participants were in charge of two responses, no effect of the social context emerged and spatial coding relied on multiple frames of reference, similarly to when the Simon task is performed individually. These findings provide insights on the influence played by the interaction between the social context (i.e. the presence of others) and task features on individual performance. PMID:26940396

  15. Mirror neurons encode the subjective value of an observed action.

    PubMed

    Caggiano, Vittorio; Fogassi, Leonardo; Rizzolatti, Giacomo; Casile, Antonino; Giese, Martin A; Thier, Peter

    2012-07-17

    Objects grasped by an agent have a value not only for the acting agent, but also for an individual observing the grasping act. The value that the observer attributes to the object that is grasped can be pivotal for selecting a possible behavioral response. Mirror neurons in area F5 of the monkey premotor cortex have been suggested to play a crucial role in the understanding of action goals. However, it has not been addressed if these neurons are also involved in representing the value of the grasped object. Here we report that observation-related neuronal responses of F5 mirror neurons are indeed modulated by the value that the monkey associates with the grasped object. These findings suggest that during action observation F5 mirror neurons have access to key information needed to shape the behavioral responses of the observer.

  16. Mirror neurons encode the subjective value of an observed action

    PubMed Central

    Caggiano, Vittorio; Fogassi, Leonardo; Rizzolatti, Giacomo; Casile, Antonino; Giese, Martin A.; Thier, Peter

    2012-01-01

    Objects grasped by an agent have a value not only for the acting agent, but also for an individual observing the grasping act. The value that the observer attributes to the object that is grasped can be pivotal for selecting a possible behavioral response. Mirror neurons in area F5 of the monkey premotor cortex have been suggested to play a crucial role in the understanding of action goals. However, it has not been addressed if these neurons are also involved in representing the value of the grasped object. Here we report that observation-related neuronal responses of F5 mirror neurons are indeed modulated by the value that the monkey associates with the grasped object. These findings suggest that during action observation F5 mirror neurons have access to key information needed to shape the behavioral responses of the observer. PMID:22753471

  17. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons

    PubMed Central

    Lee, Philip R.; Cohen, Jonathan E.; Iacobas, Dumitru A.; Iacobas, Sanda; Fields, R. Douglas

    2017-01-01

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life. PMID:28256583

  18. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons.

    PubMed

    Lee, Philip R; Cohen, Jonathan E; Iacobas, Dumitru A; Iacobas, Sanda; Fields, R Douglas

    2017-03-03

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life.

  19. User's manual to the ACTION computer code

    NASA Technical Reports Server (NTRS)

    Kamat, M. P.

    1980-01-01

    The form and interpretation of input and output data are defined. The Analysis of Crash Transients in Inelastic and Geometrically Nonlinear structures program (ACTION) performs nonlinear transient response analysis of structures subjected to time varying loads, allowing for nonlinear, time independent material properties and large geometry changes.

  20. Effects of Action Relations on the Configural Coding between Objects

    ERIC Educational Resources Information Center

    Riddoch, M. J.; Pippard, B.; Booth, L.; Rickell, J.; Summers, J.; Brownson, A.; Humphreys, G. W.

    2011-01-01

    Configural coding is known to take place between the parts of individual objects but has never been shown between separate objects. We provide novel evidence here for configural coding between separate objects through a study of the effects of action relations between objects on extinction. Patients showing visual extinction were presented with…

  1. Effects of Action Relations on the Configural Coding between Objects

    ERIC Educational Resources Information Center

    Riddoch, M. J.; Pippard, B.; Booth, L.; Rickell, J.; Summers, J.; Brownson, A.; Humphreys, G. W.

    2011-01-01

    Configural coding is known to take place between the parts of individual objects but has never been shown between separate objects. We provide novel evidence here for configural coding between separate objects through a study of the effects of action relations between objects on extinction. Patients showing visual extinction were presented with…

  2. Direct versus indirect actions of ghrelin on hypothalamic NPY neurons.

    PubMed

    Hashiguchi, Hiroshi; Sheng, Zhenyu; Routh, Vanessa; Gerzanich, Volodymyr; Simard, J Marc; Bryan, Joseph

    2017-01-01

    Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices. Depolarization resulted from a decreased input resistance (IR) in ~70% of neurons (15/22) or an increased IR in the remainder (7/22), consistent with the opening or closing of ion channels, respectively. Although tetrodotoxin (TTX) blockade of presynaptic action potentials reduced ghrelin-induced changes in MP and IR, ghrelin still significantly depolarized the MP and decreased IR in TTX-treated neurons, suggesting that ghrelin directly opens cation channel(s) in NPY neurons. In isolated NPY-GFP neurons, ghrelin produced a sustained rise of [Ca2+]c, with an EC50 ~110 pM. Pharmacologic studies confirmed that the direct action of ghrelin was through occupation of the growth hormone secretagogue receptor, GHS-R, and demonstrated the importance of the adenylate cyclase/cAMP/protein kinase A (PKA) and phospholipase C/inositol triphosphate (PLC/IP3) pathways as activators of 5' AMP-activated protein kinase (AMPK). Activation of isolated neurons was not affected by CNQX or TTX, but reducing [Na+]o suppressed activation, suggesting a role for Na+-permeable cation channels. SUR1 and two channel partners, Kir6.2 and Trpm4, were identified immunologically in NPY-GFP neurons in situ. The actions of SUR1 and Trpm4 modulators were informative: like ghrelin, diazoxide, a SUR1 agonist, elevated [Ca2+]c and glibenclamide, a SUR1 antagonist, partially suppressed ghrelin action, while 9-phenanthrol and flufenamic acid, selective Trpm4 antagonists, blocked ghrelin actions on isolated neurons. Ghrelin activation was unaffected by nifedipine and

  3. Auditory information coding by modeled cochlear nucleus neurons.

    PubMed

    Wang, Huan; Isik, Michael; Borst, Alexander; Hemmert, Werner

    2011-06-01

    In this paper we use information theory to quantify the information in the output spike trains of modeled cochlear nucleus globular bushy cells (GBCs). GBCs are part of the sound localization pathway. They are known for their precise temporal processing, and they code amplitude modulations with high fidelity. Here we investigated the information transmission for a natural sound, a recorded vowel. We conclude that the maximum information transmission rate for a single neuron was close to 1,050 bits/s, which corresponds to a value of approximately 5.8 bits per spike. For quasi-periodic signals like voiced speech, the transmitted information saturated as word duration increased. In general, approximately 80% of the available information from the spike trains was transmitted within about 20 ms. Transmitted information for speech signals concentrated around formant frequency regions. The efficiency of neural coding was above 60% up to the highest temporal resolution we investigated (20 μs). The increase in transmitted information to that precision indicates that these neurons are able to code information with extremely high fidelity, which is required for sound localization. On the other hand, only 20% of the information was captured when the temporal resolution was reduced to 4 ms. As the temporal resolution of most speech recognition systems is limited to less than 10 ms, this massive information loss might be one of the reasons which are responsible for the lack of noise robustness of these systems.

  4. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    PubMed

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Coding movement direction by burst firing in electrosensory neurons.

    PubMed

    Khosravi-Hashemi, Navid; Fortune, Eric S; Chacron, Maurice J

    2011-10-01

    Directional selectivity, in which neurons respond strongly to an object moving in a given direction ("preferred") but respond weakly or not at all to an object moving in the opposite direction ("null"), is a critical computation achieved in brain circuits. Previous measures of direction selectivity have compared the numbers of action potentials elicited by each direction of movement, but most sensory neurons display patterning, such as bursting, in their spike trains. To examine the contribution of patterned responses to direction selectivity, we recorded from midbrain neurons in weakly electric fish and found that most neurons responded with a combination of both bursts and isolated spikes to moving object stimuli. In these neurons, we separated bursts and isolated spikes using an interspike interval (ISI) threshold. The directional bias of bursts was significantly higher than that of either the full spike train or the isolated spike train. To examine the encoding and decoding of bursts, we built biologically plausible models that examine 1) the upstream mechanisms that generate these spiking patterns and 2) downstream decoders of bursts. Our model of upstream mechanisms uses an interaction between afferent input and subthreshold calcium channels to give rise to burst firing that occurs preferentially for one direction of movement. We tested this model in vivo by application of calcium antagonists, which reduced burst firing and eliminated the differences in direction selectivity between bursts, isolated spikes, and the full spike train. Our model of downstream decoders used strong synaptic facilitation to achieve qualitatively similar results to those obtained using the ISI threshold criterion. This model shows that direction selective information carried by bursts can be decoded by downstream neurons using biophysically plausible mechanisms.

  6. Short infrared laser pulses block action potentials in neurons

    NASA Astrophysics Data System (ADS)

    Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

    2017-02-01

    Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

  7. Deciphering neuronal population codes for acute thermal pain

    NASA Astrophysics Data System (ADS)

    Chen, Zhe; Zhang, Qiaosheng; Phuong Sieu Tong, Ai; Manders, Toby R.; Wang, Jing

    2017-06-01

    Objective. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Current pain research mostly focuses on molecular and synaptic changes at the spinal and peripheral levels. However, a complete understanding of pain mechanisms requires the physiological study of the neocortex. Our goal is to apply a neural decoding approach to read out the onset of acute thermal pain signals, which can be used for brain-machine interface. Approach. We used micro wire arrays to record ensemble neuronal activities from the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC) in freely behaving rats. We further investigated neural codes for acute thermal pain at both single-cell and population levels. To detect the onset of acute thermal pain signals, we developed a novel latent state-space framework to decipher the sorted or unsorted S1 and ACC ensemble spike activities, which reveal information about the onset of pain signals. Main results. The state space analysis allows us to uncover a latent state process that drives the observed ensemble spike activity, and to further detect the ‘neuronal threshold’ for acute thermal pain on a single-trial basis. Our method achieved good detection performance in sensitivity and specificity. In addition, our results suggested that an optimal strategy for detecting the onset of acute thermal pain signals may be based on combined evidence from S1 and ACC population codes. Significance. Our study is the first to detect the onset of acute pain signals based on neuronal ensemble spike activity. It is important from a mechanistic viewpoint as it relates to the significance of S1 and ACC activities in the regulation of the acute pain onset.

  8. Trophic actions of GABA on neuronal development.

    PubMed

    Represa, Alfonso; Ben-Ari, Yehezkel

    2005-06-01

    During brain development, transmitter-gated receptors are operative before synapse formation, suggesting that their action is not restricted to synaptic transmission. GABA, which is the principal excitatory transmitter in the developing brain, acts as an epigenetic factor to control processes including cell proliferation, neuroblast migration and dendritic maturation. These effects appear to be mediated through a paracrine, diffuse, non-synaptic mode of action that precedes the more focused, rapid mode of operation characteristic of synaptic connections. This sequential operation implies that GABA is used as an informative agent but in a unique context at an early developmental stage. This sequence also implies that by altering these effects, drugs acting on the GABA system could be pathogenic during pregnancy.

  9. Cholecystokinin action on layer 6b neurons in somatosensory cortex

    PubMed Central

    Chung, Leeyup; Moore, Scott D.; Cox, Charles L.

    2009-01-01

    Layer 6b in neocortex is a distinct sublamina at the ventral portion of layer 6. Corticothalamic projections arise from 6b neurons, but few studies have examined the functional properties of these cells. In the present study we examined the actions of cholecystokinin (CCK) on layer 6b neocortical neurons using whole-cell patch clamp recording techniques. We found that the general CCK receptor agonist CCK8S (sulfated CCK octapeptide) strongly depolarized the neurons, and this action persisted in the presence of tetrodotoxin, suggesting a postsynaptic site of action. The excitatory actions of CCK8S were mimicked by the selective CCKB receptor agonist CCK4, and attenuated by the selective CCKB receptor antagonist L365260, indicating a role for CCKB receptors. Voltage clamp recordings revealed that CCK8S produced a slow inward current associated with a decreased conductance with a reversal potential near the K+ equilibrium potential. In addition, intracellular cesium also blocked the inward current, suggesting the involvement of a K+ conductance, likely Kleak. Our data indicate that CCK, acting via CCKB receptors, produces a long-lasting excitation of layer 6b neocortical neurons, and this action may play a critical role in modulation of corticothalamic circuit activity. PMID:19497313

  10. Dopamine gates action potential backpropagation in midbrain dopaminergic neurons.

    PubMed

    Gentet, Luc J; Williams, Stephen R

    2007-02-21

    Dopamine is released from both axonal and somatodendritic sites of midbrain dopaminergic neurons in an action potential-dependent manner. In contrast to the majority of central neurons, the axon of dopaminergic neurons typically originates from a dendritic site, suggesting a specialized computational function. Here, we examine the initiation and spread of action potentials in dopaminergic neurons of the substantia nigra pars reticulata and reveal that the displacement of the axon to a dendritic site allows highly compartmentalized electrical signaling. In response to a train of synaptic input, action potentials initiated at axon-bearing dendritic sites formed a variable trigger for invasion to the soma and contralateral dendritic tree, with action potentials often confined to the axon-bearing dendrite. The application of dopamine increased this form of electrical compartmentalization, an effect mediated by a tonic membrane potential hyperpolarization leading to an increased availability of a class of voltage-dependent potassium channel. These data suggest that the release of dopamine from axonal and somatodendritic sites are dissociable, and that dopamine levels within the midbrain are dynamically controlled by the somatodendritic spread of action potentials.

  11. Thyroid Hormone Action: Astrocyte–Neuron Communication

    PubMed Central

    Morte, Beatriz; Bernal, Juan

    2014-01-01

    Thyroid hormone (TH) action is exerted mainly through regulation of gene expression by binding of T3 to the nuclear receptors. T4 plays an important role as a source of intracellular T3 in the central nervous system via the action of the type 2 deiodinase (D2), expressed in the astrocytes. A model of T3 availability to neural cells has been proposed and validated. The model contemplates that brain T3 has a double origin: a fraction is available directly from the circulation, and another is produced locally from T4 in the astrocytes by D2. The fetal brain depends almost entirely on the T3 generated locally. The contribution of systemic T3 increases subsequently during development to account for approximately 50% of total brain T3 in the late postnatal and adult stages. In this article, we review the experimental data in support of this model, and how the factors affecting T3 availability in the brain, such as deiodinases and transporters, play a decisive role in modulating local TH action during development. PMID:24910631

  12. Spatial and viewpoint selectivity for others' observed actions in monkey ventral premotor mirror neurons.

    PubMed

    Maranesi, Monica; Livi, Alessandro; Bonini, Luca

    2017-08-15

    The spatial location and viewpoint of observed actions are closely linked in natural social settings. For example, actions observed from a subjective viewpoint necessarily occur within the observer's peripersonal space. Neurophysiological studies have shown that mirror neurons (MNs) of the monkey ventral premotor area F5 can code the spatial location of live observed actions. Furthermore, F5 MN discharge can also be modulated by the viewpoint from which filmed actions are seen. Nonetheless, whether and to what extent MNs can integrate viewpoint and spatial location of live observed actions remains unknown. We addressed this issue by comparing the activity of 148 F5 MNs while macaque monkeys observed an experimenter grasping in three different combinations of viewpoint and spatial location, namely, lateral view in the (1) extrapersonal and (2) peripersonal space and (3) subjective view in the peripersonal space. We found that the majority of MNs were space-selective (60.8%): those selective for the peripersonal space exhibited a preference for the subjective viewpoint both at the single-neuron and population level, whereas space-unselective neurons were view invariant. These findings reveal the existence of a previously neglected link between spatial and viewpoint selectivity in MN activity during live-action observation.

  13. The Mirror Neuron System: Grasping Others' Actions from Birth?

    ERIC Educational Resources Information Center

    Lepage, Jean-Francois; Theoret, Hugo

    2007-01-01

    In the adult human brain, the presence of a system matching the observation and the execution of actions is well established. This mechanism is thought to rely primarily on the contribution of so-called "mirror neurons", cells that are active when a specific gesture is executed as well as when it is seen or heard. Despite the wealth of evidence…

  14. The Mirror Neuron System: Grasping Others' Actions from Birth?

    ERIC Educational Resources Information Center

    Lepage, Jean-Francois; Theoret, Hugo

    2007-01-01

    In the adult human brain, the presence of a system matching the observation and the execution of actions is well established. This mechanism is thought to rely primarily on the contribution of so-called "mirror neurons", cells that are active when a specific gesture is executed as well as when it is seen or heard. Despite the wealth of evidence…

  15. Economic risk coding by single neurons in the orbitofrontal cortex.

    PubMed

    O'Neill, Martin; Schultz, Wolfram

    2015-01-01

    Risk is a ubiquitous feature of the environment for all organisms. Very few things in life are achieved with absolute certainty. Therefore, it is essential that organisms process risky information efficiently to promote adaptive behaviour and enhance survival. Here we outline a clear definition of economic risk derived from economic theory and focus on two experiments in which we have shown subpopulations of single neurons in the orbitofrontal cortex of rhesus macaques that code either economic risk per se or an error-related risk signal, namely a risk prediction error. These biological risk signals are essential for processing and updating risky information in the environment to contribute to efficient decision making and adaptive behaviour. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Excitatory actions of peptide histidine isoleucine on thalamic relay neurons.

    PubMed

    Lee, Sang-Hun; Cox, Charles L

    2008-12-01

    Peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) are neuropeptides synthesized from a common precursor, prepro-VIP, and share structural similarity and biological functions in many systems. Within the central nervous system and peripheral tissues, PHI and VIP have overlapping distribution. PHI-mediated functions are generally via activation of VIP receptors; however, the potency and affinity of PHI for VIP receptors are significantly lower than VIP. In addition, several studies suggest distinct PHI receptors that are independent of VIP receptors. PHI receptors have been cloned and characterized in fish, but their existence in mammals is still unknown. This study focuses on the functional role of PHI in the thalamus because of the localization of both PHI and VIP receptors in this brain region. Using extracellular multiple-unit recording techniques, we found that PHI strongly attenuated the slow intrathalamic rhythmic activity. Using intracellular recording techniques, we found that PHI selectively depolarized thalamic relay neurons via an enhancement of the hyperpolarization-activated mixed cation current, Ih. Further, the actions of PHI were occluded by VIP and dopamine, indicating these modulators converge onto a common mechanism. In contrast to previous work, we found that PHI was more potent than VIP in producing excitatory actions on thalamic neurons. We next used the transgenic mice lacking a specific VIP receptor, VPAC2, to identify its possible role in PHI-mediated actions in the thalamus. PHI depolarized all relay neurons tested from wild-type mice (VPAC2(+/+)); however, in knockout mice (VPAC2(-/-)), PHI produced no change in membrane potential in all neurons tested. Our findings indicate that excitatory actions of PHI are mediated by VPAC2 receptors, not by its own PHI receptors and the excitatory actions of PHI clearly attenuate intrathalamic rhythmic activities, and likely influence information transfer through thalamocortical

  17. Interpersonal predictive coding, not action perception, is impaired in autism

    PubMed Central

    von der Lühe, T.; Manera, V.; Barisic, I.; Becchio, C.; Vogeley, K.

    2016-01-01

    This study was conducted to examine interpersonal predictive coding in individuals with high-functioning autism (HFA). Healthy and HFA participants observed point-light displays of two agents (A and B) performing separate actions. In the ‘communicative’ condition, the action performed by agent B responded to a communicative gesture performed by agent A. In the ‘individual’ condition, agent A's communicative action was substituted by a non-communicative action. Using a simultaneous masking-detection task, we demonstrate that observing agent A's communicative gesture enhanced visual discrimination of agent B for healthy controls, but not for participants with HFA. These results were not explained by differences in attentional factors as measured via eye-tracking, or by differences in the recognition of the point-light actions employed. Our findings, therefore, suggest that individuals with HFA are impaired in the use of social information to predict others' actions and provide behavioural evidence that such deficits could be closely related to impairments of predictive coding. PMID:27069050

  18. Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

    PubMed Central

    Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

    2011-01-01

    Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

  19. The adrenergic-neurone blocking action of some coumaran compounds

    PubMed Central

    Fielden, R.; Roe, A. M.; Willey, G. L.

    1964-01-01

    Ethyldimethyl(7-methylcoumaran-3-yl)ammonium iodide (SK&F 90,109) and its guanidine analogue [N-(7-methylcoumaran-3-yl)guanidine nitrate] (SK&F 90,238) abolish the effects of adrenergic nerve stimulation in cats, as do xylocholine and bretylium. SK&F 90,109 has slight sympathomimetic actions; these are less marked than in SK&F 90,238. Large doses of SK&F 90,109 have an action, dependent on local noradrenaline stores, that delays the appearance of adrenergic-neurone blockade in conscious cats. Responses to adrenaline are, in general, enhanced by each drug, but SK&F 90,238 transiently antagonizes tachycardia induced by adrenaline and isoprenaline. Both drugs inhibit the release of noradrenaline from the spleen during splenic nerve stimulation, but the release of catechol amines from the adrenal glands, in response to electrical or chemical stimulation, is unimpaired. In contrast to the prolonged adrenergic-neurone blocking action, any inhibition of the effects of cholinergic nerve stimulation is transient. Large intravenous doses produce neuromuscular blockade. The compounds have a slight central depressant action. In contrast to reserpine and guanethidine the noradrenaline content of rat hearts is not appreciably lowered 24 hr after a single dose of either drug. Unlike xylocholine they are not local anaesthetics. Related compounds also block the effects of adrenergic-nerve stimulation. The possible modes of action of these drugs are discussed. PMID:14256809

  20. Non-associative Potentiation of Perisomatic Inhibition Alters the Temporal Coding of Neocortical Layer 5 Pyramidal Neurons

    PubMed Central

    Lourenço, Joana; Pacioni, Simone; Rebola, Nelson; van Woerden, Geeske M.; Marinelli, Silvia; DiGregorio, David; Bacci, Alberto

    2014-01-01

    In the neocortex, the coexistence of temporally locked excitation and inhibition governs complex network activity underlying cognitive functions, and is believed to be altered in several brain diseases. Here we show that this equilibrium can be unlocked by increased activity of layer 5 pyramidal neurons of the mouse neocortex. Somatic depolarization or short bursts of action potentials of layer 5 pyramidal neurons induced a selective long-term potentiation of GABAergic synapses (LTPi) without affecting glutamatergic inputs. Remarkably, LTPi was selective for perisomatic inhibition from parvalbumin basket cells, leaving dendritic inhibition intact. It relied on retrograde signaling of nitric oxide, which persistently altered presynaptic GABA release and diffused to inhibitory synapses impinging on adjacent pyramidal neurons. LTPi reduced the time window of synaptic summation and increased the temporal precision of spike generation. Thus, increases in single cortical pyramidal neuron activity can induce an interneuron-selective GABAergic plasticity effectively altering the computation of temporally coded information. PMID:25003184

  1. Excitatory actions of GABA in developing rat hypothalamic neurones.

    PubMed Central

    Chen, G; Trombley, P Q; van den Pol, A N

    1996-01-01

    1. Gramicidin-perforated patch clamp recording was employed to study GABA-mediated responses in rat hypothalamic neurones (n = 102) with an intracellular Cl- concentration unaltered by the pipette solution. 2. In young cultures after 1-7 days in vitro (DIV), GABA induced depolarizing membrane potentials (+16.5 +/- 1.3 mV) that often surpassed the threshold for the firing of action potentials (-42 +/- 1 mV) and resulted in an increase in neuronal activity. The depolarizing responses to GABA in young cultures were dose dependent. The concentration of GABA necessary to evoke the half-maximal depolarization (EC50) was 2.8 microM. In contrast, GABA induced hyperpolarizing membrane potentials (-12.0 +/- 1.4 mV) and a decrease in neuronal activity in older neurones (20-33 DIV). Both the depolarization and the hyperpolarization induced by GABA were blocked by bicuculline, indicating a mediation by GABAA receptors. 3. The reversal potentials of the GABA-evoked currents were between -40 to -50 mV during the first week of culture, and shifted to below -70 mV after 3 weeks of culture. In parallel, neurones that were dissociated from older animals (postnatal day 5) had a more negative reversal potential for the GABA-evoked currents than cells from younger animals (embryonic day 15), suggesting that the negative shift of the reversal potential occurs both in vitro and in vivo. Our data suggest that the mechanism for GABA-induced depolarization is the depolarized Cl- reversal potential found in young but not older neurones. 4. Consistent with the depolarizing response to exogenous application of GABA, some spontaneous depolarizing postsynaptic potentials in young cultures were insensitive to AP5-CNQX, but were eliminated by bicuculline, indicating that synaptically released GABA mediated excitatory synaptic transmission in early development. 5. By combining a rapid computer-controlled delivery of GABA with subthreshold positive current injections into recorded neurones, we found

  2. Networks of VTA Neurons Encode Real-Time Information about Uncertain Numbers of Actions Executed to Earn a Reward.

    PubMed

    Wood, Jesse; Simon, Nicholas W; Koerner, F Spencer; Kass, Robert E; Moghaddam, Bita

    2017-01-01

    Multiple and unpredictable numbers of actions are often required to achieve a goal. In order to organize behavior and allocate effort so that optimal behavioral policies can be selected, it is necessary to continually monitor ongoing actions. Real-time processing of information related to actions and outcomes is typically assigned to the prefrontal cortex and basal ganglia, but also depends on midbrain regions, especially the ventral tegmental area (VTA). We were interested in how individual VTA neurons, as well as networks within the VTA, encode salient events when an unpredictable number of serial actions are required to obtain a reward. We recorded from ensembles of putative dopamine and non-dopamine neurons in the VTA as animals performed multiple cued trials in a recording session where, in each trial, serial actions were randomly rewarded. While averaging population activity did not reveal a response pattern, we observed that different neurons were selectively tuned to low, medium, or high numbered actions in a trial. This preferential tuning of putative dopamine and non-dopamine VTA neurons to different subsets of actions in a trial allowed information about binned action number to be decoded from the ensemble activity. At the network level, tuning curve similarity was positively associated with action-evoked noise correlations, suggesting that action number selectivity reflects functional connectivity within these networks. Analysis of phasic responses to cue and reward revealed that the requirement to execute multiple and uncertain numbers of actions weakens both cue-evoked responses and cue-reward response correlation. The functional connectivity and ensemble coding scheme that we observe here may allow VTA neurons to cooperatively provide a real-time account of ongoing behavior. These computations may be critical to cognitive and motivational functions that have long been associated with VTA dopamine neurons.

  3. The actions of Pasteurella multocida toxin on neuronal cells.

    PubMed

    Surguy, Susan M; Duricki, Denise A; Reilly, Joanne M; Lax, Alistair J; Robbins, Jon

    2014-02-01

    Pasteurella multocida toxin (PMT) activates the G-proteins Gαi(₁₋₃), Gα(q), Gα₁₁, Gα₁₂ and Gα₁₃ by deamidation of specific glutamine residues. A number of these alpha subunits have signalling roles in neurones. Hence we studied the action of this toxin on rat superior cervical ganglion (SCG) neurones and NG108-15 neuronal cells. Both Gα(q) and Gα₁₁ could be identified in SCGs with immunocytochemistry. PMT had no direct action on Kv7 or Cav2 channels in SCGs. However PMT treatment enhanced muscarinic receptor mediated inhibition of M-current (Kv7.2 + 7. 3) as measured by a 19-fold leftward shift in the oxotremorine-M concentration-inhibition curve. Agonists of other receptors, such as bradykinin or angiotensin, that inhibit M-current did not produce this effect. However the amount of PIP₂ hydrolysis could be enhanced by PMT for all three agonists. In a transduction system in SCGs that is unlikely to be affected by PMT, Go mediated inhibition of calcium current, PMT was ineffective whereas the response was blocked by pertussis toxin as expected. M1 muscarinic receptor evoked calcium mobilisation in transformed NG108-15 cells was enhanced by PMT. The calcium rises evoked by uridine triphosphate acting on endogenous P2Y₂ receptors in NG108-15 cells were enhanced by PMT. The time and concentration dependence of the PMT effect was different for the resting calcium compared to the calcium rise produced by activation of P2Y₂ receptors. PMT's action on these neuronal cells would suggest that if it got into the brain, symptoms of a hyperexcitable nature would be seen, such as seizures.

  4. Spatio-temporal Laplacian pyramid coding for action recognition.

    PubMed

    Shao, Ling; Zhen, Xiantong; Tao, Dacheng; Li, Xuelong

    2014-06-01

    We present a novel descriptor, called spatio-temporal Laplacian pyramid coding (STLPC), for holistic representation of human actions. In contrast to sparse representations based on detected local interest points, STLPC regards a video sequence as a whole with spatio-temporal features directly extracted from it, which prevents the loss of information in sparse representations. Through decomposing each sequence into a set of band-pass-filtered components, the proposed pyramid model localizes features residing at different scales, and therefore is able to effectively encode the motion information of actions. To make features further invariant and resistant to distortions as well as noise, a bank of 3-D Gabor filters is applied to each level of the Laplacian pyramid, followed by max pooling within filter bands and over spatio-temporal neighborhoods. Since the convolving and pooling are performed spatio-temporally, the coding model can capture structural and motion information simultaneously and provide an informative representation of actions. The proposed method achieves superb recognition rates on the KTH, the multiview IXMAS, the challenging UCF Sports, and the newly released HMDB51 datasets. It outperforms state of the art methods showing its great potential on action recognition.

  5. Action potential initiation and propagation in rat neocortical pyramidal neurons.

    PubMed

    Stuart, G; Schiller, J; Sakmann, B

    1997-12-15

    1. Initiation and propagation of action potentials evoked by extracellular synaptic stimulation was studied using simultaneous dual and triple patch pipette recordings from different locations on neocortical layer 5 pyramidal neurons in brain slices from 4-week-old rats (P26-30) at physiological temperatures. 2. Simultaneous cell-attached and whole-cell voltage recordings from the apical trunk (up to 700 microns distal to the soma) and the soma indicated that proximal synaptic stimulation (layer 4) initiated action potentials first at the soma, whereas distal stimulation (upper layer 2/3) could initiate dendritic regenerative potentials prior to somatic action potentials following stimulation at higher intensity. 3. Somatic action potentials, once initiated, propagated back into the apical dendrites in a decremented manner which was frequency dependent. The half-width of back propagating action potentials increased and their maximum rate of rise decreased with distance from the soma, with the peak of these action potentials propagating with a conduction velocity of approximately 0.5 m s-1. 4. Back-propagation of action potentials into the dendritic tree was associated with dendritic calcium electrogenesis, which was particularly prominent during bursts of somatic action potentials. 5. When dendritic regenerative potentials were evoked prior to somatic action potentials, the more distal the dendritic recording was made from the soma the longer the time between the onset of the dendritic regenerative potential relative to somatic action potential. This suggested that dendritic regenerative potentials were initiated in the distal apical dendrites, possibly in the apical tuft. 6. At any one stimulus intensity, the initiation of dendritic regenerative potentials prior to somatic action potentials could fluctuate, and was modulated by depolarizing somatic or hyperpolarizing dendritic current injection. 7. Dendritic regenerative potentials could be initiated prior to

  6. A dynamic code for economic object valuation in prefrontal cortex neurons

    PubMed Central

    Tsutsui, Ken-Ichiro; Grabenhorst, Fabian; Kobayashi, Shunsuke; Schultz, Wolfram

    2016-01-01

    Neuronal reward valuations provide the physiological basis for economic behaviour. Yet, how such valuations are converted to economic decisions remains unclear. Here we show that the dorsolateral prefrontal cortex (DLPFC) implements a flexible value code based on object-specific valuations by single neurons. As monkeys perform a reward-based foraging task, individual DLPFC neurons signal the value of specific choice objects derived from recent experience. These neuronal object values satisfy principles of competitive choice mechanisms, track performance fluctuations and follow predictions of a classical behavioural model (Herrnstein's matching law). Individual neurons dynamically encode both, the updating of object values from recently experienced rewards, and their subsequent conversion to object choices during decision-making. Decoding from unselected populations enables a read-out of motivational and decision variables not emphasized by individual neurons. These findings suggest a dynamic single-neuron and population value code in DLPFC that advances from reward experiences to economic object values and future choices. PMID:27618960

  7. Efficacy and kinetics of opioid action on acutely dissociated neurons.

    PubMed

    Ingram, S; Wilding, T J; McCleskey, E W; Williams, J T

    1997-07-01

    Opioids have been shown to cause a potent inhibition of neurons in the locus ceruleus (LC) in vivo in brain slices and isolated neurons; however, the kinetics of opioid action have not been described. In this study, we used acutely isolated LC neurons to examine opioid and alpha2-adrenoceptor action on potassium and calcium currents. [Met]Enkephalin (ME), [D-Ser2,Leu5,Thr6]-enkephalin, etorphine, and [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin increased potassium conductance, whereas morphine and naloxone were antagonists. The time constant of potassium channel activation was approximately 0.7 sec and was the same for each agonist. The amplitude of the current and the time constant of decay were dependent on the agonist, suggesting that agonist efficacy and affinity, respectively, determined these parameters. The amplitude of potassium current induced by the alpha2-adrenoceptor agonist UK14304 was not significantly different from that induced by ME, but the time constant of current activation was half that of ME, and the decline was more rapid. When potassium conductances were blocked with the combination of internal cesium and external barium, opioid and alpha2 agonists had no effect at potentials more negative than -50 mV and decreased barium currents at potentials between -40 and +20 mV. Both morphine and clonidine caused a small inhibition of barium current. In dorsal root ganglion cells, morphine alone had small and inconsistent effects on the calcium current, but it always competitively antagonized the inhibition caused by [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin. The results in isolated LC neurons suggest 1) the amplitude and time course of the opioid-induced potassium current depend on agonist efficacy and affinity and 2) the coupling of both mu-opioid and alpha2-adrenoceptors to calcium channels seems to be more efficient than that to potassium channels.

  8. Documents Pertaining to Resource Conservation and Recovery Act Corrective Action Event Codes

    EPA Pesticide Factsheets

    Document containing RCRA Corrective Action event codes and definitions, including national requirements, initiating sources, dates, and guidance, from the first facility assessment until the Corrective Action is terminated.

  9. Functional properties of parietal hand manipulation-related neurons and mirror neurons responding to vision of own hand action.

    PubMed

    Maeda, Kazutaka; Ishida, Hiroaki; Nakajima, Katsumi; Inase, Masahiko; Murata, Akira

    2015-03-01

    Parietofrontal pathways play an important role in visually guided motor control. In this pathway, hand manipulation-related neurons in the inferior parietal lobule represent 3-D properties of an object and motor patterns to grasp it. Furthermore, mirror neurons show visual responses that are concerned with the actions of others and motor-related activity during execution of the same grasping action. Because both of these categories of neurons integrate visual and motor signals, these neurons may play a role in motor control based on visual feedback signals. The aim of this study was to investigate whether these neurons in inferior parietal lobule including the anterior intraparietal area and PFG of macaques represent visual images of the monkey's own hand during a self-generated grasping action. We recorded 235 neurons related to hand manipulation tasks. Of these, 54 responded to video clips of the monkey's own hand action, the same as visual feedback during that action or clips of the experimenter's hand action in a lateral view. Of these 54 neurons, 25 responded to video clips of the monkey's own hand, even without an image of the target object. We designated these 25 neurons as "hand-type." Thirty-three of 54 neurons that were defined as mirror neurons showed visual responses to the experimenter's action and motor responses. Thirteen of these mirror neurons were classified as hand-type. These results suggest that activity of hand manipulation-related and mirror neurons in anterior intraparietal/PFG plays a fundamental role in monitoring one's own body state based on visual feedback.

  10. Temperature dependence of action potential parameters in Aplysia neurons.

    PubMed

    Hyun, Nam Gyu; Hyun, Kwang-Ho; Lee, Kyungmin; Kaang, Bong-Kiun

    2012-01-01

    Although the effects of temperature changes on the activity of neurons have been studied in Aplysia, the reproducibility of the temperature dependence of the action potential (AP) parameters has not been verified. To this end, we performed experiments using Aplysia neurons. Fourteen AP parameters were analyzed using the long-term data series recorded during the experiments. Our analysis showed that nine of the AP parameters decreased as the temperature increased: the AP amplitude (A(AP)), membrane potential at the positive peak (V(pp)), interspike interval, first half (Δt(r1)) and last half (Δt(r2)) of the temperature rising phase, first half (Δt(f1)) and last half (Δt(f2)) of the temperature falling phase, AP (Δt(AP, 1/2)), and differentiated signal (Δt(DS, 1/2)) half-width durations. Five of the AP parameters increased with temperature: the differentiated signal amplitude (A(DS)), absolute value of the membrane potential at negative peak (|V(np)|), absolute value of the maximum slope of the AP during the temperature rising (|-MSR|) and falling (|MSF|) phases, and spiking frequency (Frequency). This work could provide the basis for a better understanding of the elementary processes underlying the temperature-dependent neuronal activity in Aplysia.

  11. Energy-efficient population coding constrains network size of a neuronal array system

    PubMed Central

    Yu, Lianchun; Zhang, Chi; Liu, Liwei; Yu, Yuguo

    2016-01-01

    We consider the open issue of how the energy efficiency of the neural information transmission process, in a general neuronal array, constrains the network size, and how well this network size ensures the reliable transmission of neural information in a noisy environment. By direct mathematical analysis, we have obtained general solutions proving that there exists an optimal number of neurons in the network, where the average coding energy cost (defined as energy consumption divided by mutual information) per neuron passes through a global minimum for both subthreshold and superthreshold signals. With increases in background noise intensity, the optimal neuronal number decreases for subthreshold signals and increases for suprathreshold signals. The existence of an optimal number of neurons in an array network reveals a general rule for population coding that states that the neuronal number should be large enough to ensure reliable information transmission that is robust to the noisy environment but small enough to minimize energy cost. PMID:26781354

  12. Energy-efficient population coding constrains network size of a neuronal array system.

    PubMed

    Yu, Lianchun; Zhang, Chi; Liu, Liwei; Yu, Yuguo

    2016-01-19

    We consider the open issue of how the energy efficiency of the neural information transmission process, in a general neuronal array, constrains the network size, and how well this network size ensures the reliable transmission of neural information in a noisy environment. By direct mathematical analysis, we have obtained general solutions proving that there exists an optimal number of neurons in the network, where the average coding energy cost (defined as energy consumption divided by mutual information) per neuron passes through a global minimum for both subthreshold and superthreshold signals. With increases in background noise intensity, the optimal neuronal number decreases for subthreshold signals and increases for suprathreshold signals. The existence of an optimal number of neurons in an array network reveals a general rule for population coding that states that the neuronal number should be large enough to ensure reliable information transmission that is robust to the noisy environment but small enough to minimize energy cost.

  13. Energy-efficient population coding constrains network size of a neuronal array system

    NASA Astrophysics Data System (ADS)

    Yu, Lianchun; Zhang, Chi; Liu, Liwei; Yu, Yuguo

    2016-01-01

    We consider the open issue of how the energy efficiency of the neural information transmission process, in a general neuronal array, constrains the network size, and how well this network size ensures the reliable transmission of neural information in a noisy environment. By direct mathematical analysis, we have obtained general solutions proving that there exists an optimal number of neurons in the network, where the average coding energy cost (defined as energy consumption divided by mutual information) per neuron passes through a global minimum for both subthreshold and superthreshold signals. With increases in background noise intensity, the optimal neuronal number decreases for subthreshold signals and increases for suprathreshold signals. The existence of an optimal number of neurons in an array network reveals a general rule for population coding that states that the neuronal number should be large enough to ensure reliable information transmission that is robust to the noisy environment but small enough to minimize energy cost.

  14. Endomorphins: localization, release and action on rat dorsal horn neurons.

    PubMed

    Dun, N J; Dun, S L; Wu, S Y; Williams, C A; Kwok, E H

    2000-01-01

    Endomorphin (Endo) 1 and 2, two tetrapeptides isolated from the bovine and human brain, have been proposed to be the endogenous ligand for the mu-opiate receptor. A multi-disciplinary study was undertaken to address the issues of localization, release and biological action of Endo with respect to the rat dorsal horn. First, immunohistochemical studies showed that Endo-1- or Endo-2-like immunoreactivity (Endo-1- or Endo-2-LI) is selectively expressed in fiber-like elements occupying the superficial layers of the rat dorsal horn, which also exhibit a high level of mu-opiate receptor immunoreactivity. Second, release of immunoreactive Endo-2-like substances (irEndo) from the in vitro rat spinal cords upon electrical stimulation of dorsal root afferent fibers was detected by the immobilized antibody microprobe technique. The site of release corresponded to laminae I and II where the highest density of Endo-2-LI fibers was localized. Lastly, whole-cell patch clamp recordings from substantia gelatinosa (SG) neurons of rat lumbar spinal cord slices revealed two distinct actions of exogenous Endo-1 and Endo-2: (1) depression of excitatory and/or inhibitory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (2) hyperpolarization of SG neurons. These two effects were prevented by the selective mu-opiate receptor antagonist beta-funaltrexamine. The localization of endomorphin-positive fibers in superficial layers of the dorsal horn and the release of irEndo upon stimulation of dorsal root afferents together with the observation that Endo inhibits the activity of SG neurons by interacting with mu-opiate receptors provide additional support of a role of Endo as the endogenous ligand for the mu-opiate receptor in the rat dorsal horn.

  15. Stimulus features coded by single neurons of a macaque body category selective patch.

    PubMed

    Popivanov, Ivo D; Schyns, Philippe G; Vogels, Rufin

    2016-04-26

    Body category-selective regions of the primate temporal cortex respond to images of bodies, but it is unclear which fragments of such images drive single neurons' responses in these regions. Here we applied the Bubbles technique to the responses of single macaque middle superior temporal sulcus (midSTS) body patch neurons to reveal the image fragments the neurons respond to. We found that local image fragments such as extremities (limbs), curved boundaries, and parts of the torso drove the large majority of neurons. Bubbles revealed the whole body in only a few neurons. Neurons coded the features in a manner that was tolerant to translation and scale changes. Most image fragments were excitatory but for a few neurons both inhibitory and excitatory fragments (opponent coding) were present in the same image. The fragments we reveal here in the body patch with Bubbles differ from those suggested in previous studies of face-selective neurons in face patches. Together, our data indicate that the majority of body patch neurons respond to local image fragments that occur frequently, but not exclusively, in bodies, with a coding that is tolerant to translation and scale. Overall, the data suggest that the body category selectivity of the midSTS body patch depends more on the feature statistics of bodies (e.g., extensions occur more frequently in bodies) than on semantics (bodies as an abstract category).

  16. Geometric constraints on neuronal connectivity facilitate a concise synaptic adhesive code

    PubMed Central

    Itzkovitz, Shalev; Baruch, Leehod; Shapiro, Ehud; Segal, Eran

    2008-01-01

    The nervous system contains trillions of neurons, each forming thousands of synaptic connections. It has been suggested that this complex connectivity is determined by a synaptic “adhesive code,” where connections are dictated by a variable set of cell surface proteins, combinations of which form neuronal addresses. The estimated number of neuronal addresses is orders of magnitude smaller than the number of neurons. Here, we show that the limited number of addresses dictates constraints on the possible neuronal network topologies. We show that to encode arbitrary networks, in which each neuron can potentially connect to any other neuron, the number of neuronal addresses needed scales linearly with network size. In contrast, the number of addresses needed to encode the wiring of geometric networks grows only as the square root of network size. The more efficient encoding in geometric networks is achieved through the reutilization of the same addresses in physically independent portions of the network. We also find that ordered geometric networks, in which the same connectivity patterns are iterated throughout the network, further reduce the required number of addresses. We demonstrate our findings using simulated networks and the C. elegans neuronal network. Geometric neuronal connectivity with recurring connectivity patterns have been suggested to confer an evolutionary advantage by saving biochemical resources on the one hand and reutilizing functionally efficient neuronal circuits. Our study suggests an additional advantage of these prominent topological features—the facilitation of the ability to genetically encode neuronal networks given constraints on the number of addresses. PMID:18583478

  17. Stimulus features coded by single neurons of a macaque body category selective patch

    PubMed Central

    Popivanov, Ivo D.; Schyns, Philippe G.; Vogels, Rufin

    2016-01-01

    Body category-selective regions of the primate temporal cortex respond to images of bodies, but it is unclear which fragments of such images drive single neurons’ responses in these regions. Here we applied the Bubbles technique to the responses of single macaque middle superior temporal sulcus (midSTS) body patch neurons to reveal the image fragments the neurons respond to. We found that local image fragments such as extremities (limbs), curved boundaries, and parts of the torso drove the large majority of neurons. Bubbles revealed the whole body in only a few neurons. Neurons coded the features in a manner that was tolerant to translation and scale changes. Most image fragments were excitatory but for a few neurons both inhibitory and excitatory fragments (opponent coding) were present in the same image. The fragments we reveal here in the body patch with Bubbles differ from those suggested in previous studies of face-selective neurons in face patches. Together, our data indicate that the majority of body patch neurons respond to local image fragments that occur frequently, but not exclusively, in bodies, with a coding that is tolerant to translation and scale. Overall, the data suggest that the body category selectivity of the midSTS body patch depends more on the feature statistics of bodies (e.g., extensions occur more frequently in bodies) than on semantics (bodies as an abstract category). PMID:27071095

  18. Teaching Neurophysiology to Undergraduates using Neurons in Action

    PubMed Central

    Stuart, Ann E.

    2009-01-01

    Neurons in Action, a set of 25 hyperlinked tutorials and interactive simulations on CD-ROM, provides the student with a completely different approach to neurophysiology from that of textbooks. Guided by the tutorials, by their professor, by the urge to test their understanding, or simply by curiosity, students specify the parameters of a patch of membrane, an axon, a postsynaptic membrane, or a cell and run virtual experiments. Parameters include geometry, the number and type of ion channels in the membrane, the number of myelin wraps of the axon, the ion concentrations inside and out, synaptic variables, and temperature. Hyperlinked explanations, historical information, and classic papers on the CD provide the “textbook” material. This article describes this learning tool and details several ways in which it is being used at the undergraduate level. PMID:23493486

  19. Teaching Neurophysiology to Undergraduates using Neurons in Action.

    PubMed

    Stuart, Ann E

    2009-01-01

    Neurons in Action, a set of 25 hyperlinked tutorials and interactive simulations on CD-ROM, provides the student with a completely different approach to neurophysiology from that of textbooks. Guided by the tutorials, by their professor, by the urge to test their understanding, or simply by curiosity, students specify the parameters of a patch of membrane, an axon, a postsynaptic membrane, or a cell and run virtual experiments. Parameters include geometry, the number and type of ion channels in the membrane, the number of myelin wraps of the axon, the ion concentrations inside and out, synaptic variables, and temperature. Hyperlinked explanations, historical information, and classic papers on the CD provide the "textbook" material. This article describes this learning tool and details several ways in which it is being used at the undergraduate level.

  20. Dipole characterization of single neurons from their extracellular action potentials

    PubMed Central

    Victor, Jonathan D.

    2011-01-01

    The spatial variation of the extracellular action potentials (EAP) of a single neuron contains information about the size and location of the dominant current source of its action potential generator, which is typically in the vicinity of the soma. Using this dependence in reverse in a three-component realistic probe + brain + source model, we solved the inverse problem of characterizing the equivalent current source of an isolated neuron from the EAP data sampled by an extracellular probe at multiple independent recording locations. We used a dipole for the model source because there is extensive evidence it accurately captures the spatial roll-off of the EAP amplitude, and because, as we show, dipole localization, beyond a minimum cell-probe distance, is a more accurate alternative to approaches based on monopole source models. Dipole characterization is separable into a linear dipole moment optimization where the dipole location is fixed, and a second, nonlinear, global optimization of the source location. We solved the linear optimization on a discrete grid via the lead fields of the probe, which can be calculated for any realistic probe + brain model by the finite element method. The global source location was optimized by means of Tikhonov regularization that jointly minimizes model error and dipole size. The particular strategy chosen reflects the fact that the dipole model is used in the near field, in contrast to the typical prior applications of dipole models to EKG and EEG source analysis. We applied dipole localization to data collected with stepped tetrodes whose detailed geometry was measured via scanning electron microscopy. The optimal dipole could account for 96% of the power in the spatial variation of the EAP amplitude. Among various model error contributions to the residual, we address especially the error in probe geometry, and the extent to which it biases estimates of dipole parameters. This dipole characterization method can be applied to

  1. EquiFACS: The Equine Facial Action Coding System

    PubMed Central

    Wathan, Jen; Burrows, Anne M.; Waller, Bridget M.; McComb, Karen

    2015-01-01

    Although previous studies of horses have investigated their facial expressions in specific contexts, e.g. pain, until now there has been no methodology available that documents all the possible facial movements of the horse and provides a way to record all potential facial configurations. This is essential for an objective description of horse facial expressions across a range of contexts that reflect different emotional states. Facial Action Coding Systems (FACS) provide a systematic methodology of identifying and coding facial expressions on the basis of underlying facial musculature and muscle movement. FACS are anatomically based and document all possible facial movements rather than a configuration of movements associated with a particular situation. Consequently, FACS can be applied as a tool for a wide range of research questions. We developed FACS for the domestic horse (Equus caballus) through anatomical investigation of the underlying musculature and subsequent analysis of naturally occurring behaviour captured on high quality video. Discrete facial movements were identified and described in terms of the underlying muscle contractions, in correspondence with previous FACS systems. The reliability of others to be able to learn this system (EquiFACS) and consistently code behavioural sequences was high—and this included people with no previous experience of horses. A wide range of facial movements were identified, including many that are also seen in primates and other domestic animals (dogs and cats). EquiFACS provides a method that can now be used to document the facial movements associated with different social contexts and thus to address questions relevant to understanding social cognition and comparative psychology, as well as informing current veterinary and animal welfare practices. PMID:26244573

  2. Leptin modulates nutrient reward via inhibitory galanin action on orexin neurons

    PubMed Central

    Laque, Amanda; Yu, Sangho; Qualls-Creekmore, Emily; Gettys, Sarah; Schwartzenburg, Candice; Bui, Kelly; Rhodes, Christopher; Berthoud, Hans-Rudolf; Morrison, Christopher D.; Richards, Brenda K.; Münzberg, Heike

    2015-01-01

    Objective Leptin modulates food reward via central leptin receptor (LepRb) expressing neurons. Food reward requires stimulation of midbrain dopamine neurons and is modulated by central leptin action, but the exact central mechanisms remain unclear. Stimulatory and inhibitory leptin actions on dopamine neurons have been reported, e.g. by indirect actions on orexin neurons or via direct innervation of dopamine neurons in the ventral tegmental area. Methods We showed earlier that LepRb neurons in the lateral hypothalamus (LHA) co-express the inhibitory acting neuropeptide galanin (GAL-LepRb neurons). We studied the involvement of GAL-LepRb neurons to regulate nutrient reward in mice with selective LepRb deletion from galanin neurons (GAL-LepRbKO mice). Results We found that the rewarding value and preference for sucrose over fat was increased in GAL-LepRbKO mice compared to controls. LHA GAL-LepRb neurons innervate orexin neurons, but not the VTA. Further, expression of galanin and its receptor GalR1 are decreased in the LHA of GAL-LepRbKO mice, resulting in increased activation of orexin neurons. Conclusion We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons. PMID:26500842

  3. Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamine.

    PubMed

    Tindell, Amy J; Berridge, Kent C; Zhang, Jun; Peciña, Susana; Aldridge, J Wayne

    2005-11-01

    Neurons in ventral pallidum fire to reward and its predictive cues. We tested mesolimbic activation effects on neural reward coding. Rats learned that a Pavlovian conditioned stimulus (CS+1 tone) predicted a second conditioned stimulus (CS+2 feeder click) followed by an unconditioned stimulus (UCS sucrose reward). Some rats were sensitized to amphetamine after training. Electrophysiological activity of ventral pallidal neurons to stimuli was later recorded under the influence of vehicle or acute amphetamine injection. Both sensitization and acute amphetamine increased ventral pallidum firing at CS+2 (population code and rate code). There were no changes at CS+1 and minimal changes to UCS. With a new 'Profile Analysis', we show that mesolimbic activation by sensitization/amphetamine incrementally shifted neuronal firing profiles away from prediction signal coding (maximal at CS+1) and toward incentive coding (maximal at CS+2), without changing hedonic impact coding (maximal at UCS). This pattern suggests mesolimbic activation specifically amplifies a motivational transform of CS+ predictive information into incentive salience coded by ventral pallidal neurons. Our results support incentive-sensitization predictions and suggest why cues temporally proximal to drug presentation may precipitate cue-triggered relapse in human addicts.

  4. [Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

    PubMed

    Furong, Liu; Shengtian, L I

    2016-05-25

    To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

  5. Neuronal population coding of perceived and memorized visual features in the lateral prefrontal cortex

    PubMed Central

    Mendoza-Halliday, Diego; Martinez-Trujillo, Julio C.

    2017-01-01

    The primate lateral prefrontal cortex (LPFC) encodes visual stimulus features while they are perceived and while they are maintained in working memory. However, it remains unclear whether perceived and memorized features are encoded by the same or different neurons and population activity patterns. Here we record LPFC neuronal activity while monkeys perceive the motion direction of a stimulus that remains visually available, or memorize the direction if the stimulus disappears. We find neurons with a wide variety of combinations of coding strength for perceived and memorized directions: some neurons encode both to similar degrees while others preferentially or exclusively encode either one. Reading out the combined activity of all neurons, a machine-learning algorithm reliably decode the motion direction and determine whether it is perceived or memorized. Our results indicate that a functionally diverse population of LPFC neurons provides a substrate for discriminating between perceptual and mnemonic representations of visual features. PMID:28569756

  6. Modulation of spike coding by subthreshold extracellular electric fields and neuronal morphology

    NASA Astrophysics Data System (ADS)

    Wei, Xile; Li, Bingjie; Lu, Meili; Yi, Guosheng; Wang, Jiang

    2015-07-01

    We use a two-compartment model, which includes soma and dendrite, to explore how extracellular subthreshold sinusoidal electric fields (EFs) influence the spike coding of an active neuron. By changing the intensity and the frequency of subthreshold EFs, we find that subthreshold EFs indeed affect neuronal coding remarkably within several stimulus frequency windows where the field effects on spike timing are stronger than that on spiking rate. The field effects are maximized at several harmonics of the intrinsic spiking frequency of an active neuron. Our findings implicate the potential resonance mechanism underlying subthreshold field effects. We also discuss how neuronal morphologic properties constrain subthreshold EF effects on spike timing. The morphologic properties are represented by two parameters, gc and p, where gc is the internal conductance between soma and dendrite and geometric factor p characterizes the proportion of area occupied by soma. We find that the contribution to field effects from the variation of p is stronger than that from gc, which suggests that neuronal geometric features play a crucial role in subthreshold field effects. Theoretically, these insights into how subthreshold sinusoidal EFs modulate ongoing neuron behaviors could contribute to uncovering the relevant mechanism of subthreshold sinusoidal EFs effects on neuronal coding. Furthermore, they are useful in rationally designing noninvasive brain stimulation strategies and developing electromagnetic stimulus techniques.

  7. Molecular codes for neuronal individuality and cell assembly in the brain.

    PubMed

    Yagi, Takeshi

    2012-01-01

    The brain contains an enormous, but finite, number of neurons. The ability of this limited number of neurons to produce nearly limitless neural information over a lifetime is typically explained by combinatorial explosion; that is, by the exponential amplification of each neuron's contribution through its incorporation into "cell assemblies" and neural networks. In development, each neuron expresses diverse cellular recognition molecules that permit the formation of the appropriate neural cell assemblies to elicit various brain functions. The mechanism for generating neuronal assemblies and networks must involve molecular codes that give neurons individuality and allow them to recognize one another and join appropriate networks. The extensive molecular diversity of cell-surface proteins on neurons is likely to contribute to their individual identities. The clustered protocadherins (Pcdh) is a large subfamily within the diverse cadherin superfamily. The clustered Pcdh genes are encoded in tandem by three gene clusters, and are present in all known vertebrate genomes. The set of clustered Pcdh genes is expressed in a random and combinatorial manner in each neuron. In addition, cis-tetramers composed of heteromultimeric clustered Pcdh isoforms represent selective binding units for cell-cell interactions. Here I present the mathematical probabilities for neuronal individuality based on the random and combinatorial expression of clustered Pcdh isoforms and their formation of cis-tetramers in each neuron. Notably, clustered Pcdh gene products are known to play crucial roles in correct axonal projections, synaptic formation, and neuronal survival. Their molecular and biological features induce a hypothesis that the diverse clustered Pcdh molecules provide the molecular code by which neuronal individuality and cell assembly permit the combinatorial explosion of networks that supports enormous processing capability and plasticity of the brain.

  8. In vivo conditions influence the coding of stimulus features by bursts of action potentials.

    PubMed

    Akerberg, Oscar Avila; Chacron, Maurice J

    2011-10-01

    The functional role of burst firing (i.e. the firing of packets of action potentials followed by quiescence) in sensory processing is still under debate. Should bursts be considered as unitary events that signal the presence of a particular feature in the sensory environment or is information about stimulus attributes contained within their temporal structure? We compared the coding of stimulus attributes by bursts in vivo and in vitro of electrosensory pyramidal neurons in weakly electric fish by computing correlations between burst and stimulus attributes. Our results show that, while these correlations were strong in magnitude and significant in vitro, they were actually much weaker in magnitude if at all significant in vivo. We used a mathematical model of pyramidal neuron activity in vivo and showed that such a model could reproduce the correlations seen in vitro, thereby suggesting that differences in burst coding were not due to differences in bursting seen in vivo and in vitro. We next tested whether variability in the baseline (i.e. without stimulation) activity of ELL pyramidal neurons could account for these differences. To do so, we injected noise into our model whose intensity was calibrated to mimic baseline activity variability as quantified by the coefficient of variation. We found that this noise caused significant decreases in the magnitude of correlations between burst and stimulus attributes and could account for differences between in vitro and in vivo conditions. We then tested this prediction experimentally by directly injecting noise in vitro through the recording electrode. Our results show that this caused a lowering in magnitude of the correlations between burst and stimulus attributes in vitro and gave rise to values that were quantitatively similar to those seen under in vivo conditions. While it is expected that noise in the form of baseline activity variability will lower correlations between burst and stimulus attributes, our results

  9. In vivo conditions influence the coding of stimulus features by bursts of action potentials

    PubMed Central

    Akerberg, Oscar Avila

    2015-01-01

    The functional role of burst firing (i.e. the firing of packets of action potentials followed by quiescence) in sensory processing is still under debate. Should bursts be considered as unitary events that signal the presence of a particular feature in the sensory environment or is information about stimulus attributes contained within their temporal structure? We compared the coding of stimulus attributes by bursts in vivo and in vitro of electrosensory pyramidal neurons in weakly electric fish by computing correlations between burst and stimulus attributes. Our results show that, while these correlations were strong in magnitude and significant in vitro, they were actually much weaker in magnitude if at all significant in vivo. We used a mathematical model of pyramidal neuron activity in vivo and showed that such a model could reproduce the correlations seen in vitro, thereby suggesting that differences in burst coding were not due to differences in bursting seen in vivo and in vitro. We next tested whether variability in the baseline (i.e. without stimulation) activity of ELL pyramidal neurons could account for these differences. To do so, we injected noise into our model whose intensity was calibrated to mimic baseline activity variability as quantified by the coefficient of variation. We found that this noise caused significant decreases in the magnitude of correlations between burst and stimulus attributes and could account for differences between in vitro and in vivo conditions. We then tested this prediction experimentally by directly injecting noise in vitro through the recording electrode. Our results show that this caused a lowering in magnitude of the correlations between burst and stimulus attributes in vitro and gave rise to values that were quantitatively similar to those seen under in vivo conditions. While it is expected that noise in the form of baseline activity variability will lower correlations between burst and stimulus attributes, our results

  10. Direct action of low doses of radiation of neurons

    SciTech Connect

    Peimer, S.I.; Dudkin, A.O.; Sverdlov, A.G.

    1986-03-01

    The authors experiment with new technology of surviving mammalian brain sections for the detection of the direct action of ionizing radiation on the functioning neurons of mammals. The authors selected the rat hippocampus as the object of investigation. Sections of the hippocampus were prepared according to standard procedure, 0.3 mm thick, and incubated for several hours under the following conditions: temperature 35.5/sup 0/C, rate of perfusion 2-3 ml/min, rate of delivery of a mixture of oxygen (95%), and carbon monoxide (5%), in the perfusion solution 35 ml/min. Composition of solution (mM): NaCl 124, KCl 5, CACl/sub 2/ 2.4, MgSO/sub 4/ 1.3, NaHCO/sub 3/ 26, glucose 10; pH 7.4. In an individual series of experiments, calcium was not added to the solution, but an excess of magnesium ions was introduced up to 2.6 mM. Extracellular takeoffs were performed with glass microelectrodes. For irradiation, the authors used sources of x-rays and gamma radiation. In the 5-DI x-ray apparatus, the working voltage and current on the tube were 50 quanta and 8 mA, respectively; there were no filters. Gamma irradiation was performed using ampuls with the radionuclide cesium-137 (IGI-C-3 type), which can be delivered on a holder directly to the section for 1 min.

  11. Role of synaptic dynamics and heterogeneity in neuronal learning of temporal code

    PubMed Central

    Rotman, Ziv

    2013-01-01

    Temporal codes are believed to play important roles in neuronal representation of information. Neuronal ability to classify and learn temporal spiking patterns is thus essential for successful extraction and processing of information. Understanding neuronal learning of temporal code has been complicated, however, by the intrinsic stochasticity of synaptic transmission. Using a computational model of a learning neuron, the tempotron, we studied the effects of synaptic unreliability and short-term dynamics on the neuron's ability to learn spike timing rules. Our results suggest that such a model neuron can learn to classify spike timing patterns even with unreliable synapses, albeit with a significantly reduced success rate. We explored strategies to improve correct spike timing classification and found that firing clustered spike bursts significantly improves learning performance. Furthermore, rapid activity-dependent modulation of synaptic unreliability, implemented with realistic models of dynamic synapses, further improved classification of different burst properties and spike timing modalities. Neuronal models with only facilitating or only depressing inputs exhibited preference for specific types of spike timing rules, but a mixture of facilitating and depressing synapses permitted much improved learning of multiple rules. We tested applicability of these findings to real neurons by considering neuronal learning models with the naturally distributed input release probabilities found in excitatory hippocampal synapses. Our results suggest that spike bursts comprise several encoding modalities that can be learned effectively with stochastic dynamic synapses, and that distributed release probabilities significantly improve learning performance. Synaptic unreliability and dynamics may thus play important roles in the neuron's ability to learn spike timing rules during decoding. PMID:23926043

  12. Role of synaptic dynamics and heterogeneity in neuronal learning of temporal code.

    PubMed

    Rotman, Ziv; Klyachko, Vitaly A

    2013-11-01

    Temporal codes are believed to play important roles in neuronal representation of information. Neuronal ability to classify and learn temporal spiking patterns is thus essential for successful extraction and processing of information. Understanding neuronal learning of temporal code has been complicated, however, by the intrinsic stochasticity of synaptic transmission. Using a computational model of a learning neuron, the tempotron, we studied the effects of synaptic unreliability and short-term dynamics on the neuron's ability to learn spike timing rules. Our results suggest that such a model neuron can learn to classify spike timing patterns even with unreliable synapses, albeit with a significantly reduced success rate. We explored strategies to improve correct spike timing classification and found that firing clustered spike bursts significantly improves learning performance. Furthermore, rapid activity-dependent modulation of synaptic unreliability, implemented with realistic models of dynamic synapses, further improved classification of different burst properties and spike timing modalities. Neuronal models with only facilitating or only depressing inputs exhibited preference for specific types of spike timing rules, but a mixture of facilitating and depressing synapses permitted much improved learning of multiple rules. We tested applicability of these findings to real neurons by considering neuronal learning models with the naturally distributed input release probabilities found in excitatory hippocampal synapses. Our results suggest that spike bursts comprise several encoding modalities that can be learned effectively with stochastic dynamic synapses, and that distributed release probabilities significantly improve learning performance. Synaptic unreliability and dynamics may thus play important roles in the neuron's ability to learn spike timing rules during decoding.

  13. All optical experimental design for neuron excitation, inhibition, and action potential detection

    NASA Astrophysics Data System (ADS)

    Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

    2016-03-01

    Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

  14. Axonal sodium channel distribution shapes the depolarized action potential threshold of dentate granule neurons

    PubMed Central

    Kress, Geraldine J.; Dowling, Margaret; Eisenman, Lawrence N.; Mennerick, Steven

    2010-01-01

    Intrinsic excitability is a key feature dictating neuronal response to synaptic input. Here we investigate the recent observation that dentate granule neurons exhibit a more depolarized voltage threshold for action potential initiation than CA3 pyramidal neurons. We find no evidence that tonic GABA currents, leak or voltage-gated potassium conductances, or the expression of sodium channel isoform differences can explain this depolarized threshold. Axonal initial segment voltage-gated sodium channels, which are dominated by the NaV1.6 isoform in both cell types, distribute more proximally and exhibit lower overall density in granule neurons than in CA3 neurons. To test possible contributions of sodium channel distributions to voltage threshold and to test whether morphological differences participate, we performed simulations of dentate granule neurons and of CA3 pyramidal neurons. These simulations revealed that cell morphology and sodium channel distribution combine to yield the characteristic granule neuron action potential upswing and voltage threshold. Proximal axon sodium channel distribution strongly contributes to the higher voltage threshold of dentate granule neurons for two reasons. First, action potential initiation closer to the somatodendritic current sink causes the threshold of the initiating axon compartment to rise. Second, the proximity of the action potential initiation site to the recording site causes somatic recordings to more faithfully reflect the depolarized threshold of the axon than in cells like CA3 neurons, with distally initiating action potentials. Our results suggest that the proximal location of axon sodium channel in dentate granule neurons contributes to the intrinsic excitability differences between DG and CA3 neurons and may participate in the low-pass filtering function of dentate granule neurons. PMID:19603521

  15. Incorporating spike-rate adaptation into a rate code in mathematical and biological neurons

    PubMed Central

    Ralston, Bridget N.; Flagg, Lucas Q.; Faggin, Eric

    2016-01-01

    For a slowly varying stimulus, the simplest relationship between a neuron's input and output is a rate code, in which the spike rate is a unique function of the stimulus at that instant. In the case of spike-rate adaptation, there is no unique relationship between input and output, because the spike rate at any time depends both on the instantaneous stimulus and on prior spiking (the “history”). To improve the decoding of spike trains produced by neurons that show spike-rate adaptation, we developed a simple scheme that incorporates “history” into a rate code. We utilized this rate-history code successfully to decode spike trains produced by 1) mathematical models of a neuron in which the mechanism for adaptation (IAHP) is specified, and 2) the gastropyloric receptor (GPR2), a stretch-sensitive neuron in the stomatogastric nervous system of the crab Cancer borealis, that exhibits long-lasting adaptation of unknown origin. Moreover, when we modified the spike rate either mathematically in a model system or by applying neuromodulatory agents to the experimental system, we found that changes in the rate-history code could be related to the biophysical mechanisms responsible for altering the spiking. PMID:26888106

  16. Multimodal stimulus coding by a gustatory sensory neuron in Drosophila larvae

    PubMed Central

    van Giesen, Lena; Hernandez-Nunez, Luis; Delasoie-Baranek, Sophie; Colombo, Martino; Renaud, Philippe; Bruggmann, Rémy; Benton, Richard; Samuel, Aravinthan D. T.; Sprecher, Simon G.

    2016-01-01

    Accurate perception of taste information is crucial for animal survival. In adult Drosophila, gustatory receptor neurons (GRNs) perceive chemical stimuli of one specific gustatory modality associated with a stereotyped behavioural response, such as aversion or attraction. We show that GRNs of Drosophila larvae employ a surprisingly different mode of gustatory information coding. Using a novel method for calcium imaging in the larval gustatory system, we identify a multimodal GRN that responds to chemicals of different taste modalities with opposing valence, such as sweet sucrose and bitter denatonium, reliant on different sensory receptors. This multimodal neuron is essential for bitter compound avoidance, and its artificial activation is sufficient to mediate aversion. However, the neuron is also essential for the integration of taste blends. Our findings support a model for taste coding in larvae, in which distinct receptor proteins mediate different responses within the same, multimodal GRN. PMID:26864722

  17. Multimodal stimulus coding by a gustatory sensory neuron in Drosophila larvae.

    PubMed

    van Giesen, Lena; Hernandez-Nunez, Luis; Delasoie-Baranek, Sophie; Colombo, Martino; Renaud, Philippe; Bruggmann, Rémy; Benton, Richard; Samuel, Aravinthan D T; Sprecher, Simon G

    2016-02-11

    Accurate perception of taste information is crucial for animal survival. In adult Drosophila, gustatory receptor neurons (GRNs) perceive chemical stimuli of one specific gustatory modality associated with a stereotyped behavioural response, such as aversion or attraction. We show that GRNs of Drosophila larvae employ a surprisingly different mode of gustatory information coding. Using a novel method for calcium imaging in the larval gustatory system, we identify a multimodal GRN that responds to chemicals of different taste modalities with opposing valence, such as sweet sucrose and bitter denatonium, reliant on different sensory receptors. This multimodal neuron is essential for bitter compound avoidance, and its artificial activation is sufficient to mediate aversion. However, the neuron is also essential for the integration of taste blends. Our findings support a model for taste coding in larvae, in which distinct receptor proteins mediate different responses within the same, multimodal GRN.

  18. Dopamine neurons code subjective sensory experience and uncertainty of perceptual decisions

    PubMed Central

    de Lafuente, Victor; Romo, Ranulfo

    2011-01-01

    Midbrain dopamine (DA) neurons respond to sensory stimuli associated with future rewards. When reward is delivered probabilistically, DA neurons reflect this uncertainty by increasing their firing rates in a period between the sensory cue and reward delivery time. Probability of reward, however, has been externally conveyed by visual cues, and it is not known whether DA neurons would signal uncertainty arising internally. Here we show that DA neurons code the uncertainty associated with a perceptual judgment about the presence or absence of a vibrotactile stimulus. We observed that uncertainty modulates the activity elicited by a go cue instructing monkey subjects to communicate their decisions. That is, the same go cue generates different DA responses depending on the uncertainty level of a judgment made a few seconds before the go instruction. Easily detected suprathreshold stimuli elicit small DA responses, indicating that future reward will not be a surprising event. In contrast, the absence of a sensory stimulus generates large DA responses associated with uncertainty: was the stimulus truly absent, or did a low-amplitude vibration go undetected? In addition, the responses of DA neurons to the stimulus itself increase with vibration amplitude, but only when monkeys correctly detect its presence. This finding suggests that DA activity is not related to actual intensity but rather to perceived intensity. Therefore, in addition to their well-known role in reward prediction, DA neurons code subjective sensory experience and uncertainty arising internally from perceptual decisions. PMID:22106310

  19. M1 corticospinal mirror neurons and their role in movement suppression during action observation.

    PubMed

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2013-02-04

    Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. M1 Corticospinal Mirror Neurons and Their Role in Movement Suppression during Action Observation

    PubMed Central

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N.; Kraskov, Alexander

    2013-01-01

    Summary Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation [1, 2], a property first shown for mirror neurons in monkey premotor cortex [3]. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity. PMID:23290556

  1. Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its Relevance for Schizophrenia.

    PubMed

    Chuhma, Nao; Mingote, Susana; Kalmbach, Abigail; Yetnikoff, Leora; Rayport, Stephen

    2017-01-01

    Brain imaging has revealed alterations in dopamine uptake, release, and receptor levels in patients with schizophrenia that have been resolved on the scale of striatal subregions. However, the underlying synaptic mechanisms are on a finer scale. Dopamine neuron synaptic actions vary across the striatum, involving variations not only in dopamine release but also in dopamine neuron connectivity, cotransmission, modulation, and activity. Optogenetic studies have revealed that dopamine neurons release dopamine in a synaptic signal mode, and that the neurons also release glutamate and gamma-aminobutyric acid as cotransmitters, with striking regional variation. Fast glutamate and gamma-aminobutyric acid cotransmission convey discrete patterns of dopamine neuron activity to striatal neurons. Glutamate may function not only in a signaling role at a subset of dopamine neuron synapses, but also in mediating vesicular synergy, contributing to regional differences in loading of dopamine into synaptic vesicles. Regional differences in dopamine neuron signaling are likely to be differentially involved in the schizophrenia disease process and likely determine the subregional specificity of the action of psychostimulants that exacerbate the disorder, and antipsychotics that ameliorate the disorder. Elucidating dopamine neuron synaptic signaling offers the potential for achieving greater pharmacological specificity through intersectional pharmacological actions targeting subsets of dopamine neuron synapses. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Specification of individual adult motor neuron morphologies by combinatorial transcription factor codes

    PubMed Central

    Enriquez, Jonathan; Venkatasubramanian, Lalanti; Baek, Myungin; Peterson, Meredith; Aghayeva, Ulkar; Mann, Richard S.

    2015-01-01

    Summary How the highly stereotyped morphologies of individual neurons are genetically specified is not well understood. We identify six transcription factors (TFs) expressed in a combinatorial manner in seven post-mitotic adult leg motor neurons (MNs) that are derived from a single neuroblast in Drosophila. Unlike TFs expressed in mitotically active neuroblasts, these TFs do not regulate each other's expression. Removing the activity of a single TF resulted in specific morphological defects, including muscle targeting and dendritic arborization, and in a highly specific walking defect in adult flies. In contrast, when the expression of multiple TFs was modified nearly complete transformations in MN morphologies were generated. These results show that the morphological characteristics of a single neuron are dictated by a combinatorial code of morphology TFs (mTFs). mTFs function at a previously unidentified regulatory tier downstream of factors acting in the NB, but independently of factors that act in terminally differentiated neurons. PMID:25959734

  3. Specification of individual adult motor neuron morphologies by combinatorial transcription factor codes.

    PubMed

    Enriquez, Jonathan; Venkatasubramanian, Lalanti; Baek, Myungin; Peterson, Meredith; Aghayeva, Ulkar; Mann, Richard S

    2015-05-20

    How the highly stereotyped morphologies of individual neurons are genetically specified is not well understood. We identify six transcription factors (TFs) expressed in a combinatorial manner in seven post-mitotic adult leg motor neurons (MNs) that are derived from a single neuroblast in Drosophila. Unlike TFs expressed in mitotically active neuroblasts, these TFs do not regulate each other's expression. Removing the activity of a single TF resulted in specific morphological defects, including muscle targeting and dendritic arborization, and in a highly specific walking defect in adult flies. In contrast, when the expression of multiple TFs was modified, nearly complete transformations in MN morphologies were generated. These results show that the morphological characteristics of a single neuron are dictated by a combinatorial code of morphology TFs (mTFs). mTFs function at a previously unidentified regulatory tier downstream of factors acting in the NB but independently of factors that act in terminally differentiated neurons.

  4. Encoding binary neural codes in networks of threshold-linear neurons.

    PubMed

    Curto, Carina; Degeratu, Anda; Itskov, Vladimir

    2013-11-01

    Networks of neurons in the brain encode preferred patterns of neural activity via their synaptic connections. Despite receiving considerable attention, the precise relationship between network connectivity and encoded patterns is still poorly understood. Here we consider this problem for networks of threshold-linear neurons whose computational function is to learn and store a set of binary patterns (e.g., a neural code) as "permitted sets" of the network. We introduce a simple encoding rule that selectively turns "on" synapses between neurons that coappear in one or more patterns. The rule uses synapses that are binary, in the sense of having only two states ("on" or "off"), but also heterogeneous, with weights drawn from an underlying synaptic strength matrix S. Our main results precisely describe the stored patterns that result from the encoding rule, including unintended "spurious" states, and give an explicit characterization of the dependence on S. In particular, we find that binary patterns are successfully stored in these networks when the excitatory connections between neurons are geometrically balanced--i.e., they satisfy a set of geometric constraints. Furthermore, we find that certain types of neural codes are natural in the context of these networks, meaning that the full code can be accurately learned from a highly undersampled set of patterns. Interestingly, many commonly observed neural codes in cortical and hippocampal areas are natural in this sense. As an application, we construct networks that encode hippocampal place field codes nearly exactly, following presentation of only a small fraction of patterns. To obtain our results, we prove new theorems using classical ideas from convex and distance geometry, such as Cayley-Menger determinants, revealing a novel connection between these areas of mathematics and coding properties of neural networks.

  5. Visual coding with a population of direction-selective neurons

    PubMed Central

    Farrow, Karl; Müller, Jan; Roska, Botond; Azeredo da Silveira, Rava; Hierlemann, Andreas

    2015-01-01

    The brain decodes the visual scene from the action potentials of ∼20 retinal ganglion cell types. Among the retinal ganglion cells, direction-selective ganglion cells (DSGCs) encode motion direction. Several studies have focused on the encoding or decoding of motion direction by recording multiunit activity, mainly in the visual cortex. In this study, we simultaneously recorded from all four types of ON-OFF DSGCs of the rabbit retina using a microelectronics-based high-density microelectrode array (HDMEA) and decoded their concerted activity using probabilistic and linear decoders. Furthermore, we investigated how the modification of stimulus parameters (velocity, size, angle of moving object) and the use of different tuning curve fits influenced decoding precision. Finally, we simulated ON-OFF DSGC activity, based on real data, in order to understand how tuning curve widths and the angular distribution of the cells' preferred directions influence decoding performance. We found that probabilistic decoding strategies outperformed, on average, linear methods and that decoding precision was robust to changes in stimulus parameters such as velocity. The removal of noise correlations among cells, by random shuffling trials, caused a drop in decoding precision. Moreover, we found that tuning curves are broad in order to minimize large errors at the expense of a higher average error, and that the retinal direction-selective system would not substantially benefit, on average, from having more than four types of ON-OFF DSGCs or from a perfect alignment of the cells' preferred directions. PMID:26289471

  6. Visual coding with a population of direction-selective neurons.

    PubMed

    Fiscella, Michele; Franke, Felix; Farrow, Karl; Müller, Jan; Roska, Botond; da Silveira, Rava Azeredo; Hierlemann, Andreas

    2015-10-01

    The brain decodes the visual scene from the action potentials of ∼20 retinal ganglion cell types. Among the retinal ganglion cells, direction-selective ganglion cells (DSGCs) encode motion direction. Several studies have focused on the encoding or decoding of motion direction by recording multiunit activity, mainly in the visual cortex. In this study, we simultaneously recorded from all four types of ON-OFF DSGCs of the rabbit retina using a microelectronics-based high-density microelectrode array (HDMEA) and decoded their concerted activity using probabilistic and linear decoders. Furthermore, we investigated how the modification of stimulus parameters (velocity, size, angle of moving object) and the use of different tuning curve fits influenced decoding precision. Finally, we simulated ON-OFF DSGC activity, based on real data, in order to understand how tuning curve widths and the angular distribution of the cells' preferred directions influence decoding performance. We found that probabilistic decoding strategies outperformed, on average, linear methods and that decoding precision was robust to changes in stimulus parameters such as velocity. The removal of noise correlations among cells, by random shuffling trials, caused a drop in decoding precision. Moreover, we found that tuning curves are broad in order to minimize large errors at the expense of a higher average error, and that the retinal direction-selective system would not substantially benefit, on average, from having more than four types of ON-OFF DSGCs or from a perfect alignment of the cells' preferred directions. Copyright © 2015 the American Physiological Society.

  7. Optical magnetic detection of single-neuron action potentials using NV-diamond

    NASA Astrophysics Data System (ADS)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  8. Label-free optical detection of action potential in mammalian neurons

    PubMed Central

    Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra; Bachoo, Robert; Davé, Digant P.

    2017-01-01

    We describe an optical technique for label-free detection of the action potential in cultured mammalian neurons. Induced morphological changes due to action potential propagation in neurons are optically interrogated with a phase sensitive interferometric technique. Optical recordings composed of signal pulses mirror the electrical spike train activity of individual neurons in a network. The optical pulses are transient nanoscale oscillatory changes in the optical path length of varying peak magnitude and temporal width. Exogenous application of glutamate to cortical neuronal cultures produced coincident increase in the electrical and optical activity; both were blocked by application of a Na-channel blocker, Tetrodotoxin. The observed transient change in optical path length in a single optical pulse is primarily due to physical fluctuations of the neuronal cell membrane mediated by a yet unknown electromechanical transduction phenomenon. Our analysis suggests a traveling surface wave in the neuronal cell membrane is responsible for the measured optical signal pulses. PMID:28856044

  9. Label-free optical detection of action potential in mammalian neurons (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra K.; Davé, Digant P.

    2017-02-01

    Electrophysiology techniques are the gold standard in neuroscience for studying functionality of a single neuron to a complex neuronal network. However, electrophysiology techniques are not flawless, they are invasive nature, procedures are cumbersome to implement with limited capability of being used as a high-throughput recording system. Also, long term studies of neuronal functionality with aid of electrophysiology is not feasible. Non-invasive stimulation and detection of neuronal electrical activity has been a long standing goal in neuroscience. Introduction of optogenetics has ushered in the era of non-invasive optical stimulation of neurons, which is revolutionizing neuroscience research. Optical detection of neuronal activity that is comparable to electro-physiology is still elusive. A number of optical techniques have been reported recording of neuronal electrical activity but none is capable of reliably measuring action potential spikes that is comparable to electro-physiology. Optical detection of action potential with voltage sensitive fluorescent reporters are potential alternatives to electrophysiology techniques. The heavily rely on secondary reporters, which are often toxic in nature with background fluorescence, with slow response and low SNR making them far from ideal. The detection of one shot (without averaging)-single action potential in a true label-free way has been elusive so far. In this report, we demonstrate the optical detection of single neuronal spike in a cultured mammalian neuronal network without using any exogenous labels. To the best of our knowledge, this is the first demonstration of label free optical detection of single action potentials in a mammalian neuronal network, which was achieved using a high-speed phase sensitive interferometer. We have carried out stimulation and inhibition of neuronal firing using Glutamate and Tetrodotoxin respectively to demonstrate the different outcome (stimulation and inhibition) revealed in

  10. Disparity-based coding of three-dimensional surface orientation by macaque middle temporal neurons.

    PubMed

    Nguyenkim, Jerry D; DeAngelis, Gregory C

    2003-08-06

    Gradients of binocular disparity across the visual field provide a potent cue to the three-dimensional (3-D) orientation of surfaces in a scene. Neurons selective for 3-D surface orientation defined by disparity gradients have recently been described in parietal cortex, but little is known about where and how this selectivity arises within the visual pathways. Because the middle temporal area (MT) has previously been implicated in depth perception, we tested whether MT neurons could signal the 3-D orientation (as parameterized by tilt and slant) of planar surfaces that were depicted by random-dot stereograms containing a linear gradient of horizontal disparities. We find that many MT neurons are tuned for 3-D surface orientation, and that tilt and slant generally have independent effects on MT responses. This separable coding of tilt and slant is reminiscent of the joint coding of variables in other areas (e.g., orientation and spatial frequency in V1). We show that tilt tuning remains unchanged when all coherent motion is removed from the visual stimuli, indicating that tilt selectivity is not a byproduct of 3-D velocity coding. Moreover, tilt tuning is typically insensitive to changes in the mean disparity (depth) of gradient stimuli, indicating that tilt tuning cannot be explained by conventional tuning for frontoparallel disparities. Finally, we explore the receptive field mechanisms underlying selectivity for 3-D surface orientation, and we show that tilt tuning arises through heterogeneous disparity tuning within the receptive fields of MT neurons. Our findings show that MT neurons carry high-level signals about 3-D surface structure, in addition to coding retinal image velocities.

  11. Head direction is coded more strongly than movement direction in a population of entorhinal neurons.

    PubMed

    Raudies, Florian; Brandon, Mark P; Chapman, G William; Hasselmo, Michael E

    2015-09-24

    The spatial firing pattern of entorhinal grid cells may be important for navigation. Many different computational models of grid cell firing use path integration based on movement direction and the associated movement speed to drive grid cells. However, the response of neurons to movement direction has rarely been tested, in contrast to multiple studies showing responses of neurons to head direction. Here, we analyzed the difference between head direction and movement direction during rat movement and analyzed cells recorded from entorhinal cortex for their tuning to movement direction. During foraging behavior, movement direction differs significantly from head direction. The analysis of neuron responses shows that only 5 out of 758 medial entorhinal cells show significant coding for both movement direction and head direction when evaluating periods of rat behavior with speeds above 10 cm/s and ±30° angular difference between movement and head direction. None of the cells coded movement direction alone. In contrast, 21 cells in this population coded only head direction during behavioral epochs with these constraints, indicating much stronger coding of head direction in this population. This suggests that the movement direction signal required by most grid cell models may arise from other brain structures than the medial entorhinal cortex. This article is part of a Special Issue entitled SI: Brain and Memory.

  12. Head direction is coded more strongly than movement direction in a population of entorhinal neurons

    PubMed Central

    Raudies, Florian; Brandon, Mark P.; Chapman, G. William; Hasselmo, Michael E.

    2014-01-01

    The spatial firing pattern of entorhinal grid cells may be important for navigation. Many different computational models of grid cell firing use path integration based on movement direction and the associated movement speed to drive grid cells. However, the response of neurons to movement direction has rarely been tested, in contrast to multiple studies showing responses of neurons to head direction. Here, we analyzed the difference between head direction and movement direction during rat movement and analyzed cells recorded from entorhinal cortex for their tuning to movement direction. During foraging behavior, movement direction differs significantly from head direction. The analysis of neuron responses shows that only 5 out of 758 medial entorhinal cells show significant coding for both movement direction and head direction when evaluating periods of rat behavior with speeds above 10 cm/sec and ±30° angular difference between movement and head direction. None of the cells coded movement direction alone. In contrast, 21 cells in this population coded only head direction during behavioral epochs with these constraints, indicating much stronger coding of head direction in this population. This suggests that the movement direction signal required by most grid cell models may arise from other brain structures than the medial entorhinal cortex. PMID:25451111

  13. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

    PubMed Central

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

    2016-01-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  14. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials.

    PubMed

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J

    2016-08-11

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

  15. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    NASA Astrophysics Data System (ADS)

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-08-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

  16. Regulatory consequences of neuronal ELAV-like protein binding to coding and non-coding RNAs in human brain

    PubMed Central

    Scheckel, Claudia; Drapeau, Elodie; Frias, Maria A; Park, Christopher Y; Fak, John; Zucker-Scharff, Ilana; Kou, Yan; Haroutunian, Vahram; Ma'ayan, Avi

    2016-01-01

    Neuronal ELAV-like (nELAVL) RNA binding proteins have been linked to numerous neurological disorders. We performed crosslinking-immunoprecipitation and RNAseq on human brain, and identified nELAVL binding sites on 8681 transcripts. Using knockout mice and RNAi in human neuroblastoma cells, we showed that nELAVL intronic and 3' UTR binding regulates human RNA splicing and abundance. We validated hundreds of nELAVL targets among which were important neuronal and disease-associated transcripts, including Alzheimer's disease (AD) transcripts. We therefore investigated RNA regulation in AD brain, and observed differential splicing of 150 transcripts, which in some cases correlated with differential nELAVL binding. Unexpectedly, the most significant change of nELAVL binding was evident on non-coding Y RNAs. nELAVL/Y RNA complexes were specifically remodeled in AD and after acute UV stress in neuroblastoma cells. We propose that the increased nELAVL/Y RNA association during stress may lead to nELAVL sequestration, redistribution of nELAVL target binding, and altered neuronal RNA splicing. DOI: http://dx.doi.org/10.7554/eLife.10421.001 PMID:26894958

  17. State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

    PubMed

    Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

    2012-06-03

    Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

  18. Dynamic coding of dorsal hippocampal neurons between tasks that differ in structure and memory demand.

    PubMed

    Hallock, Henry L; Griffin, Amy L

    2013-02-01

    Hippocampal place fields show remapping between environments that contain sufficiently different contextual features, a phenomenon that may reflect a mechanism for episodic memory formation. Previous studies have shown that place fields remap to changes in the configuration of visual landmarks in an environment. Other experiments have demonstrated that remapping can occur with experience, even when the visual features of an environment remain stable. A special case of remapping may be trajectory coding, the tendency for hippocampal neurons to exhibit different firing rates depending upon recently visited or upcoming spatial locations. To further delineate the conditions under which different task features elicit remapping, we recorded from place cells in dorsal CA1 of hippocampus while rats switched between tasks that differed in memory demand and task structure; continuous spatial alternation (CA), delayed spatial alternation (DA), and tactile-visual conditional discrimination (CD). Individual hippocampal neurons and populations of simultaneously recorded neurons showed coherent remapping between CA and CD. However, task remapping was rarely seen between DA and CD. Analysis of individual units revealed that even though the population retained a coherent representation of task structure across the DA and CD tasks, the majority of individual neurons consistently remapped at some point during recording sessions. In contrast with previous studies, trajectory coding on the stem of the T-maze was virtually absent during all of the tasks, suggesting that experience with multiple tasks in the same environment reduces the likelihood that hippocampal neurons will represent distinct trajectories. Trajectory coding was, however, observed during the delay period of DA. Whether place fields change in response to task or trial type or remain stable within the same environment may depend on which aspects of the context are most salient or relevant to behavior. Copyright © 2012

  19. Action-outcome relationships are represented differently by medial prefrontal and orbitofrontal cortex neurons during action execution

    PubMed Central

    Wood, Jesse; Moghaddam, Bita

    2015-01-01

    Internal representations of action-outcome relationships are necessary for flexible adaptation of motivated behavior in dynamic environments. Prefrontal cortex (PFC) is implicated in flexible planning and execution of goal-directed actions, but little is known about how information about action-outcome relationships is represented across functionally distinct regions of PFC. Here, we observe distinct patterns of action-evoked single unit activity in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) during a task in which the relationship between outcomes and actions was independently manipulated. The mPFC encoded changes in the number of actions required to earn a reward, but not fluctuations in outcome magnitude. In contrast, OFC neurons decreased firing rates as outcome magnitude was increased, but were insensitive to changes in action requirement. A subset of OFC neurons also tracked outcome availability. Pre-outcome anticipatory activity in both mPFC and OFC was altered when reward expectation was reduced, but did not differ with outcome magnitude. These data provide novel evidence that PFC regions encode distinct information about the relationship between actions and impending outcomes during action execution. PMID:26467523

  20. Prefrontal cortex gates acute morphine action on dopamine neurons in the ventral tegmental area.

    PubMed

    Liu, Changliang; Fang, Xing; Wu, Qianqian; Jin, Guozhang; Zhen, Xuechu

    2015-08-01

    Morphine excites dopamine (DA) neurons in the ventral tegmental area (VTA), an effect mediated by both local and systemic mechanisms. While the importance of the prefrontal cortex (PFC) - VTA circuit in opiate addiction is well established, little is known about how the PFC regulates the activity of VTA DA neurons upon morphine stimulation. One major challenge is that VTA DA neurons are highly heterogeneous in terms of projection and regulation, making their responses to PFC manipulations variable. Our previous work has identified a subgroup of VTA DA neurons exhibiting significant slow oscillation in their firing sequence, and demonstrated that most of these neurons are functionally connected with the PFC. In the present study, we focus our efforts only on VTA DA neurons expressing strong slow oscillation, and report that blocking the neuronal activity in the PFC remarkably attenuates the morphine-induced excitation of these neurons. Using in vivo microdialysis, we find that inactivation of the PFC also reduces the morphine-induced elevation of DA levels in the nucleus accumbens (NAc). Furthermore, 24 h after only single morphine exposure, PFC-inactivation failed to prevent subsequent morphine challenge from exciting VTA DA neurons, which is paralleled by altered response of PFC pyramidal neurons to morphine stimulation. Our results indicate that the PFC gates acute morphine action on a subset of VTA DA neurons, which is highly plastic and can be functionally remodeled by morphine exposure.

  1. Coding of reward probability and risk by single neurons in animals.

    PubMed

    Burke, Christopher J; Tobler, Philippe N

    2011-01-01

    Probability and risk are important factors for value-based decision making and optimal foraging. In order to survive in an unpredictable world, organisms must be able to assess the probability and risk attached to future events and use this information to generate adaptive behavior. Recent studies in non-human primates and rats have shown that both probability and risk are processed in a distributed fashion throughout the brain at the level of single neurons. Reward probability has mainly been shown to be coded by phasic increases and decreases in firing rates in neurons in the basal ganglia, midbrain, parietal, and frontal cortex. Reward variance is represented in orbitofrontal and posterior cingulate cortex and through a sustained response of dopaminergic midbrain neurons.

  2. Integration of the olfactory code across dendritic claws of single mushroom body neurons

    PubMed Central

    Gruntman, Eyal; Turner, Glenn C.

    2013-01-01

    In the olfactory system, sensory inputs are arranged in different glomerular channels, which respond in combinatorial ensembles to the various chemical features of an odor. Here we investigate where and how this combinatorial code is read out deeper in the brain. We exploit the unique morphology of neurons in the mushroom body (MB), which receive input on large dendritic claws. Imaging odor responses of these dendritic claws shows that input channels with distinct odor tuning converge on individual MB neurons. We determined how these inputs interact to drive the cell to spike threshold using intracellular recordings to examine MB responses to optogenetically controlled input. Our results provide an elegant explanation for the characteristic selectivity of MB neurons: these cells receive different types of input, and require those inputs to be coactive in order to spike. These results establish the MB as an important site of integration in the fly olfactory system. PMID:24141312

  3. Correlation and synchrony transfer in integrate-and-fire neurons: basic properties and consequences for coding.

    PubMed

    Shea-Brown, Eric; Josić, Kresimir; de la Rocha, Jaime; Doiron, Brent

    2008-03-14

    We study how pairs of neurons transfer correlated input currents into correlated spikes. Over rapid time scales, correlation transfer increases with both spike time variability and rate; the dependence on variability disappears at large time scales. This persists for a nonlinear membrane model and for heterogeneous cell pairs, but strong nonmonotonicities follow from refractory effects. We present consequences for population coding and for the encoding of time-varying stimuli.

  4. Hebbian learning and predictive mirror neurons for actions, sensations and emotions.

    PubMed

    Keysers, Christian; Gazzola, Valeria

    2014-01-01

    Spike-timing-dependent plasticity is considered the neurophysiological basis of Hebbian learning and has been shown to be sensitive to both contingency and contiguity between pre- and postsynaptic activity. Here, we will examine how applying this Hebbian learning rule to a system of interconnected neurons in the presence of direct or indirect re-afference (e.g. seeing/hearing one's own actions) predicts the emergence of mirror neurons with predictive properties. In this framework, we analyse how mirror neurons become a dynamic system that performs active inferences about the actions of others and allows joint actions despite sensorimotor delays. We explore how this system performs a projection of the self onto others, with egocentric biases to contribute to mind-reading. Finally, we argue that Hebbian learning predicts mirror-like neurons for sensations and emotions and review evidence for the presence of such vicarious activations outside the motor system.

  5. Hebbian learning and predictive mirror neurons for actions, sensations and emotions

    PubMed Central

    Keysers, Christian; Gazzola, Valeria

    2014-01-01

    Spike-timing-dependent plasticity is considered the neurophysiological basis of Hebbian learning and has been shown to be sensitive to both contingency and contiguity between pre- and postsynaptic activity. Here, we will examine how applying this Hebbian learning rule to a system of interconnected neurons in the presence of direct or indirect re-afference (e.g. seeing/hearing one's own actions) predicts the emergence of mirror neurons with predictive properties. In this framework, we analyse how mirror neurons become a dynamic system that performs active inferences about the actions of others and allows joint actions despite sensorimotor delays. We explore how this system performs a projection of the self onto others, with egocentric biases to contribute to mind-reading. Finally, we argue that Hebbian learning predicts mirror-like neurons for sensations and emotions and review evidence for the presence of such vicarious activations outside the motor system. PMID:24778372

  6. Intrinsic choroidal neurons in the chicken eye: chemical coding and synaptic input

    PubMed Central

    Stübinger, Karin; Brehmer, Axel; Neuhuber, Winfried L.; Reitsamer, Herbert; Nickla, Debora

    2016-01-01

    Intrinsic choroidal neurons (ICNs) exist in some primates and bird species. They may act on both vascular and non-vascular smooth muscle cells, potentially influencing choroidal blood flow. Here, we report on the chemical coding of ICNs and eye-related cranial ganglia in the chicken, an important model in myopia research, and further to determine synaptic input onto ICN. Chicken choroid, ciliary, superior cervical, pterygopalatine, and trigeminal ganglia were prepared for double or triple immunohistochemistry of calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT), dopamine-β-hydroxylase, galanin (GAL), neuronal nitric oxide synthase (nNOS), somatostatin (SOM), tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), vesicular monoamine-transporter 2 (VMAT2), and α-smooth muscle actin. For documentation, light, fluorescence, and confocal laser scanning microscopy were used. Chicken ICNs express nNOS/VIP/GAL and do not express ChAT and SOM. ICNs are approached by TH/VMAT2-, CGRP-, and ChAT-positive nerve fibers. About 50% of the pterygopalatine ganglion neurons and about 9% of the superior cervical ganglion neurons share the same chemical code as ICN. SOM-positive neurons in the ciliary ganglion are GAL/NOS negative. CGRP-positive neurons in the trigeminal ganglion lack GAL/SOM. The neurochemical phenotype and synaptic input of ICNs in chicken resemble that of other bird and primate species. Because ICNs lack cholinergic markers, they cannot be readily incorporated into current concepts of the autonomic nervous system. The data obtained provide the basis for the interpretation of future functional experiments to clarify the role of these cells in achieving ocular homeostasis. PMID:20607273

  7. A consensus layer V pyramidal neuron can sustain interpulse-interval coding

    PubMed Central

    Singh, Chandan; Levy, William B.

    2017-01-01

    In terms of a single neuron’s long-distance communication, interpulse intervals (IPIs) are an attractive alternative to rate and binary codes. As a proxy for an IPI, a neuron’s time-to-spike can be found in the biophysical and experimental intracellular literature. Using the current, consensus layer V pyramidal neuron, the present study examines the feasibility of IPI-coding and examines the noise sources that limit the information rate of such an encoding. In descending order of importance, the noise sources are (i) synaptic variability, (ii) sodium channel shot-noise, followed by (iii) thermal noise. The biophysical simulations allow the calculation of mutual information, which is about 3.0 bits/spike. More importantly, while, by any conventional definition, the biophysical model is highly nonlinear, the underlying function that relates input intensity to the defined output variable is linear. When one assumes the perspective of a neuron coding via first hitting-time, this result justifies a pervasive and simplifying assumption of computational modelers—that a class of cortical neurons can be treated as linearly additive, computational devices. PMID:28704450

  8. What type of action understanding is subserved by mirror neurons?

    PubMed

    Sinigaglia, Corrado

    2013-04-12

    The role of the mirror mechanism in cognition remains an intriguing and hotly debated topic in cognitive neuroscience. Since its discovery in the monkey and human brain, many have claimed that the mirror mechanism is critically involved in understanding action. But what does understand mean here? What kind of action understanding, if any, can be ascribed to the mirror mechanism? The aim of the paper is to face these questions by providing a refined notion of both action and action understanding. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Depolarizing Actions of Hydrogen Sulfide on Hypothalamic Paraventricular Nucleus Neurons

    PubMed Central

    Khademullah, C. Sahara; Ferguson, Alastair V.

    2013-01-01

    Hydrogen sulfide (H2S) is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH) secretion. Since the paraventricular nucleus of the hypothalamus (PVN) is a central relay center for autonomic and endocrine functions, we sought to investigate the effects of H2S on the neuronal population of the PVN. Whole cell current clamp recordings were acquired from the PVN neurons and sodium hydrosulfide hydrate (NaHS) was bath applied at various concentrations (0.1, 1, 10, and 50 mM). NaHS (1, 10, and 50 mM) elicited a concentration-response relationship from the majority of recorded neurons, with almost exclusively depolarizing effects following administration. Cells responded and recovered from NaHS administration quickly and the effects were repeatable. Input differences from baseline and during the NaHS-induced depolarization uncovered a biphasic response, implicating both a potassium and non-selective cation conductance. The results from the neuronal population of the PVN shed light on the possible physiological role that H2S has in autonomic and endocrine function. PMID:23691233

  10. Method to reconstruct neuronal action potential train from two-photon calcium imaging

    NASA Astrophysics Data System (ADS)

    Quan, Tingwei; Liu, Xiuli; Lv, Xiaohua; Chen, Wei R.; Zeng, Shaoqun

    2010-11-01

    Identification of a small population of neuronal action potentials (APs) firing is considered essential to discover the operating principles of neuronal circuits. A promising method is to indirectly monitor the AP discharges in neurons from the recordings their intracellular calcium fluorescence transients. However, it is hard to reveal the nonlinear relationship between neuronal calcium fluorescence transients and the corresponding AP burst discharging. We propose a method to reconstruct the neuronal AP train from calcium fluorescence diversifications based on a multiscale filter and a convolution operation. Results of experimental data processing show that the false-positive rate and the event detection rate are about 10 and 90%, respectively. Meanwhile, the APs firing at a high frequency up to 40 Hz can also be successfully identified. From the results, it can be concluded that the method has strong power to reconstruct a neuronal AP train from a burst firing.

  11. Citizen Action Can Help the Code Adoption Process for Radon-Resistant New Construction: Decatur, Alabama

    EPA Pesticide Factsheets

    Adopting a code requiring radon-resistant new construction (RRNC) in Decatur, Alabama, took months of effort by four people. Their actions demonstrate the influence that passionate residents can have on reversing a city council’s direction.

  12. Selective excitatory actions of DNQX and CNQX in rat thalamic neurons.

    PubMed

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

    2010-04-01

    The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from glutamatergic afferents from thalamocortical relay neurons and deep layer corticothalamic neurons, and they produce excitation via both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Quinoxaline derivatives [e.g., 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] have routinely been used as non-NMDA receptor antagonists over the last two decades. In this study, we examined whether quinoxaline derivatives alter the intrinsic properties of thalamic neurons in light of recent findings indicating that these compounds can alter neuronal excitability in hippocampal and cerebellar neurons via transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Whole cell recordings were obtained from TRN and ventrobasal (VB) thalamic relay neurons in vitro. DNQX and CNQX produced a consistent depolarization in all TRN neurons tested. The depolarization persisted in tetrodotoxin and low Ca²+/high Mg²+ conditions, suggesting a postsynaptic site of action. In contrast, DNQX and CNQX produced little or no change in VB thalamocortical relay neurons. The nonspecific ionotropic glutamate receptor antagonist, kynurenic acid, and the selective AMPAR antagonist, 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzenamine hydrochloride, blocked the DNQX-mediated depolarizations. Our results indicate that the DNQX- and CNQX-mediated depolarizations are mediated by AMPAR but not kainate receptors in TRN neurons. The AMPAR-positive allosteric modulator, trichloromethiazide, potentiated the DNQX-mediated depolarization in TRN neurons but did not unmask any excitatory actions of DNQX/CNQX in relay neurons. This selective action may not only reveal a differential TARP distribution among thalamic neurons but also may provide insight into

  13. Selective Excitatory Actions of DNQX and CNQX in Rat Thalamic Neurons

    PubMed Central

    Lee, Sang-Hun; Govindaiah, G.

    2010-01-01

    The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from glutamatergic afferents from thalamocortical relay neurons and deep layer corticothalamic neurons, and they produce excitation via both N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Quinoxaline derivatives [e.g., 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] have routinely been used as non-NMDA receptor antagonists over the last two decades. In this study, we examined whether quinoxaline derivatives alter the intrinsic properties of thalamic neurons in light of recent findings indicating that these compounds can alter neuronal excitability in hippocampal and cerebellar neurons via transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Whole cell recordings were obtained from TRN and ventrobasal (VB) thalamic relay neurons in vitro. DNQX and CNQX produced a consistent depolarization in all TRN neurons tested. The depolarization persisted in tetrodotoxin and low Ca2+/high Mg2+ conditions, suggesting a postsynaptic site of action. In contrast, DNQX and CNQX produced little or no change in VB thalamocortical relay neurons. The nonspecific ionotropic glutamate receptor antagonist, kynurenic acid, and the selective AMPAR antagonist, 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-y l)-benzenamine hydrochloride, blocked the DNQX-mediated depolarizations. Our results indicate that the DNQX- and CNQX-mediated depolarizations are mediated by AMPAR but not kainate receptors in TRN neurons. The AMPAR-positive allosteric modulator, trichloromethiazide, potentiated the DNQX-mediated depolarization in TRN neurons but did not unmask any excitatory actions of DNQX/CNQX in relay neurons. This selective action may not only reveal a differential TARP distribution among thalamic neurons but also may provide insight into

  14. Coding and decoding with adapting neurons: a population approach to the peri-stimulus time histogram.

    PubMed

    Naud, Richard; Gerstner, Wulfram

    2012-01-01

    The response of a neuron to a time-dependent stimulus, as measured in a Peri-Stimulus-Time-Histogram (PSTH), exhibits an intricate temporal structure that reflects potential temporal coding principles. Here we analyze the encoding and decoding of PSTHs for spiking neurons with arbitrary refractoriness and adaptation. As a modeling framework, we use the spike response model, also known as the generalized linear neuron model. Because of refractoriness, the effect of the most recent spike on the spiking probability a few milliseconds later is very strong. The influence of the last spike needs therefore to be described with high precision, while the rest of the neuronal spiking history merely introduces an average self-inhibition or adaptation that depends on the expected number of past spikes but not on the exact spike timings. Based on these insights, we derive a 'quasi-renewal equation' which is shown to yield an excellent description of the firing rate of adapting neurons. We explore the domain of validity of the quasi-renewal equation and compare it with other rate equations for populations of spiking neurons. The problem of decoding the stimulus from the population response (or PSTH) is addressed analogously. We find that for small levels of activity and weak adaptation, a simple accumulator of the past activity is sufficient to decode the original input, but when refractory effects become large decoding becomes a non-linear function of the past activity. The results presented here can be applied to the mean-field analysis of coupled neuron networks, but also to arbitrary point processes with negative self-interaction.

  15. Action potential bursts in central snail neurons elicited by procaine: roles of ionic currents.

    PubMed

    Lin, Chia-Hsien; Lin, Pei-Lin; Tsai, Ming-Cheng; Hsu, Hui-Yu; Yang, Han-Yin; Chuang, Chieh-Min; Chen, Yi-Hung

    2010-10-31

    The role of ionic currents on procaine-elicited action potential bursts was studied in an identifiable RP1 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage clamp method. The RP1 neuron generated spontaneous action potentials and bath application of procaine at 10 mM reversibly elicited action potential bursts in a concentration-dependent manner. Voltage clamp studies revealed that procaine at 10 mM decreased [1] the Ca2+ current, [2] the Na+ current, [3] the delayed rectifying K+ current I(KD), and [4] the fast-inactivating K+ current (I(A)). Action potential bursts were not elicited by 4-aminopyridine (4-AP), an inhibitor of I(A), whereas they were seen after application of tetraethylammonium chloride (TEA), a blocker of the I(K)(Ca) and I(KD) currents, and tacrine, an inhibitor of I(KD). Pretreatment with U73122, a phospholipase C inhibitor, blocked the action potential bursts elicited by procaine. U73122 did not affect the I(KD) of the RP1 neuron; however, U73122 decreased the inhibitory effect of procaine on the I(KD). Tacrine decreased the TEA-sensitive I(KD) of RP1 neuron but did not significantly affect the I(A). Tacrine also successfully induced action potential bursts in the RP1 neuron. It is concluded that the inhibition on the I(KD) is responsible for the generation of action potential bursts in the central snail RP1 neuron. Further, phospholipase C activity is involved in the procaine-elicited I(KD) inhibition and action potential bursts.

  16. Ca2+ involvement in the action potential generation of myenteric neurones in the rat oesophagus.

    PubMed

    De Laet, A; Cornelissen, W; Adriaensen, D; Van Bogaert, P-P; Scheuermann, D W; Timmermans, J-P

    2002-04-01

    Intracellular recordings were used to study the physiological behaviour of rat oesophageal myenteric neurones, which are embedded in striated muscle. Injection of depolarizing pulses evoked action potentials with a clear 'shoulder' in all neurones. This shoulder disappeared under low Ca2+/high Mg2+ conditions. Tetrodotoxin (TTX; 1 micromol L-1) did not impede spike firing, whereas under combined TTX and low Ca2+/high Mg2+ conditions the action potentials were completely abolished, indicating that TTX- resistant action potentials are mediated by a Ca2+ current. Further experiments with omega-conotoxin GVIA (100 nmol L-1) revealed that these Ca2+ currents enter the cell via N-type voltage-activated Ca2+ channels (see also accompanying paper). Tetraethylammonium (10 mmol L-1) caused broadening of the action potentials, which probably resulted from prolonged Ca2+ influx due to blockade of the delayed rectifier K+ channel. Although Ca2+ appears to be involved in the spike generation of all rat oesophageal myenteric neurones, only a minority (14%) shows a slow afterhyperpolarization. Thus, no strict correlation exists between the presence of a shoulder and a slow afterhyperpolarization. Furthermore, morphological identification of 25 of the impaled neurones revealed that there was no strict correlation between morphology and electrophysiological behaviour. Consequently, rat oesophageal myenteric neurones appear to differ in several aspects from myenteric neurones in smooth muscle regions of the gastrointestinal tract.

  17. Additivity of Pyrethroid Actions on Sodium Influx in Cortical Neurons in Cerebrocortical Neurons in Primary Culture

    EPA Science Inventory

    BACKGROUND: Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Although previous work has tested the additivity of pyrethroids in vivo, this has not been assessed directly at the primary molecular ...

  18. Additivity of Pyrethroid Actions on Sodium Influx in Cortical Neurons in Cerebrocortical Neurons in Primary Culture

    EPA Science Inventory

    BACKGROUND: Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Although previous work has tested the additivity of pyrethroids in vivo, this has not been assessed directly at the primary molecular ...

  19. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.

    PubMed

    Raman, I M; Bean, B P

    1997-06-15

    Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive inward current was elicited when the membrane was repolarized to voltages between -60 and -20 mV after depolarizations to +30 mV long enough to produce maximal inactivation. At -40 mV, this "resurgent" current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on average approximately 120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at -40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at approximately 30 Hz. Hyperpolarization to -85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltage-clamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.

  20. The role of action potentials in determining neuron-type-specific responses to nitric oxide.

    PubMed

    Estes, Stephen; Zhong, Lei Ray; Artinian, Liana; Tornieri, Karine; Rehder, Vincent

    2015-05-01

    The electrical activity in developing and mature neurons determines the intracellular calcium concentration ([Ca(2+)]i), which in turn is translated into biochemical activities through various signaling cascades. Electrical activity is under control of neuromodulators, which can alter neuronal responses to incoming signals and increase the fidelity of neuronal communication. Conversely, the effects of neuromodulators can depend on the ongoing electrical activity within target neurons; however, these activity-dependent effects of neuromodulators are less well understood. Here, we present evidence that the neuronal firing frequency and intrinsic properties of the action potential (AP) waveform set the [Ca(2+)]i in growth cones and determine how neurons respond to the neuromodulator nitric oxide (NO). We used two well-characterized neurons from the freshwater snail Helisoma trivolvis that show different growth cone morphological responses to NO: B5 neurons elongate filopodia, while those of B19 neurons do not. Combining whole-cell patch clamp recordings with simultaneous calcium imaging, we show that the duration of an AP contributes to neuron-specific differences in [Ca(2+)]i, with shorter APs in B19 neurons yielding lower growth cone [Ca(2+)]i. Through the partial inhibition of voltage-gated K(+) channels, we increased the B19 AP duration resulting in a significant increase in [Ca(2+)]i that was then sufficient to cause filopodial elongation following NO treatment. Our results demonstrate a neuron-type specific correlation between AP shape, [Ca(2+)]i, and growth cone motility, providing an explanation to how growth cone responses to guidance cues depend on intrinsic electrical properties and helping explain the diverse effects of NO across neuronal populations.

  1. New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs

    PubMed Central

    Schouten, Marijn; Buijink, M. Renate; Lucassen, Paul J.; Fitzsimons, Carlos P.

    2012-01-01

    Adult neurogenesis generates functional neurons from neural stem cells present in specific brain regions. It is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus (DG), in the hippocampus. With age, the function of the hippocampus and particularly the DG is impaired. For instance, adult neurogenesis is decreased with aging, in both proliferating and differentiation of newborn cells, while in parallel an age-associated decline in cognitive performance is often seen. Surprisingly, the synaptogenic potential of adult-born neurons is only marginally influenced by aging. Therefore, although proliferation, differentiation, and synaptogenesis of adult-born new neurons in the DG are closely related to each other, they are differentially affected by aging. In this review we discuss the crucial roles of a novel class of recently discovered modulators of gene expression, the small non-coding RNAs, in the regulation of adult neurogenesis. Multiple small non-coding RNAs are differentially expressed in the hippocampus. In particular a subgroup of the small non-coding RNAs, the microRNAs, fine-tune the progression of adult neurogenesis. This makes small non-coding RNAs appealing candidates to orchestrate the functional alterations in adult neurogenesis and cognition associated with aging. Finally, we summarize observations that link changes in circulating levels of steroid hormones with alterations in adult neurogenesis, cognitive decline, and vulnerability to psychopathology in advanced age, and discuss a potential interplay between steroid hormone receptors and microRNAs in cognitive decline in aging individuals. PMID:22363255

  2. NEURONAL ACTION ON THE DEVELOPING BLOOD VESSEL PATTERN

    PubMed Central

    James, Jennifer M.; Mukouyama, Yoh-suke

    2011-01-01

    The nervous system relies on a highly specialized network of blood vessels for development and neuronal survival. Recent evidence suggests that both the central and peripheral nervous systems (CNS and PNS) employ multiple mechanisms to shape the vascular tree to meet its specific metabolic demands, such as promoting nerve-artery alignment in the PNS or the development the blood brain barrier in the CNS. In this article we discuss how the nervous system directly influences blood vessel patterning resulting in neuro-vascular congruence that is maintained throughout development and in the adult. PMID:21978864

  3. Prolonged modification of action potential shape by synaptic inputs in molluscan neurones.

    PubMed

    Winlow, W

    1985-01-01

    1. Somatic action potentials of Lymnaea neurons are modified by excitatory or inhibitory synaptic inputs and have been studied using phase-plane techniques and an action potential duration monitor. 2. Excitatory synaptic inputs increase the rate of neuronal discharge, cause action potential broadening, a decrease in the maximum rate of depolarization (Vd) and a decrease in the maximum rate of repolarization (Vr). 3. Inhibitory synaptic inputs decrease the discharge rate and cause narrowing of action potentials, an increase in Vd and an increase in Vr. 4. The effects reported above outlast the original synaptic inputs by many seconds and, if the somatic action potentials are similar to those in the axon terminals, they may have far-reaching effects on transmitter release.

  4. Eight Problems for the Mirror Neuron Theory of Action Understanding in Monkeys and Humans

    PubMed Central

    Hickok, Gregory

    2009-01-01

    The discovery of mirror neurons in macaque frontal cortex has sparked a resurgence of interest in motor/embodied theories of cognition. This critical review examines the evidence in support of one of these theories, namely that the mirror neurons provide the basis of action understanding. It is argued that there is no evidence from monkey data that directly tests this theory, and evidence from humans makes a strong case against the position. PMID:19199415

  5. The structure of affective action representations: temporal binding of affective response codes.

    PubMed

    Eder, Andreas B; Müsseler, Jochen; Hommel, Bernhard

    2012-01-01

    Two experiments examined the hypothesis that preparing an action with a specific affective connotation involves the binding of this action to an affective code reflecting this connotation. This integration into an action plan should lead to a temporary occupation of the affective code, which should impair the concurrent representation of affectively congruent events, such as the planning of another action with the same valence. This hypothesis was tested with a dual-task setup that required a speeded choice between approach- and avoidance-type lever movements after having planned and before having executed an evaluative button press. In line with the code-occupation hypothesis, slower lever movements were observed when the lever movement was affectively compatible with the prepared evaluative button press than when the two actions were affectively incompatible. Lever movements related to approach and avoidance and evaluative button presses thus seem to share a code that represents affective meaning. A model of affective action control that is based on the theory of event coding is discussed.

  6. The NEST Dry-Run Mode: Efficient Dynamic Analysis of Neuronal Network Simulation Code.

    PubMed

    Kunkel, Susanne; Schenck, Wolfram

    2017-01-01

    NEST is a simulator for spiking neuronal networks that commits to a general purpose approach: It allows for high flexibility in the design of network models, and its applications range from small-scale simulations on laptops to brain-scale simulations on supercomputers. Hence, developers need to test their code for various use cases and ensure that changes to code do not impair scalability. However, running a full set of benchmarks on a supercomputer takes up precious compute-time resources and can entail long queuing times. Here, we present the NEST dry-run mode, which enables comprehensive dynamic code analysis without requiring access to high-performance computing facilities. A dry-run simulation is carried out by a single process, which performs all simulation steps except communication as if it was part of a parallel environment with many processes. We show that measurements of memory usage and runtime of neuronal network simulations closely match the corresponding dry-run data. Furthermore, we demonstrate the successful application of the dry-run mode in the areas of profiling and performance modeling.

  7. Effect of GABAergic inhibition on odorant concentration coding in mushroom body intrinsic neurons of the honeybee.

    PubMed

    Froese, Anja; Szyszka, Paul; Menzel, Randolf

    2014-03-01

    Kenyon cells, the intrinsic neurons of the insect mushroom body, have the intriguing property of responding in a sparse way to odorants. Sparse neuronal codes are often invariant to changes in stimulus intensity and duration, and sparse coding often depends on global inhibition. We tested if this is the case for honeybees' Kenyon cells, too, and used in vivo Ca²⁺ imaging to record their responses to different odorant concentrations. Kenyon cells responded not only to the onset of odorant stimuli (ON responses), but also to their termination (OFF responses). Both, ON and OFF responses increased with increasing odorant concentration. ON responses were phasic and invariant to the duration of odorant stimuli, while OFF responses increased with increasing odorant duration. Pharmacological blocking of GABA receptors in the brain revealed that ionotropic GABA(A) and metabotropic GABA(B) receptors attenuate Kenyon cells' ON responses without changing their OFF responses. Ionotropic GABA(A) receptors attenuated Kenyon cell ON responses more strongly than metabotropic GABA(B) receptors. However, the response dynamic, temporal resolution and paired-pulse depression did not depend on GABA(A) transmission. These data are discussed in the context of mechanisms leading to sparse coding in Kenyon cells.

  8. The NEST Dry-Run Mode: Efficient Dynamic Analysis of Neuronal Network Simulation Code

    PubMed Central

    Kunkel, Susanne; Schenck, Wolfram

    2017-01-01

    NEST is a simulator for spiking neuronal networks that commits to a general purpose approach: It allows for high flexibility in the design of network models, and its applications range from small-scale simulations on laptops to brain-scale simulations on supercomputers. Hence, developers need to test their code for various use cases and ensure that changes to code do not impair scalability. However, running a full set of benchmarks on a supercomputer takes up precious compute-time resources and can entail long queuing times. Here, we present the NEST dry-run mode, which enables comprehensive dynamic code analysis without requiring access to high-performance computing facilities. A dry-run simulation is carried out by a single process, which performs all simulation steps except communication as if it was part of a parallel environment with many processes. We show that measurements of memory usage and runtime of neuronal network simulations closely match the corresponding dry-run data. Furthermore, we demonstrate the successful application of the dry-run mode in the areas of profiling and performance modeling. PMID:28701946

  9. Long Non-coding RNA in Neurons: New Players in Early Response to BDNF Stimulation.

    PubMed

    Aliperti, Vincenza; Donizetti, Aldo

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin family member that is highly expressed and widely distributed in the brain. BDNF is critical for neural survival and plasticity both during development and in adulthood, and dysfunction in its signaling may contribute to a number of neurodegenerative disorders. Deep understanding of the BDNF-activated molecular cascade may thus help to find new biomarkers and therapeutic targets. One interesting direction is related to the early phase of BDNF-dependent gene expression regulation, which is responsible for the activation of selective gene programs that lead to stable functional and structural remodeling of neurons. Immediate-early coding genes activated by BDNF are under investigation, but the involvement of the non-coding RNAs is largely unexplored, especially the long non-coding RNAs (lncRNAs). lncRNAs are emerging as key regulators that can orchestrate different aspects of nervous system development, homeostasis, and plasticity, making them attractive candidate markers and therapeutic targets for brain diseases. We used microarray technology to identify differentially expressed lncRNAs in the immediate response phase of BDNF stimulation in a neuronal cell model. Our observations on the putative functional role of lncRNAs provide clues to their involvement as master regulators of gene expression cascade triggered by BDNF.

  10. Metabolic Interplay between Astrocytes and Neurons Regulates Endocannabinoid Action

    PubMed Central

    Viader, Andreu; Blankman, Jacqueline L.; Zhong, Peng; Liu, Xiaojie; Schlosburg, Joel E.; Joslyn, Christopher M.; Liu, Qing-Song; Tomarchio, Aaron J.; Lichtman, Aron H.; Selley, Dana E.; Sim-Selley, Laura J.; Cravatt, Benjamin F.

    2015-01-01

    Summary The endocannabinoid 2-arachidonoylglycerol (2-AG) is a retrograde lipid messenger that modulates synaptic function, neurophysiology, and behavior. 2-AG signaling is terminated by enzymatic hydrolysis—a reaction that is principally performed by monoacylglycerol lipase (MAGL). MAGL is broadly expressed throughout the nervous system, and the contributions of different brain cell types to regulating 2-AG activity have remained unclear. Here, we genetically dissect the cellular anatomy of MAGL-mediated 2-AG metabolism in the brain and show that neurons and astrocytes coordinately regulate 2-AG content and endocannabinoid-dependent forms of synaptic plasticity and behavior. We also find that astrocytic MAGL is mainly responsible for converting 2-AG to neuroinflammatory prostaglandins via a mechanism that may involve transcellular shuttling of lipid substrates. Astrocytic-neuronal interplay thus provides distributed oversight of 2-AG metabolism and function, and, through doing so, protects the nervous system from excessive CB1 receptor activation and promotes endocannabinoid crosstalk with other lipid transmitter systems. PMID:26212325

  11. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons

    PubMed Central

    Nikitin, Evgeny S.; Bal, Natalia V.; Malyshev, Aleksey; Ierusalimsky, Victor N.; Spivak, Yulia; Balaban, Pavel M.; Volgushev, Maxim

    2017-01-01

    The ability of neocortical neurons to detect and encode rapid changes at their inputs is crucial for basic neuronal computations, such as coincidence detection, precise synchronization of activity and spike-timing dependent plasticity. Indeed, populations of cortical neurons can respond to subtle changes of the input very fast, on a millisecond time scale. Theoretical studies and model simulations linked the encoding abilities of neuronal populations to the fast onset dynamics of action potentials (APs). Experimental results support this idea, however mechanisms of fast onset of APs in cortical neurons remain elusive. Studies in neuronal cultures, that are allowing for accurate control over conditions of growth and microenvironment during the development of neurons and provide better access to the spike initiation zone, may help to shed light on mechanisms of AP generation and encoding. Here we characterize properties of AP encoding in neocortical neurons grown for 11–25 days in culture. We show that encoding of high frequencies improves upon culture maturation, which is accompanied by the development of passive electrophysiological properties and AP generation. The onset of APs becomes faster with culture maturation. Statistical analysis using correlations and linear model approaches identified the onset dynamics of APs as a major predictor of age-dependent changes of encoding. Encoding of high frequencies strongly correlated also with the input resistance of neurons. Finally, we show that maturation of encoding properties of neurons in cultures is similar to the maturation of encoding in neurons studied in slices. These results show that maturation of AP generators and encoding is, to a large extent, determined genetically and takes place even without normal micro-environment and activity of the whole brain in vivo. This establishes neuronal cultures as a valid experimental model for studying mechanisms of AP generation and encoding, and their maturation. PMID

  12. M-type potassium conductance controls the emergence of neural phase codes: a combined experimental and neuron modelling study.

    PubMed

    Kwag, Jeehyun; Jang, Hyun Jae; Kim, Mincheol; Lee, Sujeong

    2014-10-06

    Rate and phase codes are believed to be important in neural information processing. Hippocampal place cells provide a good example where both coding schemes coexist during spatial information processing. Spike rate increases in the place field, whereas spike phase precesses relative to the ongoing theta oscillation. However, what intrinsic mechanism allows for a single neuron to generate spike output patterns that contain both neural codes is unknown. Using dynamic clamp, we simulate an in vivo-like subthreshold dynamics of place cells to in vitro CA1 pyramidal neurons to establish an in vitro model of spike phase precession. Using this in vitro model, we show that membrane potential oscillation (MPO) dynamics is important in the emergence of spike phase codes: blocking the slowly activating, non-inactivating K+ current (IM), which is known to control subthreshold MPO, disrupts MPO and abolishes spike phase precession. We verify the importance of adaptive IM in the generation of phase codes using both an adaptive integrate-and-fire and a Hodgkin-Huxley (HH) neuron model. Especially, using the HH model, we further show that it is the perisomatically located IM with slow activation kinetics that is crucial for the generation of phase codes. These results suggest an important functional role of IM in single neuron computation, where IM serves as an intrinsic mechanism allowing for dual rate and phase coding in single neurons.

  13. Scene-selective coding by single neurons in the human parahippocampal cortex

    PubMed Central

    Mormann, Florian; Kornblith, Simon; Cerf, Moran; Kraskov, Alexander; Tran, Michelle; Knieling, Simeon; Quian Quiroga, Rodrigo; Koch, Christof; Fried, Itzhak

    2017-01-01

    Imaging, electrophysiological, and lesion studies have shown a relationship between the parahippocampal cortex (PHC) and the processing of spatial scenes. Our present knowledge of PHC, however, is restricted to the macroscopic properties and dynamics of bulk tissue; the behavior and selectivity of single parahippocampal neurons remains largely unknown. In this study, we analyzed responses from 630 parahippocampal neurons in 24 neurosurgical patients during visual stimulus presentation. We found a spatially clustered subpopulation of scene-selective units with an associated event-related field potential. These units form a population code that is more distributed for scenes than for other stimulus categories, and less sparse than elsewhere in the medial temporal lobe. Our electrophysiological findings provide insight into how individual units give rise to the population response observed with functional imaging in the parahippocampal place area. PMID:28096381

  14. Robust conjunctive item-place coding by hippocampal neurons parallels learning what happens where

    PubMed Central

    Komorowski, Robert W.; Manns, Joseph R.; Eichenbaum, Howard

    2009-01-01

    Previous research indicates a critical role of the hippocampus in memory for events in the context in which they occur. However, studies to date have not provided compelling evidence that hippocampal neurons encode event-context conjunctions directly associated with this kind of learning. Here we report that, as animals learn different meanings for items in distinct contexts, individual hippocampal neurons develop responses to specific stimuli in the places where they have differential significance. Furthermore, this conjunctive coding evolves in the form of enhanced item-specific responses within a subset of the pre-existing spatial representation. These findings support the view that conjunctive representations in the hippocampus underlie the acquisition of context specific memories. PMID:19657042

  15. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.

    PubMed

    Hlubek, M D; Cobbett, P

    2000-09-15

    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  16. Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons

    PubMed Central

    Williams, Stephen R; Stuart, Greg J

    1999-01-01

    Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro.Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing.High frequency (330 ± 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250–500 μm; n = 8) to, the perfusion medium.The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nm; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mm; n = 5).Apical dendritic depolarisation resulted in low frequency (157 ± 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11).Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 μm from the soma.Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression.A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from

  17. Adhesion to Carbon Nanotube Conductive Scaffolds Forces Action-Potential Appearance in Immature Rat Spinal Neurons

    PubMed Central

    Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies. PMID:23951361

  18. UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals

    PubMed Central

    Andrews, Zane B.; Liu, Zhong-Wu; Walllingford, Nicholas; Erion, Derek M.; Borok, Erzsebet; Friedman, Jeffery M.; Tschöp, Matthias H.; Shanabrough, Marya; Cline, Gary; Shulman, Gerald I.; Coppola, Anna; Gao, Xiao-Bing; Horvath, Tamas L.; Diano, Sabrina

    2014-01-01

    The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour. PMID:18668043

  19. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    PubMed

    Fabbro, Alessandra; Sucapane, Antonietta; Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  20. Networks of spiking neurons that compute linear functions using action potential timing

    NASA Astrophysics Data System (ADS)

    Ruf, Berthold

    1999-03-01

    For fast neural computations within the brain it is very likely that the timing of single firing events is relevant. Recently Maass has shown that under certain weak assumptions a weighted sum can be computed in temporal coding by leaky integrate-and-fire neurons. This construction can be extended to approximate arbitrary functions. In comparison to integrate-and-fire neurons there are several sources in biologically more realistic neurons for additional nonlinear effects like e.g. the spatial and temporal interaction of postsynaptic potentials or voltage-gated ion channels at the soma. Here we demonstrate with the help of computer simulations using GENESIS that despite of these nonlinearities such neurons can compute linear functions in a natural and straightforward way based on the main principles of the construction given by Maass. One only has to assume that a neuron receives all its inputs in a time interval of approximately the length of the rising segment of its excitatory postsynaptic potentials. We also show that under certain assumptions there exists within this construction some type of activation function being computed by such neurons. Finally we demonstrate that on the basis of these results it is possible to realize in a simple way pattern analysis with spiking neurons. It allows the analysis of a mixture of several learned patterns within a few milliseconds.

  1. Axonal actin in action: Imaging actin dynamics in neurons.

    PubMed

    Ladt, Kelsey; Ganguly, Archan; Roy, Subhojit

    2016-01-01

    Actin is a highly conserved, key cytoskeletal protein involved in numerous structural and functional roles. In neurons, actin has been intensively investigated in axon terminals-growth cones-and dendritic spines, but details about actin structure and dynamics in axon shafts have remained obscure for decades. A major barrier in the field has been imaging actin. Actin exists as soluble monomers (G-actin) as well as actin filaments (F-actin), and labeling actin with conventional fluorescent probes like GFP/RFP typically leads to a diffuse haze that makes it difficult to discern kinetic behaviors. In a recent publication, we used F-actin selective probes to visualize actin dynamics in axons, resolving striking actin behaviors that have not been described before. However, using these probes to visualize actin dynamics is challenging as they can cause bundling of actin filaments; thus, experimental parameters need to be strictly optimized. Here we describe some practical methodological details related to using these probes for visualizing F-actin dynamics in axons.

  2. Inferring thought and action in motor neurone disease.

    PubMed

    Gibbons, Z C; Snowden, J S; Thompson, J C; Happé, F; Richardson, A; Neary, D

    2007-03-25

    The traditional assumption that classical motor neurone disease (MND) invariably spares cognitive function is now recognised to be incorrect. Deficits have most commonly been demonstrated on executive tasks suggesting impaired function of frontal systems. Yet, crucial aspects of frontal lobe function have not hitherto been explored. The study used tests of theory of mind (ToM) (interpretation of cartoons and stories) to examine the ability of 16 patients with MND to interpret social situations and ascribe mental states to others. Only minor differences were elicited in the MND group as a whole compared to controls, and performance was not differentially affected for cartoons and stories requiring inference of another's mental state (mental) compared to control (physical) cartoons and stories. However, abnormalities were elicited on both mental and physical tasks in a subgroup of patients with bulbar signs. Moreover, examination of individual patient scores revealed a spectrum of performance ranging from normal to severely impaired. Errors were qualitatively similar to those seen in frontotemporal dementia (FTD). Performance on the ToM tasks was significantly correlated with conventional, untimed measures of executive function, suggesting that ToM deficits in MND are likely to be linked to a more general executive failure. The findings contribute to the understanding of ToM performance in neurodegenerative disease and provide further evidence of the association between MND and FTD.

  3. Neural Code-Neural Self-information Theory on How Cell-Assembly Code Rises from Spike Time and Neuronal Variability.

    PubMed

    Li, Meng; Tsien, Joe Z

    2017-01-01

    A major stumbling block to cracking the real-time neural code is neuronal variability - neurons discharge spikes with enormous variability not only across trials within the same experiments but also in resting states. Such variability is widely regarded as a noise which is often deliberately averaged out during data analyses. In contrast to such a dogma, we put forth the Neural Self-Information Theory that neural coding is operated based on the self-information principle under which variability in the time durations of inter-spike-intervals (ISI), or neuronal silence durations, is self-tagged with discrete information. As the self-information processor, each ISI carries a certain amount of information based on its variability-probability distribution; higher-probability ISIs which reflect the balanced excitation-inhibition ground state convey minimal information, whereas lower-probability ISIs which signify rare-occurrence surprisals in the form of extremely transient or prolonged silence carry most information. These variable silence durations are naturally coupled with intracellular biochemical cascades, energy equilibrium and dynamic regulation of protein and gene expression levels. As such, this silence variability-based self-information code is completely intrinsic to the neurons themselves, with no need for outside observers to set any reference point as typically used in the rate code, population code and temporal code models. Moreover, temporally coordinated ISI surprisals across cell population can inherently give rise to robust real-time cell-assembly codes which can be readily sensed by the downstream neural clique assemblies. One immediate utility of this self-information code is a general decoding strategy to uncover a variety of cell-assembly patterns underlying external and internal categorical or continuous variables in an unbiased manner.

  4. Different mRNAs code for dopa decarboxylase in tissues of neuronal and nonneuronal origin

    SciTech Connect

    Krieger, M.; Coge, F.; Gros, F.; Thibault, J. )

    1991-03-15

    A cDNA clone for dopa decarboxylase has been isolated from a rat pheochromocytoma cDNA library and the cDNA sequence has been determined. It corresponds to an mRNA of 2094 nucleotides. The length of the mRNA was measured by primer-extension of rat pheochromocytoma RNA and the 5{prime} end of the sequence of the mRNA was confirmed by the PCR. A probe spanning the translation initiation site of the mRNA was used to hybridize with mRNAs from various organs of the rat. S1 nuclease digestion of the mRNAs annealed with this probe revealed two classes of mRNAs. The comparison of the cDNA sequence and published sequences for rat liver, human pheochromocytoma, and Droxophila dopa decarboxylase supported the conclusion that two mRNAs are produced: one is specific for tissue of neuronal origin and the other is specific for tissues of nonneuronal (mesodermal or endodermal) origin. The neuronal mRNA contains a 5{prime} untranslated sequence that is highly conserved between human and rat pheochromocytoma including a GA stretch. The coding sequence and the 3{prime} untranslated sequence of mRNAs from rat liver and pheochromocytoma are identical. The rat mRNA differs only in the 5{prime} untranslated region. Thus a unique gene codes for dopa decarboxylase and this gene gives rise to at least two transcripts presumably in response to different signals during development.

  5. Differential Sensitivity of Specific Neuronal Populations of the Rat Hypothalamus to Prolactin Action

    PubMed Central

    Sapsford, Tony J.; Kokay, Ilona C.; Östberg, Lovisa; Bridges, Robert S.; Grattan, David R.

    2014-01-01

    Prolactin stimulates dopamine release from neuroendocrine dopaminergic (NEDA) neurons in the hypothalamic arcuate nucleus (ARC) to maintain low levels of serum prolactin. Elevated prolactin levels during pregnancy and lactation may mediate actions in other hypothalamic regions such as the paraventricular nucleus (PVN) and rostral preoptic area (rPOA). We predicted that NEDA neurons would be more sensitive prolactin targets than neurons in other regions because they are required to regulate basal prolactin secretion. Moreover, differences in the accessibility of the ARC to prolactin in blood may influence the responsiveness of this population. Therefore, we compared prolactin-induced signaling in different hypothalamic neuronal populations following either systemic or intracerebroventricular (icv) prolactin administration. Phosphorylation of the signal transduction factor, STAT5 (pSTAT5), was used to identify prolactin-responsive neurons. In response to systemic prolactin, pSTAT5-labeled cells were widely observed in the ARC but absent from the rPOA and PVN. Many of these responsive cells in the ARC were identified as NEDA neurons. The lowest icv prolactin dose (10 ng) induced pSTAT5 in the ARC, but with higher doses (>500 ng) pSTAT5 was detected in numerous regions, including the rPOA and PVN. NEDA neurons were maximally labeled with nuclear pSTAT5 in response to 500 ng prolactin and appeared to be more sensitive than dopaminergic neurons in the rPOA. Subpopulations of oxytocin neurons in the hypothalamus were also found to be differentially sensitive to prolactin. These data suggest that differences in the accessibility of the arcuate nucleus to prolactin, together with intrinsic differences in the NEDA neurons, may facilitate homeostatic feedback regulation of prolactin release. PMID:21953590

  6. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

    PubMed Central

    Barry, John F.; Turner, Matthew J.; Schloss, Jennifer M.; Glenn, David R.; Song, Yuyu; Lukin, Mikhail D.; Park, Hongkun; Walsworth, Ronald L.

    2016-01-01

    Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution—e.g., magnetic resonance imaging methods and magnetoencephalography—or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector. PMID:27911765

  7. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    PubMed Central

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  8. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond.

    PubMed

    Barry, John F; Turner, Matthew J; Schloss, Jennifer M; Glenn, David R; Song, Yuyu; Lukin, Mikhail D; Park, Hongkun; Walsworth, Ronald L

    2016-12-06

    Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution-e.g., magnetic resonance imaging methods and magnetoencephalography-or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector.

  9. Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin.

    PubMed

    Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L; Mosher, Christina; Berglund, Eric D; Elmquist, Joel K; Zigman, Jeffrey M

    2014-02-01

    The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreER(T2) transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia.

  10. Actions of methoxylated amphetamine hallucinogens on serotonergic neurons of the brain.

    PubMed

    Penington, N J

    1996-08-01

    1. Previous studies of phenethylamine hallucinogenic drugs have reported that intravenous injection of DOI or similar compounds produce an inhibition of the firing rate of serotonergic dorsal raphe neurons of the rat; potentially lowering levels of 5-HT throughout the brain. 2. Direct application by iontophoresis demonstrated only weak non-specific effects, but injection into the nucleus produced slowing of cell firing possibly due to the reduction of on-going synaptic excitation. 3. The literature concerning phenethylamine hallucinogens is discussed in the context of new results obtained from acutely isolated raphe neurons. The effect of DOI (10 microM) was tested on isolated DR neurons that responded to 5-HT with the activation of an inwardly rectifying K+ current but it was without effect. Under conditions that isolated inward Ca2+ current in raphe neurons that was inhibited by 5-HT, DOI was similarly without effect, neither blocking nor mimicking the action of 5-HT. Brief applications of glutamate produced an inward current similar to those produced by synaptic excitation in a slice preparation, but DOI failed to influence the size or duration of these responses. 4. These results suggest that DOI does not directly influence the cell bodies of DR neurons. 5. Further studies using raphe slices subject to synaptic influences will be required to reveal any indirectly mediated mechanism that may underlie the effects of DOI on DR neurons. Alternative indirect mechanisms of DR neuronal inhibition by i.v. DOI and DOM are suggested.

  11. The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states

    PubMed Central

    Barry, Guy; Briggs, James A.; Hwang, Do Won; Nayler, Sam P.; Fortuna, Patrick R. J.; Jonkhout, Nicky; Dachet, Fabien; Maag, Jesper L. V.; Mestdagh, Pieter; Singh, Erin M.; Avesson, Lotta; Kaczorowski, Dominik C.; Ozturk, Ezgi; Jones, Nigel C.; Vetter, Irina; Arriola-Martinez, Luis; Hu, Jianfei; Franco, Gloria R.; Warn, Victoria M.; Gong, Andrew; Dinger, Marcel E.; Rigo, Frank; Lipovich, Leonard; Morris, Margaret J.; O’Brien, Terence J.; Lee, Dong Soo; Loeb, Jeffrey A.; Blackshaw, Seth; Mattick, John S.; Wolvetang, Ernst J.

    2017-01-01

    Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown. Next generation sequencing reveals a strong association of NEAT1 with increased ion channel gene expression upon activation of iPSC-derived neurons following NEAT1 knockdown. Furthermore, we show that while NEAT1 is acutely down-regulated in response to neuronal activity, repeated stimulation results in NEAT1 becoming chronically unresponsive in independent in vivo rat model systems relevant to temporal lobe epilepsy. We extended previous studies showing increased NEAT1 expression in resected cortical tissue from high spiking regions of patients suffering from intractable seizures. Our results indicate a role for NEAT1 in modulating human neuronal activity and suggest a novel mechanistic link between an activity-dependent long non-coding RNA and epilepsy. PMID:28054653

  12. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    PubMed

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  13. Plasticity-driven individualization of olfactory coding in mushroom body output neurons

    PubMed Central

    Hige, Toshihide; Aso, Yoshinori; Rubin, Gerald M.; Turner, Glenn C.

    2015-01-01

    Although all sensory circuits ascend to higher brain areas where stimuli are represented in sparse, stimulus-specific activity patterns, relatively little is known about sensory coding on the descending side of neural circuits, as a network converges. In insects, mushroom bodies (MBs) have been an important model system for studying sparse coding in the olfactory system1–3, where this format is important for accurate memory formation4–6. In Drosophila, it has recently been shown that the 2000 Kenyon cells (KCs) of the MB converge onto a population of only 35 MB output neurons (MBONs), that fall into 22 anatomically distinct cell types7,8. Here we provide the first comprehensive view of olfactory representations at the fourth layer of the circuit, where we find a clear transition in the principles of sensory coding. We show that MBON tuning curves are highly correlated with one another. This is in sharp contrast to the process of progressive decorrelation of tuning in the earlier layers of the circuit2,9. Instead, at the population level, odor representations are reformatted so that positive and negative correlations arise between representations of different odors. At the single-cell level, we show that uniquely identifiable MBONs display profoundly different tuning across different animals, but tuning of the same neuron across the two hemispheres of an individual fly was nearly identical. Thus, individualized coordination of tuning arises at this level of the olfactory circuit. Furthermore, we find that this individualization is an active process that requires a learning-related gene, rutabaga. Ultimately, neural circuits have to flexibly map highly stimulus-specific information in sparse layers onto a limited number of different motor outputs. The reformatting of sensory representations we observe here may mark the beginning of this sensory-motor transition in the olfactory system. PMID:26416731

  14. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

    PubMed

    Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang

    2015-12-01

    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network.

  15. Understanding the role of mirror neurons in action understanding will require more than a domain-general account.

    PubMed

    Martin, Alia; Santos, Laurie R

    2014-04-01

    Cook et al. propose that mirror neurons emerge developmentally through a domain-general associative mechanism. We argue that experience-sensitivity does not rule out an adaptive or genetic argument for mirror neuron function, and that current evidence suggests that mirror neurons are more specialized than the authors' account would predict. We propose that future work integrate behavioral and neurophysiological techniques used with primates to examine the proposed functions of mirror neurons in action understanding.

  16. Inhibition by morphine and its analogs of action potentials in adult rat dorsal root ganglion neurons.

    PubMed

    Mizuta, Kotaro; Fujita, Tsugumi; Kumamoto, Eiichi

    2012-09-01

    Although opioids inhibit action potential (AP) conduction in primary-afferent fibers, this has not yet been fully examined. We investigated by using the sharp glass microelectrode technique how opioids (morphine, codeine, and ethylmorphine) affect APs recorded from adult rat dorsal root ganglion (DRG) neurons in response to sciatic nerve stimulation. The DRG neurons were classified into three types, Aα/β, Aδ, and C, according to AP characteristics, including the fiber conduction velocity (CV) of the neuron. AP of the Aα/β neuron was reduced in peak amplitude by each of the opioids in a reversible and concentration-dependent manner. The potency sequence was ethylmorphine > codeine = morphine (IC(50) = 0.70, 2.5, and 2.9 mM, respectively), indicating that this AP inhibition is related to the chemical structure of the opioid. Each of the Aδ and C neuron APs was also inhibited by the opioids; ethylmorphine had a tendency to inhibit APs more effectively than codeine and morphine. This inhibition was variable in extent among neurons and was either comparable to or greater than that of the Aα/β neuron AP. The opioid-induced AP inhibitions were unaffected by nonspecific opioid-receptor antagonist naloxone; opioid-receptor agonists did not affect APs. In conclusion, the opioids inhibited APs in DRG neurons without opioid-receptor activation; this inhibition was different among neurons having different primary-afferent fiber CVs and also among the three kinds of opioid. The inhibition by opioid of primary-afferent fiber AP conduction is suggested to be distinct in extent among fibers conveying distinct types of nociceptive information. Copyright © 2012 Wiley Periodicals, Inc.

  17. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    PubMed Central

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  18. Kv2 channel regulation of action potential repolarization and firing patterns in superior cervical ganglion neurons and hippocampal CA1 pyramidal neurons.

    PubMed

    Liu, Pin W; Bean, Bruce P

    2014-04-02

    Kv2 family "delayed-rectifier" potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60-80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from -70 mV, but not -80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at -70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation.

  19. [Effect of pulse magnetic field on distribution of neuronal action potential].

    PubMed

    Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

    2014-08-25

    The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

  20. Direct Evaluation of L-DOPA Actions on Neuronal Activity of Parkinsonian Tissue In Vitro

    PubMed Central

    Plata, Víctor; Pérez-Ortega, Jesús E.; Galarraga, Elvira; Bargas, José

    2013-01-01

    Physiological and biochemical experiments in vivo and in vitro have explored striatal receptor signaling and neuronal excitability to posit pathophysiological models of Parkinson's disease. However, when therapeutic approaches, such as dopamine agonists, need to be evaluated, behavioral tests using animal models of Parkinson's disease are employed. To our knowledge, recordings of population neuronal activity in vitro to assess anti-Parkinsonian drugs and the correlation of circuit dynamics with disease state have only recently been attempted. We have shown that Parkinsonian pathological activity of neuronal striatal circuits can be characterized in in vitro cerebral tissue. Here, we show that calcium imaging techniques, capable of recording dozens of neurons simultaneously with single-cell resolution, can be extended to assess the action of therapeutic drugs. We used L-DOPA as a prototypical anti-Parkinsonian drug to show the efficiency of this proposed bioassay. In a rodent model of early Parkinson's disease, Parkinsonian neuronal activity can be returned to control levels by the bath addition of L-DOPA in a reversible way. This result raises the possibility to use calcium imaging techniques to measure, quantitatively, the actions of anti-Parkinsonian drugs over time and to obtain correlations with disease evolution and behavior. PMID:24151606

  1. Direct evaluation of L-DOPA actions on neuronal activity of Parkinsonian tissue in vitro.

    PubMed

    Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús E; Barroso-Flores, Janet; Galarraga, Elvira; Bargas, José

    2013-01-01

    Physiological and biochemical experiments in vivo and in vitro have explored striatal receptor signaling and neuronal excitability to posit pathophysiological models of Parkinson's disease. However, when therapeutic approaches, such as dopamine agonists, need to be evaluated, behavioral tests using animal models of Parkinson's disease are employed. To our knowledge, recordings of population neuronal activity in vitro to assess anti-Parkinsonian drugs and the correlation of circuit dynamics with disease state have only recently been attempted. We have shown that Parkinsonian pathological activity of neuronal striatal circuits can be characterized in in vitro cerebral tissue. Here, we show that calcium imaging techniques, capable of recording dozens of neurons simultaneously with single-cell resolution, can be extended to assess the action of therapeutic drugs. We used L-DOPA as a prototypical anti-Parkinsonian drug to show the efficiency of this proposed bioassay. In a rodent model of early Parkinson's disease, Parkinsonian neuronal activity can be returned to control levels by the bath addition of L-DOPA in a reversible way. This result raises the possibility to use calcium imaging techniques to measure, quantitatively, the actions of anti-Parkinsonian drugs over time and to obtain correlations with disease evolution and behavior.

  2. Mirror neurons in monkey area F5 do not adapt to the observation of repeated actions.

    PubMed

    Caggiano, Vittorio; Pomper, Joern K; Fleischer, Falk; Fogassi, Leonardo; Giese, Martin; Thier, Peter

    2013-01-01

    Repetitive presentation of the same visual stimulus entails a response decrease in the action potential discharge of neurons in various areas of the monkey visual cortex. It is still unclear whether this repetition suppression effect is also present in single neurons in cortical premotor areas responding to visual stimuli, as suggested by the human functional magnetic resonance imaging literature. Here we report the responses of 'mirror neurons' in monkey area F5 to the repeated presentation of action movies. We find that most single neurons and the population at large do not show a significant decrease of the firing rate. On the other hand, simultaneously recorded local field potentials exhibit repetition suppression. As local field potentials are believed to be better linked to the blood-oxygen-level-dependent (BOLD) signal exploited by functional magnetic resonance imaging, these findings suggest caution when trying to derive conclusions on the spiking activity of neurons in a given area based on the observation of BOLD repetition suppression.

  3. Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action.

    PubMed

    Shin, Andrew C; Filatova, Nika; Lindtner, Claudia; Chi, Tiffany; Degann, Seta; Oberlin, Douglas; Buettner, Christoph

    2017-06-01

    Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the central nervous system by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue insulin action. Mice lacking the insulin receptor in AgRP neurons (AgRP IR KO) exhibited impaired hepatic insulin action because the ability of insulin to suppress hepatic glucose production (hGP) was reduced, but the ability of insulin to suppress lipolysis was unaltered. To the contrary, in POMC IR KO mice, insulin lowered hGP but failed to suppress adipose tissue lipolysis. High-fat diet equally worsened glucose tolerance in AgRP and POMC IR KO mice and their respective controls but increased hepatic triglyceride levels only in POMC IR KO mice, consistent with impaired lipolytic regulation resulting in fatty liver. These data suggest that although insulin signaling in AgRP neurons is important in regulating glucose metabolism, insulin signaling in POMC neurons controls adipose tissue lipolysis and prevents high-fat diet-induced hepatic steatosis. © 2017 by the American Diabetes Association.

  4. Synaptic diversity enables temporal coding of coincident multi-sensory inputs in single neurons

    PubMed Central

    Chabrol, François P.; Arenz, Alexander; Wiechert, Martin T.; Margrie, Troy W.; DiGregorio, David A.

    2015-01-01

    The ability of the brain to rapidly process information from multiple pathways is critical for reliable execution of complex sensory-motor behaviors, yet the cellular mechanisms underlying a neuronal representation of multimodal stimuli are poorly understood. Here we explored the possibility that the physiological diversity of mossy fiber (MF) to granule cell (GC) synapses within the mouse vestibulocerebellum may contribute to the processing of coincident multisensory information at the level of individual GCs. We found that the strength and short-term dynamics of individual MF-GC synapses can act as biophysical signatures for primary vestibular, secondary vestibular and visual input pathways. The majority of GCs receive inputs from different modalities, which when co-activated, produced enhanced GC firing rates and distinct first spike latencies. Thus, pathway-specific synaptic response properties permit temporal coding of correlated multisensory input by single GCs, thereby enriching sensory representation and facilitating pattern separation. PMID:25821914

  5. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics.

    PubMed

    Kapucu, Fikret E; Tanskanen, Jarno M A; Mikkonen, Jarno E; Ylä-Outinen, Laura; Narkilahti, Susanna; Hyttinen, Jari A K

    2012-01-01

    In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESCs), exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI) histograms. Moreover, the algorithm calculates ISI thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average (CMA) and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA) data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  6. A General Odorant Background Affects the Coding of Pheromone Stimulus Intermittency in Specialist Olfactory Receptor Neurones

    PubMed Central

    Rouyar, Angela; Party, Virginie; Prešern, Janez; Blejec, Andrej; Renou, Michel

    2011-01-01

    In nature the aerial trace of pheromone used by male moths to find a female appears as a train of discontinuous pulses separated by gaps among a complex odorant background constituted of plant volatiles. We investigated the effect of such background odor on behavior and coding of temporal parameters of pheromone pulse trains in the pheromone olfactory receptor neurons of Spodoptera littoralis. Effects of linalool background were tested by measuring walking behavior towards a source of pheromone. While velocity and orientation index did drop when linalool was turned on, both parameters recovered back to pre-background values after 40 s with linalool still present. Photo-ionization detector was used to characterize pulse delivery by our stimulator. The photo-ionization detector signal reached 71% of maximum amplitude at 50 ms pulses and followed the stimulus period at repetition rates up to 10 pulses/s. However, at high pulse rates the concentration of the odorant did not return to base level during inter-pulse intervals. Linalool decreased the intensity and shortened the response of receptor neurons to pulses. High contrast (>10 dB) in firing rate between pulses and inter-pulse intervals was observed for 1 and 4 pulses/s, both with and without background. Significantly more neurons followed the 4 pulses/s pattern when delivered over linalool; at the same time the information content was preserved almost to the control values. Rapid recovery of behavior shows that change of perceived intensity is more important than absolute stimulus intensity. While decreasing the response intensity, background odor preserved the temporal parameters of the specific signal. PMID:22028879

  7. Vibrotactile Discrimination in the Rat Whisker System is Based on Neuronal Coding of Instantaneous Kinematic Cues

    PubMed Central

    Waiblinger, Christian; Brugger, Dominik; Schwarz, Cornelius

    2015-01-01

    Which physical parameter of vibrissa deflections is extracted by the rodent tactile system for discrimination? Particularly, it remains unclear whether perception has access to instantaneous kinematic parameters (i.e., the details of the trajectory) or relies on temporally integration of the movement trajectory such as frequency (e.g., spectral information) and intensity (e.g., mean speed). Here, we use a novel detection of change paradigm in head-fixed rats, which presents pulsatile vibrissa stimuli in seamless sequence for discrimination. This procedure ensures that processes of decision making can directly tap into sensory signals (no memory functions involved). We find that discrimination performance based on instantaneous kinematic cues far exceeds the ones provided by frequency and intensity. Neuronal modeling based on barrel cortex single units shows that small populations of sensitive neurons provide a transient signal that optimally fits the characteristic of the subject's perception. The present study is the first to show that perceptual read-out is superior in situations allowing the subject to base perception on detailed trajectory cues, that is, instantaneous kinematic variables. A possible impact of this finding on tactile systems of other species is suggested by evidence for instantaneous coding also in primates. PMID:24169940

  8. Carbenoxolone blockade of neuronal network activity in culture is not mediated by an action on gap junctions

    PubMed Central

    Rouach, N; Segal, M; Koulakoff, A; Giaume, C; Avignone, E

    2003-01-01

    Spontaneous activity in the central nervous system is strongly suppressed by blockers of gap junctions (GJs), suggesting that GJs contribute to network activity. However, the lack of selective GJ blockers prohibits the determination of their site of action, i.e. neuronal versus glial. Astrocytes are strongly coupled through GJs and have recently been shown to modulate synaptic transmission, yet their role in neuronal network activity was not analysed. The present study investigated the effects and site of action of the GJ blocker, carbenoxolone (CBX), on neuronal network activity. To this end, we used cultures of hippocampal or cortical neurons, plated on astrocytes. In these cultures neurons display spontaneous synchronous activity and GJs are found only in astrocytes. CBX induced in these neurons a reversible suppression of spontaneous action potential discharges, synaptic currents and synchronised calcium oscillations. Moreover, CBX inhibited oscillatory activity induced by the GABAA antagonist, bicuculline. These effects were not due to blockade of astrocytic GJs, since they were not mimicked nor occluded by endothelin-1 (ET-1), a peptide known to block astrocytic GJs. Also, these effects were still present in co-cultures of wild-type neurons plated on astrocytes originating from connexin-43 (Cx43) knockout mice, and in neuronal cultures which contain few isolated astrocytes. CBX was not likely to exert its effect through neuronal GJs either, as immunostaining for major neuronal connexins (Cx) as well as dye or electrical coupling, were not detected in the different models of cultured neurons examined. Finally while CBX (at 100 μm) did not modify presynaptic transmitter release and postsynaptic responses to glutamate, it did cause an increase in the action potential threshold and strongly decreased the firing rate in response to a sustained depolarising current. These data demonstrate that CBX does not exert its action on network activity of cultured neurons

  9. A Shab potassium channel contributes to action potential broadening in peptidergic neurons.

    PubMed

    Quattrocki, E A; Marshall, J; Kaczmarek, L K

    1994-01-01

    We have cloned the gene for a potassium channel, Aplysia Shab, that is expressed in the bag cell neurons of Aplysia. The voltage dependence and kinetics of the Aplysia Shab current in oocytes match those of IK2, one of the two delayed rectifiers in these neurons. Like IK2, but in contrast with other members of the Shab subfamily, the Aplysia Shab current inactivates within several hundred milliseconds. This inactivation occurs by a process whose properties do not match those previously described for C-type and N-type mechanisms. Neither truncation of the N-terminus nor block by tetraethylammonium alters the time course of inactivation. By incorporating the characteristics of Aplysia Shab into a computational model, we have shown how this current contributes to the normal enhancement of action potentials that occurs in the bag cell neurons at the onset of neuropeptide secretion.

  10. User-action-driven view and rate scalable multiview video coding.

    PubMed

    Chakareski, Jacob; Velisavljevic, Vladan; Stankovic, Vladimir

    2013-09-01

    We derive an optimization framework for joint view and rate scalable coding of multi-view video content represented in the texture plus depth format. The optimization enables the sender to select the subset of coded views and their encoding rates such that the aggregate distortion over a continuum of synthesized views is minimized. We construct the view and rate embedded bitstream such that it delivers optimal performance simultaneously over a discrete set of transmission rates. In conjunction, we develop a user interaction model that characterizes the view selection actions of the client as a Markov chain over a discrete state-space. We exploit the model within the context of our optimization to compute user-action-driven coding strategies that aim at enhancing the client's performance in terms of latency and video quality. Our optimization outperforms the state-of-the-art H.264 SVC codec as well as a multi-view wavelet-based coder equipped with a uniform rate allocation strategy, across all scenarios studied in our experiments. Equally important, we can achieve an arbitrarily fine granularity of encoding bit rates, while providing a novel functionality of view embedded encoding, unlike the other encoding methods that we examined. Finally, we observe that the interactivity-aware coding delivers superior performance over conventional allocation techniques that do not anticipate the client's view selection actions in their operation.

  11. Actions of motor neurons and leg muscles in jumping by planthopper insects (hemiptera, issidae).

    PubMed

    Burrows, Malcolm; Bräunig, Peter

    2010-04-15

    To understand the catapult mechanism that propels jumping in a planthopper insect, the innervation and action of key muscles were analyzed. The large trochanteral depressor muscle, M133b,c, is innervated by two motor neurons and by two dorsal unpaired median (DUM) neurons, all with axons in N3C. A smaller depressor muscle, M133a, is innervated by two neurons, one with a large-diameter cell body, a large, blind-ending dendrite, and a giant ovoid, axon measuring 50 microm by 30 microm in nerve N5A. The trochanteral levator muscles (M132) and (M131) are innervated by N4 and N3B, respectively. The actions of these muscles in a restrained jump were divisible into a three-phase pattern. First, both hind legs were moved into a cocked position by high-frequency bursts of spikes in the levator muscles lasting about 0.5 seconds. Second, and once both legs were cocked, M133b,c received a long continuous sequence of motor spikes, but the two levators spiked only sporadically. The spikes in the two motor neurons to M133b,c on one side were closely coupled to each other and to the spikes on the other side. If one hind leg was cocked then the spikes only occurred in motor neurons to that side. The final phase was the jump movement itself, which occurred when the depressor spikes ceased and which lasted 1 ms. Muscles 133b,c activated synchronously on both sides, are responsible for generating the power, and M133a and its giant neuron may play a role in triggering the release of a jump.

  12. Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

    PubMed Central

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

  13. Computational and Electronic Analog Implementation of the Hodgkin-Huxley Model of Action Potentials in Neurons

    NASA Astrophysics Data System (ADS)

    Smith, Peter; Link, Justin

    2012-02-01

    Alan Loyd Hodgkin and Andrew Huxley's mathematical model of action potential initiation and propagation in neurons is one of the greatest hallmarks of biophysics. Two techniques for implementing the Hodgkin-Huxley model were explored: computational and electronic analog. Computational modeling was done using NEURON 7.1. NEURON is a free, robust, and relatively user friendly simulation environment that enables quantitatively accurate computational modeling of neurons and neural networks. An analog electronic circuit was built using field-effect transistors (FETs) to simulate the non-linear, voltage-dependent (sodium and potassium) conductances that are responsible for membrane excitability. While the electronic analog qualitatively reproduces many of the key features of the action potential including overall shape, inactivation period, and propagation, it was difficult to quantitatively reproduce the Hodgkin-Huxley model. In addition, while the relative cost to build circuits equivalent to small membrane patches is minimal (˜50), implementation of larger cells or networks would prove uneconomical. Still, both techniques are viable avenues toward introducing interdisciplinary research into either a computational or electronics lab setting at the undergraduate level.

  14. Actions of neuropoietic cytokines and cyclic AMP in regenerative conditioning of rat primary sensory neurons.

    PubMed

    Wu, Dongsheng; Zhang, Yi; Bo, Xuenong; Huang, Wenlong; Xiao, Fang; Zhang, Xinyu; Miao, Tizong; Magoulas, Charalambos; Subang, Maria C; Richardson, Peter M

    2007-03-01

    A conditioning lesion to peripheral axons of primary sensory neurons accelerates regeneration of their central axons in vivo or neurite outgrowth if the neurons are grown in vitro. Previous evidence has implicated neuropoietic cytokines and also cyclic AMP in regenerative conditioning. In experiments reported here, delivery through a lentivirus vector of ciliary neurotrophic factor to the appropriate dorsal root ganglion in rats was sufficient to mimic the conditioning effect of peripheral nerve injury on the regeneration of dorsal spinal nerve root axons. Regeneration in this experimental preparation was also stimulated by intraganglionic injection of dibutyryl cyclic AMP but the effects of ciliary neurotrophic factor and dibutyryl cyclic AMP were not additive. Dibutyryl cyclic AMP injection into the dorsal root ganglion induced mRNAs for two other neuropoietic cytokines, interleukin-6 and leukemia inhibitory factor and increased the accumulation of phosphorylated STAT3 in neuronal nuclei. The in vitro conditioning action of dibutyryl cyclic AMP was partially blocked by a pharmacological inhibitor of Janus kinase 2, a neuropoietic cytokine signaling molecule. We suggest that the beneficial actions of increased cyclic AMP activity on axonal regeneration of primary sensory neurons are mediated, at least in part, through the induction of neuropoietic cytokine synthesis within the dorsal root ganglion.

  15. T-type calcium channels consolidate tonic action potential output of thalamic neurons to neocortex.

    PubMed

    Deleuze, Charlotte; David, François; Béhuret, Sébastien; Sadoc, Gérard; Shin, Hee-Sup; Uebele, Victor N; Renger, John J; Lambert, Régis C; Leresche, Nathalie; Bal, Thierry

    2012-08-29

    The thalamic output during different behavioral states is strictly controlled by the firing modes of thalamocortical neurons. During sleep, their hyperpolarized membrane potential allows activation of the T-type calcium channels, promoting rhythmic high-frequency burst firing that reduces sensory information transfer. In contrast, in the waking state thalamic neurons mostly exhibit action potentials at low frequency (i.e., tonic firing), enabling the reliable transfer of incoming sensory inputs to cortex. Because of their nearly complete inactivation at the depolarized potentials that are experienced during the wake state, T-channels are not believed to modulate tonic action potential discharges. Here, we demonstrate using mice brain slices that activation of T-channels in thalamocortical neurons maintained in the depolarized/wake-like state is critical for the reliable expression of tonic firing, securing their excitability over changes in membrane potential that occur in the depolarized state. Our results establish a novel mechanism for the integration of sensory information by thalamocortical neurons and point to an unexpected role for T-channels in the early stage of information processing.

  16. Effects of some heavy metals on the action potentials of an identified Helix pomatia photosensitive neuron.

    PubMed

    Kartelija, Gordana; Radenović, Lidija; Todorović, Natasa; Nedeljković, Miodrag

    2005-06-01

    In the photosensitive MB neuron in the left parietal ganglion of Helix pomatia, the onset of light prolongs significantly (by about 40%) the duration of the action potential. The broadening of the action potential after the onset of light was found to be due to its calcium component and could not be induced after blocking Ca(2+) channels by Cd(2+) and Pb(2+) and in absence of Ca(2+) in medium. The blocking effect of both compounds was reversible. It was found that CdCl(2) exhibited a more intense blocking effect than PbCl(2).

  17. Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

    PubMed

    Lu, Siyuan; Madhukar, Anupam

    2013-02-01

    Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Emotional Actions Are Coded via Two Mechanisms: With and without Identity Representation

    PubMed Central

    Wincenciak, Joanna; Ingham, Jennie; Jellema, Tjeerd; Barraclough, Nick E.

    2016-01-01

    Accurate perception of an individual's identity and emotion derived from their actions and behavior is essential for successful social functioning. Here we determined the role of identity in the representation of emotional whole-body actions using visual adaptation paradigms. Participants adapted to actors performing different whole-body actions in a happy and sad fashion. Following adaptation subsequent neutral actions appeared to convey the opposite emotion. We demonstrate two different emotional action aftereffects showing distinctive adaptation characteristics. For one short-lived aftereffect, adaptation to the emotion expressed by an individual resulted in biases in the perception of the expression of emotion by other individuals, indicating an identity-independent representation of emotional actions. A second, longer lasting, aftereffect was observed where adaptation to the emotion expressed by an individual resulted in longer-term biases in the perception of the expressions of emotion only by the same individual; this indicated an additional identity-dependent representation of emotional actions. Together, the presence of these two aftereffects indicates the existence of two mechanisms for coding emotional actions, only one of which takes into account the actor's identity. The results that we observe might parallel processing of emotion from face and voice. PMID:27242606

  19. Emotional Actions Are Coded via Two Mechanisms: With and without Identity Representation.

    PubMed

    Wincenciak, Joanna; Ingham, Jennie; Jellema, Tjeerd; Barraclough, Nick E

    2016-01-01

    Accurate perception of an individual's identity and emotion derived from their actions and behavior is essential for successful social functioning. Here we determined the role of identity in the representation of emotional whole-body actions using visual adaptation paradigms. Participants adapted to actors performing different whole-body actions in a happy and sad fashion. Following adaptation subsequent neutral actions appeared to convey the opposite emotion. We demonstrate two different emotional action aftereffects showing distinctive adaptation characteristics. For one short-lived aftereffect, adaptation to the emotion expressed by an individual resulted in biases in the perception of the expression of emotion by other individuals, indicating an identity-independent representation of emotional actions. A second, longer lasting, aftereffect was observed where adaptation to the emotion expressed by an individual resulted in longer-term biases in the perception of the expressions of emotion only by the same individual; this indicated an additional identity-dependent representation of emotional actions. Together, the presence of these two aftereffects indicates the existence of two mechanisms for coding emotional actions, only one of which takes into account the actor's identity. The results that we observe might parallel processing of emotion from face and voice.

  20. Sensitivity of Locus Ceruleus Neurons to Reward Value for Goal-Directed Actions

    PubMed Central

    Richmond, Barry J.

    2015-01-01

    The noradrenergic nucleus locus ceruleus (LC) is associated classically with arousal and attention. Recent data suggest that it might also play a role in motivation. To study how LC neuronal responses are related to motivational intensity, we recorded 121 single neurons from two monkeys while reward size (one, two, or four drops) and the manner of obtaining reward (passive vs active) were both manipulated. The monkeys received reward under three conditions: (1) releasing a bar when a visual target changed color; (2) passively holding a bar; or (3) touching and releasing a bar. In the first two conditions, a visual cue indicated the size of the upcoming reward, and, in the third, the reward was constant through each block of 25 trials. Performance levels and lipping intensity (an appetitive behavior) both showed that the monkeys' motivation in the task was related to the predicted reward size. In conditions 1 and 2, LC neurons were activated phasically in relation to cue onset, and this activation strengthened with increasing expected reward size. In conditions 1 and 3, LC neurons were activated before the bar-release action, and the activation weakened with increasing expected reward size but only in task 1. These effects evolved as monkeys progressed through behavioral sessions, because increasing fatigue and satiety presumably progressively decreased the value of the upcoming reward. These data indicate that LC neurons integrate motivationally relevant information: both external cues and internal drives. The LC might provide the impetus to act when the predicted outcome value is low. PMID:25740528

  1. Ionic differences between somatic and axonal action potentials in snail giant neurones

    PubMed Central

    Wald, Flora

    1972-01-01

    1. The ionic requirements of the somatic and axonal action potentials of `H' neurones of the snail Cryptomphallus aspersa were studied using intracellular micro-electrodes. 2. The overshoot of the somatic action potential increased by 10 mV for a tenfold increase in [Ca2+]o. In calcium-free media the action potential decreased gradually to values of 50 to 90% of the control and they could be completely eliminated with 2 mM-EGTA. The maximum rate of rise also varied with [Ca2+]o. 3. After 2 hr in sodium-free solution the somatic action potential decreased 6% in overshoot and 24% in rate of rise. 4. The somatic action potential was not affected by TTX, 5 × 10-6 g/ml. Procaine, 18 mM, reduced its rate of rise but did not eliminate it whereas 30 mM-CoCl2 did. 5. The size of the axonal action potential increased with increased [Na+]o, but decreased with an increase in [Ca2+]o. 6. Procaine, 18 mM, abolished the axonal action potential whereas it was not affected by TTX, 5 × 10-6 g/ml., nor, usually, by 30 mM-CoCl2. 7. The results obtained by studying the compound action potential of the nerves were similar to those from axonal action potentials. 8. The possibility that the somatic action potential is mainly calcium dependent while the axonal action potential is mainly produced by sodium is discussed. PMID:5014099

  2. Frequency-dependent action potential prolongation in Aplysia pleural sensory neurones.

    PubMed

    Edstrom, J P; Lukowiak, K D

    1985-10-01

    The effects of repetitive activity on action-potential shape in Aplysia californica pleural sensory cells are described. Action potentials were evoked by intracellular current injection at frequencies between 7.41 and 0.2 Hz. In contrast to other molluscan neurons having brief action potentials, it was found that at these firing rates the normally brief action potential develops a prominent shoulder or plateau during the repolarization phase. Higher stimulus rates broaden the action potential more rapidly and to a greater extent than lower stimulus rates. Inactivation is slow relative to activation; effects of 3-s 6-Hz trains are detectable after 1 min rest. The amplitude of the plateau voltage reaches a maximum of 50-70 mV at the highest stimulus rates tested. Frequency-dependent increases in action-potential duration measured at half-amplitude normally range between 6 and 15 ms. Cadmium, at concentrations between 0.05 and 0.5 mM, antagonizes frequency-dependent broadening. The increases in duration induced by repetitive activity are more sensitive to cadmium than are the increases in plateau amplitude. Tetraethylammonium, at concentrations between 0.5 and 10 mM, slightly increases the duration and amplitude of single action potentials. During repetitive activity at high stimulus rates the maximum duration and rate of broadening are both increased but the amplitude of the plateau potential is not affected by these tetraethylammonium concentrations. Above 10 mM, tetraethylammonium greatly increases the duration and amplitude of single action potentials as well as the rates of action-potential duration and amplitude increase during repetitive activity. These high tetraethylammonium concentrations also cause the normally smoothly increasing duration and amplitude to reach a maximum value early in a train and then decline slowly during the remainder of the train. The consequences of frequency-dependent spike broadening in these neurons have not yet been investigated

  3. Layer I neurons of rat neocortex. I. Action potential and repetitive firing properties.

    PubMed

    Zhou, F M; Hablitz, J J

    1996-08-01

    1. Whole cell patch-clamp techniques, combined with direct visualization of neurons, were used to study action potential (AP) and repetitive firing properties of layer I neurons in slices of rat neocortex. 2. Layer I neurons had resting membrane potentials (RMP) of -59.8 +/- 4.7 mV (mean +/- SD) and input resistances (RN) of 592 +/- 284 M Omega. Layer II/III pyramidal neurons had RMPs and RNs of -61.5 +/- 5.6 mV and 320 +/- 113 M omega, respectively. A double exponential function was needed to describe the charging curves of both neuron types. In layer I neurons, tau(0) was 45 +/- 22 ms and tau(1) was 5 +/- 3.3 ms whereas in layer II/III pyramidal neurons, tau(0) was 41 +/- 11 ms and tau(1) was 3 +/- 2.6 ms. Estimates of specific membrane resistance (Rm) for layer I and layer II/III cells were 45 +/- 22 and 41 +/- 11 k omega cm2, respectively (Cm was assumed to be 1 microF/cm2). 3. AP threshold was -41 +/- 2 mV in layer I neurons. Spike amplitudes, measured from threshold to peak, were 90.6 +/- 7.7 mV. AP durations, measured both at the base and half maximal amplitude, were 2.5 +/- 0.4 and 1.1 +/- 0.2 ms, respectively. AP 10-90% rise and repolarization times were 0.6 +/- 0.1 and 1.1 +/- 0.2 ms, respectively. In layer II/III pyramidal neurons, AP threshold was -41 +/- 2.5 mV and spike amplitude was 97 +/- 9.7 mV. AP duration at base and half maximal amplitude was 5.4 +/- 1.1 ms and 1.8 +/- 0.2 ms, respectively. AP 10-90% rise and decay times were 0.6 +/- 0.1 ms and 2.8 +/- 0.6 ms, respectively. 4. Layer I neurons were fast spiking cells that showed little frequency adaptation, a large fast afterhyperpolarization (fAHP), and no slow afterhyperpolarization (sAHP). Some cells had a medium afterhyperpolarization (mAHP) and a slow afterdepolarization (sADP). All pyramidal cells in layer II/III and "atypical" pyramidal neurons in upper layer II showed regular spiking behavior, prominent frequency adaptation, and marked sAHPs. 5. In both layer I neurons and layer II

  4. Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord

    PubMed Central

    Ishii, Hideaki; Kohno, Tatsuro; Yamakura, Tomohiro; Ikoma, Miho; Baba, Hiroshi

    2008-01-01

    Dexmedetomidine is a highly specific, potent and selective α2-adrenoceptor agonist. Although intrathecal and epidural administration of dexmedetomidine has been found to produce analgesia, whether this analgesia results from an effect on spinal cord substantia gelatinosa (SG) neurons remains unclear. Here, we investigated the effects of dexmedetomidine on postsynaptic transmission in SG neurons of rat spinal cord slices using the whole-cell patch-clamp technique. In 92% of the SG neurons examined (n= 84), bath-applied dexmedetomidine induced outward currents at −70 mV in a concentration-dependent manner, with the value of effective concentration producing a half-maximal response (0.62 μm). The outward currents induced by dexmedetomidine were suppressed by the α2-adrenoceptor antagonist yohimbine, but not by prazosin, an α1-, α2B- and α2C-adrenoceptor antagonist. Moreover, the dexmedetomidine-induced currents were partially suppressed by the α2C-adrenoceptor antagonist JP-1302, while simultaneous application of JP-1302 and the α2A-adrenoceptor antagonist BRL44408 abolished the current completely. The action of dexmedetomidine was mimicked by the α2A-adrenoceptor agonist oxymetazoline. Plots of the current–voltage relationship revealed a reversal potential at around −86 mV. Dexmedetomidine-induced currents were blocked by the addition of GDP-β-S [guanosine-5′-O-(2-thiodiphosphate)] or Cs+ to the pipette solution. These findings suggest that dexmedetomidine hyperpolarizes the membrane potentials of SG neurons by G-protein-mediated activation of K+ channels through α2A- and α2C-adrenoceptors. This action of dexmedetomidine might contribute, at least in part, to its antinociceptive action in the spinal cord. PMID:18554299

  5. Zinc-dependent action potentials in giant neurons of the snail, Euhadra quaestia.

    PubMed

    Kawa, K

    1979-09-14

    In giant neurons of subesophageal ganglion of the Japanese land snail, Euhadra quaestia Deshayes, permeation of Zn ions through Ca channels were investigated with a conventional current clamp method. All-or-none action potentials of long duration (90 to 120 sec) were evoked in 24 mM Zn containing salines. The overshoots were about +10 mV and the maximum rate of rises (MRRs) was about 2.9 V/sec. The amplitudes and the MRRs of the action potentials depended on external Zn ion concentrations. The action potentials were suppressed by specific Ca-channel inhibitors such as Co2+, La3+ and Verapamil, but they were resistant to Na-channel inhibitor, tetrodotoxin, even at 30 microM. It is concluded that these action potentials are generated by Zn ions permeating Ca channels in snail neuronal membrane. On the basis of Hagiwara and Takahashi's (S. Hagiwara & K. Takahashi, 1967, J. Gen. Physiol. 50:583) model of Ca channels, it is inferred that Zn ions are 5 to 10 times stronger in affinity to Ca channels than Ca ions, but 10 to 20 times less permeable.

  6. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

    PubMed

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

  7. Acetylsalicylic acid-induced changes in the chemical coding of extrinsic sensory neurons supplying the prepyloric area of the porcine stomach.

    PubMed

    Rytel, L; Calka, J

    2016-03-23

    Acetylsalicylic acid is a popular drug that is commonly used to treat fever and inflammation, but which can also negativity affect the mucosal layer of the stomach, although knowledge concerning its influence on gastric innervation is very scarce. Thus, the aim of the present study was to study the influence of prolonged acetylsalicylic acid supplementation on the extrinsic primary sensory neurons supplying the porcine stomach prepyloric region. Fast Blue (FB) was injected into the above-mentioned region of the stomach. Acetylsalicylic acid was then given orally to the experimental gilts from the seventh day after FB injection to the 27th day of the experiment. After euthanasia, the nodose ganglia (NG) and dorsal root ganglia (DRG) were collected. Sections of these ganglia were processed for routine double-labelling immunofluorescence technique for substance P (SP), calcitonine gene related peptide (CGRP), galanin (GAL), neuronal isoform of nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP). Under physiological conditions within the nodose ganglia, the percentage of the FB-labeled neurons immunoreactive to particular substances ranged between 17.9 ± 2.7% (VIP-like immunoreactive (LI) neurons in the right NG) and 60.4 ± 1.7% (SP-LI cells within the left NG). Acetylsalicylic acid supplementation caused a considerable increase in the expression of all active substances studied within both left and right NG and the percentage of neurons positive to particular substances fluctuated from 47.2 ± 3.6% (GAL-LI neurons in the right NG) to 67.2 ± 2.0% (cells immunoreactive to SP in the left NG). All studied substances were also observed in DRG neurons supplying the prepyloric region of the stomach, but the number of immunoreactive neurons was too small to conduct a statistical analysis. The obtained results show that ASA may influence chemical coding of the sensory neurons supplying the porcine stomach, but the exact mechanisms of this action still

  8. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons

    PubMed Central

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C.

    2016-01-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca2+ entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca2+ buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca2+-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca2+ elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377724

  9. 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.

  10. Channelrhodopsin-2-expressed dorsal root ganglion neurons activates calcium channel currents and increases action potential in spinal cord.

    PubMed

    Zhang, Yi; Yue, Jing; Ai, Midan; Ji, Zhigang; Liu, Zhiguo; Cao, Xuehong; Li, Li

    2014-07-01

    We used optogenetic techniques in spinal cord and dorsal root ganglion (DRG) neuron studies. This study investigated changes in channelrhodopsin-2 (ChR2) expression in the spinal cord and DRG neurons using optogenetic techniques. The results show the possibility of using optogenetics to treat neuropathic pain. Previous studies have shown that activated ChR2 induces an increase in DRG neuron action potential. Western blot analysis was used to measure ChR2 protein levels in the spinal cord and DRG neurons or rats intrathecally injected with ChR2 lentivirus. Electrophysiology recording was used to detect differences in action potential levels in the spinal cord and calcium channel currents in the DRG neurons. Our studies showed that ChR2 expression increased the action potential in the spinal cord and increased calcium channel currents in DRG neurons. We successfully expressed the ChR2 protein in the spinal cord and DRG neurons. We also found that ChR2 increased the action potential in the spinal cord and activated the calcium channel in DRG neurons. These findings support the research possibilities of using optogenetic studies to improve treatment for neuropathic pain. N/A.

  11. Activity dependence of action potential duration in rat supraoptic neurosecretory neurones recorded in vitro.

    PubMed

    Bourque, C W; Renaud, L P

    1985-06-01

    Action potential durations, measured at one-third peak amplitude, were examined during intracellular recordings in 134 supraoptic nucleus neurones maintained in vitro in perfused hypothalamic explants. Spike durations ranged between 1.2 and 3.9 ms and were dependent on firing frequency. Shortest measurements (1.74 +/- 0.03 ms; mean +/- S.E. of mean) were obtained during relative quiescence, i.e. less than or equal to 0.5 Hz. A gradual increase in firing frequency through continuous injection of depolarizing current prolonged spike duration, with maximum levels (2.68 +/- 0.05 ms) achieved at 20 Hz. When interspike interval variability was eliminated and firing was more precisely regulated by brief 15-20 ms intracellular current pulses given at pre-determined frequencies, a proportional relationship between increasing spike duration and firing frequency was retained but the change in spike duration at frequencies between 2 and 10 Hz was less pronounced. Once action potentials had achieved the long duration configuration, their return to the shorter duration took place gradually during any succeeding silent interval with a time constant of 4.9 s. Action potential broadening occurred progressively and was most pronounced at the onset of spontaneous or current-induced bursts. In thirty-six phasically active neurones, spike broadening at the onset of a burst was concurrent with the presence of 5-10 consecutive short (less than or equal to 100 ms) interspike intervals; thereafter, despite a greater than 50% reduction in firing frequency, action potential durations remained prolonged throughout the burst. In all of nineteen cells tested, frequency-dependent changes in spike duration were reversibly decreased or blocked by Cd2+, Co2+ and Mn2+, or when CaCl2 was exchanged for equimolar amounts of EGTA in the perfusion medium. These observations indicate that a Ca2+ conductance contributes to frequency- and firing-pattern-dependent changes in spike duration in rat supraoptic

  12. Spike Timing Matters in Novel Neuronal Code Involved in Vibrotactile Frequency Perception.

    PubMed

    Birznieks, Ingvars; Vickery, Richard M

    2017-05-22

    Skin vibrations sensed by tactile receptors contribute significantly to the perception of object properties during tactile exploration [1-4] and to sensorimotor control during object manipulation [5]. Sustained low-frequency skin vibration (<60 Hz) evokes a distinct tactile sensation referred to as flutter whose frequency can be clearly perceived [6]. How afferent spiking activity translates into the perception of frequency is still unknown. Measures based on mean spike rates of neurons in the primary somatosensory cortex are sufficient to explain performance in some frequency discrimination tasks [7-11]; however, there is emerging evidence that stimuli can be distinguished based also on temporal features of neural activity [12, 13]. Our study's advance is to demonstrate that temporal features are fundamental for vibrotactile frequency perception. Pulsatile mechanical stimuli were used to elicit specified temporal spike train patterns in tactile afferents, and subsequently psychophysical methods were employed to characterize human frequency perception. Remarkably, the most salient temporal feature determining vibrotactile frequency was not the underlying periodicity but, rather, the duration of the silent gap between successive bursts of neural activity. This burst gap code for frequency represents a previously unknown form of neural coding in the tactile sensory system, which parallels auditory pitch perception mechanisms based on purely temporal information where longer inter-pulse intervals receive higher perceptual weights than short intervals [14]. Our study also demonstrates that human perception of stimuli can be determined exclusively by temporal features of spike trains independent of the mean spike rate and without contribution from population response factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    PubMed Central

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-01-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz–10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology. PMID:24785307

  14. Alcohol action on a neuronal membrane receptor: evidence for a direct interaction with the receptor protein.

    PubMed Central

    Li, C; Peoples, R W; Weight, F F

    1994-01-01

    For almost a century, alcohols have been thought to produce their effects by actions on the membrane lipids of central nervous system neurons--the well known "lipid theory" of alcohol action. The rationale for this theory is the correlation of potency with oil/water or membrane/buffer partition coefficient. Although a number of recent studies have shown that alcohols can affect the function of certain neuronal neurotransmitter receptors, there is no evidence that the alcohols interact directly with these membrane proteins. In the present study, we report that inhibition of a neuronal neurotransmitter receptor, an ATP-gated ion channel, by a series of alcohols exhibits a distinct cutoff effect. For alcohols with a molecular volume of < or = 42.2 ml/mol, potency for inhibiting ATP-activated current was correlated with lipid solubility (order of potency: 1-propanol = trifluoroethanol > monochloroethanol > ethanol > methanol). However, despite increased lipid solubility, alcohols with a molecular volume of > or = 46.1 ml/mol (1-butanol, 1-pentanol, trichloroethanol, and dichloroethanol) were without effect on the ATP-activated current. The results suggest that alcohols inhibit the function of this neurotransmitter receptor by interacting with a small hydrophobic pocket on the receptor protein. PMID:8058780

  15. Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

    PubMed

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

    2009-12-24

    The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. 2009 Elsevier Inc. All rights reserved.

  16. Depolarising and hyperpolarising actions of GABAA receptor activation on GnRH neurons: towards an emerging consensus

    PubMed Central

    Herbison, Allan E.; Moenter, Suzanne M.

    2011-01-01

    The gonadotropin-releasing hormone (GnRH) neurons represent the final output neurons of a complex neuronal network that controls fertility. It is now appreciated that GABAergic neurons within this network provide an important regulatory influence on GnRH neurons. However, the consequences of direct GABAA receptor activation on adult GnRH neurons have been controversial for nearly a decade now, with both hyperpolarising and depolarising effects reported. This review provides (i) an overview of GABAA receptor function and its investigation using electrophysiological approaches and (ii) re-examines the past and present results relating to GABAergic regulation of the GnRH neuron, with a focus on mouse brain slice data. Although it remains difficult to reconcile the results of the early studies, there is a growing consensus that GABA can act through the GABAA receptor to exert both depolarising and hyperpolarising effects on GnRH neurons. The most recent studies examining the effects of endogenous GABA release on GnRH neurons indicate that the predominant action is that of excitation. However, we are still far from a complete understanding of the effects of GABAA receptor activation upon GnRH neurons. We argue that this will require not only a better understanding of chloride ion homeostasis in individual GnRH neurons, and within subcellular compartments of the GnRH neuron, but also a more integrative view of how multiple neurotransmitters, neuromodulators and intrinsic conductances act together to regulate the activity of these important cells. PMID:21518033

  17. Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates

    PubMed Central

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B.; Niven, Jeremy E.

    2010-01-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na+ and K+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin–Huxley model of the squid axon, optimizing the kinetics or number of Na+ and K+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

  18. Robust temporal coding of contrast by V1 neurons for transient but not for steady-state stimuli.

    PubMed

    Mechler, F; Victor, J D; Purpura, K P; Shapley, R

    1998-08-15

    We show that spike timing adds to the information content of spike trains for transiently presented stimuli but not for comparable steady-state stimuli, even if the latter elicit transient responses. Contrast responses of 22 single neurons in macaque V1 to periodic presentation of steady-state stimuli (drifting sinusoidal gratings) and transient stimuli (drifting edges) of optimal spatiotemporal parameters were recorded extracellularly. The responses were analyzed for contrast-dependent clustering in spaces determined by metrics sensitive to the temporal structure of spike trains. Two types of metrics, cost-based spike time metrics and metrics based on Fourier harmonics of the response, were used. With both families of metrics, temporal coding of contrast is lacking in responses to drifting sinusoidal gratings of most (simple and complex) V1 neurons. However, two-thirds of all neurons, mostly complex cells, displayed significant temporal coding of contrast for edge stimuli. The Fourier metrics indicated that different response harmonics are partially independent, and their combined use increases information about transient stimuli. Our results demonstrate the importance of stimulus transience for temporal coding. This finding is significant for natural vision because moving edges, which are present in moving object boundaries, and saccades induce transients. We think that an abrupt change in the adapted state of the local visual circuitry triggers the temporal structuring of spike trains in V1 neurons.

  19. The tactile motion aftereffect suggests an intensive code for speed in neurons sensitive to both speed and direction of motion

    PubMed Central

    Birznieks, I.; Vickery, R. M.; Holcombe, A. O.; Seizova-Cajic, T.

    2016-01-01

    Neurophysiological studies in primates have found that direction-sensitive neurons in the primary somatosensory cortex (SI) generally increase their response rate with increasing speed of object motion across the skin and show little evidence of speed tuning. We employed psychophysics to determine whether human perception of motion direction could be explained by features of such neurons and whether evidence can be found for a speed-tuned process. After adaptation to motion across the skin, a subsequently presented dynamic test stimulus yields an impression of motion in the opposite direction. We measured the strength of this tactile motion aftereffect (tMAE) induced with different combinations of adapting and test speeds. Distal-to-proximal or proximal-to-distal adapting motion was applied to participants' index fingers using a tactile array, after which participants reported the perceived direction of a bidirectional test stimulus. An intensive code for speed, like that observed in SI neurons, predicts greater adaptation (and a stronger tMAE) the faster the adapting speed, regardless of the test speed. In contrast, speed tuning of direction-sensitive neurons predicts the greatest tMAE when the adapting and test stimuli have matching speeds. We found that the strength of the tMAE increased monotonically with adapting speed, regardless of the test speed, showing no evidence of speed tuning. Our data are consistent with neurophysiological findings that suggest an intensive code for speed along the motion processing pathways comprising neurons sensitive both to speed and direction of motion. PMID:26823511

  20. Slow Cholinergic Modulation of Spike Probability in Ultra-Fast Time-Coding Sensory Neurons

    PubMed Central

    Goyer, David; Kurth, Stefanie; Rübsamen, Rudolf

    2016-01-01

    Abstract Sensory processing in the lower auditory pathway is generally considered to be rigid and thus less subject to modulation than central processing. However, in addition to the powerful bottom-up excitation by auditory nerve fibers, the ventral cochlear nucleus also receives efferent cholinergic innervation from both auditory and nonauditory top–down sources. We thus tested the influence of cholinergic modulation on highly precise time-coding neurons in the cochlear nucleus of the Mongolian gerbil. By combining electrophysiological recordings with pharmacological application in vitro and in vivo, we found 55–72% of spherical bushy cells (SBCs) to be depolarized by carbachol on two time scales, ranging from hundreds of milliseconds to minutes. These effects were mediated by nicotinic and muscarinic acetylcholine receptors, respectively. Pharmacological block of muscarinic receptors hyperpolarized the resting membrane potential, suggesting a novel mechanism of setting the resting membrane potential for SBC. The cholinergic depolarization led to an increase of spike probability in SBCs without compromising the temporal precision of the SBC output in vitro. In vivo, iontophoretic application of carbachol resulted in an increase in spontaneous SBC activity. The inclusion of cholinergic modulation in an SBC model predicted an expansion of the dynamic range of sound responses and increased temporal acuity. Our results thus suggest of a top–down modulatory system mediated by acetylcholine which influences temporally precise information processing in the lower auditory pathway. PMID:27699207

  1. Theta-Gamma Coding Meets Communication-through-Coherence: Neuronal Oscillatory Multiplexing Theories Reconciled.

    PubMed

    McLelland, Douglas; VanRullen, Rufin

    2016-10-01

    Several theories have been advanced to explain how cross-frequency coupling, the interaction of neuronal oscillations at different frequencies, could enable item multiplexing in neural systems. The communication-through-coherence theory proposes that phase-matching of gamma oscillations between areas enables selective processing of a single item at a time, and a later refinement of the theory includes a theta-frequency oscillation that provides a periodic reset of the system. Alternatively, the theta-gamma neural code theory proposes that a sequence of items is processed, one per gamma cycle, and that this sequence is repeated or updated across theta cycles. In short, both theories serve to segregate representations via the temporal domain, but differ on the number of objects concurrently represented. In this study, we set out to test whether each of these theories is actually physiologically plausible, by implementing them within a single model inspired by physiological data. Using a spiking network model of visual processing, we show that each of these theories is physiologically plausible and computationally useful. Both theories were implemented within a single network architecture, with two areas connected in a feedforward manner, and gamma oscillations generated by feedback inhibition within areas. Simply increasing the amplitude of global inhibition in the lower area, equivalent to an increase in the spatial scope of the gamma oscillation, yielded a switch from one mode to the other. Thus, these different processing modes may co-exist in the brain, enabling dynamic switching between exploratory and selective modes of attention.

  2. Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe.

    PubMed

    Jin, Lei; Han, Zhou; Platisa, Jelena; Wooltorton, Julian R A; Cohen, Lawrence B; Pieribone, Vincent A

    2012-09-06

    Monitoring neuronal electrical activity using fluorescent protein-based voltage sensors has been limited by small response magnitudes and slow kinetics of existing probes. Here we report the development of a fluorescent protein voltage sensor, named ArcLight, and derivative probes that exhibit large changes in fluorescence intensity in response to voltage changes. ArcLight consists of the voltage-sensing domain of Ciona intestinalis voltage-sensitive phosphatase and super ecliptic pHluorin that carries the point mutation A227D. The fluorescence intensity of ArcLight A242 decreases by 35% in response to a 100 mV depolarization when measured in HEK293 cells, which is more than five times larger than the signals from previously reported fluorescent protein voltage sensors. We show that the combination of signal size and response speed of these new probes allows the reliable detection of single action potentials and excitatory potentials in individual neurons and dendrites.

  3. Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron.

    PubMed

    Lin, Pei-Lin; Tsai, Ming-Cheng; Lu, Guan-Ling; Lu, Dah-Yuu; Chuang, Chieh-Min; Yang, Han-Yin; Huang, Shiang-Suo; Chen, Yi-Hung

    2010-01-01

    This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol

  4. An excitatory action of iontophoretically administered lithium on mammalian central neurones.

    PubMed Central

    Haas, H L; Ryall, R W

    1977-01-01

    1 The action of iontophoretically administered lithium was studied on spinal Renshaw cells an interneurones and on supraspinal neurones in cerebral cortex, thalamus, hypothalamus and brain stem in anaesthetized cats and rats. 2 There was a correlation between the effects of Li+ and those of acetylcholine (ACh), although rather more cells were unaffected by Li+ than by ACh. 3 The usual effect was an excitation of rather slow onset, but occasionally effects were produced with time courses similar to those of ACh. The excitation was blocked by ACh antagonists and was best demonstrated with dihydro-beta-erythroidine on Renshaw cells. 4 The postsynaptic excitant action of ACh on Renshaw cells was reduced by Li+. 5 Depressant actions of Li+ were encountered on cells also depressed by ACh. 6 It is concluded that Li+ may facilitate cholinergic transmission at some sites in the CNS by increasing the release of ACh by an unknown mechanism. Similar effects at non-cholinergic synapses might also occur but would appear to be of less importance. Since facilitation of neuronal firing with Li+ was usually observed, the depressant effects on postsynaptic responses to ACh may be of little consequence. PMID:880430

  5. Autocrine action of BDNF on dendrite development of adult-born hippocampal neurons.

    PubMed

    Wang, Liang; Chang, Xingya; She, Liang; Xu, Duo; Huang, Wei; Poo, Mu-ming

    2015-06-03

    Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor.

  6. Optimal size of stochastic Hodgkin-Huxley neuronal systems for maximal energy efficiency in coding pulse signals.

    PubMed

    Yu, Lianchun; Liu, Liwei

    2014-03-01

    The generation and conduction of action potentials (APs) represents a fundamental means of communication in the nervous system and is a metabolically expensive process. In this paper, we investigate the energy efficiency of neural systems in transferring pulse signals with APs. By analytically solving a bistable neuron model that mimics the AP generation with a particle crossing the barrier of a double well, we find the optimal number of ion channels that maximizes the energy efficiency of a neuron. We also investigate the energy efficiency of a neuron population in which the input pulse signals are represented with synchronized spikes and read out with a downstream coincidence detector neuron. We find an optimal number of neurons in neuron population, as well as the number of ion channels in each neuron that maximizes the energy efficiency. The energy efficiency also depends on the characters of the input signals, e.g., the pulse strength and the interpulse intervals. These results are confirmed by computer simulation of the stochastic Hodgkin-Huxley model with a detailed description of the ion channel random gating. We argue that the tradeoff between signal transmission reliability and energy cost may influence the size of the neural systems when energy use is constrained.

  7. Optimal size of stochastic Hodgkin-Huxley neuronal systems for maximal energy efficiency in coding pulse signals

    NASA Astrophysics Data System (ADS)

    Yu, Lianchun; Liu, Liwei

    2014-03-01

    The generation and conduction of action potentials (APs) represents a fundamental means of communication in the nervous system and is a metabolically expensive process. In this paper, we investigate the energy efficiency of neural systems in transferring pulse signals with APs. By analytically solving a bistable neuron model that mimics the AP generation with a particle crossing the barrier of a double well, we find the optimal number of ion channels that maximizes the energy efficiency of a neuron. We also investigate the energy efficiency of a neuron population in which the input pulse signals are represented with synchronized spikes and read out with a downstream coincidence detector neuron. We find an optimal number of neurons in neuron population, as well as the number of ion channels in each neuron that maximizes the energy efficiency. The energy efficiency also depends on the characters of the input signals, e.g., the pulse strength and the interpulse intervals. These results are confirmed by computer simulation of the stochastic Hodgkin-Huxley model with a detailed description of the ion channel random gating. We argue that the tradeoff between signal transmission reliability and energy cost may influence the size of the neural systems when energy use is constrained.

  8. Botulinum toxin type A-induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder.

    PubMed

    Bossowska, A; Majewski, M

    2012-01-01

    Botulinum toxin type A (BTX) is a potent neurotoxin, which in recent years has been effectively applied in experimental treatments of many neurogenic disorders of the urinary bladder. BTX is a selective, presynaptically-acting blocking agent of acetylcholine release from nerve terminals what, in turn, leads to the cessation of somatic motor and/or parasympathetic transmission. However, application of this toxin in urological practice is still in the developmental stages and the full mechanism of its action remain elusive. Thus, the present study was aimed at investigating the neurochemical characterization of dorsal root ganglion (DRG) neurons supplying the porcine urinary bladder after BTX treatment. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall in six juvenile female pigs and three weeks later, intramural bladder injections of BTX (100 IU per animal) were carried out in all the animals. After a week, DRG from L1 to Cql were harvested from the pigs and neurochemical characterization of FB+ neurons was performed using double- labeling immunofluorescence technique on 10-microm-thick cryostat sections. BTX injections led to a significant decrease in the number of FB+ neurons containing substance P (SP), calcitonin gene-related peptide (CGRP), calbindin (CB), somatostatin (SOM) and neuronal nitric oxide synthase (nNOS) when compared with that found in the healthy animals (19% vs. 45%, 18% vs. 36%, 0.6% vs. 3%, 0.4 vs. 4% and 0.1% vs. 6%, respectively) These data demonstrated that BTX changed the chemical coding of bladder sensory neurons, and therefore this drug should be taken into consideration when it planning experimental therapy of selected neurogenic bladder disorders.

  9. Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles

    PubMed Central

    Tucker, Kristal R.; Block, Ethan R.; Levitan, Edwin S.

    2015-01-01

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H+-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca2+-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP+), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H+ countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs. PMID:26216995

  10. Adult-like action potential properties and abundant GABAergic synaptic responses in amygdala neurons from newborn marmosets

    PubMed Central

    Yamada, Daisuke; Miyajima, Moeko; Ishibashi, Hidetoshi; Wada, Keiji; Seki, Kazuhiko; Sekiguchi, Masayuki

    2012-01-01

    The amygdala plays an important role in the processing of emotional events. This information processing is altered by development, but little is known about the development of electrophysiological properties of neurons in the amygdala. We studied the postnatal development of electrophysiological properties of neurons in the basolateral amygdala (BLA) of the common marmoset (Callithrix jacchus). Whole-cell patch-clamp recordings were obtained from BLA pyramidal neurons in brain slices prepared from developing and adult marmosets, and electrophysiological properties known to change during development in rats were analysed. Two passive electrical properties of the neuronal membrane – the input resistance (Rin) and the membrane time constant (τ) – significantly decreased with postnatal development. In contrast, the action potential only showed a slight decrease in duration during the first month of life, whereas the amplitude did not change after birth. Passive electrical properties and action potentials in neurons of 4-week-old marmosets were similar to those in neurons of 4-year-old marmosets. The development of the action potential duration was not correlated with the development of Rin or τ, whereas the development of Rin and τ was correlated with each other. Abundant spontaneous and noradrenaline-induced GABAergic currents were present immediately after birth and did not change during postnatal development. These results suggest that newborn infant marmoset BLA pyramidal neurons possess relatively mature action potentials and receive vigorous GABAergic synaptic inputs, and that they acquire adult-like electrophysiological properties by the fourth week of life. PMID:22966158

  11. Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

    PubMed

    Magou, George C; Pfister, Bryan J; Berlin, Joshua R

    2015-10-22

    The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

  12. One’s motor performance predictably modulates the understanding of others’ actions through adaptation of premotor visuo-motor neurons

    PubMed Central

    Barchiesi, Guido; Tabarelli, Davide; Arfeller, Carola; Sato, Marc; Glenberg, Arthur M.

    2011-01-01

    Neurons firing both during self and other’s motor behavior (mirror neurons) have been described in the brain of vertebrates including humans. The activation of somatic motor programs driven by perceived behavior has been taken as evidence for mirror neurons’ contribution to cognition. The inverse relation, that is the influence of motor behavior on perception, is needed for demonstrating the long-hypothesized causal role of mirror neurons in action understanding. We provide here conclusive behavioral and neurophysiological evidence for that causal role by means of cross-modal adaptation coupled with a novel transcranial magnetic stimulation (TMS)-adaptation paradigm. Blindfolded repeated motor performance of an object-directed action (push or pull) induced in healthy participants a strong visual after-effect when categorizing others’ actions, as a result of motor-to-visual adaptation of visuo-motor neurons. TMS over the ventral premotor cortex, but not over the primary motor cortex, suppressed the after-effect, thus localizing the population of adapted visuo-motor neurons in the premotor cortex. These data are exquisitely consistent in humans with the existence of premotor mirror neurons that have access to the action meaning. We also show that controlled manipulation of the firing properties of this neural population produces strong predictable changes in the way we categorize others’ actions. PMID:21186167

  13. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    PubMed

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  14. Do monkey F5 mirror neurons show changes in firing rate during repeated observation of natural actions?

    PubMed

    Kilner, J M; Kraskov, A; Lemon, R N

    2014-03-01

    Mirror neurons were first discovered in area F5 of macaque monkeys. In humans, noninvasive studies have demonstrated an increased blood oxygen level-dependent (BOLD) signal in homologous motor areas during action observation. One approach to demonstrating that this indicates the existence of mirror neurons in humans has been to employ functional (f)MRI adaptation to test whether the same population of neurons is active during both observation and execution conditions. Although a number of human studies have reported fMRI adaptation in these areas, a recent study has shown that macaque mirror neurons do not attenuate their firing rate with two repetitions. Here we investigated whether mirror neurons modulate their firing rate when monkeys observed the same repeated natural action multiple times. We recorded from 67 mirror neurons in area F5 of two macaque monkeys while they observed an experimenter perform a reach-to-grasp action on a small food reward using a precision grip. Although no changes were detectable for the first two repetitions, we show that both the firing rate and the latency at which mirror neurons discharged during observation were subtly modulated by the repetition of the observed action over 7-10 trials. Significant adaption was mostly found in the period immediately before the grasp was performed. We also found that the local field potential activity in F5 (beta-frequency range, 16-23 Hz), which is attenuated during action observation, also showed systematic changes with repeated observation. These LFP changes occurred well in advance of the mirror neuron adaptation. We conclude that macaque mirror neurons can show intra-modal adaptation, but whether this is related to fMRI adaptation of the BOLD signal requires further investigation.

  15. Do monkey F5 mirror neurons show changes in firing rate during repeated observation of natural actions?

    PubMed Central

    Kraskov, A.; Lemon, R. N.

    2013-01-01

    Mirror neurons were first discovered in area F5 of macaque monkeys. In humans, noninvasive studies have demonstrated an increased blood oxygen level-dependent (BOLD) signal in homologous motor areas during action observation. One approach to demonstrating that this indicates the existence of mirror neurons in humans has been to employ functional (f)MRI adaptation to test whether the same population of neurons is active during both observation and execution conditions. Although a number of human studies have reported fMRI adaptation in these areas, a recent study has shown that macaque mirror neurons do not attenuate their firing rate with two repetitions. Here we investigated whether mirror neurons modulate their firing rate when monkeys observed the same repeated natural action multiple times. We recorded from 67 mirror neurons in area F5 of two macaque monkeys while they observed an experimenter perform a reach-to-grasp action on a small food reward using a precision grip. Although no changes were detectable for the first two repetitions, we show that both the firing rate and the latency at which mirror neurons discharged during observation were subtly modulated by the repetition of the observed action over 7–10 trials. Significant adaption was mostly found in the period immediately before the grasp was performed. We also found that the local field potential activity in F5 (beta-frequency range, 16–23 Hz), which is attenuated during action observation, also showed systematic changes with repeated observation. These LFP changes occurred well in advance of the mirror neuron adaptation. We conclude that macaque mirror neurons can show intra-modal adaptation, but whether this is related to fMRI adaptation of the BOLD signal requires further investigation. PMID:24371289

  16. Learning to Select Actions with Spiking Neurons in the Basal Ganglia

    PubMed Central

    Stewart, Terrence C.; Bekolay, Trevor; Eliasmith, Chris

    2012-01-01

    We expand our existing spiking neuron model of decision making in the cortex and basal ganglia to include local learning on the synaptic connections between the cortex and striatum, modulated by a dopaminergic reward signal. We then compare this model to animal data in the bandit task, which is used to test rodent learning in conditions involving forced choice under rewards. Our results indicate a good match in terms of both behavioral learning results and spike patterns in the ventral striatum. The model successfully generalizes to learning the utilities of multiple actions, and can learn to choose different actions in different states. The purpose of our model is to provide both high-level behavioral predictions and low-level spike timing predictions while respecting known neurophysiology and neuroanatomy. PMID:22319465

  17. Modeling the attenuation and failure of action potentials in the dendrites of hippocampal neurons.

    PubMed Central

    Migliore, M

    1996-01-01

    We modeled two different mechanisms, a shunting conductance and a slow sodium inactivation, to test whether they could modulate the active propagation of a train of action potentials in a dendritic tree. Computer simulations, using a compartmental model of a pyramidal neuron, suggest that each of these two mechanisms could account for the activity-dependent attenuation and failure of the action potentials in the dendrites during the train. Each mechanism is shown to be in good qualitative agreement with experimental findings on somatic or dendritic stimulation and on the effects of hyperpolarization. The conditions under which branch point failures can be observed, and a few experimentally testable predictions, are presented and discussed. PMID:8913580

  18. Actions of endomorphins on synaptic transmission of Adelta-fibers in spinal cord dorsal horn neurons.

    PubMed

    Yajiri, Y; Huang, L Y

    2000-01-01

    The effects of endogenous mu-opioid ligands, endomorphins, on Adelta-afferent-evoked excitatory postsynaptic currents (EPSCs) were studied in substantia gelatinosa neurons in spinal cord slices. Under voltage-clamp conditions, endomorphins blocked the evoked EPSCs in a dose-dependent manner. To determine if the block resulted from changes in transmitter release from glutamatergic synaptic terminals, the opioid actions on miniature excitatory postsynaptic currents (mEPSCs) were examined. Endomorphins (1 microM) reduced the frequency but not the amplitude of mEPSCs, suggesting that endomorphins directly act on presynaptic terminals. The effects of endomorphins on the unitary (quantal) properties of the evoked EPSCs were also studied. Endomorphins reduced unitary content without significantly changing unitary amplitude. These results suggest that in addition to presynaptic actions on interneurons, endomorphins also inhibit evoked EPSCs by reducing transmitter release from Adelta-afferent terminals.

  19. Plasticity and response to action observation: a longitudinal FMRI study of potential mirror neurons in patients with subacute stroke.

    PubMed

    Brunner, Iris C; Skouen, Jan Sture; Ersland, Lars; Grüner, Renate

    2014-01-01

    Action observation has been suggested as a possible gateway to retraining arm motor function post stroke. However, it is unclear if the neuronal response to action observation is affected by stroke and if it changes during the course of recovery. To examine longitudinal changes in neuronal activity in a group of patients with subacute stroke when observing and executing a bimanual movement task. Eighteen patients were examined twice using 3-T functional magnetic resonance imaging; 1 to 2 weeks and 3 months post stroke symptom onset. Eighteen control participants were examined once. Image time series were analyzed (SPM8) and correlated with clinical motor function scores. During action observation and execution, an overlap of neuronal activation was observed in the superior and inferior parietal lobe, precentral gyrus, insula, and inferior temporal gyrus in both control participants and patients (P < .05; false discovery rate corrected). The neuronal response in the observation task increased from 1 to 2 weeks to 3 months after stroke. Most activated clusters were observed in the inferior temporal gyrus, the thalamus and movement-related areas, such as the premotor, supplementary and motor cortex (BA4, BA6). Increased activation of cerebellum and premotor area correlated with improved arm motor function. Most patients had regained full movement ability. Plastic changes in neurons responding to action observation and action execution occurred in accordance with clinical recovery. The involvement of motor areas when observing actions early and later after stroke may constitute a possible access to the motor system. © The Author(s) 2014.

  20. Theta-Gamma Coding Meets Communication-through-Coherence: Neuronal Oscillatory Multiplexing Theories Reconciled

    PubMed Central

    VanRullen, Rufin

    2016-01-01

    Several theories have been advanced to explain how cross-frequency coupling, the interaction of neuronal oscillations at different frequencies, could enable item multiplexing in neural systems. The communication-through-coherence theory proposes that phase-matching of gamma oscillations between areas enables selective processing of a single item at a time, and a later refinement of the theory includes a theta-frequency oscillation that provides a periodic reset of the system. Alternatively, the theta-gamma neural code theory proposes that a sequence of items is processed, one per gamma cycle, and that this sequence is repeated or updated across theta cycles. In short, both theories serve to segregate representations via the temporal domain, but differ on the number of objects concurrently represented. In this study, we set out to test whether each of these theories is actually physiologically plausible, by implementing them within a single model inspired by physiological data. Using a spiking network model of visual processing, we show that each of these theories is physiologically plausible and computationally useful. Both theories were implemented within a single network architecture, with two areas connected in a feedforward manner, and gamma oscillations generated by feedback inhibition within areas. Simply increasing the amplitude of global inhibition in the lower area, equivalent to an increase in the spatial scope of the gamma oscillation, yielded a switch from one mode to the other. Thus, these different processing modes may co-exist in the brain, enabling dynamic switching between exploratory and selective modes of attention. PMID:27741229

  1. Corticospinal Neurons in Macaque Ventral Premotor Cortex with Mirror Properties: A Potential Mechanism for Action Suppression?

    PubMed Central

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M.; Shepherd, Samantha; Lemon, Roger N.

    2009-01-01

    Summary The discovery of “mirror neurons” in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited “mirror-like” activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. PMID:20064397

  2. Sensitivity of the human mirror neuron system for abstract traces of actions: An EEG-study.

    PubMed

    Hoenen, Matthias; Lübke, Katrin T; Pause, Bettina M

    2017-03-01

    Theories of neuroaesthetics assume, that looking at traces of actions used in creating artwork (e.g. brush marks) is associated with a simulation of these actions in the observer's sensorimotor-cortex. The aim of the current study is to dissociate the activation of the sensorimotor-cortex by the observation of action traces from associated visual processes. Twenty-eight participants observed handmade graphics (acrylic paint on paper) of different complexity (line, triangle, shape of a house) and computer-generated counterparts. Central mu-activity, as an index of sensorimotor-cortex activity, and occipital alpha-activity, as an index of visual cortex activity were recorded in the 8-13Hz EEG-band. In line with the hypothesis, mu-activity at electrode C4 is sensitive for the complexity of handmade (p=0.001), but not computer-generated graphics (p>0.500). In contrast, occipital alpha-activity is sensitive for the complexity of both handmade and computer-generated graphics (p<0.001). Furthermore, the more empathic the participants rated themselves, the stronger mu-suppression was induced by handmade graphics compared to computer-generated graphics (electrode C4; r=-0.612, p=0.001). These results support the involvement of the sensorimotor-cortex in the recognition of action traces and strengthen evidence that individuals scoring high in emotional empathy feature a particularly responsive mirror neuron system. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Modulation of action potential and calcium signaling by levetiracetam in rat sensory neurons.

    PubMed

    Ozcan, Mete; Ayar, Ahmet

    2012-06-01

    Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca(2+)](i). This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.

  4. Divergent Hox Coding and Evasion of Retinoid Signaling Specifies Motor Neurons Innervating Digit Muscles.

    PubMed

    Mendelsohn, Alana I; Dasen, Jeremy S; Jessell, Thomas M

    2017-02-22

    The establishment of spinal motor neuron subclass diversity is achieved through developmental programs that are aligned with the organization of muscle targets in the limb. The evolutionary emergence of digits represents a specialized adaptation of limb morphology, yet it remains unclear how the specification of digit-innervating motor neuron subtypes parallels the elaboration of digits. We show that digit-innervating motor neurons can be defined by selective gene markers and distinguished from other LMC neurons by the expression of a variant Hox gene repertoire and by the failure to express a key enzyme involved in retinoic acid synthesis. This divergent developmental program is sufficient to induce the specification of digit-innervating motor neurons, emphasizing the specialized status of digit control in the evolution of skilled motor behaviors. Our findings suggest that the emergence of digits in the limb is matched by distinct mechanisms for specifying motor neurons that innervate digit muscles.

  5. Neuronal Competition for Action Potential Initiation Sites in a Circuit Controlling Simple Learning

    PubMed Central

    Cruz, Georgina E.; Sahley, Christie L.; Muller, Kenneth J.

    2007-01-01

    The spatial and temporal patterns of action potential initiations were studied in a behaving leech preparation to determine the basis of increased firing that accompanies sensitization, a form of non-associative learning requiring the S-interneurons. Little is known at the network level about mechanisms of behavioral sensitization. The S-interneurons, one in each ganglion and linked by electrical synapses with both neighbors to form a chain, are interposed between sensory and motor neurons. In sensitized preparations the strength of shortening is related to S-cell firing, which itself is the result of impulses initiating in several S-cells. Because the S-cells, as independent initiation sites, all contribute to activity in the chain, it was hypothesized that during sensitization, increased multi-site activity increased the chain's firing rate. However, it was found that during sensitization, the single site with the largest initiation rate, the S-cell in the stimulated segment, suppressed initiations in adjacent ganglia. Experiments showed this was both because (1) it received the earliest, greatest input and (2) the delayed synaptic input to the adjacent S-cells coincided with the action potential refractory period. A compartmental model of the S-cell and its inputs showed that a simple, intrinsic mechanism of inexcitability after each action potential may account for suppression of impulse initiations. Thus, a non-synaptic competition between neurons alters synaptic integration in the chain. In one mode, inputs to different sites sum independently, whereas in another, synaptic input to a single site precisely specifies the overall pattern of activity. PMID:17644266

  6. The tactile motion aftereffect suggests an intensive code for speed in neurons sensitive to both speed and direction of motion.

    PubMed

    McIntyre, S; Birznieks, I; Vickery, R M; Holcombe, A O; Seizova-Cajic, T

    2016-03-01

    Neurophysiological studies in primates have found that direction-sensitive neurons in the primary somatosensory cortex (SI) generally increase their response rate with increasing speed of object motion across the skin and show little evidence of speed tuning. We employed psychophysics to determine whether human perception of motion direction could be explained by features of such neurons and whether evidence can be found for a speed-tuned process. After adaptation to motion across the skin, a subsequently presented dynamic test stimulus yields an impression of motion in the opposite direction. We measured the strength of this tactile motion aftereffect (tMAE) induced with different combinations of adapting and test speeds. Distal-to-proximal or proximal-to-distal adapting motion was applied to participants' index fingers using a tactile array, after which participants reported the perceived direction of a bidirectional test stimulus. An intensive code for speed, like that observed in SI neurons, predicts greater adaptation (and a stronger tMAE) the faster the adapting speed, regardless of the test speed. In contrast, speed tuning of direction-sensitive neurons predicts the greatest tMAE when the adapting and test stimuli have matching speeds. We found that the strength of the tMAE increased monotonically with adapting speed, regardless of the test speed, showing no evidence of speed tuning. Our data are consistent with neurophysiological findings that suggest an intensive code for speed along the motion processing pathways comprising neurons sensitive both to speed and direction of motion. Copyright © 2016 the American Physiological Society.

  7. Neural coding of 3D features of objects for hand action in the parietal cortex of the monkey.

    PubMed Central

    Sakata, H; Taira, M; Kusunoki, M; Murata, A; Tanaka, Y; Tsutsui, K

    1998-01-01

    In our previous studies of hand manipulation task-related neurons, we found many neurons of the parietal association cortex which responded to the sight of three-dimensional (3D) objects. Most of the task-related neurons in the AIP area (the lateral bank of the anterior intraparietal sulcus) were visually responsive and half of them responded to objects for manipulation. Most of these neurons were selective for the 3D features of the objects. More recently, we have found binocular visual neurons in the lateral bank of the caudal intraparietal sulcus (c-IPS area) that preferentially respond to a luminous bar or place at a particular orientation in space. We studied the responses of axis-orientation selective (AOS) neurons and surface-orientation selective (SOS) neurons in this area with stimuli presented on a 3D computer graphics display. The AOS neurons showed a stronger response to elongated stimuli and showed tuning to the orientation of the longitudinal axis. Many of them preferred a tilted stimulus in depth and appeared to be sensitive to orientation disparity and/or width disparity. The SOS neurons showed a stronger response to a flat than to an elongated stimulus and showed tuning to the 3D orientation of the surface. Their responses increased with the width or length of the stimulus. A considerable number of SOS neurons responded to a square in a random dot stereogram and were tuned to orientation in depth, suggesting their sensitivity to the gradient of disparity. We also found several SOS neurons that responded to a square with tilted or slanted contours, suggesting their sensitivity to orientation disparity and/or width disparity. Area c-IPS is likely to send visual signals of the 3D features of an object to area AIP for the visual guidance of hand actions. PMID:9770229

  8. Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice.

    PubMed

    Kim, Young-Cho; Han, Sang-Woo; Alberico, Stephanie L; Ruggiero, Rafael N; De Corte, Benjamin; Chen, Kuan-Hua; Narayanan, Nandakumar S

    2017-01-09

    Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson's disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigated whether these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction. We report three main results. First, both PD patients and mice with ventral tegmental area (VTA) dopamine depletion had attenuated delta activity (1-4 Hz) in the medial frontal cortex (MFC) during interval timing. Second, we found that optogenetically stimulating MFC D1DR neurons could increase ramping activity among MFC neurons. Finally, stimulating MFC D1DR neurons specifically at delta frequencies (2 Hz) compensated for deficits in temporal control of action caused by VTA dopamine depletion. Our results suggest that cortical networks can be targeted by frequency-specific brain stimulation to improve dopamine-dependent cognitive processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Learning of Spatial Relationships between Observed and Imitated Actions allows Invariant Inverse Computation in the Frontal Mirror Neuron System

    PubMed Central

    Oh, Hyuk; Gentili, Rodolphe J.; Reggia, James A.; Contreras-Vidal, José L.

    2014-01-01

    It has been suggested that the human mirror neuron system can facilitate learning by imitation through coupling of observation and action execution. During imitation of observed actions, the functional relationship between and within the inferior frontal cortex, the posterior parietal cortex, and the superior temporal sulcus can be modeled within the internal model framework. The proposed biologically plausible mirror neuron system model extends currently available models by explicitly modeling the intraparietal sulcus and the superior parietal lobule in implementing the function of a frame of reference transformation during imitation. Moreover, the model posits the ventral premotor cortex as performing an inverse computation. The simulations reveal that: i) the transformation system can learn and represent the changes in extrinsic to intrinsic coordinates when an imitator observes a demonstrator; ii) the inverse model of the imitator’s frontal mirror neuron system can be trained to provide the motor plans for the imitated actions. PMID:22255261

  10. Calcium-Activated Chloride Channels (CaCCs) Regulate Action Potential and Synaptic Response in Hippocampal Neurons

    PubMed Central

    Huang, Wendy C.; Xiao, Shaohua; Huang, Fen; Harfe, Brian D.; Jan, Yuh Nung; Jan, Lily Yeh

    2012-01-01

    SUMMARY Central neurons respond to synaptic inputs from other neurons by generating synaptic potentials. Once the summated synaptic potentials reach threshold for action potential firing, the signal propagates leading to transmitter release at the synapse. The calcium influx accompanying such signaling opens calcium-activated ion channels for feedback regulation. Here we report a novel mechanism for modulating hippocampal neuronal signaling that involves calcium-activated chloride channels (CaCCs). We present the first evidence that CaCCs reside in hippocampal neurons and are in close proximity of calcium channels and NMDA receptors to shorten action potential duration, dampen excitatory synaptic potentials, impede temporal summation, and raise the threshold for action potential generation by synaptic potential. Having recently identified TMEM16A and TMEM16B as CaCCs, we further show that TMEM16B but not TMEM16A is important for hippocampal CaCC, laying the groundwork for deciphering the dynamic CaCC modulation of neuronal signaling in neurons important for learning and memory. PMID:22500639

  11. Depolarising and hyperpolarising actions of GABA(A) receptor activation on gonadotrophin-releasing hormone neurones: towards an emerging consensus.

    PubMed

    Herbison, A E; Moenter, S M

    2011-07-01

    The gonadotrophin-releasing hormone (GnRH) neurones represent the final output neurones of a complex neuronal network that controls fertility. It is now appreciated that GABAergic neurones within this network provide an important regulatory influence on GnRH neurones. However, the consequences of direct GABA(A) receptor activation on adult GnRH neurones have been controversial for nearly a decade now, with both hyperpolarising and depolarising effects being reported. This review provides: (i) an overview of GABA(A) receptor function and its investigation using electrophysiological approaches and (ii) re-examines the past and present results relating to GABAergic regulation of the GnRH neurone, with a focus on mouse brain slice data. Although it remains difficult to reconcile the results of the early studies, there is a growing consensus that GABA can act through the GABA(A) receptor to exert both depolarising and hyperpolarising effects on GnRH neurones. The most recent studies examining the effects of endogenous GABA release on GnRH neurones indicate that the predominant action is that of excitation. However, we are still far from a complete understanding of the effects of GABA(A) receptor activation upon GnRH neurones. We argue that this will require not only a better understanding of chloride ion homeostasis in individual GnRH neurones, and within subcellular compartments of the GnRH neurone, but also a more integrative view of how multiple neurotransmitters, neuromodulators and intrinsic conductances act together to regulate the activity of these important cells. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  12. ETHANOL ACTION ON DOPAMINERGIC NEURONS IN THE VENTRAL TEGMENTAL AREA: INTERACTION WITH INTRINSIC ION CHANNELS AND NEUROTRANSMITTER INPUTS

    PubMed Central

    Morikawa, Hitoshi; Morrisett, Richard A.

    2010-01-01

    The dopaminergic system originating in the midbrain ventral tegmental area (VTA) has been extensively studied over the past decades as a critical neural substrate involved in the development of alcoholism and addiction to other drugs of abuse. Accumulating evidence indicates that ethanol modulates the functional output of this system by directly affecting the firing activity of VTA dopamine neurons, whereas withdrawal from chronic ethanol exposure leads to a reduction in the functional output of these neurons. This chapter will provide an update on the mechanistic investigations of the acute ethanol action on dopamine neuron activity and the neuroadaptations/plasticities in the VTA produced by previous ethanol experience. PMID:20813245

  13. The organizational and aromatization hypotheses apply to rapid, nonclassical hormone action: neonatal masculinization eliminates rapid estradiol action in female hippocampal neurons.

    PubMed

    Meitzen, John; Grove, Danielle D; Mermelstein, Paul G

    2012-10-01

    Early exposure to the steroid sex hormone testosterone and its estrogen metabolite estradiol masculinize neural tissue during a developmental critical period. Many aspects of neuron anatomy and physiology are permanently altered, including later sensitivity to estradiol. Although it is well established that early hormone exposure alters neuronal responsiveness regarding classical estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet been determined whether it also alters neuronal processing of nonclassical estrogen receptor signaling, including the actions of membrane-associated estrogen receptors. Hence, we tested whether membrane estrogen receptor regulation of cAMP response element binding protein (CREB) phosphorylation observed in female (but not male) hippocampal pyramidal neurons is due to the lack of androgen and/or estrogen exposure in females during this critical period. Female rat neonates on postnatal d 0 and 1 were systemically injected with one of four compounds: vehicle, testosterone, the nonaromatizable androgen dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron cultures were generated from these animals. After 8-9 d in culture, we assessed whether estradiol affected CREB phosphorylation. Neurons from female neonates exposed to testosterone lacked estradiol signaling to CREB. In contrast, dihydrotestosterone injections of female neonates did not disrupt estradiol regulation of CREB. Estradiol injections of female neonates, however, eliminated estradiol signaling to CREB. These findings indicate that testosterone aromatization to estradiol leads to a masculinization/defeminization process whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB. Broadly, these findings extend the organizational and aromatization hypotheses to rapid, nonclassical hormone action.

  14. The Organizational and Aromatization Hypotheses Apply to Rapid, Nonclassical Hormone Action: Neonatal Masculinization Eliminates Rapid Estradiol Action in Female Hippocampal Neurons

    PubMed Central

    Grove, Danielle D.; Mermelstein, Paul G.

    2012-01-01

    Early exposure to the steroid sex hormone testosterone and its estrogen metabolite estradiol masculinize neural tissue during a developmental critical period. Many aspects of neuron anatomy and physiology are permanently altered, including later sensitivity to estradiol. Although it is well established that early hormone exposure alters neuronal responsiveness regarding classical estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet been determined whether it also alters neuronal processing of nonclassical estrogen receptor signaling, including the actions of membrane-associated estrogen receptors. Hence, we tested whether membrane estrogen receptor regulation of cAMP response element binding protein (CREB) phosphorylation observed in female (but not male) hippocampal pyramidal neurons is due to the lack of androgen and/or estrogen exposure in females during this critical period. Female rat neonates on postnatal d 0 and 1 were systemically injected with one of four compounds: vehicle, testosterone, the nonaromatizable androgen dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron cultures were generated from these animals. After 8–9 d in culture, we assessed whether estradiol affected CREB phosphorylation. Neurons from female neonates exposed to testosterone lacked estradiol signaling to CREB. In contrast, dihydrotestosterone injections of female neonates did not disrupt estradiol regulation of CREB. Estradiol injections of female neonates, however, eliminated estradiol signaling to CREB. These findings indicate that testosterone aromatization to estradiol leads to a masculinization/defeminization process whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB. Broadly, these findings extend the organizational and aromatization hypotheses to rapid, nonclassical hormone action. PMID:22865367

  15. Recording Single Neurons' Action Potentials from Freely Moving Pigeons Across Three Stages of Learning

    PubMed Central

    Güntürkün, Onur

    2014-01-01

    While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.1 for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning. PMID:24961391

  16. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    PubMed

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-03

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine.

    PubMed

    Dobbs, Lauren K; Kaplan, Alanna R; Lemos, Julia C; Matsui, Aya; Rubinstein, Marcelo; Alvarez, Veronica A

    2016-06-01

    Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response. VIDEO ABSTRACT.

  18. Nonlinear Dynamic Modeling of Neuron Action Potential Threshold During Synaptically Driven Broadband Intracellular Activity

    PubMed Central

    Roach, Shane M.; Song, Dong; Berger, Theodore W.

    2012-01-01

    Activity-dependent variation of neuronal thresholds for action potential (AP) generation is one of the key determinants of spike-train temporal-pattern transformations from presynaptic to postsynaptic spike trains. In this study, we model the nonlinear dynamics of the threshold variation during synaptically driven broadband intracellular activity. First, membrane potentials of single CA1 pyramidal cells were recorded under physiologically plausible broadband stimulation conditions. Second, a method was developed to measure AP thresholds from the continuous recordings of membrane potentials. It involves measuring the turning points of APs by analyzing the third-order derivatives of the membrane potentials. Four stimulation paradigms with different temporal patterns were applied to validate this method by comparing the measured AP turning points and the actual AP thresholds estimated with varying stimulation intensities. Results show that the AP turning points provide consistent measurement of the AP thresholds, except for a constant offset. It indicates that 1) the variation of AP turning points represents the nonlinearities of threshold dynamics; and 2) an optimization of the constant offset is required to achieve accurate spike prediction. Third, a nonlinear dynamical third-order Volterra model was built to describe the relations between the threshold dynamics and the AP activities. Results show that the model can predict threshold accurately based on the preceding APs. Finally, the dynamic threshold model was integrated into a previously developed single neuron model and resulted in a 33% improvement in spike prediction. PMID:22156947

  19. Multifocal Fluorescence Microscope for Fast Optical Recordings of Neuronal Action Potentials

    PubMed Central

    Shtrahman, Matthew; Aharoni, Daniel B.; Hardy, Nicholas F.; Buonomano, Dean V.; Arisaka, Katsushi; Otis, Thomas S.

    2015-01-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera’s native frame rate. We demonstrate that this approach is capable of recording Ca2+ transients resulting from APs in neurons labeled with the Ca2+ sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  20. 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

  1. Immature Hippocampal Neuronal Networks do not Develop Tolerance to the Excitatory Actions of Ethanol

    PubMed Central

    Galindo, Rafael; Valenzuela, C. Fernando

    2007-01-01

    EtOH (ethanol) damages the hippocampus, a brain region that is involved in learning and memory processes. The mechanisms responsible for this effect of EtOH are not fully understood. We recently demonstrated that acute EtOH exposure potently stimulates oscillatory activity driven by the excitatory actions of GABA in the CA3 region of the neonatal rat hippocampus. This activity can be recorded during the growth spurt period as giant depolarizing potentials (GDPs). Here, we characterized the effects of prolonged EtOH exposure on GDPs. In the first study, we prepared hippocampal coronal slices from neonatal rats and exposed these to control artificial cerebrospinal fluid (ACSF) or ACSF plus 50 mM EtOH for 3–4 hr. We then performed whole-cell patch-clamp electrophysiological recordings from CA3 pyramidal neurons, which revealed that tolerance to the GDP stimulating effects of EtOH did not occur after continuous exposure. In the second study, we exposed neonatal rats to air or air plus 1.9 g/dL EtOH in vapor chambers for 4 hours/day for 1 or 3 days (neonatal peak blood EtOH concentration = 40–45 mM). We then performed slice electrophysiological studies 24 hours after the end of EtOH exposure and found that there was no statistically significant difference in the acute effect of 50 mM EtOH on GDP frequency in samples from neonates exposed to air or air plus EtOH. These findings indicate that EtOH persistently stimulates network-driven oscillatory activity in the developing hippocampus. We propose that the lack of adaptive response to continuous EtOH exposure could make immature neuronal networks particularly vulnerable to the actions of this agent. PMID:17307647

  2. Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior.

    PubMed

    Narahashi, T; Fenster, C P; Quick, M W; Lester, R A; Marszalec, W; Aistrup, G L; Sattelle, D B; Martin, B R; Levin, E D

    2000-10-01

    Nicotine has long been known to interact with nicotinic acetylcholine (ACh) receptors since Langley used it extensively to chart sympathetic ganglia a century ago. It has also been used as an effective insecticide. However, it was not until the 1990s that the significance of nicotine was increasingly recognized from the toxicological, pharmacological, and environmental points of view. This is partly because studies of neuronal nicotinic ACh receptors are rapidly emerging from orphan status, fueled by several lines of research. Since Alzheimer's disease is known to be associated with down-regulation of cholinergic activity in the brain, a variety of nicotine derivatives are being tested and developed for treatment of the disease. Public awareness of the adverse effects of nicotine has reached the highest level recently. Since insect resistance to insecticides is one of the most serious issues in the pest-control arena, it is an urgent requirement to develop new insecticides that act on target sites not shared by the existing insecticides. The neuronal nicotinic ACh receptor is one of them, and new nicotinoids are being developed. Thus, the time is ripe to discuss the mechanism of action of nicotine from a variety of angles, including the molecular, physiological, and behavioral points of view. This Symposium covered a wide area of nicotine studies: genetic, genomic, and functional aspects of nicotinic ACh receptors were studied, as related to anthelmintics and insecticides; interactions between ethanol and nicotine out the ACh receptor were analyzed, in an attempt to explain the well-known heavy drinker-heavy smoker correlation; the mechanisms that underlie the desensitization of ACh receptors were studied as related to nicotine action; selective pharmacological profiles of nicotine, and descriptions of some derivatives were described; and chronic nicotine infusion effects on memory were examined using animal models.

  3. Design of time-pulse coded optoelectronic neuronal elements for nonlinear transformation and integration

    NASA Astrophysics Data System (ADS)

    Krasilenko, Vladimir G.; Nikolsky, Alexander I.; Lazarev, Alexander A.; Lazareva, Maria V.

    2008-03-01

    In the paper the actuality of neurophysiologically motivated neuron arrays with flexibly programmable functions and operations with possibility to select required accuracy and type of nonlinear transformation and learning are shown. We consider neurons design and simulation results of multichannel spatio-time algebraic accumulation - integration of optical signals. Advantages for nonlinear transformation and summation - integration are shown. The offered circuits are simple and can have intellectual properties such as learning and adaptation. The integrator-neuron is based on CMOS current mirrors and comparators. The performance: consumable power - 100...500 μW, signal period- 0.1...1ms, input optical signals power - 0.2...20 μW time delays - less 1μs, the number of optical signals - 2...10, integration time - 10...100 of signal periods, accuracy or integration error - about 1%. Various modifications of the neuron-integrators with improved performance and for different applications are considered in the paper.

  4. Rapid Sensitization of Physiological, Neuronal, and Locomotor Effects of Nicotine: Critical Role of Peripheral Drug Actions

    PubMed Central

    Lenoir, Magalie; Tang, Jeremy S.; Woods, Amina S.

    2013-01-01

    Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotinePM, 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotinePM injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization. PMID:23761889

  5. From perception to action: temporal integrative functions of prefrontal and parietal neurons.

    PubMed

    Quintana, J; Fuster, J M

    1999-01-01

    The dorsolateral prefrontal cortex (DPFC) and the posterior parietal cortex (PPC) are anatomically and functionally interconnected, and have been implicated in working memory and the preparation for behavioral action. To substantiate those functions at the neuronal level, we designed a visuomotor task that dissociated the perceptual and executive aspects of the perception-action cycle in both space and time. In that task, the trial-initiating cue (a color) indicated with different degrees of certainty the direction of the correct manual response 12 s later. We recorded extracellular activity from 258 prefrontal and 223 parietal units in two monkeys performing the task. In the DPFC, some units (memory cells) were attuned to the color of the cue, independent of the response-direction it connoted. Their discharge tended to diminish in the course of the delay between cue and response. In contrast, few color-related units were found in PPC, and these did not show decreasing patterns of delay activity. Other units in both cortices (set cells) were attuned to response-direction and tended to accelerate their firing in anticipation of the response and in proportion to the predictability of its direction. A third group of units was related to the determinacy of the act; their firing was attuned to the certainty with which the animal could predict the correct response, whatever its direction. Cells of the three types were found closely intermingled histologically. These findings further support and define the role of DPFC in executive functions and in the temporal closure of the perception-action cycle. The findings also agree with the involvement of PPC in spatial aspects of visuomotor behavior, and add a temporal integrative dimension to that involvement. Together, the results provide physiological evidence for the role of a prefrontal-parietal network in the integration of perception with action across time.

  6. [Pain assessment using the Facial Action Coding System. A systematic review].

    PubMed

    Rojo, Rosa; Prados-Frutos, Juan Carlos; López-Valverde, Antonio

    2015-10-21

    Self-reporting is the most widely used pain measurement tool, although it may not be useful in patients with loss or deficit in communication skills. The aim of this paper was to undertake a systematic review of the literature of pain assessment through the Facial Action Coding System (FACS). The initial search found 4,335 references and, within the restriction «FACS», these were reduced to 40 (after exclusion of duplicates). Finally, only 26 articles meeting the inclusion criteria were included. Methodological quality was assessed using the GRADE system. Most patients were adults and elderly health conditions, or cognitive deficits and/or chronic pain. Our conclusion is that FACS is a reliable and objective tool in the detection and quantification of pain in all patients.

  7. The growth cones of Aplysia sensory neurons: Modulation by serotonin of action potential duration and single potassium channel currents.

    PubMed

    Belardetti, F; Schacher, S; Kandel, E R; Siegelbaum, S A

    1986-09-01

    Serotonin (5-HT) closes a specific K channel ("S") in the cell body of Aplysia sensory neurons, resulting in a slow excitatory postsynaptic potential and spike broadening. To determine whether the S channel is present and can be modulated in processes of the neuron other than the cell body, we studied the effects of 5-HT on growth cones of sensory neurons in culture by using the patch-clamp technique. Simultaneous application of 5-HT to the cell body and to the growth cones of sensory neurons produced, in both, a slow depolarization of approximately 5 mV. Also, 5-HT produced a lengthening of the duration of action potential in the growth cone and cell body by 20-30%. Similar effects were observed in isolated growth cones that had been severed from the rest of the neuron, implying that the growth cones contain all the molecular components (i.e., receptors, channels, cAMP cascade) necessary for 5-HT action. Cell-attached patch-clamp recordings demonstrated the presence of S channels in sensory neuron growth cones. Application of serotonin to the bath produced long-lasting all-or-none closures of these channels in a manner identical to the previously characterized action of 5-HT in the cell body. Thus, channel modulation is not restricted to the cell body and probably occurs throughout the sensory neuron. This strengthens the view that S-channel modulation may also occur at the sensory neuron presynaptic terminal, where it could play a role in the presynaptic facilitation produced by 5-HT.

  8. Actions of baclofen on components of the Ca-current in rat and mouse DRG neurones in culture.

    PubMed Central

    Green, K. A.; Cottrell, G. A.

    1988-01-01

    1. Ca currents in rat and mouse sensory dorsal root ganglion (DRG) neurones were inhibited by concentrations of (-)-baclofen as low as 1 micron. The proportion of neurones responding to baclofen was low (less than 20%), except in young cultures of neonate rat DRG neurones (3 days in culture), where 86% of the neurones were responsive. 2. Three types of unitary Ca currents were observed in the rat DRG neurones, corresponding to the T-, N- and L-type currents of chick DRG neurones. 3. Baclofen produced two types of response on whole-cell currents of DRG neurones from both species. The first was on an early inactivating component of the Ca current. This early current was partially inactivated at a holding potential of -40 mV. It was also reduced during the second of a pair of depolarizing command pulses. The results suggest that this action of baclofen is due to an action on an N-type component of the current. The second response to baclofen persisted throughout the command step and was not reduced during the second of a pair of command pulses, indicating that this effect is due to an action on the L-type current. 4. Unitary or ensemble Ca currents recorded in cell-attached patches, on neurones previously shown to respond to baclofen in whole-cell clamp mode, were generally not inhibited by baclofen application external to the patch electrode. This indicates that a readily diffusible internal second messenger substance is probably not involved in coupling the GABAB receptor to the ion channels. PMID:2456810

  9. Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action

    PubMed Central

    Laque, Amanda; Zhang, Yan; Gettys, Sarah; Nguyen, Tu-Anh; Bui, Kelly; Morrison, Christopher D.

    2013-01-01

    Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions. LepRb neurons are found throughout the brain, and several distinct populations contribute to energy homeostasis control. However, the function of most LepRb populations remains unknown, and their contribution to regulate energy homeostasis has not been studied. Galanin has been hypothesized to interact with the leptin signaling system, but literature investigating colocalization of LepRb and galanin has been inconsistent, which is likely due to technical difficulties to visualize both. We used reporter mice with green fluorescent protein expression from the galanin locus to recapitulate the colocalization of galanin and leptin-induced p-STAT3 as a marker for LepRb expression. Here, we report the existence of two populations of galanin-expressing LepRb neurons (Gal-LepRb neurons): in the hypothalamus overspanning the perifornical area and adjacent dorsomedial and lateral hypothalamus [collectively named extended perifornical area (exPFA)] and in the brainstem (nucleus of the solitary tract). Surprisingly, despite the known orexigenic galanin action, leptin induces galanin mRNA expression and stimulates LepRb neurons in the exPFA, thus conflicting with the expected anorexigenic leptin action. However, we confirmed that intra-exPFA leptin injections were indeed sufficient to mediate anorexic responses. Interestingly, LepRb and galanin-expressing neurons are distinct from orexin or melanin-concentrating hormone (MCH)-expressing neurons, but exPFA galanin neurons colocalized with the anorexigenic neuropeptides neurotensin and cocaine- and amphetamine-regulated transcript (CART). Based on galanin's known inhibitory function, we speculate that in exPFA Gal-LepRb neurons galanin acts inhibitory rather than orexigenic. PMID:23482448

  10. Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity.

    PubMed

    Dietrich, Marcelo O; Antunes, Catiele; Geliang, Gan; Liu, Zhong-Wu; Borok, Erzsebet; Nie, Yongzhan; Xu, Allison W; Souza, Diogo O; Gao, Qian; Diano, Sabrina; Gao, Xiao-Bing; Horvath, Tamas L

    2010-09-01

    Sirt1 has been associated with various effects of calorie restriction, including an increase in lifespan. Here we show in mice that a central regulatory component in energy metabolism, the hypothalamic melanocortin system, is affected by Sirt1, which promotes the activity and connectivity of this system resulting in negative energy balance. In adult mice, the pharmacological inhibition of brain Sirt1 activity decreased Agrp neuronal activity and the inhibitory tone on the anorexigenic POMC neurons, as measured by the number of synaptic inputs to these neurons. When a Sirt1 inhibitor (EX-527) was injected either peripherally (i.p., 10 mg/kg) or directly into the brain (i.c.v., 1.5 nmol/mouse), it decreased both food intake during the dark cycle and ghrelin-induced food intake. This effect on feeding is mediated by upstream melanocortin receptors, because the MC4R antagonist, SHU9119, reversed Sirt1's effect on food intake. This action of Sirt1 required an appropriate shift in the mitochondrial redox state: in the absence of such an adaptation enabled by the mitochondrial protein, UCP2, Sirt1-induced cellular and behavioral responses were impaired. In accordance with the pharmacological results, the selective knock-out of Sirt1 in hypothalamic Agrp neurons through the use of Cre-Lox technology decreased electric responses of Agrp neurons to ghrelin and decreased food intake, leading to decreased lean mass, fat mass, and body weight. The present data indicate that Sirt1 has a central mode of action by acting on the NPY/Agrp neurons to affect body metabolism.

  11. Automated Facial Action Coding System for Dynamic Analysis of Facial Expressions in Neuropsychiatric Disorders

    PubMed Central

    Hamm, Jihun; Kohler, Christian G.; Gur, Ruben C.; Verma, Ragini

    2011-01-01

    Facial expression is widely used to evaluate emotional impairment in neuropsychiatric disorders. Ekman and Friesen’s Facial Action Coding System (FACS) encodes movements of individual facial muscles from distinct momentary changes in facial appearance. Unlike facial expression ratings based on categorization of expressions into prototypical emotions (happiness, sadness, anger, fear, disgust, etc.), FACS can encode ambiguous and subtle expressions, and therefore is potentially more suitable for analyzing the small differences in facial affect. However, FACS rating requires extensive training, and is time consuming and subjective thus prone to bias. To overcome these limitations, we developed an automated FACS based on advanced computer science technology. The system automatically tracks faces in a video, extracts geometric and texture features, and produces temporal profiles of each facial muscle movement. These profiles are quantified to compute frequencies of single and combined Action Units (AUs) in videos, which can facilitate statistical study of large populations in disorders affecting facial expression. We derived quantitative measures of flat and inappropriate facial affect automatically from temporal AU profiles. Applicability of the automated FACS was illustrated in a pilot study, by applying it to data of videos from eight schizophrenia patients and controls. We created temporal AU profiles that provided rich information on the dynamics of facial muscle movements for each subject. The quantitative measures of flatness and inappropriateness showed clear differences between patients and the controls, highlighting their potential in automatic and objective quantification of symptom severity. PMID:21741407

  12. Automated Facial Action Coding System for dynamic analysis of facial expressions in neuropsychiatric disorders.

    PubMed

    Hamm, Jihun; Kohler, Christian G; Gur, Ruben C; Verma, Ragini

    2011-09-15

    Facial expression is widely used to evaluate emotional impairment in neuropsychiatric disorders. Ekman and Friesen's Facial Action Coding System (FACS) encodes movements of individual facial muscles from distinct momentary changes in facial appearance. Unlike facial expression ratings based on categorization of expressions into prototypical emotions (happiness, sadness, anger, fear, disgust, etc.), FACS can encode ambiguous and subtle expressions, and therefore is potentially more suitable for analyzing the small differences in facial affect. However, FACS rating requires extensive training, and is time consuming and subjective thus prone to bias. To overcome these limitations, we developed an automated FACS based on advanced computer science technology. The system automatically tracks faces in a video, extracts geometric and texture features, and produces temporal profiles of each facial muscle movement. These profiles are quantified to compute frequencies of single and combined Action Units (AUs) in videos, and they can facilitate a statistical study of large populations in disorders known to impact facial expression. We derived quantitative measures of flat and inappropriate facial affect automatically from temporal AU profiles. Applicability of the automated FACS was illustrated in a pilot study, by applying it to data of videos from eight schizophrenia patients and controls. We created temporal AU profiles that provided rich information on the dynamics of facial muscle movements for each subject. The quantitative measures of flatness and inappropriateness showed clear differences between patients and the controls, highlighting their potential in automatic and objective quantification of symptom severity. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism.

    PubMed

    Marcelin, Geneviève; Jo, Young-Hwan; Li, Xiaosong; Schwartz, Gary J; Zhang, Ying; Dun, Nae J; Lyu, Rong-Ming; Blouet, Clémence; Chang, Jaw K; Chua, Streamson

    2014-02-01

    Tight control of glucose excursions has been a long-standing goal of treatment for patients with type 2 diabetes mellitus in order to ameliorate the morbidity and mortality associated with hyperglycemia. Fibroblast growth factor (FGF) 19 is a hormone-like enterokine released postprandially that emerged as a potential therapeutic agent for metabolic disorders, including diabetes and obesity. Remarkably, FGF19 treatment has hypoglycemic actions that remain potent in models of genetic and acquired insulin resistance. Here, we provided evidence that the central nervous system responds to FGF19 administered in the periphery. Then, in two mouse models of insulin resistance, leptin-deficiency and high-fat diet feeding, third intra-cerebro-ventricular infusions of FGF19 improved glycemic status, reduced insulin resistance and potentiated insulin signaling in the periphery. In addition, our study highlights a new mechanism of central FGF19 action, involving the suppression of AGRP/NPY neuronal activity. Overall, our work unveils novel regulatory pathways induced by FGF19 that will be useful in the design of novel strategies to control diabetes in obesity.

  14. Two-dimensional spatiotemporal coding of linear acceleration in vestibular nuclei neurons

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Bush, G. A.; Perachio, A. A.

    1993-01-01

    Response properties of vertical (VC) and horizontal (HC) canal/otolith-convergent vestibular nuclei neurons were studied in decerebrate rats during stimulation with sinusoidal linear accelerations (0.2-1.4 Hz) along different directions in the head horizontal plane. A novel characteristic of the majority of tested neurons was the nonzero response often elicited during stimulation along the "null" direction (i.e., the direction perpendicular to the maximum sensitivity vector, Smax). The tuning ratio (Smin gain/Smax gain), a measure of the two-dimensional spatial sensitivity, depended on stimulus frequency. For most vestibular nuclei neurons, the tuning ratio was small at the lowest stimulus frequencies and progressively increased with frequency. Specifically, HC neurons were characterized by a flat Smax gain and an approximately 10-fold increase of Smin gain per frequency decade. Thus, these neurons encode linear acceleration when stimulated along their maximum sensitivity direction, and the rate of change of linear acceleration (jerk) when stimulated along their minimum sensitivity direction. While the Smax vectors were distributed throughout the horizontal plane, the Smin vectors were concentrated mainly ipsilaterally with respect to head acceleration and clustered around the naso-occipital head axis. The properties of VC neurons were distinctly different from those of HC cells. The majority of VC cells showed decreasing Smax gains and small, relatively flat, Smin gains as a function of frequency. The Smax vectors were distributed ipsilaterally relative to the induced (apparent) head tilt. In type I anterior or posterior VC neurons, Smax vectors were clustered around the projection of the respective ipsilateral canal plane onto the horizontal head plane. These distinct spatial and temporal properties of HC and VC neurons during linear acceleration are compatible with the spatiotemporal organization of the horizontal and the vertical/torsional ocular responses

  15. Global and fine information coded by single neurons in the temporal visual cortex

    NASA Astrophysics Data System (ADS)

    Sugase, Yasuko; Yamane, Shigeru; Ueno, Shoogo; Kawano, Kenji

    1999-08-01

    When we see a person's face, we can easily recognize their species, individual identity and emotional state. How does the brain represent such complex information? A substantial number of neurons in the macaque temporal cortex respond to faces. However, the neuronal mechanisms underlying the processing ofcomplex information are not yet clear. Here we recorded the activity of single neurons in the temporal cortex of macaque monkeys while presenting visual stimuli consisting of geometric shapes, and monkey and human faces with various expressions. Information theory was used to investigate how well the neuronal responses could categorize the stimuli. We found that single neurons conveyed two different scales of facial information intheir firing patterns, starting at different latencies. Global information, categorizing stimuli as monkey faces, human faces or shapes, was conveyed in the earliest part of the responses. Fineinformation about identity or expression was conveyed later,beginning on average 51ms after global information. We speculate that global information could be used as a `header' to prepare destination areas for receiving more detailed information.

  16. Preferential coding of eye/hand motor actions in the human ventral occipito-temporal cortex.

    PubMed

    Tosoni, Annalisa; Guidotti, Roberto; Del Gratta, Cosimo; Committeri, Giorgia; Sestieri, Carlo

    2016-12-01

    The human ventral occipito-temporal cortex (OTC) contains areas specialized for particular perceptual/semantic categories, such as faces (fusiform face area, FFA) and places (parahippocampal place area, PPA). This organization has been interpreted as reflecting the visual structure of the world, i.e. perceptual similarity and/or eccentricity biases. However, recent functional magnetic resonance imaging (fMRI) studies have shown not only that regions of the OTC are modulated by non-visual, action-related object properties but also by motor planning and execution, although the functional role and specificity of this motor-related activity are still unclear. Here, through a reanalysis of previously published data, we tested whether the selectivity for perceptual/semantic categories in the OTC corresponds to a preference for particular motor actions. The results demonstrate for the first time that face- and place-selective regions of the OTC exhibit preferential BOLD response to the execution of hand pointing and saccadic eye movements, respectively. Moreover, multivariate analyses provide novel evidence for the consistency across neural representations of stimulus category and movement effector in OTC. According to a 'spatial hypothesis', this pattern of results originates from the match between the region eccentricity bias and the typical action space of the motor effectors. Alternatively, the double dissociation may be caused by the different effect produced by hand vs. eye movements on regions coding for body representation. Overall, the present findings offer novel insights on the coupling between visual and motor cortical representations. Copyright © 2016. Published by Elsevier Ltd.

  17. The synergistic inhibitory actions of oxcarbazepine on voltage-gated sodium and potassium currents in differentiated NG108-15 neuronal cells and model neurons.

    PubMed

    Huang, Chin-Wei; Huang, Chao-Ching; Lin, Ming-Wei; Tsai, Jing-Jane; Wu, Sheng-Nan

    2008-08-01

    Oxcarbazepine (OXC), one of the newer anti-epileptic drugs, has been demonstrating its efficacy on wide-spectrum neuropsychiatric disorders. However, the ionic mechanism of OXC actions in neurons remains incompletely understood. With the aid of patch-clamp technology, we first investigated the effects of OXC on ion currents in NG108-15 neuronal cells differentiated with cyclic AMP. We found OXC (0.3-30 microm) caused a reversible reduction in the amplitude of voltage-gated Na+ current (INa). The IC50 value required for the inhibition of INa by OXC was 3.1 microm. OXC (3 microm) could shift the steady-state inactivation of INa to a more negative membrane potential by approximately -9 mV with no effect on the slope of the inactivation curve, and produce a significant prolongation in the recovery of INa inactivation. Additionally, OXC was effective in suppressing persistent INa (INa(P)) elicited by long ramp pulses. The blockade of INa by OXC does not simply reduce current magnitude, but alters current kinetics. Moreover, OXC could suppress the amplitude of delayed rectifier K+ current (IK(DR)), with no effect on M-type K+ current (IK(M)). In current-clamp configuration, OXC could reduce the amplitude of action potentials and prolong action-potential duration. Furthermore, the simulations, based on hippocampal pyramidal neurons (Pinsky-Rinzel model) and a network of the Hodgkin-Huxley model, were analysed to investigate the effect of OXC on action potentials. Taken together, our results suggest that the synergistic blocking effects on INa and IK(DR) may contribute to the underlying mechanisms through which OXC affects neuronal function in vivo.

  18. Ventral tegmental area neurons are either excited or inhibited by cocaine’s actions in the peripheral nervous system

    PubMed Central

    Mejías-Aponte, Carlos A.; Kiyatkin, Eugene A.

    2012-01-01

    Cocaine’s multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via peripheral actions, and whether this precedes its central actions. In urethane-anesthetized rats, we recorded VTA neurons responses to intravenous injections of two cocaine analogs: cocaine-hydrochloride (HCl, 0.25 mg/kg) that readily cross the blood-brain barrier (BBB) and cocaine-methiodide (MI, 0.33 mg/kg) that does not cross the BBB. Both cocaine analogs produced sustained changes in discharge rates that began 5s after the initiation of a 10s drug infusion. Within the first 90s post-injection the magnitudes of neuronal responsive of both cocaine analogs were comparable, but later in time the effects of cocaine-HCl were stronger and persisted longer than those of cocaine-MI. The proportion of neurons responsive to cocaine-HCl was twice to that of cocaine-MI (74% and 35% respectively). Both analogs also differed in the response onsets. Cocaine-MI rarely evoked responses after 1 min whereas cocaine-HCl continued to evoke responses within 3 min post-injection. VTA neurons were either excited or inhibited by both cocaine analogs. Most units responsive to cocaine-MI, regardless of excitation or inhibition, had electrophysiological characteristics of putative DA neurons. Units inhibited by cocaine-HCl also had characteristic of DA neurons whereas excited neurons had widely varying action potential durations and discharge rates. Cocaine-MI and cocaine-HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened, the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and

  19. 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

  20. Conantokin G-induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder.

    PubMed

    Bossowska, A; Majewski, M

    2012-01-01

    Conantokin G (CTG), isolated from the venom of the marine cone snail Conus geographus, is an antagonist of N-methyl-d-aspartate receptors (NMDARs), the activation of which, especially those located on the central afferent terminals and dorsal horn neurons, leads to hypersensitivity and pain. Thus, CTG blocking of NMDARs, has an antinociceptive effect, particularly in the case of neurogenic pain treatment. As many urinary bladder disorders are caused by hyperactivity of sensory bladder innervation, it seems useful to estimate the influence of CTG on the plasticity of sensory neurons supplying the organ. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall of six juvenile female pigs. Three weeks later, intramural bladder injections of CTG (120 microg per animal) were carried out in all animals. After a week, dorsal root ganglia of interest were harvested from all animals and neurochemical characterization of FB+ neurons was performed using a routine double-immunofluorescence labeling technique on 10-microm-thick cryostat sections. CTG injections led to a significant decrease in the number of FB+ neurons containing substance P (SP), pituitary adenylate cyclase activating polypeptide (PACAP), somatostatin (SOM), calbindin (CB) and nitric oxide synthase (NOS) when compared with healthy animals (20% vs. 45%, 13% vs. 26%, 1.3% vs. 3%, 1.2 vs. 4% and 0.9% vs. 6% respectively) and to an increase in the number of cells immunolabelled for galanin (GAL, 39% vs. 6.5%). These data demonstrated that CTG changed the chemical coding of bladder sensory neurons, thus indicating that CTG could eventually be used in the therapy of selected neurogenic bladder illnesses.

  1. Selective and graded coding of reward-uncertainty by neurons in the primate anterodorsal septal region

    PubMed Central

    Monosov, Ilya E.; Hikosaka, Okihide

    2014-01-01

    Natural environments are uncertain. Uncertainty of emotional outcomes can induce anxiety and raise vigilance, promote and signal the opportunity for learning, modulate economic choice, and regulate risk seeking. Here we demonstrate that a subset of neurons in the anterodorsal region of the primate septum (ADS) are primarily devoted to processing uncertainty in a highly specific manner. Those neurons were selectively activated by visual cues indicating probabilistic delivery of reward (e.g. 25%, 50%, 75% reward) and did not respond to cues indicating certain outcomes (0% and 100% reward). The average ADS uncertainty response was graded with the magnitude of reward uncertainty, and selectively signaled uncertainty about rewards rather than punishments. The selective and graded information about reward uncertainty encoded by many neurons in the ADS may underlie uncertainty-modulation of value- and sensorimotor- related areas to regulate goal-directed behavior. PMID:23666181

  2. Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma

    PubMed Central

    Michalikova, Martina; Kempter, Richard

    2017-01-01

    Spikelets are small spike-like depolarizations that can be measured in somatic intracellular recordings. Their origin in pyramidal neurons remains controversial. To explain spikelet generation, we propose a novel single-cell mechanism: somato-dendritic input generates action potentials at the axon initial segment that may fail to activate the soma and manifest as somatic spikelets. Using mathematical analysis and numerical simulations of compartmental neuron models, we identified four key factors controlling spikelet generation: (1) difference in firing threshold, (2) impedance mismatch, and (3) electrotonic separation between the soma and the axon initial segment, as well as (4) input amplitude. Because spikelets involve forward propagation of action potentials along the axon while they avoid full depolarization of the somato-dendritic compartments, we conjecture that this mode of operation saves energy and regulates dendritic plasticity while still allowing for a read-out of results of neuronal computations. PMID:28068338

  3. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglia neurons

    PubMed Central

    Schink, Martin; Leipolcf, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H.

    2016-01-01

    Dorsal root ganglia (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 µM) or low-intensity blue-light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8−/−), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and at higher concentrations progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure. PMID:26383867

  4. Pattern Separation, Pattern Completion, and New Neuronal Codes within a Continuous CA3 Map

    ERIC Educational Resources Information Center

    Leutgeb, Stefan; Leutgeb, Jill K.

    2007-01-01

    The hippocampal CA3 subregion is critical for rapidly encoding new memories, which suggests that neuronal computations are implemented in its circuitry that cannot be performed elsewhere in the hippocampus or in the neocortex. Recording studies show that CA3 cells are bound to a large degree to a spatial coordinate system, while CA1 cells can…

  5. Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

    PubMed Central

    Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

    2009-01-01

    Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

  6. [Double action potentials in the command neurons of Helix pomatia in response to the action of cobalt ions].

    PubMed

    Palikhova, T A; Khludova, L K; Sokolov, E N

    1987-01-01

    Cobalt chloride (20 mmol/l) in physiological solution results in generation of doublets of spikes in Helix pomatia command neurons in response to intracellularly injected depolarizing current. The extraspikes arise in arborizations of neuron and are determined by influx sodium ions. It is supposed that facilitation of extraspikes in apparently due to long-lasting blockade of calcium-dependent potassium current by Co2+ ions.

  7. Ability of primary auditory cortical neurons to detect amplitude modulation with rate and temporal codes: neurometric analysis

    PubMed Central

    Johnson, Jeffrey S.; Yin, Pingbo; O'Connor, Kevin N.

    2012-01-01

    Amplitude modulation (AM) is a common feature of natural sounds, and its detection is biologically important. Even though most sounds are not fully modulated, the majority of physiological studies have focused on fully modulated (100% modulation depth) sounds. We presented AM noise at a range of modulation depths to awake macaque monkeys while recording from neurons in primary auditory cortex (A1). The ability of neurons to detect partial AM with rate and temporal codes was assessed with signal detection methods. On average, single-cell synchrony was as or more sensitive than spike count in modulation detection. Cells are less sensitive to modulation depth if tested away from their best modulation frequency, particularly for temporal measures. Mean neural modulation detection thresholds in A1 are not as sensitive as behavioral thresholds, but with phase locking the most sensitive neurons are more sensitive, suggesting that for temporal measures the lower-envelope principle cannot account for thresholds. Three methods of preanalysis pooling of spike trains (multiunit, similar to convergence from a cortical column; within cell, similar to convergence of cells with matched response properties; across cell, similar to indiscriminate convergence of cells) all result in an increase in neural sensitivity to modulation depth for both temporal and rate codes. For the across-cell method, pooling of a few dozen cells can result in detection thresholds that approximate those of the behaving animal. With synchrony measures, indiscriminate pooling results in sensitive detection of modulation frequencies between 20 and 60 Hz, suggesting that differences in AM response phase are minor in A1. PMID:22422997

  8. Automated and objective action coding of facial expressions in patients with acute facial palsy.

    PubMed

    Haase, Daniel; Minnigerode, Laura; Volk, Gerd Fabian; Denzler, Joachim; Guntinas-Lichius, Orlando

    2015-05-01

    Aim of the present observational single center study was to objectively assess facial function in patients with idiopathic facial palsy with a new computer-based system that automatically recognizes action units (AUs) defined by the Facial Action Coding System (FACS). Still photographs using posed facial expressions of 28 healthy subjects and of 299 patients with acute facial palsy were automatically analyzed for bilateral AU expression profiles. All palsies were graded with the House-Brackmann (HB) grading system and with the Stennert Index (SI). Changes of the AU profiles during follow-up were analyzed for 77 patients. The initial HB grading of all patients was 3.3 ± 1.2. SI at rest was 1.86 ± 1.3 and during motion 3.79 ± 4.3. Healthy subjects showed a significant AU asymmetry score of 21 ± 11 % and there was no significant difference to patients (p = 0.128). At initial examination of patients, the number of activated AUs was significantly lower on the paralyzed side than on the healthy side (p < 0.0001). The final examination for patients took place 4 ± 6 months post baseline. The number of activated AUs and the ratio between affected and healthy side increased significantly between baseline and final examination (both p < 0.0001). The asymmetry score decreased between baseline and final examination (p < 0.0001). The number of activated AUs on the healthy side did not change significantly (p = 0.779). Radical rethinking in facial grading is worthwhile: automated FACS delivers fast and objective global and regional data on facial motor function for use in clinical routine and clinical trials.

  9. Conopressin affects excitability, firing, and action potential shape through stimulation of transient and persistent inward currents in mulluscan neurons.

    PubMed

    van Soest, P F; Kits, K S

    1998-04-01

    The molluscan vasopressin/oxytocin-related neuropeptide conopressin activates two persistent inward currents in neurons from the anterior lobe of the right cerebral ganglion of Lymnaea stagnalis that are involved in the control of male copulatory behavior. The low-voltage-activated (LVA) current is activated at a wide range of membrane potentials, its amplitude being only weakly voltage dependent. The high-voltage-activated (HVA) current is activated at potentials positive to -40 mV only and shows a steep voltage dependence. Occurrence of both currents varies from cell to cell, some expressing both and others only the HVA current. In most neurons that have the LVA current, a conopressin-independent persistent inward current (INSR) is found that resembles the HVA current in its voltage dependence. The functional importance of the LVA and HVA currents was studied under current-clamp conditions in isolated anterior lobe neurons. In cells exhibiting both current types, the effect of activation of the LVA current alone was investigated as follows: previously recorded LVA current profiles were injected into the neurons, and the effects were compared with responses induced by conopressin. Both treatments resulted in a strong depolarization and firing activity. No differences in firing frequency and burst duration were observed, indicating that activation of the LVA current is sufficient to evoke bursts. In cells exhibiting only the HVA current, the effect of conopressin on the response to a depolarizing stimulus was tested. Conopressin reversibly increased the number of action potentials generated by the stimulus, suggesting that the HVA current enhances excitability and counteracts accommodation. Conopressin enhanced action potential broadening during depolarizing stimuli in many neurons. Voltage-clamp experiments performed under ion-selective conditions revealed the presence of transient sodium and calcium currents. Using the action potential clamp technique, it was

  10. Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate.

    PubMed

    Tyzio, Roman; Allene, Camille; Nardou, Romain; Picardo, Michel A; Yamamoto, Sumii; Sivakumaran, Sudhir; Caiati, Maddalena D; Rheims, Sylvain; Minlebaev, Marat; Milh, Mathieu; Ferré, Pascal; Khazipov, Rustem; Romette, Jean-Louis; Lorquin, Jean; Cossart, Rosa; Khalilov, Ilgam; Nehlig, Astrid; Cherubini, Enrico; Ben-Ari, Yehezkel

    2011-01-05

    GABA depolarizes immature neurons because of a high [Cl(-)](i) and orchestrates giant depolarizing potential (GDP) generation. Zilberter and coworkers (Rheims et al., 2009; Holmgren et al., 2010) showed recently that the ketone body metabolite DL-3-hydroxybutyrate (DL-BHB) (4 mM), lactate (4 mM), or pyruvate (5 mM) shifted GABA actions to hyperpolarizing, suggesting that the depolarizing effects of GABA are attributable to inadequate energy supply when glucose is the sole energy source. We now report that, in rat pups (postnatal days 4-7), plasma D-BHB, lactate, and pyruvate levels are 0.9, 1.5, and 0.12 mM, respectively. Then, we show that DL-BHB (4 mM) and pyruvate (200 μM) do not affect (i) the driving force for GABA(A) receptor-mediated currents (DF(GABA)) in cell-attached single-channel recordings, (2) the resting membrane potential and reversal potential of synaptic GABA(A) receptor-mediated responses in perforated patch recordings, (3) the action potentials triggered by focal GABA applications, or (4) the GDPs determined with electrophysiological recordings and dynamic two-photon calcium imaging. Only very high nonphysiological concentrations of pyruvate (5 mM) reduced DF(GABA) and blocked GDPs. Therefore, DL-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect. There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain.

  11. Differential actions of fipronil and dieldrin insecticides on GABA-gated chloride channels in cockroach neurons.

    PubMed

    Zhao, Xilong; Salgado, Vincent L; Yeh, Jay Z; Narahashi, Toshio

    2003-09-01

    Fipronil and dieldrin are known to inhibit GABA receptors in both mammals and insects. However, the mechanism of selective toxicity of these insecticides between mammals and insects remains to be seen. One possible mechanism is that insect GABA receptors are more sensitive than mammalian GABAA receptors to fipronil and dieldrin. We examined differential actions of fipronil and dieldrin on GABA-gated chloride channels in insects and compared them with the data on mammalian GABAA receptors. Neurons were acutely dissociated from the American cockroach thoracic ganglia, and currents evoked by GABA were recorded by the whole-cell patch-clamp technique. GABA-evoked currents were carried by chloride ions, blocked by picrotoxinin, but not by bicuculline. Fipronil inhibited GABA currents with an IC50 value of 28 nM, whereas dieldrin exhibited a dual action potentiation with an EC50 value of 4 nM followed by inhibition with an IC50 value of 16 nM. Fipronil and dieldrin acted on the resting receptor at comparable rates, whereas fipronil blocked the activated receptor 10 times faster than dieldrin. Fipronil inhibition was partially reversible, whereas dieldrin inhibition was irreversible. Fipronil was 59 times more potent on cockroach GABA receptors than on rat GABAA receptors. However, the potentiating and inhibitory potencies of dieldrin in cockroach GABA receptors were comparable with those in rat GABAA receptors. It was concluded that the higher toxicity of fipronil in insects than in mammals is due partially to the higher sensitivity of GABA receptors. The mechanism of dieldrin's selective toxicity must lie in factors other than the sensitivity of GABA receptors.

  12. Decoupling kinematics and mechanics reveals coding properties of trigeminal ganglion neurons in the rat vibrissal system

    PubMed Central

    Bush, Nicholas E; Schroeder, Christopher L; Hobbs, Jennifer A; Yang, Anne ET; Huet, Lucie A; Solla, Sara A; Hartmann, Mitra JZ

    2016-01-01

    Tactile information available to the rat vibrissal system begins as external forces that cause whisker deformations, which in turn excite mechanoreceptors in the follicle. Despite the fundamental mechanical origin of tactile information, primary sensory neurons in the trigeminal ganglion (Vg) have often been described as encoding the kinematics (geometry) of object contact. Here we aimed to determine the extent to which Vg neurons encode the kinematics vs. mechanics of contact. We used models of whisker bending to quantify mechanical signals (forces and moments) at the whisker base while simultaneously monitoring whisker kinematics and recording single Vg units in both anesthetized rats and awake, body restrained rats. We employed a novel manual stimulation technique to deflect whiskers in a way that decouples kinematics from mechanics, and used Generalized Linear Models (GLMs) to show that Vg neurons more directly encode mechanical signals when the whisker is deflected in this decoupled stimulus space. DOI: http://dx.doi.org/10.7554/eLife.13969.001 PMID:27348221

  13. Population coding of saccadic eye movements by neurons in the superior colliculus

    NASA Astrophysics Data System (ADS)

    Lee, Choongkil; Rohrer, William H.; Sparks, David L.

    1988-03-01

    The deeper layers of the superior colliculus are involved in the initiation and execution of saccadic (high velocity) eye movements1. A large population of coarsely tuned collicular neurons is active before each saccade. The mechanisms by which the signals that precisely control the direction and amplitude of a saccade are extracted from the activity of the population are unknown. It has been assumed2 6 that the exact trajectory of a saccade is determined by the activity of the entire population and that information is not extracted from only the most active cells in the population at a subsequent stage of neural processing. The trajectory of a saccade could be based on vector summation of the movement tendencies provided by each member of the population of active neurons4 or be determined by a weighted average of the vector contributions of each neuron in the active population2. Here we present the results of experiments in which a small subset of the active population was reversibly deactivated with lidocaine. These results are consistent with the predictions of the latter population-averaging hypothesis and support the general idea that the direction, amplitude and velocity of saccadic eye movements are based on the responses of the entire population of cells active before a saccadic eye movement.

  14. The ways of action of long non-coding RNAs in cytoplasm and nucleus.

    PubMed

    Zhang, Kun; Shi, Zhe-Min; Chang, Ya-Nan; Hu, Zhi-Mei; Qi, Hai-Xia; Hong, Wei

    2014-08-15

    Over the past fifteen years, small regulatory RNAs, such as siRNA and miRNA, have been extensively investigated and the underlying molecular mechanisms have been well documented, suggesting that ncRNAs play a major function in many cellular processes. An expanding body of evidence reveals that long non-coding RNAs (lncRNAs), once described as dark matter, are involved in diverse cellular progresses, including regulation of gene expression, dosage compensation, genomic imprinting, nuclear organization and nuclear-cytoplasm trafficking via a number of complex mechanisms. The emerging links between lncRNAs and diseases as well as their tissue-specific expression patterns also indicate that lncRNAs comprise a core transcriptional regulatory circuitry. The function of lncRNAs is based on their sequence and structure; and they can combine with DNA, RNA, and proteins both in the nucleus and the cytoplasm. However, detailed insights into their biological and mechanistic functions are only beginning to emerge. In this review, we will mainly talk about diverse ways of action of lncRNAs in different sub-cellular locations and provide clues for following studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila

    PubMed Central

    Aso, Yoshinori; Sitaraman, Divya; Ichinose, Toshiharu; Kaun, Karla R; Vogt, Katrin; Belliart-Guérin, Ghislain; Plaçais, Pierre-Yves; Robie, Alice A; Yamagata, Nobuhiro; Schnaitmann, Christopher; Rowell, William J; Johnston, Rebecca M; Ngo, Teri-T B; Chen, Nan; Korff, Wyatt; Nitabach, Michael N; Heberlein, Ulrike; Preat, Thomas; Branson, Kristin M; Tanimoto, Hiromu; Rubin, Gerald M

    2014-01-01

    Animals discriminate stimuli, learn their predictive value and use this knowledge to modify their behavior. In Drosophila, the mushroom body (MB) plays a key role in these processes. Sensory stimuli are sparsely represented by ∼2000 Kenyon cells, which converge onto 34 output neurons (MBONs) of 21 types. We studied the role of MBONs in several associative learning tasks and in sleep regulation, revealing the extent to which information flow is segregated into distinct channels and suggesting possible roles for the multi-layered MBON network. We also show that optogenetic activation of MBONs can, depending on cell type, induce repulsion or attraction in flies. The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence. We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli. Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection. DOI: http://dx.doi.org/10.7554/eLife.04580.001 PMID:25535794

  16. Different cholinergic synapses converging onto neurons in Aplysia produce the same synaptic action.

    PubMed

    Segal, M; Koester, J

    1980-10-20

    We have investigated neurons that receive inputs from more than one cholinergic interneuron, to see whether one cholinergic input can depolarize and the other hyperpolarize by virtue of activating different ACh receptors. We have examined synapses made in the abdominal ganglion of Aplysia californica by 3 cholinergic interneurons. Two of those interneurons have previously been shown to be cholinergic. Using both biochemical and pharmacological tests we have shown a third interneuron to be cholinergic. For 7 postsynaptic cells, we compared 6 new connections that we have identified from cholinergic interneurons, and 12 previously known connections. In each case we found that different cholinergic inputs onto any given cell produced the same synaptic action. This finding held even for L7, a cell known to have two types of ACh receptors. These data are consistent with the hypothesis that a postsynaptic cell does not segregate different types of ACh receptors. If generally true, this lack of segregation may help explain why a nervous system uses more than one neurotransmitter as well as why certain interneurons are needed in neural networks.

  17. Nature of the neurotoxic membrane actions of amyloid-β on hippocampal neurons in Alzheimer's disease.

    PubMed

    Sepúlveda, Fernando J; Fierro, Humberto; Fernandez, Eduardo; Castillo, Carolina; Peoples, Robert W; Opazo, Carlos; Aguayo, Luis G

    2014-03-01

    The mechanism by which amyloid-β (Aβ) produces brain dysfunction in patients with Alzheimer's disease is largely unknown. According to previous studies, Aβ might share perforating properties with gramicidin, a well-accepted membrane-disrupting peptide. Therefore, we hypothesize that the key steps leading to synaptotoxicity by Aβ and gramicidin involve peptide aggregation, pore formation, and calcium dysregulation. Here, we show that Aβ and gramicidin form aggregates enriched in β-sheet structures using electron microscopy, and Thioflavin and Congo Red staining techniques. Also, we found that Aβ and gramicidin display fairly similar actions in hippocampal cell membranes, i.e. inducing Ca(2+) entry and synaptoxicity characterized by the loss of synaptic proteins and a decrease in neuronal viability. These effects were not observed in a Ca(2+) free solution, indicating that both Aβ and gramicidin induce neurotoxicity by a Ca(2+)-dependent mechanism. Using combined perforated patch clamp and imaging recordings, we found that only Aβ produced a perforation that progressed from a small (Cl(-)-selective pore) to a larger perforation that allowed the entry of fluorescent molecules. Therefore, based on these results, we propose that the perforation at the plasma membrane by Aβ is a dynamic process that is critical in producing neurotoxicity similar to that found in the brains of AD patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. A model of inward and outward membrane currents in cultured embryonic amphibian spinal neurons and reconstruction of the action potential.

    PubMed

    Barish, M E

    1985-01-01

    A model of the membrane currents in embryonic amphibian neurons has been developed in order to investigate the ionic mechanisms underlying developmental changes in excitability. Differentiating amphibian neurons both in situ and in vitro show a gradual change in the ionic sensitivity of their action potential from Ca- to Na-dependent, with an intermediate period in which the action potential shows a mixed ionic sensitivity. The model developed incorporates quantitative descriptions of Na, Ca and voltage-dependent K currents recorded (using whole-cell gigaohm-seal recording techniques) from presumptive neurons isolated from neural plate stage embryos of the axolotl Amblystoma during their in vitro differentiation. The kinetic descriptions of the currents were developed using the form of those of Hodgkin and Huxley. Na and K currents were modeled as voltage-dependent conductances showing m3h and n4 kinetics, respectively. Ca current was modeled (using the constant field relation) as a voltage-dependent permeability with s2 activation kinetics. Ca currents in whole-cell recordings were non-inactivating, and no inactivation mechanism was specified in the model. When modeled current amplitudes and kinetics were scaled as appropriate for a cell at an intermediate stage of differentiation (when the action potential recorded with microelectrodes shows a mixed Na- and Ca-dependence), the action potential predicted by the model showed a similar waveform and ionic dependence. The utility of this model lies in its ability to indicate the activity of each ionic current during an action potential at any developmental stage, and to unambiguously test the effects on neuronal excitability of alterations in the magnitude and/or kinetics of any of the ionic currents present in the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Excitatory action of GABA on immature neurons is not due to absence of ketone bodies metabolites or other energy substrates.

    PubMed

    Ben-Ari, Yehezkel; Tyzio, Roman; Nehlig, Astrid

    2011-09-01

    Brain slices incubated with glucose have provided most of our knowledge on cellular, synaptic, and network driven mechanisms. It has been recently suggested that γ-aminobutyric acid (GABA) excites neonatal neurons in conventional glucose-perfused slices but not when ketone bodies metabolites, pyruvate, and/or lactate are added, suggesting that the excitatory actions of GABA are due to energy deprivation when glucose is the sole energy source. In this article, we review the vast number of studies that show that slices are not energy deprived in glucose-containing medium, and that addition of other energy substrates at physiologic concentrations does not alter the excitatory actions of GABA on neonatal neurons. In contrast, lactate, like other weak acids, can produce an intracellular acidification that will cause a reduction of intracellular chloride and a shift of GABA actions. The effects of high concentrations of lactate, and particularly of pyruvate (4-5 mm), as used are relevant primarily to pathologic conditions; these concentrations not being found in the brain in normal "control" conditions. Slices in glucose-containing medium may not be ideal, but additional energy substrates neither correspond to physiologic conditions nor alter GABA actions. In keeping with extensive observations in a wide range of animal species and brain structures, GABA depolarizes immature neurons and the reduction of the intracellular concentration of chloride ([Cl(-)](i)) is a basic property of brain maturation that has been preserved throughout evolution. In addition, this developmental sequence has important clinical implications, notably concerning the higher incidence of seizures early in life and their long-lasting deleterious sequels. Immature neurons have difficulties exporting chloride that accumulates during seizures, leading to permanent increase of [Cl(-)](i) that converts the inhibitory actions of GABA to excitatory and hampers the efficacy of GABA-acting antiepileptic

  20. Action potential modulation in CA1 pyramidal neuron axons facilitates OLM interneuron activation in recurrent inhibitory microcircuits of rat hippocampus.

    PubMed

    Kim, Sooyun

    2014-01-01

    Oriens-lacunosum moleculare (O-LM) interneurons in the CA1 region of the hippocampus play a key role in feedback inhibition and in the control of network activity. However, how these cells are efficiently activated in the network remains unclear. To address this question, I performed recordings from CA1 pyramidal neuron axons, the presynaptic fibers that provide feedback innervation of these interneurons. Two forms of axonal action potential (AP) modulation were identified. First, repetitive stimulation resulted in activity-dependent AP broadening. Broadening showed fast onset, with marked changes in AP shape following a single AP. Second, tonic depolarization in CA1 pyramidal neuron somata induced AP broadening in the axon, and depolarization-induced broadening summated with activity-dependent broadening. Outside-out patch recordings from CA1 pyramidal neuron axons revealed a high density of α-dendrotoxin (α-DTX)-sensitive, inactivating K+ channels, suggesting that K+ channel inactivation mechanistically contributes to AP broadening. To examine the functional consequences of axonal AP modulation for synaptic transmission, I performed paired recordings between synaptically connected CA1 pyramidal neurons and O-LM interneurons. CA1 pyramidal neuron-O-LM interneuron excitatory postsynaptic currents (EPSCs) showed facilitation during both repetitive stimulation and tonic depolarization of the presynaptic neuron. Both effects were mimicked and occluded by α-DTX, suggesting that they were mediated by K+ channel inactivation. Therefore, axonal AP modulation can greatly facilitate the activation of O-LM interneurons. In conclusion, modulation of AP shape in CA1 pyramidal neuron axons substantially enhances the efficacy of principal neuron-interneuron synapses, promoting the activation of O-LM interneurons in recurrent inhibitory microcircuits.

  1. 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

  2. The isolation, from electromotor neurone perikarya, of messenger RNAs coding for synaptic proteins.

    PubMed

    Schmid, D; Stadler, H; Whittaker, V P

    1982-03-01

    Poly(A)-containing mRNA was isolated from the electric lobe, cerebellum and forebrain of Torpedo marmorata and from cholinergic electromotor perikarya isolated from the electric lobe. All the mRNA preparations were translated by a cell-free protein-synthesizing system from rabbit reticulocytes; no brain-specific factors were required. The highest stimulation rate was found with the perikaryal mRNA suggesting that this purely neuronal mRNA is a preferred template in the protein-synthesis system; the molecular basis of this phenomenon remains to be elucidated. The translation products of the perikaryal mRNA were analysed by two-dimensional gel electrophoresis and compared with the proteins of synaptosomes derived from the electromotor nerve terminals. The majority of the synaptosomal proteins comigrated with synthesized products. More than 100 synthesized proteins were detected as individual spots in the gel pattern, among them actin, subunits of neurofilamentous proteins and a protein considered to be a specific component of electromotor synaptic vesicles. Identities were confirmed in some cases by immunochemical methods. The results suggest that protein synthesis in the perikaryon of the electromotor neurone is largely directed to the production of proteins needed to maintain synaptic integrity. A comparison of the translation products of mRNA derived from the highly cholinergic electric lobe and a brain region, the cerebellum, which is non-cholinergic, revealed, as expected, some common translation products and others which appeared to be specific for the brain regions concerned. This approach may lead to the identification of protein specific for neurones of different transmitter types.

  3. Agonist actions of neonicotinoids on nicotinic acetylcholine receptors expressed by cockroach neurons.

    PubMed

    Tan, Jianguo; Galligan, James J; Hollingworth, Robert M

    2007-07-01

    The agonist actions of seven commercial neonicotinoid insecticides and nicotine were studied on nicotinic acetylcholine receptors (nAChRs) expressed by neurons isolated from the three thoracic ganglia of the American cockroach, Periplaneta americana. Single electrode voltage clamp recording was used to measure agonist-induced inward currents. Acetylcholine, nicotine and all neonicotinoids tested, except thiamethoxam, caused inward currents which were blocked reversibly by methyllycaconitine, a nAChR antagonist. Based on maximum inward currents, neonicotinoids could be divided into two subgroups: (1) those with a heterocyclic ring in their electronegative pharmacophore moiety (i.e. nicotine, imidacloprid and thiacloprid) were relatively weak partial agonists causing only 20-25% of the maximum ACh current and (2) open chain compounds (i.e. acetamiprid, dinotefuran, nitenpyram, and clothiandin) which were much more effective agonists producing 60-100% of the maximum ACh current. These compounds also elicited different symptoms of poisoning in American cockroaches with excitatory responses evident for the low efficacy agonists but depressive and paralytic responses predominating for the most efficacious agonists. No correlation was observed between agonist affinity and efficacy on these nAChRs. Thiamethoxam, even at 100 microM, failed to cause an inward current and showed no competitive interaction with other neonicotinoids on nAChRs, indicating that it is not a direct-acting agonist or antagonist. Despite the probable presence of multiple subtypes of nAChRs on cockroach neurons, competition studies between neonicotinoids did not reveal evidence that separate binding sites exist for the tested compounds. The size of inward currents induced by co-application of neonicotinoid pairs at equal concentration (100 microM) were predominantly determined by the one with higher binding affinity as indicated by EC(50) values, rather than by the one with higher binding efficacy as

  4. Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge.

    PubMed

    Michel, K; Michaelis, M; Mazzuoli, G; Mueller, K; Vanden Berghe, P; Schemann, M

    2011-12-15

    Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by -conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores.

  5. A mixture of sparse coding models explaining properties of face neurons related to holistic and parts-based processing.

    PubMed

    Hosoya, Haruo; Hyvärinen, Aapo

    2017-07-01

    Experimental studies have revealed evidence of both parts-based and holistic representations of objects and faces in the primate visual system. However, it is still a mystery how such seemingly contradictory types of processing can coexist within a single system. Here, we propose a novel theory called mixture of sparse coding models, inspired by the formation of category-specific subregions in the inferotemporal (IT) cortex. We developed a hierarchical network that constructed a mixture of two sparse coding submodels on top of a simple Gabor analysis. The submodels were each trained with face or non-face object images, which resulted in separate representations of facial parts and object parts. Importantly, evoked neural activities were modeled by Bayesian inference, which had a top-down explaining-away effect that enabled recognition of an individual part to depend strongly on the category of the whole input. We show that this explaining-away effect was indeed crucial for the units in the face submodel to exhibit significant selectivity to face images over object images in a similar way to actual face-selective neurons in the macaque IT cortex. Furthermore, the model explained, qualitatively and quantitatively, several tuning properties to facial features found in the middle patch of face processing in IT as documented by Freiwald, Tsao, and Livingstone (2009). These included, in particular, tuning to only a small number of facial features that were often related to geometrically large parts like face outline and hair, preference and anti-preference of extreme facial features (e.g., very large/small inter-eye distance), and reduction of the gain of feature tuning for partial face stimuli compared to whole face stimuli. Thus, we hypothesize that the coding principle of facial features in the middle patch of face processing in the macaque IT cortex may be closely related to mixture of sparse coding models.

  6. Involvement of G Protein-Coupled Receptor 30 (GPR30) in Rapid Action of Estrogen in Primate LHRH Neurons

    PubMed Central

    Noel, Sekoni D.; Keen, Kim L.; Baumann, David I.; Filardo, Edward J.; Terasawa, Ei

    2009-01-01

    Previously, we have reported that 17β-estradiol (E2) induces an increase in firing activity of primate LH-releasing hormone (LHRH) neurons. The present study investigates whether E2 alters LHRH release as well as the pattern of intracellular calcium ([Ca2+]i) oscillations and whether G protein-coupled receptor 30 (GPR30) plays a role in mediating the rapid E2 action in primate LHRH neurons. Results are summarized: 1) E2, the nuclear membrane-impermeable estrogen, estrogen-dendrimer conjugate, and the plasma membrane-impermeable estrogen, E2-BSA conjugate, all stimulated LHRH release within 10 min of exposure; 2) whereas the estrogen receptor antagonist, ICI 182,780, did not block the E2-induced LHRH release, E2 application to cells treated with pertussis toxin failed to induce LHRH release; 3) GPR30 mRNA was expressed in olfactory placode cultures, and GPR30 protein was expressed in a subset of LHRH neurons; 4) pertussis toxin treatment blocked the E2-induced increase in [Ca2+]i oscillations; 5) knockdown of GPR30 in primate LHRH neurons by transfection with small interfering RNA (siRNA) for GPR30 completely abrogated the E2-induced changes in [Ca2+]i oscillations, whereas transfection with control siRNA did not; 6) the estrogen-dendrimer conjugate-induced increase in [Ca2+]i oscillations also did not occur in LHRH neurons transfected with GPR30 siRNA; and 7) G1, a GPR30 agonist, resulted in changes in [Ca2+]i oscillations, similar to those observed with E2. Collectively, E2 induces a rapid excitatory effect on primate LHRH neurons, and this rapid action of E2 appears to be mediated, in part, through GPR30. PMID:19131510

  7. A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats

    PubMed Central

    McClelland, David; Evans, Rhian M; Barkworth, Louise; Martin, Duncan J; Scott, Roderick H

    2004-01-01

    Background Gabapentin and pregabalin have wide-ranging therapeutic actions, and are structurally related to the inhibitory neurotransmitter GABA. Gabapentin, pregablin and GABA can all modulate voltage-activated Ca2+ channels. In this study we have used whole cell patch clamp recording and fura-2 Ca2+ imaging to characterise the actions of pregabalin on the electrophysiological properties of cultured dorsal root ganglion (DRG) neurones from neonatal rats. The aims of this study were to determine whether pregabalin and gabapentin had additive inhibitory effects on high voltage-activated Ca2+ channels, evaluate whether the actions of pregabalin were dependent on GABA receptors and characterise the actions of pregabalin on voltage-activated potassium currents. Results Pregabalin (25 nM – 2.5 μM) inhibited 20–30% of the high voltage-activated Ca2+ current in cultured DRG neurones. The residual Ca2+ current recorded in the presence of pregabalin was sensitive to the L-type Ca2+ channel modulator, Bay K8644. Saturating concentrations of gabapentin failed to have additive effects when applied with pregabalin, indicating that these two compounds act on the same type(s) of voltage-activated Ca2+ channels but the majority of Ca2+ current was resistant to both drugs. The continual application of GABA, the GABAB receptor antagonist CGP52432, or intracellular photorelease of GTP-γ-S had no effect on pregabalin-induced inhibition of Ca2+ currents. Although clear inhibition of Ca2+ influx was produced by pregabalin in a population of small neurones, a significant population of larger neurones showed enhanced Ca2+ influx in response to pregabalin. The enhanced Ca2+ influx evoked by pregabalin was mimicked by partial block of K+ conductances with tetraethylammonium. Pregabalin produced biphasic effects on voltage-activated K+ currents, the inhibitory effect of pregabalin was prevented with apamin. The delayed enhancement of K+ currents was attenuated by pertussis toxin and by

  8. Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds

    PubMed Central

    Ishihara, Yasuhiro; Takemoto, Takuya; Yamazaki, Takeshi

    2015-01-01

    Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury. PMID:25815107

  9. Frequency and topography in monkey electroencephalogram during action observation: possible neural correlates of the mirror neuron system

    PubMed Central

    Coudé, G.; Vanderwert, R. E.; Thorpe, S.; Festante, F.; Bimbi, M.; Fox, N. A.; Ferrari, P. F.

    2014-01-01

    The observation of actions executed by others results in desynchronization of electroencephalogram (EEG) in the alpha and beta frequency bands recorded from the central regions in humans. On the other hand, mirror neurons, which are thought to be responsible for this effect, have been studied only in macaque monkeys, using single-cell recordings. Here, as a first step in a research programme aimed at understanding the parallels between human and monkey mirror neuron systems (MNS), we recorded EEG from the scalp of two monkeys during action observation. The monkeys were trained to fixate on the face of a human agent and subsequently to fixate on a target upon which the agent performed a grasping action. We found that action observation produced desynchronization in the 19–25 Hz band that was strongest over anterior and central electrodes. These results are in line with human data showing that specific frequency bands within the power spectrum of the ongoing EEG may be modulated by observation of actions and therefore might be a specific marker of MNS activity. PMID:24778383

  10. Diarrhetic effect of okadaic acid could be related with its neuronal action: Changes in neuropeptide Y.

    PubMed

    Louzao, M Carmen; Fernández, Diego A; Abal, Paula; Fraga, Maria; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

    2015-09-02

    Okadaic acid (OA) and dinophysistoxins (DTXs) are a group of marine toxins that cause diarrheic shellfish poisoning (DSP) in humans and animals. These compounds are produced by dinoflagellates of the Prorocentrum and Dinophysis genera and can accumulate in filter-feeding bivalves, posing a serious health risk for shellfish consumers. The enteric nervous system (ENS) plays a crucial role in the regulation of the gastrointestinal tract. In addition, neuropeptides produced by ENS affects the epithelial barrier functions. In the present work we used a two-compartment human coculture model containing the SH-SY5Y neuroblastoma cell line and polarized colonic epithelial monolayers (Caco-2) to study the OA intestinal permeability. First, we have determined OA cytotoxicity and we have found that OA reduces the viability of SH-SY5Y in a dose-dependent way, even though DTX1 is 4 to 5 times more potent than OA. Besides DTX1 is 15 to 18 orders of magnitude more potent than OA in decreasing transepithelial electrical resistance (TEER) of caco-2 cells without inducing cytotoxicity. Permeability assays indicate that OA cross the monolayer and modulates the neuropeptide Y (NPY) secretion by neuroblastoma cells. This NPY also affects the permeability of OA. This offers a novel approach to establish the influence of OA neuronal action on their diarrheic effects through a cross talk between ENS and intestine via OA induced NPY secretion. Therefore, the OA mechanisms of toxicity that were long attributed only to the inhibition of protein phosphatases, would require a reevaluation.

  11. Action of thyroxine on the survival and neurite maintenance of cerebellar granule neurons in culture.

    PubMed

    Oyanagi, Koshi; Negishi, Takayuki; Tashiro, Tomoko

    2015-04-01

    Developmental hypothyroidism causes severe impairments in the cerebellum. To understand the role of thyroid hormones (THs) in cerebellar development, we examined the effect of three different THs, thyroxine (T4), 3,5,3'-triidothyronine (T3), and 3,3',5'-triiodothyronine (reverse T3; rT3), on the survival and morphology of cerebellar granule neurons (CGNs) in culture and found novel actions specific to T4. Rat CGNs obtained at postnatal day 6 were first cultured for 2 days in serum-containing medium with 25 mM K(+) (K25), then switched to serum-free medium with physiological 5 mM K(+) (K5) or with K25 and cultured for an additional 2 or 4 days. CGNs underwent apoptosis in K5 but survived in K25. Addition of T4 at concentrations of 100-200 nM but not T3 or rT3 rescued CGNs from cell death in K5 in a dose-dependent manner. Furthermore, 200 nM T4 was also effective in maintaining the neurites of CGNs in K5. In K5, T4 suppressed tau phosphorylation at two developmentally regulated sites as well as phosphorylation of c-jun N-terminal kinase (JNK) necessary for its activation and localization to axons. These results suggest that, during cerebellar development, T4 exerts its activity in cell survival and neurite maintenance in a manner distinct from the other two thyroid hormones through regulating the activity and localization of JNK.

  12. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices.

    PubMed

    Greene, R W; Haas, H L

    1985-09-01

    Intracellular recordings with a bridge amplifier of CA1 pyramidal neurones in vitro were employed to study the mechanisms of action of exogenously applied adenosine in the hippocampal slice preparation of the rat. Adenosine enhanced the calcium-dependent, long-duration after-hyperpolarization (a.h.p.) at least in part by a reduction in the rate of decay of the a.h.p. Both the reduced rate of decay and that of the control can be described with a single exponential. Antagonism of the calcium-dependent potassium current (and as a result, the a.h.p.) by bath application of CdCl2 or intracellular injection of EGTA (ethyleneglycolbis-(beta-aminoethyl ether)N,N'-tetraacetic acid) did not reduce the adenosine-evoked hyperpolarization or decrease in input resistance. Similarly, TEA (tetraethylammonium), which antagonizes both the voltage- and calcium-sensitive, delayed, outward rectification, had no effect on the adenosine-evoked changes in resting membrane properties. Adenosine did not affect the early, transient, outward rectification. During exposure to 4-aminopyridine (4-AP) in concentrations sufficient to antagonize this early rectification, the changes in resting membrane properties evoked by adenosine were unaffected. We conclude that the enhancement of the a.h.p. and accommodation by adenosine may be mediated by a change in the regulation of intracellular calcium. However, the mechanism responsible for the hyperpolarization and decrease in input resistance evoked by adenosine is both calcium and voltage insensitive. Thus, it appears distinct from that mediating the enhancement of the a.h.p. and accommodation.

  13. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices.

    PubMed Central

    Greene, R W; Haas, H L

    1985-01-01

    Intracellular recordings with a bridge amplifier of CA1 pyramidal neurones in vitro were employed to study the mechanisms of action of exogenously applied adenosine in the hippocampal slice preparation of the rat. Adenosine enhanced the calcium-dependent, long-duration after-hyperpolarization (a.h.p.) at least in part by a reduction in the rate of decay of the a.h.p. Both the reduced rate of decay and that of the control can be described with a single exponential. Antagonism of the calcium-dependent potassium current (and as a result, the a.h.p.) by bath application of CdCl2 or intracellular injection of EGTA (ethyleneglycolbis-(beta-aminoethyl ether)N,N'-tetraacetic acid) did not reduce the adenosine-evoked hyperpolarization or decrease in input resistance. Similarly, TEA (tetraethylammonium), which antagonizes both the voltage- and calcium-sensitive, delayed, outward rectification, had no effect on the adenosine-evoked changes in resting membrane properties. Adenosine did not affect the early, transient, outward rectification. During exposure to 4-aminopyridine (4-AP) in concentrations sufficient to antagonize this early rectification, the changes in resting membrane properties evoked by adenosine were unaffected. We conclude that the enhancement of the a.h.p. and accommodation by adenosine may be mediated by a change in the regulation of intracellular calcium. However, the mechanism responsible for the hyperpolarization and decrease in input resistance evoked by adenosine is both calcium and voltage insensitive. Thus, it appears distinct from that mediating the enhancement of the a.h.p. and accommodation. PMID:3932644

  14. Action potential broadening in capsaicin-sensitive DRG neurons from frequency-dependent reduction of Kv3 current.

    PubMed

    Liu, Pin; Blair, Nathaniel T; Bean, Bruce P

    2017-09-06

    Action potential shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the action potentials. Stimulation at 10 Hz for three seconds resulted in an increase in action potential width by an average of 76 ± 7% at 22 °C and by 38 ± 3% at 35 °C. Action potential clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC50 <100 μM) and block by the peptide inhibitor BDS-I. There was a small component of Kv1-mediated current during action potential repolarization but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could underlie the frequency-dependent increases in conduction velocity typical of C-fiber axons.SIGNIFICANCE STATEMENTSmall-diameter dorsal root ganglion neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We find that action potentials of small-diameter rat dorsal root

  15. Back-propagating action potentials in pyramidal neurons: a putative signaling mechanism for the induction of Hebbian synaptic plasticity.

    PubMed

    Colbert, C M

    2001-01-01

    A hallmark of synaptic plasticity is the associative, or Hebbian, nature of its induction. By associative, we mean that the timing relationships between activity of the pre- and postsynaptic elements of a synapse determine whether synaptic strengths are modified. lt is well-established that associativity results, in large part, from the dual requirements for activation of the N-methyl-D-aspartate receptor-ionophore, namely presynaptic neurotransmitter release and postsynaptic depolarization. However, the specific dendritic events that provide the postsynaptic depolarization have been relatively unexplored. Increasing evidence suggests that back-propagating (i.e., antidromic) Na(+) action potentials provide the necessary postsynaptic depolarization to allow induction of associative synaptic plasticities. In hippocampal CAI and neocortical layer V pyramidal neurons, these action potentials provide much greater levels of dendritic depolarization than would be expected from synaptic currents alone. Moreover, they provide a relatively brief and synchronous depolarization throughout the dendritic arbor, allowing timing relationships to more directly reflect pre- and postsynaptic cell firing. Interestingly, certain properties of the back-propagating actions potentials differ from axonal or somatic action potentials in ways that seem to reflect their function. For example, the all-or-none property of action potential amplitude does not hold in the dendrites. In this review we discuss the back-propagating action potential as a dendritic signal that provides information to synapses about the firing state of the postsynaptic neuron. First, we consider the evidence that action potentials propagate back from the axon. Second, we describe the characteristics of the back-propagating action potential in terms of interactions of its underlying ionic currents. Third, we describe how these properties contribute to the timing aspects of the induction of long-term potentiation. Finally

  16. Action potential initiation in a two-compartment model of pyramidal neuron mediated by dendritic Ca(2+) spike.

    PubMed

    Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

    2017-04-03

    Dendritic Ca(2+) spike endows cortical pyramidal cell with powerful ability of synaptic integration, which is critical for neuronal computation. Here we propose a two-compartment conductance-based model to investigate how the Ca(2+) activity of apical dendrite participates in the action potential (AP) initiation to affect the firing properties of pyramidal neurons. We have shown that the apical input with sufficient intensity triggers a dendritic Ca(2+) spike, which significantly boosts dendritic inputs as it propagates to soma. Such event instantaneously shifts the limit cycle attractor of the neuron and results in a burst of APs, which makes its firing rate reach a plateau steady-state level. Delivering current to two chambers simultaneously increases the level of neuronal excitability and decreases the threshold of input-output relation. Here the back-propagating APs facilitate the initiation of dendritic Ca(2+) spike and evoke BAC firing. These findings indicate that the proposed model is capable of reproducing in vitro experimental observations. By determining spike initiating dynamics, we have provided a fundamental link between dendritic Ca(2+) spike and output APs, which could contribute to mechanically interpreting how dendritic Ca(2+) activity participates in the simple computations of pyramidal neuron.

  17. Action potential initiation in a two-compartment model of pyramidal neuron mediated by dendritic Ca2+ spike

    PubMed Central

    Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

    2017-01-01

    Dendritic Ca2+ spike endows cortical pyramidal cell with powerful ability of synaptic integration, which is critical for neuronal computation. Here we propose a two-compartment conductance-based model to investigate how the Ca2+ activity of apical dendrite participates in the action potential (AP) initiation to affect the firing properties of pyramidal neurons. We have shown that the apical input with sufficient intensity triggers a dendritic Ca2+ spike, which significantly boosts dendritic inputs as it propagates to soma. Such event instantaneously shifts the limit cycle attractor of the neuron and results in a burst of APs, which makes its firing rate reach a plateau steady-state level. Delivering current to two chambers simultaneously increases the level of neuronal excitability and decreases the threshold of input-output relation. Here the back-propagating APs facilitate the initiation of dendritic Ca2+ spike and evoke BAC firing. These findings indicate that the proposed model is capable of reproducing in vitro experimental observations. By determining spike initiating dynamics, we have provided a fundamental link between dendritic Ca2+ spike and output APs, which could contribute to mechanically interpreting how dendritic Ca2+ activity participates in the simple computations of pyramidal neuron. PMID:28367964

  18. View-based encoding of actions in mirror neurons of area f5 in macaque premotor cortex.

    PubMed

    Caggiano, Vittorio; Fogassi, Leonardo; Rizzolatti, Giacomo; Pomper, Joern K; Thier, Peter; Giese, Martin A; Casile, Antonino

    2011-01-25

    Converging experimental evidence indicates that mirror neurons in the monkey premotor area F5 encode the goals of observed motor acts [1-3]. However, it is unknown whether they also contribute to encoding the perspective from which the motor acts of others are seen. In order to address this issue, we recorded the visual responses of mirror neurons of monkey area F5 by using a novel experimental paradigm based on the presentation of movies showing grasping motor acts from different visual perspectives. We found that the majority of the tested mirror neurons (74%) exhibited view-dependent activity with responses tuned to specific points of view. A minority of the tested mirror neurons (26%) exhibited view-independent responses. We conclude that view-independent mirror neurons encode action goals irrespective of the details of the observed motor acts, whereas the view-dependent ones might either form an intermediate step in the formation of view independence or contribute to a modulation of view-dependent representations in higher-level visual areas, potentially linking the goals of observed motor acts with their pictorial aspects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Multiple actions of a molluscan cardioexcitatory neuropeptide and related peptides on identified Helix neurones.

    PubMed Central

    Cottrell, G A; Davies, N W; Green, K A

    1984-01-01

    The effects of the molluscan neuropeptide Phe-Met-Arg-Phe-NH2 (FMRF amide) and related peptides (Price & Greenberg, 1977) were tested on Helix aspersa neurones. Ionophoretic application of FMRFamide depolarized and excited some neurones, but hyperpolarized and inhibited others. In some neurones the sign of the response was dependent on the membrane potential. Two responses resulted from an increase in membrane conductance, a depolarizing response mediated mainly by an increase in Na+ ion permeability, and a hyperpolarizing response mediated by an increase in K+ ion permeability. In the C1 neurone a voltage-dependent response was observed, which only occurred when the neurone was depolarized from its resting level. This response was recorded as an inward current during voltage clamp and resulted from a decrease in K current(s), possibly Ca-activated K current. More than one response may occur in a single neurone. In the C1 neurone, the K-mediated hyperpolarization occurred as well as the voltage-dependent response, while the depolarization seen in the F2 neurone was a combination of an increase in Na conductance and an increase in K conductance. PMID:6097674

  20. A spiking neuron model of the cortico-basal ganglia circuits for goal-directed and habitual action learning.

    PubMed

    Chersi, Fabian; Mirolli, Marco; Pezzulo, Giovanni; Baldassarre, Gianluca

    2013-05-01

    Dual-system theories postulate that actions are supported either by a goal-directed or by a habit-driven response system. Neuroimaging and anatomo-functional studies have provided evidence that the prefrontal cortex plays a fundamental role in the first type of action control, while internal brain areas such as the basal ganglia are more active during habitual and overtrained responses. Additionally, it has been shown that areas of the cortex and the basal ganglia are connected through multiple parallel "channels", which are thought to function as an action selection mechanism resolving competitions between alternative options available in a given context. In this paper we propose a multi-layer network of spiking neurons that implements in detail the thalamo-cortical circuits that are believed to be involved in action learning and execution. A key feature of this model is that neurons are organized in small pools in the motor cortex and form independent loops with specific pools of the basal ganglia where inhibitory circuits implement a multistep selection mechanism. The described model has been validated utilizing it to control the actions of a virtual monkey that has to learn to turn on briefly flashing lights by pressing corresponding buttons on a board. When the animal is able to fluently execute the task the button-light associations are remapped so that it has to suppress its habitual behavior in order to execute goal-directed actions. The model nicely shows how sensory-motor associations for action sequences are formed at the cortico-basal ganglia level and how goal-directed decisions may override automatic motor responses.

  1. Positive, but not negative feedback actions of estradiol in adult female mice require estrogen receptor α in kisspeptin neurons.

    PubMed

    Dubois, Sharon L; Acosta-Martínez, Maricedes; DeJoseph, Mary R; Wolfe, Andrew; Radovick, Sally; Boehm, Ulrich; Urban, Janice H; Levine, Jon E

    2015-03-01

    Hypothalamic kisspeptin (Kiss1) neurons express estrogen receptor α (ERα) and exert control over GnRH/LH secretion in female rodents. It has been proposed that estradiol (E2) activation of ERα in kisspeptin neurons in the arcuate nucleus (ARC) suppresses GnRH/LH secretion (negative feedback), whereas E2 activation of ERα in kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) mediates the release of preovulatory GnRH/LH surges (positive feedback). To test these hypotheses, we generated mice bearing kisspeptin cell-specific deletion of ERα (KERαKO) and treated them with E2 regimens that evoke either negative or positive feedback actions on GnRH/LH secretion. Using negative feedback regimens, as expected, E2 effectively suppressed LH levels in ovariectomized (OVX) wild-type (WT) mice to the levels seen in ovary-intact mice. Surprisingly, however, despite the fact that E2 regulation of Kiss1 mRNA expression was abrogated in both the ARC and AVPV of KERαKO mice, E2 also effectively decreased LH levels in OVX KERαKO mice to the levels seen in ovary-intact mice. Conversely, using a positive feedback regimen, E2 stimulated LH surges in WT mice, but had no effect in KERαKO mice. These experiments clearly demonstrate that ERα in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice. It remains to be determined whether the failure of KERαKO mice to exhibit GnRH/LH surges reflects the role of ERα in the development of kisspeptin neurons, in the active signaling processes leading to the release of GnRH/LH surges, or both.

  2. 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.

  3. Anti-obesity actions of mastication driven by histamine neurons in rats.

    PubMed

    Sakata, Toshiie; Yoshimatsu, Hironobu; Masaki, Takayuki; Tsuda, Kaoru

    2003-11-01

    Implications of mastication in energy intake and expenditure regulated by histamine (HA) neurons were investigated in rats. Depletion of neuronal HA from the mesencephalic trigeminal sensory nucleus (Me5) reduced eating speed, but that from a satiety center of the ventromedial hypothalamus (VMH) increased both meal size and its duration leaving eating speed unaffected. Turnover of neuronal HA in the Me5 was elevated at the early phase of feeding and that in the VMH was at the later phase. This elevated turnover was abolished by gastric intubations of an isocaloric liquid diet or an equivolume of water. Mastication-induced activation of HA neurons suppressed physiological food intake through H1-receptor in the hypothalamic paraventricular nucleus (PVN) and the VMH. On the other hand, the HA neurons activation accelerated lipolysis particularly in the visceral adipose tissues and up-regulated mRNA expression of uncoupling protein family through sympathetic efferent nerve. Mastication thus plays an important role as a potent input signal to activate HA neurons. Our recent findings have evidently shown how tightly and elegantly HA neurons are concordant with leptin signaling system through a negative feedback loop.

  4. Action Potential Modulation in CA1 Pyramidal Neuron Axons Facilitates OLM Interneuron Activation in Recurrent Inhibitory Microcircuits of Rat Hippocampus

    PubMed Central

    Kim, Sooyun

    2014-01-01

    Oriens-lacunosum moleculare (O-LM) interneurons in the CA1 region of the hippocampus play a key role in feedback inhibition and in the control of network activity. However, how these cells are efficiently activated in the network remains unclear. To address this question, I performed recordings from CA1 pyramidal neuron axons, the presynaptic fibers that provide feedback innervation of these interneurons. Two forms of axonal action potential (AP) modulation were identified. First, repetitive stimulation resulted in activity-dependent AP broadening. Broadening showed fast onset, with marked changes in AP shape following a single AP. Second, tonic depolarization in CA1 pyramidal neuron somata induced AP broadening in the axon, and depolarization-induced broadening summated with activity-dependent broadening. Outside-out patch recordings from CA1 pyramidal neuron axons revealed a high density of α-dendrotoxin (α-DTX)-sensitive, inactivating K+ channels, suggesting that K+ channel inactivation mechanistically contributes to AP broadening. To examine the functional consequences of axonal AP modulation for synaptic transmission, I performed paired recordings between synaptically connected CA1 pyramidal neurons and O-LM interneurons. CA1 pyramidal neuron–O-LM interneuron excitatory postsynaptic currents (EPSCs) showed facilitation during both repetitive stimulation and tonic depolarization of the presynaptic neuron. Both effects were mimicked and occluded by α-DTX, suggesting that they were mediated by K+ channel inactivation. Therefore, axonal AP modulation can greatly facilitate the activation of O-LM interneurons. In conclusion, modulation of AP shape in CA1 pyramidal neuron axons substantially enhances the efficacy of principal neuron–interneuron synapses, promoting the activation of O-LM interneurons in recurrent inhibitory microcircuits. PMID:25409299

  5. Firing Dynamics and Modulatory Actions of Supraspinal Dopaminergic Neurons during Zebrafish Locomotor Behavior

    PubMed Central

    Jay, Michael; De Faveri, Francesca; McDearmid, Jonathan Robert

    2015-01-01

    Summary Background Dopamine (DA) has long been known to have modulatory effects on vertebrate motor circuits. However, the types of information encoded by supraspinal DAergic neurons and their relationship to motor behavior remain unknown. Results By conducting electrophysiological recordings from awake, paralyzed zebrafish larvae that can produce behaviorally relevant activity patterns, we show that supraspinal DAergic neurons generate two forms of output: tonic spiking and phasic bursting. Using paired supraspinal DA neuron and motoneuron recordings, we further show that these firing modes are associated with specific behavioral states. Tonic spiking is prevalent during periods of inactivity while bursting strongly correlates with locomotor output. Targeted laser ablation of supraspinal DA neurons reduces motor episode frequency without affecting basic parameters of motor output, strongly suggesting that these cells regulate spinal network excitability. Conclusions Our findings reveal how vertebrate motor circuit flexibility is temporally controlled by supraspinal DAergic pathways and provide important insights into the functional significance of this evolutionarily conserved cell population. PMID:25639243

  6. Increased transient Na(+) conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1(-/y) mouse.

    PubMed

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1(-/y) mice. In fmr1(-/y) L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na(+) conductance density is higher in fmr1(-/y) L2/3 neurons. Measurements of three biophysically distinct K(+) currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K(+) conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1(-/y) mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1(-/y) mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1(-/y) neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na(+) current was significantly larger in fmr1(-/y) neurons. Furthermore, the activation curve of somatic A-type K(+) current was depolarized. Realistic conductance-based simulations revealed that these biophysical

  7. Branch specific and spike-order specific action potential invasion in basal, oblique, and apical dendrites of cortical pyramidal neurons

    PubMed Central

    Zhou, Wen-Liang; Short, Shaina M.; Rich, Matthew T.; Oikonomou, Katerina D.; Singh, Mandakini B.; Sterjanaj, Enas V.; Antic, Srdjan D.

    2014-01-01

    Abstract. In neocortical pyramidal neurons, action potentials (APs) propagate from the axon into the dendritic tree to influence distal synapses. Traditionally, AP backpropagation was studied in the thick apical trunk. Here, we used the principles of optical imaging developed by Cohen to investigate AP invasion into thin dendritic branches (basal, oblique, and tuft) of prefrontal cortical L5 pyramidal neurons. Multisite optical recordings from neighboring dendrites revealed a clear dichotomy between two seemingly equal dendritic branches belonging to the same cell (“sister branches”). We documented the variable efficacy of AP invasion in basal and oblique branches by revealing their AP voltage waveforms. Using fast multisite calcium imaging, we found that trains of APs are filtered differently between two apical tuft branches. Although one dendritic branch passes all spikes in an AP train, another branch belonging to the same neuron, same cortical layer, and same path distance from the cell body, experiences only one spike. Our data indicate that the vast differences in dendritic voltage and calcium transients, detected in dendrites of pyramidal neurons, arise from a nonuniform distribution of A-type K+ conductance, an aggregate number of branch points in the path of the AP propagation and minute differences in dendritic diameter. PMID:26157997

  8. Adaptation in Coding by Large Populations of Neurons in the Retina

    NASA Astrophysics Data System (ADS)

    Ioffe, Mark L.

    A comprehensive theory of neural computation requires an understanding of the statistical properties of the neural population code. The focus of this work is the experimental study and theoretical analysis of the statistical properties of neural activity in the tiger salamander retina. This is an accessible yet complex system, for which we control the visual input and record from a substantial portion--greater than a half--of the ganglion cell population generating the spiking output. Our experiments probe adaptation of the retina to visual statistics: a central feature of sensory systems which have to adjust their limited dynamic range to a far larger space of possible inputs. In Chapter 1 we place our work in context with a brief overview of the relevant background. In Chapter 2 we describe the experimental methodology of recording from 100+ ganglion cells in the tiger salamander retina. In Chapter 3 we first present the measurements of adaptation of individual cells to changes in stimulation statistics and then investigate whether pairwise correlations in fluctuations of ganglion cell activity change across different stimulation conditions. We then transition to a study of the population-level probability distribution of the retinal response captured with maximum-entropy models. Convergence of the model inference is presented in Chapter 4. In Chapter 5 we first test the empirical presence of a phase transition in such models fitting the retinal response to different experimental conditions, and then proceed to develop other characterizations which are sensitive to complexity in the interaction matrix. This includes an analysis of the dynamics of sampling at finite temperature, which demonstrates a range of subtle attractor-like properties in the energy landscape. These are largely conserved when ambient illumination is varied 1000-fold, a result not necessarily apparent from the measured low-order statistics of the distribution. Our results form a consistent

  9. fMRI Adaptation between Action Observation and Action Execution Reveals Cortical Areas with Mirror Neuron Properties in Human BA 44/45.

    PubMed

    de la Rosa, Stephan; Schillinger, Frieder L; Bülthoff, Heinrich H; Schultz, Johannes; Uludag, Kamil

    2016-01-01

    Mirror neurons (MNs) are considered to be the supporting neural mechanism for action understanding. MNs have been identified in monkey's area F5. The identification of MNs in the human homolog of monkeys' area F5 Broadmann Area 44/45 (BA 44/45) has been proven methodologically difficult. Cross-modal functional MRI (fMRI) adaptation studies supporting the existence of MNs restricted their analysis to a priori candidate regions, whereas studies that failed to find evidence used non-object-directed (NDA) actions. We tackled these limitations by using object-directed actions (ODAs) differing only in terms of their object directedness in combination with a cross-modal adaptation paradigm and a whole-brain analysis. Additionally, we tested voxels' blood oxygenation level-dependent (BOLD) response patterns for several properties previously reported as typical MN response properties. Our results revealed 52 voxels in left inferior frontal gyrus (IFG; particularly BA 44/45), which respond to both motor and visual stimulation and exhibit cross-modal adaptation between the execution and observation of the same action. These results demonstrate that part of human IFG, specifically BA 44/45, has BOLD response characteristics very similar to monkey's area F5.

  10. fMRI Adaptation between Action Observation and Action Execution Reveals Cortical Areas with Mirror Neuron Properties in Human BA 44/45

    PubMed Central

    de la Rosa, Stephan; Schillinger, Frieder L.; Bülthoff, Heinrich H.; Schultz, Johannes; Uludag, Kamil

    2016-01-01

    Mirror neurons (MNs) are considered to be the supporting neural mechanism for action understanding. MNs have been identified in monkey’s area F5. The identification of MNs in the human homolog of monkeys’ area F5 Broadmann Area 44/45 (BA 44/45) has been proven methodologically difficult. Cross-modal functional MRI (fMRI) adaptation studies supporting the existence of MNs restricted their analysis to a priori candidate regions, whereas studies that failed to find evidence used non-object-directed (NDA) actions. We tackled these limitations by using object-directed actions (ODAs) differing only in terms of their object directedness in combination with a cross-modal adaptation paradigm and a whole-brain analysis. Additionally, we tested voxels’ blood oxygenation level-dependent (BOLD) response patterns for several properties previously reported as typical MN response properties. Our results revealed 52 voxels in left inferior frontal gyrus (IFG; particularly BA 44/45), which respond to both motor and visual stimulation and exhibit cross-modal adaptation between the execution and observation of the same action. These results demonstrate that part of human IFG, specifically BA 44/45, has BOLD response characteristics very similar to monkey’s area F5. PMID:26973496

  11. Two cold-sensitive neurons within one sensillum code for different parameters of the thermal environment in the ant Camponotus rufipes

    PubMed Central

    Nagel, Manuel; Kleineidam, Christoph J.

    2015-01-01

    Ants show high sensitivity when responding to minute temperature changes and are able to track preferred temperatures with amazing precision. As social insects, they have to detect and cope with thermal fluctuations not only for their individual benefit but also for the developmental benefit of the colony and its brood. In this study we investigate the sensory basis for the fine-tuned, temperature guided behaviors found in ants, specifically what information about their thermal environment they can assess. We describe the dose-response curves of two cold-sensitive neurons, associated with the sensillum coelocapitulum on the antenna of the carpenter ant Camponotus rufipes.One cold-sensitive neuron codes for temperature changes, thus functioning as a thermal flux-detector. Neurons of such type continuously provide the ant with information about temperature transients (TT-neuron). The TT-neurons are able to resolve a relative change of 37% in stimulus intensity (ΔT) and antennal scanning of the thermal environment may aid the ant’s ability to use temperature differences for orientation.The second cold-sensitive neuron in the S. coelocapitulum responds to temperature only within a narrow temperature range. A temperature difference of 1.6°C can be resolved by this neuron type. Since the working range matches the preferred temperature range for brood care of Camponotus rufipes, we hypothesize that this temperature sensor can function as a thermal switch to trigger brood care behavior, based on absolute (steady state) temperature. PMID:26388753

  12. Two cold-sensitive neurons within one sensillum code for different parameters of the thermal environment in the ant Camponotus rufipes.

    PubMed

    Nagel, Manuel; Kleineidam, Christoph J

    2015-01-01

    Ants show high sensitivity when responding to minute temperature changes and are able to track preferred temperatures with amazing precision. As social insects, they have to detect and cope with thermal fluctuations not only for their individual benefit but also for the developmental benefit of the colony and its brood. In this study we investigate the sensory basis for the fine-tuned, temperature guided behaviors found in ants, specifically what information about their thermal environment they can assess. We describe the dose-response curves of two cold-sensitive neurons, associated with the sensillum coelocapitulum on the antenna of the carpenter ant Camponotus rufipes.One cold-sensitive neuron codes for temperature changes, thus functioning as a thermal flux-detector. Neurons of such type continuously provide the ant with information about temperature transients (TT-neuron). The TT-neurons are able to resolve a relative change of 37% in stimulus intensity (ΔT) and antennal scanning of the thermal environment may aid the ant's ability to use temperature differences for orientation.The second cold-sensitive neuron in the S. coelocapitulum responds to temperature only within a narrow temperature range. A temperature difference of 1.6°C can be resolved by this neuron type. Since the working range matches the preferred temperature range for brood care of Camponotus rufipes, we hypothesize that this temperature sensor can function as a thermal switch to trigger brood care behavior, based on absolute (steady state) temperature.

  13. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons.

    PubMed

    Colbert, C M; Johnston, D

    1996-11-01

    A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

  14. Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons.

    PubMed

    Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A

    2010-05-19

    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By using a recent improvement in voltage-sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission.

  15. A survey of the effective factors in students' adherence to university dress code policy, using the theory of reasoned action.

    PubMed

    Kaveh, Mohammad Hossein; Moradi, Leila; Hesampour, Maryam; Hasan Zadeh, Jafar

    2015-07-01

    Recognizing the determinants of behavior plays a major role in identification and application of effective strategies for encouraging individuals to follow the intended pattern of behavior. The present study aimed to analyze the university students' behaviors regarding the amenability to dress code, using the theory of reasoned action (TRA). In this cross sectional study, 472 students were selected through multi-stage random sampling. The data were collected using a researcher-made questionnaire whose validity was confirmed by specialists. Besides, its reliability was confirmed by conducting a pilot study revealing Cronbach's alpha coefficients of 0.93 for attitude, 0.83 for subjective norms, 0.94 for behavioral intention and 0.77 for behavior. The data were entered into the SPSS statistical software and analyzed using descriptive and inferential statistics (Mann-Whitney, correlation and regression analysis). Based on the students' self-reports, conformity of clothes to the university's dress code was below the expected level in 28.87% of the female students and 28.55% of the male ones. The mean scores of attitude, subjective norms, and behavioral intention to comply with dress code policy were 28.78±10.08, 28.51±8.25 and 11.12±3.84, respectively. The students of different colleges were different from each other concerning TRA constructs. Yet, subjective norms played a more critical role in explaining the variance of dress code behavior among the students. Theory of reasoned action explained the students' dress code behaviors relatively well. The study results suggest paying attention to appropriate approaches in educational, cultural activities, including promotion of student-teacher communication.

  16. A survey of the effective factors in students' adherence to university dress code policy, using the theory of reasoned action

    PubMed Central

    KAVEH, MOHAMMAD HOSSEIN; MORADI, LEILA; HESAMPOUR, MARYAM; HASAN ZADEH, JAFAR

    2015-01-01

    Introduction Recognizing the determinants of behavior plays a major role in identification and application of effective strategies for encouraging individuals to follow the intended pattern of behavior. The present study aimed to analyze the university students’ behaviors regarding the amenability to dress code, using the theory of reasoned action (TRA). Methods In this cross sectional study, 472 students were selected through multi-stage random sampling. The data were collected using a researcher-made questionnaire whose validity was confirmed by specialists. Besides, its reliability was confirmed by conducting a pilot study revealing Cronbach’s alpha coefficients of 0.93 for attitude, 0.83 for subjective norms, 0.94 for behavioral intention and 0.77 for behavior. The data were entered into the SPSS statistical software and analyzed using descriptive and inferential statistics (Mann-Whitney, correlation and regression analysis). Results Based on the students’ self-reports, conformity of clothes to the university’s dress code was below the expected level in 28.87% of the female students and 28.55% of the male ones. The mean scores of attitude, subjective norms, and behavioral intention to comply with dress code policy were 28.78±10.08, 28.51±8.25 and 11.12±3.84, respectively. The students of different colleges were different from each other concerning TRA constructs. Yet, subjective norms played a more critical role in explaining the variance of dress code behavior among the students. Conclusion Theory of reasoned action explained the students’ dress code behaviors relatively well. The study results suggest paying attention to appropriate approaches in educational, cultural activities, including promotion of student-teacher communication. PMID:26269790

  17. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease

    PubMed Central

    Pissadaki, Eleftheria K.; Bolam, J. Paul

    2013-01-01

    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD. PMID:23515615

  18. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease.

    PubMed

    Pissadaki, Eleftheria K; Bolam, J Paul

    2013-01-01

    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD.

  19. Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on trigeminal sensory neurons

    PubMed Central

    Price, Theodore J; Patwardhan, Amol; Akopian, Armen N; Hargreaves, Kenneth M; Flores, Christopher M

    2004-01-01

    The prototypical aminoalkylindole cannabinoid WIN 55,212-2 (WIN-2) has been shown to produce antihyperalgesia through a peripheral mechanism of action. However, it is not known whether WIN-2 exerts this action directly via cannabinoid receptors located on primary afferents or if other, perhaps indirect or noncannabinoid, mechanisms are involved. To address this question, we have examined the specific actions of WIN-2 on trigeminal ganglion (TG) neurons in vitro by quantifying its ability to modulate the evoked secretion of the proinflammatory neuropeptide CGRP as well as the inflammatory mediator-induced generation of cAMP. WIN-2 evoked CGRP release from TG neurons in vitro (EC50=26 μM) in a concentration- and calcium-dependent manner, which was mimicked by the cannabinoid receptor-inactive enantiomer WIN 55,212-3 (WIN-3). Moreover, WIN-2-evoked CGRP release was attenuated by the nonselective cation channel blocker ruthenium red but not by the vanilloid receptor type 1 (TRPV1) antagonist capsazepine, suggesting that, unlike certain endogenous and synthetic cannabinoids, WIN-2 is not a TRPV1 agonist but rather acts at an as yet unidentified cation channel. The inhibitory effects of WIN-2 on TG neurons were also examined. WIN-2 neither inhibited capsaicin-evoked CGRP release nor did it inhibit forskolin-, isoproteranol- or prostaglandin E2-stimulated cAMP accumulation. On the other hand, WIN-2 significantly inhibited (EC50=1.7 μM) 50 mM K+-evoked CGRP release by approximately 70%. WIN-2 inhibition of 50 mM K+-evoked CGRP release was not reversed by antagonists of cannabinoid type 1 (CB1) receptor, but was mimicked in magnitude and potency (EC50=2.7 μM) by its cannabinoid-inactive enantiomer WIN-3. These findings indicate that WIN-2 exerts both excitatory and inhibitory effects on TG neurons, neither of which appear to be mediated by CB1, CB2 or TRPV1 receptors, but by a novel calcium-dependent mechanism. The ramifications of these results are discussed in relation

  20. Action Processing and Mirror Neuron Function in Patients with Amyotrophic Lateral Sclerosis: An fMRI Study

    PubMed Central

    Jelsone-Swain, Laura; Persad, Carol; Burkard, David; Welsh, Robert C.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a highly debilitating and rapidly fatal neurodegenerative disease. It has been suggested that social cognition may be affected, such as impairment in theory of mind (ToM) ability. Despite these findings, research in this area is scarce and the investigation of neural mechanisms behind such impairment is absent. Nineteen patients with ALS and eighteen healthy controls participated in this study. Because the mirror neuron system (MNS) is thought to be involved in theory of mind, we first implemented a straightforward action-execution and observation task to assess basic MNS function. Second, we examined the social-cognitive ability to understand actions of others, which is a component of ToM. We used fMRI to assess BOLD activity differences between groups during both experiments. Theory of mind was also measured behaviorally using the Reading the Mind in the Eyes test (RME). ALS patients displayed greater BOLD activity during the action-execution and observation task, especially throughout right anterior cortical regions. These areas included the right inferior operculum, premotor and primary motor regions, and left inferior parietal lobe. A conjunction analysis showed significantly more co-activated voxels during both the observation and action-execution conditions in the patient group throughout MNS regions. These results support a compensatory response in the MNS during action processing. In the action understanding experiment, healthy controls performed better behaviorally and subsequently recruited greater regions of activity throughout the prefrontal cortex and middle temporal gyrus. Lastly, action understanding performance was able to cluster patients with ALS into high and lower performing groups, which then differentiated RME performance. Collectively, these data suggest that social cognition, particularly theory of mind, may be affected in a subset of patients with ALS. This impairment may be related to functioning of

  1. Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea.

    PubMed

    Carr, Richard W; Pianova, Svetlana; McKemy, David D; Brock, James A

    2009-03-15

    The site at which action potentials initiate within the terminal region of unmyelinated sensory axons has not been resolved. Combining recordings of nerve terminal impulses (NTIs) and collision analysis, the site of action potential initiation in guinea-pig corneal cold receptors was determined. For most receptors (77%), initiation mapped to a point in the time domain that was closer to the nerve terminal than to the site of electrical stimulation at the back of the eye. Guinea-pig corneal cold receptors are Adelta-neurones that lose their myelin sheath at the point where they enter the cornea, and therefore their axons conduct more slowly within the cornea. Allowing for this inhomogeneity in conduction speed, the resulting spatial estimates of action potential initiation sites correlated with changes in NTI shape predicted by simulation of action potentials initiating within a nerve terminal. In some receptors, more than one NTI shape was observed. Simulations of NTI shape suggest that the origin of differing NTI shapes result from action potentials initiating at different, spatially discrete, locations within the nerve terminal. Importantly, the relative incidence of NTI shapes resulting from action potential initiation close to the nerve termination increased during warming when nerve activity decreased, indicating that the favoured site of action potential initiation shifts toward the nerve terminal when it hyperpolarizes. This finding can be explained by a hyperpolarization-induced relief of Na(+) channel inactivation in the nerve terminal. The results provide direct evidence that the molecular entities responsible for stimulus transduction and action potential initiation reside in parallel with one another in the unmyelinated nerve terminals of cold receptors.

  2. Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea

    PubMed Central

    Carr, Richard W; Pianova, Svetlana; McKemy, David D; Brock, James A

    2009-01-01

    The site at which action potentials initiate within the terminal region of unmyelinated sensory axons has not been resolved. Combining recordings of nerve terminal impulses (NTIs) and collision analysis, the site of action potential initiation in guinea-pig corneal cold receptors was determined. For most receptors (77%), initiation mapped to a point in the time domain that was closer to the nerve terminal than to the site of electrical stimulation at the back of the eye. Guinea-pig corneal cold receptors are Aδ-neurones that lose their myelin sheath at the point where they enter the cornea, and therefore their axons conduct more slowly within the cornea. Allowing for this inhomogeneity in conduction speed, the resulting spatial estimates of action potential initiation sites correlated with changes in NTI shape predicted by simulation of action potentials initiating within a nerve terminal. In some receptors, more than one NTI shape was observed. Simulations of NTI shape suggest that the origin of differing NTI shapes result from action potentials initiating at different, spatially discrete, locations within the nerve terminal. Importantly, the relative incidence of NTI shapes resulting from action potential initiation close to the nerve termination increased during warming when nerve activity decreased, indicating that the favoured site of action potential initiation shifts toward the nerve terminal when it hyperpolarizes. This finding can be explained by a hyperpolarization-induced relief of Na+ channel inactivation in the nerve terminal. The results provide direct evidence that the molecular entities responsible for stimulus transduction and action potential initiation reside in parallel with one another in the unmyelinated nerve terminals of cold receptors. PMID:19171652

  3. Object visibility alters the relative contribution of ventral visual stream and mirror neuron system to goal anticipation during action observation.

    PubMed

    Thioux, Marc; Keysers, Christian

    2015-01-15

    We used fMRI to study the effect of hiding the target of a grasping action on the cerebral activity of an observer whose task was to anticipate the size of the object being grasped. Activity in the putative mirror neuron system (pMNS) was higher when the target was concealed from the view of the observer and anticipating the size of the object being grasped requested paying attention to the hand kinematics. In contrast, activity in ventral visual areas outside the pMNS increased when the target was fully visible, and the performance improved in this condition. A repetition suppression analysis demonstrated that in full view, the size of the object being grasped by the actor was encoded in the ventral visual stream. Dynamic causal modeling showed that monitoring a grasping action increased the coupling between the parietal and ventral premotor nodes of the pMNS. The modulation of the functional connectivity between these nodes was correlated with the subject's capability to detect the size of hidden objects. In full view, synaptic activity increased within the ventral visual stream, and the connectivity with the pMNS was diminished. The re-enactment of observed actions in the pMNS is crucial when interpreting others' actions requires paying attention to the body kinematics. However, when the context permits, visual-spatial information processing may complement pMNS computations for improved action anticipation accuracy.

  4. Action-perception coupling in pianists: learned mappings or spatial musical association of response codes (SMARC) effect?

    PubMed

    Stewart, Lauren; Verdonschot, Rinus G; Nasralla, Patrick; Lanipekun, Jennifer

    2013-01-01

    The principle of common coding suggests that a joint representation is formed when actions are repeatedly paired with a specific perceptual event. Musicians are occupationally specialized with regard to the coupling between actions and their auditory effects. In the present study, we employed a novel paradigm to demonstrate automatic action-effect associations in pianists. Pianists and nonmusicians pressed keys according to aurally presented number sequences. Numbers were presented at pitches that were neutral, congruent, or incongruent with respect to pitches that would normally be produced by such actions. Response time differences were seen between congruent and incongruent sequences in pianists alone. A second experiment was conducted to determine whether these effects could be attributed to the existence of previously documented spatial/pitch compatibility effects. In a "stretched" version of the task, the pitch distance over which the numbers were presented was enlarged to a range that could not be produced by the hand span used in Experiment 1. The finding of a larger response time difference between congruent and incongruent trials in the original, standard, version compared with the stretched version, in pianists, but not in nonmusicians, indicates that the effects obtained are, at least partially, attributable to learned action effects.

  5. Adaptive coding of orofacial and speech actions in motor and somatosensory spaces with and without overt motor behavior.

    PubMed

    Sato, Marc; Vilain, Coriandre; Lamalle, Laurent; Grabski, Krystyna

    2015-02-01

    Studies of speech motor control suggest that articulatory and phonemic goals are defined in multidimensional motor, somatosensory, and auditory spaces. To test whether motor simulation might rely on sensory-motor coding common with those for motor execution, we used a repetition suppression (RS) paradigm while measuring neural activity with sparse sampling fMRI during repeated overt and covert orofacial and speech actions. RS refers to the phenomenon that repeated stimuli or motor acts lead to decreased activity in specific neural populations and are associated with enhanced adaptive learning related to the repeated stimulus attributes. Common suppressed neural responses were observed in motor and posterior parietal regions in the achievement of both repeated overt and covert orofacial and speech actions, including the left premotor cortex and inferior frontal gyrus, the superior parietal cortex and adjacent intraprietal sulcus, and the left IC and the SMA. Interestingly, reduced activity of the auditory cortex was observed during overt but not covert speech production, a finding likely reflecting a motor rather an auditory imagery strategy by the participants. By providing evidence for adaptive changes in premotor and associative somatosensory brain areas, the observed RS suggests online state coding of both orofacial and speech actions in somatosensory and motor spaces with and without motor behavior and sensory feedback.

  6. The distribution and chemical coding of intramural neurons supplying the porcine stomach - the study on normal pigs and on animals suffering from swine dysentery.

    PubMed

    Kaleczyc, J; Klimczuk, M; Franke-Radowiecka, A; Sienkiewicz, W; Majewski, M; Łakomy, M

    2007-06-01

    The present study was designed to investigate the expression of biologically active substances by intramural neurons supplying the stomach in normal (control) pigs and in pigs suffering from dysentery. Eight juvenile female pigs were used. Both dysenteric (n = 4; inoculated with Brachyspira hyodysenteriae) and control (n = 4) animals were deeply anaesthetized, transcardially perfused with buffered paraformalehyde, and tissue samples comprising all layers of the wall of the ventricular fundus were collected. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5) and their chemical coding using antibodies against vesicular acetylcholine (ACh) transporter (VAChT), nitric oxide synthase (NOS), galanin (GAL), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), Leu(5)-enkephalin (LENK), substance P (SP) and calcitonin gene-related peptide (CGRP). In both inner and outer submucosal plexuses of the control pigs, the majority of neurons were SP (55% and 58%, respectively)- or VAChT (54%)-positive. Many neurons stained also for CGRP (43 and 45%) or GAL (20% and 18%) and solitary perikarya were NOS-, SOM- or VIP-positive. The myenteric plexus neurons stained for NOS (20%), VAChT (15%), GAL (10%), VIP (7%), SP (6%) or CGRP (solitary neurons), but they were SOM-negative. No intramural neurons immunoreactive to LENK were found. The most remarkable difference in the chemical coding of enteric neurons between the control and dysenteric pigs was a very increased number of GAL- and VAChT-positive nerve cells (up to 61% and 85%, respectively) in submucosal plexuses of the infected animals. The present results suggest that GAL and ACh have a specific role in local neural circuits of the inflamed porcine stomach in the course of swine dysentery.

  7. Biological basis of miRNA action when their targets are located in human protein coding region.

    PubMed

    Gu, Wanjun; Wang, Xiaofei; Zhai, Chuanying; Zhou, Tong; Xie, Xueying

    2013-01-01

    Recent analyses have revealed many functional microRNA (miRNA) targets in mammalian protein coding regions. But, the mechanisms that ensure miRNA function when their target sites are located in protein coding regions of mammalian mRNA transcripts are largely unknown. In this paper, we investigate some potential biological factors, such as target site accessibility and local translation efficiency. We computationally analyze these two factors using experimentally identified miRNA targets in human protein coding region. We find site accessibility is significantly increased in miRNA target region to facilitate miRNA binding. At the mean time, local translation efficiency is also selectively decreased near miRNA target region. GC-poor codons are preferred in the flank region of miRNA target sites to ease the access of miRNA targets. Within-genome analysis shows substantial variations of site accessibility and local translation efficiency among different miRNA targets in the genome. Further analyses suggest target gene's GC content and conservation level could explain some of the differences in site accessibility. On the other hand, target gene's functional importance and conservation level can affect local translation efficiency near miRNA target region. We hence propose both site accessibility and local translation efficiency are important in miRNA action when miRNA target sites are located in mammalian protein coding regions.

  8. MaqFACS (Macaque Facial Action Coding System) can be used to document facial movements in Barbary macaques (Macaca sylvanus)

    PubMed Central

    Julle-Danière, Églantine; Whitehouse, Jamie; Joly, Marine; Gass, Carolin; Burrows, Anne M.; Waller, Bridget M.

    2015-01-01

    Human and non-human primates exhibit facial movements or displays to communicate with one another. The evolution of form and function of those displays could be better understood through multispecies comparisons. Anatomically based coding systems (Facial Action Coding Systems: FACS) are developed to enable such comparisons because they are standardized and systematic and aid identification of homologous expressions underpinned by similar muscle contractions. To date, FACS has been developed for humans, and subsequently modified for chimpanzees, rhesus macaques, orangutans, hylobatids, dogs, and cats. Here, we wanted to test whether the MaqFACS system developed in rhesus macaques (Macaca mulatta) could be used to code facial movements in Barbary macaques (M. sylvanus), a species phylogenetically close to the rhesus macaques. The findings show that the facial movement capacity of Barbary macaques can be reliably coded using the MaqFACS. We found differences in use and form of some movements, most likely due to specializations in the communicative repertoire of each species, rather than morphological differences. PMID:26401458

  9. Direct action and modulating effect of (+)- and (-)-nicotine on ion channels expressed in trigeminal sensory neurons.

    PubMed

    Schreiner, Benjamin S P; Lehmann, Ramona; Thiel, Ulrike; Ziemba, Paul M; Beltrán, Leopoldo R; Sherkheli, Muhammad A; Jeanbourquin, Philippe; Hugi, Alain; Werner, Markus; Gisselmann, Günter; Hatt, Hanns

    2014-04-05

    Nicotine sensory perception is generally thought to be mediated by nicotinic acetylcholine (nACh) receptors. However, recent data strongly support the idea that other receptors (e.g., transient receptor potential A1 channel, TRPA1) and other pathways contribute to the detection mechanisms underlying the olfactory and trigeminal cell response to nicotine flavor. This is in accordance with the reported ability of humans to discriminate between (+)- and (-)- nicotine enantiomers. To get a more detailed understanding of the molecular and cellular basis underlying the sensory perception of nicotine, we studied the activity of (+)- and (-)-nicotine on cultured murine trigeminal sensory neurons and on a range of heterologously expressed receptors. The human TRPA1 channel is activated by (-)-nicotine. In this work, we show that (+)-nicotine is also an activator of this channel. Pharmacological experiments using nicotinic acetylcholine receptors and transient receptor potential blockers revealed that trigeminal neurons express one or more unidentified receptors that are sensitive to (+)- and/or (-)-nicotine. Results also indicate that the presence of extracellular calcium ions is required to elicit trigeminal neuron responses to (+)- and (-)-nicotine. Results also show that both (+)-nicotine and (-)-nicotine can block 5-hydroxytryptamine type 3 (5-HT3) receptor-mediated responses in recombinant expression systems and in cultured trigeminal neurons expressing 5-HT3 receptors. Our investigations broaden the spectra of receptors that are targets for nicotine enantiomers and give new insights into the physiological role of nicotine.

  10. [Blocking action of Nephila clavata spider toxin on ionic currents activated by glutamate and its agonists in isolated hippocampal neurons].

    PubMed

    Kiskin, N I; Kliuchko, E M; Kryshtal', O A; Tsyndrenko, A Ia; Akaike, N

    1989-01-01

    The blocking action of the Nephila clavata spider neurotoxin was studied using the concentration clamp method in isolated neurons of the rat hippocampus. Crude venom JSTX blocked L-glutamate-, quisqualate- and kainate-activated ionic currents mediated by activation of the non-N-methyl-D-aspartate (non-NMDA) membrane receptors. Ionic currents elicited by all agonists were depressed by crude JSTX venom to 34-35% of its initial amplitude with no recovery during prolonged washing. An active fraction of JSTX venom blocked ionic currents almost completely, but its action was partially reversible. The concentration dependences of blocking kinetics allowed determining the rate constants of JSTX interaction with glutamate receptors. It is supposed that JSTX blocks the non-NMDA ionic channels in some of their open states and may be one of useful tools in further biochemical and electrophysiological characterization of the glutamate-mediated synaptic transmission.

  11. Behavioral and TMS Markers of Action Observation Might Reflect Distinct Neuronal Processes.

    PubMed

    Hétu, Sébastien; Taschereau-Dumouchel, Vincent; Meziane, Hadj Boumediene; Jackson, Philip L; Mercier, Catherine

    2016-01-01

    Transcranial magnetic stimulation (TMS) studies have shown that observing an action induces muscle-specific changes in corticospinal excitability. From a signal detection theory standpoint, this pattern can be related to sensitivity, which here would measure the capacity to distinguish between two action observation conditions. In parallel to these TMS studies, action observation has also been linked to behavioral effects such as motor priming and interference. It has been hypothesized that behavioral markers of action observation could be related to TMS markers and thus represent a potentially cost-effective mean of assessing the functioning of the action-perception system. However, very few studies have looked at possible relationships between these two measures. The aim of this study was to investigate if individual differences in sensitivity to action observation could be related to the behavioral motor priming and interference effects produced by action observation. To this end, 14 healthy participants observed index and little finger movements during a TMS task and a stimulus-response compatibility task. Index muscle displayed sensitivity to action observation, and action observation resulted in significant motor priming+interference, while no significant effect was observed for the little finger in both task. Nevertheless, our results indicate that the sensitivity measured in TMS was not related to the behavioral changes measured in the stimulus-response compatibility task. Contrary to a widespread assumption, the current results indicate that individual differences in physiological and behavioral markers of action observation may be unrelated. This could have important impacts on the potential use of behavioral markers in place of more costly physiological markers of action observation in clinical settings.

  12. Behavioral and TMS Markers of Action Observation Might Reflect Distinct Neuronal Processes

    PubMed Central

    Hétu, Sébastien; Taschereau-Dumouchel, Vincent; Meziane, Hadj Boumediene; Jackson, Philip L.; Mercier, Catherine

    2016-01-01

    Transcranial magnetic stimulation (TMS) studies have shown that observing an action induces muscle-specific changes in corticospinal excitability. From a signal detection theory standpoint, this pattern can be related to sensitivity, which here would measure the capacity to distinguish between two action observation conditions. In parallel to these TMS studies, action observation has also been linked to behavioral effects such as motor priming and interference. It has been hypothesized that behavioral markers of action observation could be related to TMS markers and thus represent a potentially cost-effective mean of assessing the functioning of the action-perception system. However, very few studies have looked at possible relationships between these two measures. The aim of this study was to investigate if individual differences in sensitivity to action observation could be related to the behavioral motor priming and interference effects produced by action observation. To this end, 14 healthy participants observed index and little finger movements during a TMS task and a stimulus–response compatibility task. Index muscle displayed sensitivity to action observation, and action observation resulted in significant motor priming+interference, while no significant effect was observed for the little finger in both task. Nevertheless, our results indicate that the sensitivity measured in TMS was not related to the behavioral changes measured in the stimulus–response compatibility task. Contrary to a widespread assumption, the current results indicate that individual differences in physiological and behavioral markers of action observation may be unrelated. This could have important impacts on the potential use of behavioral markers in place of more costly physiological markers of action observation in clinical settings. PMID:27683548

  13. Amantadine protects dopamine neurons by a dual action: reducing activation of microglia and inducing expression of GDNF in astroglia [corrected].

    PubMed

    Ossola, Bernardino; Schendzielorz, Nadia; Chen, Shih-Heng; Bird, Gary S; Tuominen, Raimo K; Männistö, Pekka T; Hong, Jau-Shyong

    2011-09-01

    Amantadine is commonly given to alleviate L-DOPA-induced dyskinesia of Parkinson's disease (PD) patients. Animal and human evidence showed that amantadine may also exert neuroprotection in several neurological disorders. Additionally, it is generally believed that this neuroprotection results from the ability of amantadine to inhibit glutamatergic NMDA receptor. However, several lines of evidence questioned the neuroprotective capacity of NMDA receptor antagonists in animal models of PD. Thus the cellular and molecular mechanism of neuroprotection of amantadine remains unclear. Using primary cultures with different composition of neurons, microglia, and astroglia we investigated the direct role of these glial cell types in the neuroprotective effect of amantadine. First, amantadine protected rat midbrain cultures from either MPP(+) or lipopolysaccharide (LPS), two toxins commonly used as PD models. Second, our studies revealed that amantadine reduced both LPS- and MPP(+)-induced toxicity of dopamine neurons through 1) the inhibition of the release of microglial pro-inflammatory factors, 2) an increase in expression of neurotrophic factors such as GDNF from astroglia. Lastly, differently from the general view on amantadine's action, we provided evidence suggesting that NMDA receptor inhibition was not crucial for the neuroprotective effect of amantadine. In conclusion, we report that amantadine protected dopamine neurons in two PD models through a novel dual mechanism, namely reducing the release of pro-inflammatory factors from activated microglia and increasing the expression of GNDF in astroglia.

  14. Antidromic firing occurs spontaneously on thalamic relay neurons: triggering of somatic intrinsic burst discharges by ectopic action potentials.

    PubMed

    Pinault, D; Pumain, R

    1989-01-01

    Eighty-two identified thalamocortical relay neurons were recorded extracellularly in the ventral posterior thalamic nucleus in 29 urethane-anaesthetized rats. Electrical stimulations were applied to the contralateral vibrissae or to the ipsilateral neocortex for ortho- or antidromic activation. The critical period following a known somatic action potential and during which no antidromic response could reach the soma was systematically determined for each cell using a collision test. Thus, the possible ectopic axonal origin of a given impulse could be determined. Thalamic neurons displayed either tonic or phasic firing modes, the latter characterized by episodes of rhythmic high-frequency burst discharges. The present results suggest that such bursts were generated at the soma and probably involved an intrinsic mechanism, since: (1) a modulation of the somatic excitability with an excitatory or inhibitory amino acid affected the intra-burst structure; (2) an antidromic test action potential collided with the second or any of the later impulses of such bursts; (3) an orthodromic activation could evoke a burst structurally similar to a natural one; and (4) the duration of the first interval of such an evoked burst was always inferior to the sum of the critical period plus the antidromic conduction time, ruling out the possibility that it might have been entirely ectopically generated on thalamic terminals. The results further show that a spontaneous ectopic axonal impulse could trigger a somatic burst, since: (1) an electrically-evoked antidromic action potential could trigger a burst structurally similar to a spontaneous one; (2) on 42% of the tested thalamic cells, a known antidromic action potential delivered during the critical period following a spontaneous single impulse could not collide with it: in many cases such non-collisions were seen with the first action potential of a burst; and (3) with increasing ionophoretic doses, GABA could: (i) convert bursts to

  15. A code to compute the action-angle transformation for a particle in an abritrary potential well

    SciTech Connect

    Berg, J.S.; Warnock, R.L.

    1995-06-01

    For a Vlasov treatment of longitudinal stability under an arbitrary wake field, with the solution of the Haiessinski equation as the unperturbed distribution, it is important to have the action-angle transformation for the distorted potential well in a convenient form. The authors have written a code that gives the transformation q,p {yields} J, {phi}, with q(J,{phi}) as a Fourier series in {phi}, the Fourier coefficients and the Hamiltonian H(J) being spline functions of J in C{sup 2} (having continuous second derivatives).

  16. Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.

    PubMed

    Hussy, N; Deleuze, C; Pantaloni, A; Desarménien, M G; Moos, F

    1997-08-01

    1. To evaluate the implication of taurine in the physiology of supraoptic neurones, we (i) investigated the agonist properties of taurine on glycine and GABAA receptors of supraoptic magnocellular neurones acutely dissociated from adult rats, using whole-cell voltage clamp, (ii) studied the effects of taurine and strychnine in vivo by extracellular recordings of supraoptic vasopressin neurones in anaesthetized rats, and (iii) measured the osmolarity-dependent release of endogenous taurine from isolated supraoptic nuclei by HPLC. 2. GABA, glycine and taurine evoked rapidly activating currents that all reversed close to the equilibrium potential for Cl-, indicating activation of Cl(-)-selective channels. Glycine-activated currents were reversibly blocked by strychnine (IC50 of 35 nM with 100 microM glycine), but were unaffected by the GABAA antagonist gabazine (1-3 microM). GABA-activated currents were reversibly antagonized by 3 microM gabazine, but not by strychnine (up to 1 microM). 3. Responses to 1 mM taurine were blocked by strychnine but not by gabazine and showed no additivity with glycine-induced currents, indicating selective activation of glycine receptors. Responses to 10 mM taurine were partially antagonized by gabazine, the residual current being blocked by strychnine. Thus, taurine is also a weak agonist of GABAA receptors. 4. In the presence of gabazine, taurine activated glycine receptors with an EC50 of 406 microM. Taurine activated at most 70% of maximal glycine currents, suggesting that it is a partial agonist of glycine receptors. 5. In vivo, locally applied strychnine (300 nM) increased and taurine (1 mM) decreased the basal electrical activity of vasopressin neurones in normally hydrated rats. The effect of strychnine was markedly more pronounced in water-loaded rats. 6. Taurine, which is concentrated in supraoptic glial cells, could be released from isolated supraoptic nuclei upon hyposmotic stimulation. Decreases in osmolarity of 15 and 30

  17. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study

    PubMed Central

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-01-01

    Abstract The spatial pattern of Na+ channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na+ channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (Vm imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  18. Signed language and human action processing: evidence for functional constraints on the human mirror-neuron system.

    PubMed

    Corina, David P; Knapp, Heather Patterson

    2008-12-01

    In the quest to further understand the neural underpinning of human communication, researchers have turned to studies of naturally occurring signed languages used in Deaf communities. The comparison of the commonalities and differences between spoken and signed languages provides an opportunity to determine core neural systems responsible for linguistic communication independent of the modality in which a language is expressed. The present article examines such studies, and in addition asks what we can learn about human languages by contrasting formal visual-gestural linguistic systems (signed languages) with more general human action perception. To understand visual language perception, it is important to distinguish the demands of general human motion processing from the highly task-dependent demands associated with extracting linguistic meaning from arbitrary, conventionalized gestures. This endeavor is particularly important because theorists have suggested close homologies between perception and production of actions and functions of human language and social communication. We review recent behavioral, functional imaging, and neuropsychological studies that explore dissociations between the processing of human actions and signed languages. These data suggest incomplete overlap between the mirror-neuron systems proposed to mediate human action and language.

  19. Granularity within the mirror system is not informative on action perception. Comment on "Grasping synergies: A motor-control approach to the mirror neuron mechanism" by D'Ausilio et al.

    NASA Astrophysics Data System (ADS)

    Cattaneo, Luigi

    2015-03-01

    The present work [1] reviews a part of the now vast literature on visuomotor stimulus-response associations in the domain of action observation, commonly referred to as mirror mechanism or mirror system. The aim of the study is to propose a solution to a currently debated problem, namely in what frame of reference are mirror neurons coding movement. The solution proposed here is that, if the mirror system is part of the motor system, then the motor responses to action observation must be in the same frames of reference as that generally observed in the production of voluntary actions. This idea is part of the very first conceptualizations of the mirror system ("Each time an individual sees an action done by another individual, neurons that represent that action are activated in the observer's premotor cortex. This automatically induced, motor representation of the observed action corresponds to that which is spontaneously generated during active action and whose outcome is known to the acting individual" [2]) and has been explicitly proposed earlier [3] in the attempt of reconciling the very different findings in the literature on the mirror system's frames of reference. The novelty of the present approach is the explicit reference to the 'motor synergy' theory of voluntary hand movements. This theory states that the high number of degrees of freedom intrinsic to hand anatomy is reduced by the motor system to few principal components named motor synergies that are the building blocks of voluntary behavior [4]. I am enthusiastic about two points proposed by D'Ausilio in the present review and I am skeptical about some other points.

  20. Neuronal activity in the human subthalamic nucleus encodes decision conflict during action selection

    PubMed Central

    Zaghloul, Kareem A.; Weidemann, Christoph T.; Lega, Bradley C.; Jaggi, Jurg L.; Baltuch, Gordon H.; Kahana, Michael J.

    2012-01-01

    The subthalamic nucleus (STN), which receives excitatory inputs from the cortex and has direct connections with the inhibitory pathways of the basal ganglia, is well positioned to efficiently mediate action selection. Here, we use microelectrode recordings captured during deep brain stimulation surgery as participants engage in a decision task to examine the role of the human STN in action selection. We demonstrate that spiking activity in the STN increases when participants engage in a decision, and that the level of spiking activity increases with the degree of decision conflict. These data implicate the STN as an important mediator of action selection during decision processes. PMID:22396419

  1. Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N-type calcium channels

    PubMed Central

    Kasten, Michael R; Rudy, Bernardo; Anderson, Matthew P

    2007-01-01

    Sensory signals of widely differing dynamic range and intensity are transformed into a common firing rate code by thalamocortical neurons. While a great deal is known about the ionic currents, far less is known about the specific channel subtypes regulating thalamic firing rates. We hypothesized that different K+ and Ca2+ channel subtypes control different stimulus–response curve properties. To define the channels, we measured firing rate while pharmacologically or genetically modulating specific channel subtypes. Inhibiting Kv3.2 K+ channels strongly suppressed maximum firing rate by impairing membrane potential repolarization, while playing no role in the firing response to threshold stimuli. By contrast, inhibiting Kv1 channels with α-dendrotoxin or maurotoxin strongly increased firing rates to threshold stimuli by reducing the membrane potential where action potentials fire (Vth). Inhibiting SK Ca2+-activated K+ channels with apamin robustly increased gain (slope of the stimulus–response curve) and maximum firing rate, with minimum effects on threshold responses. Inhibiting N-type Ca2+ channels with ω-conotoxin GVIA or ω-conotoxin MVIIC partially mimicked apamin, while inhibiting L-type and P/Q-type Ca2+ channels had small or no effects. EPSC-like current injections closely mimicked the results from tonic currents. Our results show that Kv3.2, Kv1, SK potassium and N-type calcium channels strongly regulate thalamic relay neuron sensory transmission and that each channel subtype controls a different stimulus–response curve property. Differential regulation of threshold, gain and maximum firing rate may help vary the stimulus–response properties across and within thalamic nuclei, normalize responses to diverse sensory inputs, and underlie sensory perception disorders. PMID:17761775

  2. Protective action of erythropoietin on neuronal damage induced by activated microglia.

    PubMed

    Wenker, Shirley D; Chamorro, María E; Vittori, Daniela C; Nesse, Alcira B

    2013-04-01

    Inflammation is a physiological defense response, but may also represent a potential pathological process in neurological diseases. In this regard, microglia have a crucial role in either progression or amelioration of degenerative neuronal damage. Because of the role of hypoxia in pro-inflammatory mechanisms in the nervous system, and the potential anti-inflammatory protective effect of erythropoietin (Epo), we focused our investigation on the role of this factor on activation of microglia and neuroprotection. Activation of microglial cells (EOC-2) was achieved by chemical hypoxia induced by cobalt chloride (CoCl2 ) and characterized by increased levels of nitrite, tumor necrosis factor-α and reactive oxygen species production, as well as up-regulation of inducible nitric oxide synthase expression. Under these conditions, cell proliferation data and proliferating cell nuclear antigen (PCNA) staining demonstrated a mitogenic effect of chemical hypoxia. Even though pre-treatment with Epo did not prevent nitrite production, inducible nitric oxide synthase protein expression or tumor necrosis factor-α secretion, it prevented the oxidative stress induced by CoCl2 as well as cell proliferation. Neuronal cells (SH-SY5Y) cultured in the presence of conditioned medium from activated EOC-2 cells or macrophages (RAW 264.7) developed significant apoptosis, an effect that was abolished by Epo via Epo/Epo receptor activation. The results show that even though Epo did not exert a direct anti-inflammatory effect on microglia activation, it did increase the resistance of neurons to subsequent damage from pro-inflammatory agents. In addition to its anti-apoptotic ability, the Epo antioxidant effect may have an indirect influence on neuronal survival by modulation of the pro-inflammatory environment.

  3. Cl− uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1

    PubMed Central

    Yamada, Junko; Okabe, Akihito; Toyoda, Hiroki; Kilb, Werner; Luhmann, Heiko J; Fukuda, Atsuo

    2004-01-01

    GABA is the principal inhibitory neurotransmitter in the mature brain, but during early postnatal development the elevated [Cl−]i in immature neocortical neurones causes GABAA receptor activation to be depolarizing. The molecular mechanisms underlying this intracellular Cl− accumulation remain controversial. Therefore, the GABA reversal potential (EGABA) or [Cl−]i in early postnatal rat neocortical neurones was measured by the gramicidin-perforated patch-clamp method, and the relative expression levels of the cation−Cl− cotransporter mRNAs (in the same cells) were examined by semiquantitative single-cell multiplex RT-PCR to look for statistical correlations with [Cl−]i. The mRNA expression levels were positively (the Cl− accumulating Na+,K+−2Cl− cotransporter NKCC1) or negatively (the Cl− extruding K+−Cl− cotransporter KCC2) correlated with [Cl−]i. NKCC1 mRNA expression was high in early postnatal days, but decreased during postnatal development, whereas KCC2 mRNA expression displayed the opposite pattern. [Cl−]i and NKCC1 mRNA expression were each higher in cortical plate (CP) neurones than in the presumably older layer V/VI pyramidal neurones in a given slice. The pharmacological effects of bumetanide on EGABA were consistent with the different expression levels of NKCC1 mRNA. These data suggest that NKCC1 may play a pivotal role in the generation of GABA-mediated depolarization in immature CP cells, while KCC2 promotes the later maturation of GABAergic inhibition in the rat neocortex. PMID:15090604

  4. Actions of amylin on subfornical organ neurons and on drinking behavior in rats.

    PubMed

    Riediger, T; Rauch, M; Schmid, H A

    1999-02-01

    Amylin, a peptide hormone secreted by pancreatic beta-cells after food intake, contributes to metabolic control by regulating nutrient influx into the blood, whereas insulin promotes nutrient efflux and storage. We now report that amylin activates neurons in the subfornical organ (SFO), a structure in which the lack of a functional blood-brain barrier and the presence of a high density of amylin receptors may render it accessible and sensitive to circulating amylin. In an in vitro slice preparation of the rat SFO, 73% of 78 neurons were excited by superfusion with rat amylin (10(-8)-10(-7) M); the remainder were insensitive. The threshold concentration for the excitatory response of amylin was <10(-8) M and thus similar in potency to a previously reported excitatory effect of ANG II on the same neurons. The excitatory effect of amylin was completely blocked by coapplication of the selective amylin receptor antagonist AC-187 (10(-6)-10(-5) M) but was not affected by losartan (10(-5) M). Subcutaneous injections of 40 nmol of amylin significantly increased water intake in euhydrated rats, as did an equimolar dose of ANG II, which is a well-described SFO-mediated effect of circulating ANG II. These results point to the SFO as a sensory central nervous target for amylin released systemically in response to metabolic changes. Furthermore, we suggest that amylin release during food intake may stimulate prandial drinking.

  5. Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury.

    PubMed

    Gu, Shixin; Xie, Rong; Liu, Xiaodong; Shou, Jiajun; Gu, Wentao; Che, Xiaoming

    2017-04-01

    Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI

  6. The Influence of Tetrodotoxin (TTX) on the Distribution and Chemical Coding of Caudal Mesenteric Ganglion (CaMG) Neurons Supplying the Porcine Urinary Bladder.

    PubMed

    Lepiarczyk, Ewa; Bossowska, Agnieszka; Kaleczyc, Jerzy; Majewska, Marta; Gonkowski, Sławomir; Majewski, Mariusz

    2017-03-30

    The treatment of micturition disorders creates a serious problem for urologists. Recently, new therapeutic agents, such as neurotoxins, are being considered for the therapy of urological patients. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG) neurons supplying the porcine urinary bladder after intravesical instillation of tetrodotoxin (TTX). The CaMG neurons were visualized with retrograde tracer Fast blue (FB) and their chemical profile was disclosed with double-labeling immunohistochemistry using antibodies against tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), calbindin (CB), galanin (GAL) and neuronal nitric oxide synthase (nNOS). It was found that in both the control (n = 6) and TTX-treated pigs (n = 6), the vast majority (92.6% ± 3.4% and 88.8% ± 2%, respectively) of FB-positive (FB+) nerve cells were TH+. TTX instillation caused a decrease in the number of FB+/TH+ neurons immunopositive to NPY (88.9% ± 5.3% in the control animals vs. 10.6% ± 5.3% in TTX-treated pigs) or VIP (1.7% ± 0.6% vs. 0%), and an increase in the number of FB+/TH+ neurons immunoreactive to SOM (8.8% ± 1.6% vs. 39% ± 12.8%), CB (1.8% ± 0.7% vs. 12.6% ± 2.7%), GAL (1.7% ± 0.8% vs. 10.9% ± 2.6%) or nNOS (0% vs. 1.1% ± 0.3%). The present study is the first to suggest that TTX modifies the chemical coding of CaMG neurons supplying the porcine urinary bladder.

  7. Action-potential broadening and endogenously sustained bursting are substrates of command ability in a feeding neuron of Pleurobranchaea.

    PubMed

    Gillette, R; Gillette, M U; Davis, W J

    1980-03-01

    1. The ventral white cells (VWC's) of the buccal ganglion of Pleurobranchaea, so named for their position and color, are a bilateral pair of neuron somata. Each sends a single axon out its contralateral stomatogastric nerve and has a dendritic field originating close to the soma. 2. The vwcs exhibit spontaneous episodes of prolonged depolarization (duration 1--4 min) accompanied by repetitive action-potential activity and separated by regular intervals of 3--30 min. Such prolonged burst episodes can be triggered by short pulses of depolarizing current. During the repetitive activity of the spontaneous bursts or that driven by imposed depolarization, the action potentials progressively broaden to 5--16 times their initial duration. 3. During spontaneous bursting or activity driven by imposed depolarization, the cyclic motor output of the feeding network is initiated or accelerated with a latency corresponding with the development of appreciable VWC spike broadening. When broadening of antidromic VWC spikes is suppressed by imposed hyperpolarization of the soma, the frequency of feeding cycles is significantly lower than when broadened spikes are allowed to develop. When trains of spikes are driven by depolarizing current, the motor output of the feeding network is not initiated until the VWC spikes have broadened to a repeatable "threshold" duration, regardless of the intensity of the depolarizing current. 4. The endogenous production of prolonged burst episodes, triggered by depolarizing current pulses, and progressive spike broadening can be demonstrated in the surgically isolated VWC soma. 5. The paired VWCs are strongly electrically coupled and display highly synchronous activity. They receive synaptic inputs from many previously identified interneurons of the feeding network and are thus reciprocally coupled within the network. 6. These results demonstrate that the capacity of this neuron to generate broadened action potentials during repetitive activity

  8. A G protein-coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior.

    PubMed

    Lear, Bridget C; Merrill, C Elaine; Lin, Jui-Ming; Schroeder, Analyne; Zhang, Luoying; Allada, Ravi

    2005-10-20

    The neuropeptide Pigment-Dispersing Factor (PDF) plays a critical role in mediating circadian control of behavior in Drosophila. Here we identify mutants (groom-of-PDF; gop) that display phase-advanced evening activity and poor free-running rhythmicity, phenocopying pdf mutants. In gop mutants, a spontaneous retrotransposon disrupts a coding exon of a G protein-coupled receptor, CG13758. Disruption of the receptor is accompanied by phase-advanced oscillations of the core clock protein PERIOD. Moreover, effects on circadian timing induced by perturbation of PDF neurons require gop. Yet PDF oscillations themselves remain robust in gop mutants, suggesting that GOP acts downstream of PDF. gop is expressed most strongly in the dorsal brain in regions that lie in proximity to PDF-containing nerve terminals. Taken together, these studies implicate GOP as a PDF receptor in Drosophila.

  9. Processing and Integration of Contextual Information in Monkey Ventrolateral Prefrontal Neurons during Selection and Execution of Goal-Directed Manipulative Actions.

    PubMed

    Bruni, Stefania; Giorgetti, Valentina; Bonini, Luca; Fogassi, Leonardo

    2015-08-26

    The prefrontal cortex (PFC) is deemed to underlie the complexity, flexibility, and goal-directedness of primates' behavior. Most neurophysiological studies performed so far investigated PFC functions with arm-reaching or oculomotor tasks, thus leaving unclear whether, and to which extent, PFC neurons also play a role in goal-directed manipulative actions, such as those commonly used by primates during most of their daily activities. Here we trained two macaques to perform or withhold grasp-to-eat and grasp-to-place actions, depending on the combination of two subsequently presented cues: an auditory go/no-go cue (high/low tone) and a visually presented target (food/object). By varying the order of presentation of the two cues, we could segment and independently evaluate the processing and integration of contextual information allowing the monkey to make a decision on whether or not to act, and what action to perform. We recorded 403 task-related neurons from the ventrolateral prefrontal cortex (VLPFC): unimodal sensory-driven (37%), motor-related (21%), unimodal sensory-and-motor (23%), and multisensory (19%) neurons. Target and go/no-go selectivity characterized most of the recorded neurons, particularly those endowed with motor-related discharge. Interestingly, multisensory neurons appeared to encode a behavioral decision independently from the sensory modality of the stimulus allowing the monkey to make it: some of them reflected the decision to act or refraining from acting (56%), whereas others (44%) encoded the decision to perform (or withhold) a specific action (e.g., grasp-to-eat). Our findings indicate that VLPFC neurons play a role in the processing of contextual information underlying motor decision during goal-directed manipulative actions. We demonstrated that macaque ventrolateral prefrontal cortex (VLPFC) neurons show remarkable selectivity for different aspects of the contextual information allowing the monkey to select and execute goal

  10. Actions of adiponectin on the excitability of subfornical organ neurons are altered by food deprivation.

    PubMed

    Alim, Ishraq; Fry, W Mark; Walsh, Michael H; Ferguson, Alastair V

    2010-05-12

    Adiponectin (ADP) is a peptide produced by adipose tissue, which acts as an insulin sensitizing hormone. Recent studies have shown that adiponectin receptors (AdipoR1 and AdipoR2) are present in the CNS, and although adiponectin does appear in both circulation and the cerebrospinal fluid there is still some debate as to whether or not ADP crosses the blood brain barrier (BBB). Circumventricular organs (CVO) are CNS sites which lack normal BBB, and thus represent sites at which circulating adiponectin may act to directly influence the CNS. The subfornical organ (SFO) is a CVO that has been implicated in the regulation of energy balance as a consequence of the ability of SFO neurons to respond to a number of different circulating satiety signals including amylin, CCK, PYY and ghrelin. Our recent microarray analysis suggested the presence of adiponectin receptors in the SFO. We report here that the SFO shows a high density of mRNA for both adiponectin receptors (AdipoR1 and AdipoR2), and that ADP influences the excitability of dissociated SFO neurons. Separate subpopulations of SFO neurons were either depolarized (8.9+/-0.9 mV, 21 of 97 cells), or hyperpolarized (-8.0+/-0.5 mV, 34 of 97 cells), by bath application of 10nM ADP, effects which were concentration dependent and reversible. Our microarray analysis also suggested that 48 h of food deprivation resulted in specific increases in AdipoR2 mRNA expression (no effect on AdipoR1 mRNA), observations which we confirm here using real-time PCR techniques. The effects of food deprivation also resulted in a change in the responsiveness of SFO neurons to adiponectin with 77% (8/11) of cells tested responding to adiponectin with depolarization, while no hyperpolarizations were observed. These observations support the concept that the SFO may be a key player in sensing circulating ADP and transmitting such information to critical CNS sites involved in the regulation of energy balance. (c) 2010. Published by Elsevier B.V. All

  11. Properties and ionic basis of the action potentials in the periaqueductal grey neurones of the guinea-pig.

    PubMed Central

    Sánchez, D; Ribas, J

    1991-01-01

    1. Action potentials of neurones of the ventral part of the guinea-pig periaqueductal grey (PAG) were studied by intracellular recording in a mesencephalic slice preparation maintained in vitro. 2. Fast spikes spontaneously fired last 2.8 +/- 0.6 ms (mean +/- S.D.) and have an amplitude of 72.3 +/- 5.3 mV (n = 28). The neurones could be antidromically activated from the neighbouring white matter and these spikes show an initial segment component that triggers the soma-dendritic spike. These two components were dissociated by hyperpolarization. Action potentials are Na+ dependent and a Ca2+ conductance is responsible for the hump on the falling phase. Hyperpolarization makes the hump disappear and a faster rate of rise and fall are seen. Accommodation of the firing threshold is observed in response to depolarizing ramps, which is eliminated with hyperpolarization. 3. High-threshold Ca2+ spikes are evoked in either Na(+)-free solution or in the presence of tetrodotoxin (TTX). These presumed dendritic action potentials display a fast repolarization and a large after-hyperpolarization (AHP) that prevent repetitive firing. This AHP is mainly generated by Ca(2+)-dependent K+ conductances. 4. The repolarization of fast action potentials depends on the activation of K+ conductances as well as a Na+ inactivation process. A fast-activated tetraethyl-ammonium (TEA)-sensitive K+ conductance, that could be Ca2+ dependent, and a K+ conductance blocked by apamin seem to be involved in the repolarization. 5. Each fast action potential is followed by a pronounced AHP with two components, an initial fast and a slow decaying phase. Membrane hyperpolarization around -60 mV eliminated the first component and the AHP acquired a plateau-like shape. At -90 mV the AHP was nullified. The slow phase was Ca2+ dependent and an apamin-sensitive K+ conductance is involved in its generation. This conductance may be active during the early part of the AHP, but a fast-activated TEA-sensitive K

  12. Voltage-gated potassium currents are targets of diurnal changes in estradiol feedback regulation and kisspeptin action on gonadotropin-releasing hormone neurons in mice.

    PubMed

    Pielecka-Fortuna, Justyna; DeFazio, R Anthony; Moenter, Suzanne M

    2011-11-01

    Estradiol has both negative and positive feedback actions upon gonadotropin-releasing hormone (GnRH) release; the latter actions trigger the preovulatory GnRH surge. Although neurobiological mechanisms of the transitions between feedback modes are becoming better understood, the roles of voltage-gated potassium currents, major contributors to neuronal excitability, are unknown. Estradiol alters two components of potassium currents in these cells: a transient current, I(A), and a sustained current, I(K). Kisspeptin is a potential mediator between estradiol and GnRH neurons and can act directly on GnRH neurons. We examined how estradiol, time of day, and kisspeptin interact to regulate these conductances in a mouse model exhibiting daily switches between estradiol negative (morning) and positive feedback (evening). Whole-cell voltage clamp recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice and from OVX mice treated with estradiol (OVX+E). There were no diurnal changes in either I(A) or I(K) in GnRH neurons from OVX mice. In contrast, in GnRH neurons from OVX+E mice, I(A) and I(K) were greater during the morning when GnRH neuron activity is low and smaller in the evening when GnRH neuron activity is high. Estradiol increased I(A) in the morning and decreased it in the evening, relative to that in cells from OVX mice. Exogenously applied kisspeptin reduced I(A) regardless of time of day or estradiol status. Estradiol, interacting with time of day, and kisspeptin both depolarized I(A) activation. These findings extend our understanding of both the neurobiological mechanisms of estradiol negative vs. positive regulation of GnRH neurons and of kisspeptin action on these cells.

  13. Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones.

    PubMed

    Kim, Jinhyun; Wei, Dong-Sheng; Hoffman, Dax A

    2005-11-15

    A-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (APs) into dendrites of hippocampal CA1 pyramidal neurones. Recent molecular cloning studies have found several families of voltage-gated K(+) channel genes expressed in the mammalian brain. At present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated K(+) channels is lacking. Here we used a combination of molecular, electrophysiological and imaging techniques to show that one such gene, Kv4.2, controls AP half-width, frequency-dependent AP broadening and dendritic action potential propagation. Using a modified Sindbis virus, we expressed either the enhanced green fluorescence protein (EGFP)-tagged Kv4.2 or an EGFP-tagged dominant negative mutant of Kv4.2 (Kv4.2g(W362F)) in CA1 pyramidal neurones of organotypic slice cultures. Neurones expressing Kv4.2g(W362F) displayed broader action potentials with an increase in frequency-dependent AP broadening during a train compared with control neurones. In addition, Ca(2)(+) imaging of Kv4.2g(W362F) expressing dendrites revealed enhanced AP back-propagation compared to control neurones. Conversely, neurones expressing an increased A-type current through overexpression of Kv4.2 displayed narrower APs with less frequency dependent broadening and decreased dendritic propagation. These results point to Kv4.2 as the major contributor to the A-current in hippocampal CA1 neurones and suggest a prominent role for Kv4.2 in regulating AP shape and dendritic signalling. As Ca(2)(+) influx occurs primarily during AP repolarization, Kv4.2 activity can regulate cellular processes involving Ca(2)(+)-dependent second messenger cascades such as gene expression and synaptic plasticity.

  14. Prevention of Ca(2+)-mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current.

    PubMed Central

    Pape, H C; Budde, T; Mager, R; Kisvárday, Z F

    1994-01-01

    1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole-cell current-clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue, with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole-cell voltage-clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage-dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na(+)-K(+)-mediated spikes: the T-type Ca2+ current (IT) and an A-type K+ current (IA). Taking into account the differences in membrane surface area, the average size of IT was similar in the two types of neurones, and interneurones possessed a slightly larger A-conductance. 4. In local circuit neurones, the ranges of steady-state inactivation and activation of IT and IA were largely overlapping (VH = 81.1 vs. -82.8 mV), both currents activated at around -70 mV, and they rapidly increased in amplitude with further depolarization. In relay cells, the inactivation curve of IT was negatively shifted along the voltage axis by about 20 mV compared with that of IA (Vh = -86.1 vs. -69.2 mV), and the activation threshold for IT (at -80 mV) was 20 mV more negative than that for IA. In interneurones, the activation range of IT was shifted to values more positive than that in relay cells (Vh = -54.9 vs. -64.5 mV), whereas the activation range of IA was more negative (Vh = -25.2 vs. -14.5 mV). 5. Under whole

  15. Electrophysiological estimation of the actions of acetylcholinesterase inhibitors on acetylcholine receptor and cholinesterase in physically isolated Aplysia neurones.

    PubMed Central

    Oyama, Y.; Hori, N.; Evans, M. L.; Allen, C. N.; Carpenter, D. O.

    1989-01-01

    1. The actions of representative cholinesterase inhibitors on the acetylcholine responses of physically isolated single neurones from the pedal ganglion of Aplysia californica were studied, using electrophysiological techniques and rapid agonist application to analyse both the inhibitory actions on the acetylcholine receptor-channel complex and the degree of inhibition of acetylcholinesterase activity on the same neurone. The inhibitors used were physostigmine, edrophonium and diisopropylfluorophosphate (DFP). 2. When selected neurones were suddenly exposed to 50 microM acetylcholine by a 'concentration clamp' technique a large Na-dependent inward current was initiated, and decayed in the continued presence of acetylcholine without external perfusion. However, if perfusion of the acetylcholine solution was reinitiated the current increased somewhat, indicating that the decay of current was due to some combination of receptor desensitization and local depletion of acetylcholine at the membrane by acetylcholinesterase. 3. With simultaneous application of acetylcholine (50 microM) and physostigmine (0.1 to 100 microM) there was a dose-dependent reduction of peak amplitude of the acetylcholine response. However, physostigmine at low concentrations (0.1 to 10 microM) caused a time-dependent increase in the current amplitude alone with a time- and dose-dependent inhibition of acetylcholinesterase activity. At the highest concentration of physostigmine (100 microM) acetylcholinesterase activity was abolished but the current peak was very depressed. After removal of physostigmine from the bathing solution, the current amplitude decreased toward the control at the two lower concentrations as the inhibitory actions on acetylcholinesterase activity were almost reversible, while at the two higher concentrations (10 and 100 microM) the current increased and the inhibition of acethylcholinesterase remained. 4. When acetylcholine (50 microM) and edrophonium (0.1 to 10 micro

  16. The influence of intravesical administration of resiniferatoxin (RTX) on the chemical coding of sympathetic chain ganglia (SChG) neurons supplying the porcine urinary bladder.

    PubMed

    Lepiarczyk, Ewa; Majewski, Mariusz; Bossowska, Agnieszka

    2015-11-01

    Resiniferatoxin (RTX) is used as an experimental drug in therapy of neurogenic urinary bladder disorders. The present study investigated the chemical coding of sympathetic chain ganglia (SChG) neurons supplying porcine urinary bladder after intravesical RTX instillation. The SChG neurons were visualized with retrograde tracing method and their chemical profile was disclosed with double-labeling immunohistochemistry using antibodies against dopamine β-hydroxylase (DβH; marker of noradrenergic neurons), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin, Leu(5)-enkephalin and neuronal nitric oxide synthase (nNOS). It was found that in both the control (n = 5) and RTX-treated pigs (n = 5), the vast majority (90.4 ± 2.8 and 89.7 ± 2.3%, respectively) of FB-positive (FB+) nerve cells were DβH+. RTX instillation caused a decrease in the number of FB+/DβH+ neurons immunopositive to NPY (71.1 ± 12.1 vs 43.2 ± 6.7%), VIP (21.3 ± 10.7 vs 5.3 ± 4.3%) or SOM (16.5 ± 4.6 vs 2.3 ± 2.6%) and a distinct increase in the number of FB+/DβH+ neurons immunoreactive to nNOS (0.8 ± 1 vs 5.3 ± 1.9 %). The present study for the first time has provided some information that therapeutic effects of RTX on the mammalian urinary bladder can be partly mediated by SChG neurons.

  17. Striatal and Tegmental Neurons Code Critical Signals for Temporal-Difference Learning of State Value in Domestic Chicks

    PubMed Central

    Wen, Chentao; Ogura, Yukiko; Matsushima, Toshiya

    2016-01-01

    To ensure survival, animals must update the internal representations of their environment in a trial-and-error fashion. Psychological studies of associative learning and neurophysiological analyses of dopaminergic neurons have suggested that this updating process involves the temporal-difference (TD) method in the basal ganglia network. However, the way in which the component variables of the TD method are implemented at the neuronal level is unclear. To investigate the underlying neural mechanisms, we trained domestic chicks to associate color cues with food rewards. We recorded neuronal activities from the medial striatum or tegmentum in a freely behaving condition and examined how reward omission changed neuronal firing. To compare neuronal activities with the signals assumed in the TD method, we simulated the behavioral task in the form of a finite sequence composed of discrete steps of time. The three signals assumed in the simulated task were the prediction signal, the target signal for updating, and the TD-error signal. In both the medial striatum and tegmentum, the majority of recorded neurons were categorized into three types according to their fitness for three models, though these neurons tended to form a continuum spectrum without distinct differences in the firing rate. Specifically, two types of striatal neurons successfully mimicked the target signal and the prediction signal. A linear summation of these two types of striatum neurons was a good fit for the activity of one type of tegmental neurons mimicking the TD-error signal. The present study thus demonstrates that the striatum and tegmentum can convey the signals critically required for the TD method. Based on the theoretical and neurophysiological studies, together with tract-tracing data, we propose a novel model to explain how the convergence of signals represented in the striatum could lead to the computation of TD error in tegmental dopaminergic neurons. PMID:27877100

  18. Protective action of green tea catechins in neuronal mitochondria during aging.

    PubMed

    Assuncao, Marco; Andrade, Jose Paulo

    2015-01-01

    Mitochondria are central players in the regulation of cell homeostasis. They are essential for energy production but at the same time, reactive oxygen species accumulate as byproducts of the electron transport chain causing mitochondrial damage. In the central nervous system, senescence and neurodegeneration occur as a consequence of mitochondrial oxidative insults and impaired electron transfer. The accumulation of several oxidation products in neurons during aging prompts the idea that consumption of antioxidant compounds may delay neurodegenerative processes. Tea, one of the most consumed beverages in the world, presents benefits to human health that have been associated to its abundance in polyphenols, mainly catechins, that possess powerful antioxidant properties in vivo and in vitro. In this review, the focus will be placed on the effects of green tea catechins in neuronal mitochondria. Although these compounds reach the brain in small quantities, there are several possible targets, signaling pathways and molecular machinery impinging in the mitochondria that will be highlighted. Accumulated evidence thus far seems to indicate that catechins help prevent neurodegeneration and delay brain function decline.

  19. IRS2 signaling in LepR-b neurons suppresses FoxO1 to control energy balance independently of leptin action.

    PubMed

    Sadagurski, Marianna; Leshan, Rebecca L; Patterson, Christa; Rozzo, Aldo; Kuznetsova, Alexandra; Skorupski, Josh; Jones, Justin C; Depinho, Ronald A; Myers, Martin G; White, Morris F

    2012-05-02

    Irs2-mediated insulin/IGF1 signaling in the CNS modulates energy balance and glucose homeostasis; however, the site for Irs2 function is unknown. The hormone leptin mediates energy balance by acting on leptin receptor (LepR-b)-expressing neurons. To determine whether LepR-b neurons mediate the metabolic actions of Irs2 in the brain, we utilized Lepr(cre) together with Irs2(L/L) to ablate Irs2 expression in LepR-b neurons (Lepr(ΔIrs2)). Lepr(ΔIrs2) mice developed obesity, glucose intolerance, and insulin resistance. Leptin action was not altered in young Lepr(ΔIrs2) mice, although insulin-stimulated FoxO1 nuclear exclusion was reduced in Lepr(ΔIrs2) mice. Indeed, deletion of Foxo1 from LepR-b neurons in Lepr(ΔIrs2) mice normalized energy balance, glucose homeostasis, and arcuate nucleus gene expression. Thus, Irs2 signaling in LepR-b neurons plays a crucial role in metabolic sensing and regulation. While not required for leptin action, Irs2 suppresses FoxO1 signaling in LepR-b neurons to promote energy balance and metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Shp2 signaling in POMC neurons is important for leptin's actions on blood pressure, energy balance, and glucose regulation

    PubMed Central

    da Silva, Alexandre A.; Ebaady, Sabira E.; Sessums, Price O.; Abraham, Ralph S.; Elmquist, Joel K.; Lowell, Bradford B.; Hall, John E.

    2014-01-01

    Previous studies showed that Src homology-2 tyrosine phosphatase (Shp2) is an important regulator of body weight. In this study, we examined the impact of Shp2 deficiency specifically in proopiomelanocortin (POMC) neurons on metabolic and cardiovascular function and on chronic blood pressure (BP) and metabolic responses to leptin. Mice with Shp2 deleted in POMC neurons (Shp2/Pomc-cre) and control mice (Shp2flox/flox) were implanted with telemetry probes and venous catheters for measurement of mean arterial pressure (MAP) and leptin infusion. After at least 5 days of stable control measurements, mice received leptin infusion (2 μg·kg−1·day−1 iv) for 7 days. Compared with Shp2flox/flox controls, Shp2/Pomc-cre mice at 22 wk of age were slightly heavier (34 ± 1 vs. 31 ± 1 g) but consumed a similar amount of food (3.9 ± 0.3 vs. 3.8 ± 0.2 g/day). Leptin infusion reduced food intake in Shp2flox/flox mice (2.6 ± 0.5 g) and Shp2/Pomc-cre mice (3.2 ± 0.3 g). Despite decreasing food intake, leptin infusion increased MAP in control mice, whereas no significant change in MAP was observed in Shp2/Pomc-cre mice. Leptin infusion also decreased plasma glucose and insulin levels in controls (12 ± 1 to 6 ± 1 μU/ml and 142 ± 12 to 81 ± 8 mg/100 ml) but not in Shp2/Pomc-cre mice. Leptin increased V̇o2 by 16 ± 2% in controls and 7 ± 1% in Shp2/Pomc-cre mice. These results indicate that Shp2 signaling in POMC neurons contributes to the long-term BP and antidiabetic actions of leptin and may play a modest role in normal regulation of body weight. PMID:25339680

  1. Blockade of sensory neuron action potentials by a static magnetic field in the 10 mT range

    SciTech Connect

    McLean, M.J.; Holcomb, R.R.; Wamil, A.W.; Pickett, J.D.; Cavopol, A.V.

    1995-05-01

    To characterize the inhibitory effect of a static magnetic field, action potentials (AP) were elicited by intracellular application of 1 ms depolarizing current pulses of constant amplitude to the somata of adult mouse dorsal root ganglion neurons in monolayer dissociated cell culture. During the control period, < 5% of stimuli failed to elicit AP. During exposure to an {approximately}11 mT static magnetic field at the cell position produced by an array of four permanent center-charged neodymium magnets of alternating polarity (MAG-4A), 66% of stimuli failed to elicit AP. The number of failures was maximal after about 200--250 s in the field and returned gradually to baseline over 400--600 s. A direct or indirect effect on the conformation of AP generating sodium channels could account for these results because (1) failure was preceded often by reduction of maximal rate of rise, an indirect measure of sodium current; (2) recovery was significantly prolonged in more than one-half of neurons that were not stimulated during exposure to the MAG-4A field; and (3) resting membrane potential, input resistance, and chronaxie were unaffected by the field. The effect was diminished or prevented by moving the MAG-4A array along the X or Z axis away from the neuron under study and by increasing the distance between magnets in the XY plane. Reduction of AP firing during exposure to the {approximately}0.1 mT field produced by a MAG-4A array of micromagnets was about the same as that produced by a MAG-4A array of the large magnets above. The {approximately}28 mT field produced at cell position by two magnets of alternating polarity and the {approximately}88 mT field produced by a single magnet had no significant effect on AP firing. These findings suggest that field strength alone cannot account for AP blockade.

  2. 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

  3. Intracellular and Extracellular Recording of Spontaneous Action Potentials in Mammalian Neurons and Cardiac Cells with 3D Plasmonic Nanoelectrodes.

    PubMed

    Dipalo, Michele; Amin, Hayder; Lovato, Laura; Moia, Fabio; Caprettini, Valeria; Messina, Gabriele C; Tantussi, Francesco; Berdondini, Luca; De Angelis, Francesco

    2017-06-14

    Three-dimensional vertical micro- and nanostructures can enhance the signal quality of multielectrode arrays and promise to become the prime methodology for the investigation of large networks of electrogenic cells. So far, access to the intracellular environment has been obtained via spontaneous poration, electroporation, or by surface functionalization of the micro/nanostructures; however, these methods still suffer from some limitations due to their intrinsic characteristics that limit their widespread use. Here, we demonstrate the ability to continuously record both extracellular and intracellular-like action potentials at each electrode site in spontaneously active mammalian neurons and HL-1 cardiac-derived cells via the combination of vertical nanoelectrodes with plasmonic optoporation. We demonstrate long-term and stable recordings with a very good signal-to-noise ratio. Additionally, plasmonic optoporation does not perturb the spontaneous electrical activity; it permits continuous recording even during the poration process and can regulate extracellular and intracellular contributions by means of partial cellular poration.

  4. Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons.

    PubMed

    Martinez-Espinosa, Pedro L; Wu, Jianping; Yang, Chengtao; Gonzalez-Perez, Vivian; Zhou, Huifang; Liang, Hongwu; Xia, Xiao-Ming; Lingle, Christopher J

    2015-11-11

    Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na(+)-dependent K(+) (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations.

  5. Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control.

    PubMed

    de Kloet, Annette D; Liu, Meng; Rodríguez, Vermalí; Krause, Eric G; Sumners, Colin

    2015-09-01

    Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT1R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function.

  6. Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons

    PubMed Central

    Martinez-Espinosa, Pedro L; Wu, Jianping; Yang, Chengtao; Gonzalez-Perez, Vivian; Zhou, Huifang; Liang, Hongwu; Xia, Xiao-Ming; Lingle, Christopher J

    2015-01-01

    Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na+-dependent K+ (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations. DOI: http://dx.doi.org/10.7554/eLife.10013.001 PMID:26559620

  7. Neuronal actions of endorphins and enkephalins among brain regions: a comparative microiontophoretic study.

    PubMed Central

    Nicoll, R A; Siggins, G R; Ling, N; Bloom, F E; Guillemin, R

    1977-01-01

    The brain peptides alpha- and beta-endorphin, leucine- and methionine-enkephalin, as well as the opiate normorphine, have been evaluated by microiontophoresis for their effects on neuronal activity in several regions of the rat brain. In cerebral cortex, brainstem, caudate nucleus, and thalamus, most responsive cells were inhibited by the peptides and by normorphine, while in hippocampus all responsive cells were excited. Both inhibitory and excitatory responses were blocked by the narcotic antagonist naloxone. Occurrence of responsive cells encountered in a particular region was loosely correlated with density of stereospecific opiate binding sites as reported by others. These results are consistent with the hypothesis that the endorphins and enkephalins may represent a new class of central neurotransmitters; among other functions, these peptides may play a role in the regulation of behavior and the expression of psychopharmacological agents such as the opiate alkaloids. PMID:267951

  8. Weak action potential backpropagation is associated with high-frequency axonal firing capability in principal neurons of the gerbil medial superior olive.

    PubMed

    Scott, Luisa L; Hage, Travis A; Golding, Nace L

    2007-09-01

    Principal neurons of the medial superior olive (MSO) convey azimuthal sound localization cues through modulation of their rate of action potential firing. Previous intracellular studies in vitro have shown that action potentials appear highly attenuated at the soma of MSO neurons, potentially reflecting specialized action potential initiation and/or a physically distant site of generation. To examine this more directly, we made dual patch-clamp recordings from MSO principal neurons in gerbil brainstem slices. Using somatic and dendritic whole-cell recordings, we show that graded action potentials at the soma are highly sensitive to the rate of rise of excitation and undergo strong attenuation in their backpropagation into the dendrites (length constant, 76 microm), particularly during strong dendritic excitation. Using paired somatic whole-cell and axonal loose-patch recordings, we show that action potentials recorded in the axon at distances > 25 microm are all-or-none, and uniform in amplitude even when action potentials appear graded at the soma. This proximal zone corresponded to the start of myelination in the axon, as assessed with immunocytochemical staining for myelin basic protein in single-labelled neurons. Finally, the axon was capable of sustaining remarkably high firing rates, with perfect entrainment occurring at frequencies of up to 1 kHz. Together, our findings show that action potential signalling in MSO principal neurons is highly secure, but shows a restricted invasion of the somatodendritic compartment of the cell. This restriction may be important for minimizing distortions in synaptic integration during the high frequencies of synaptic input encountered in the MSO.

  9. Action of nereistoxin on recombinant neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes.

    PubMed

    Raymond Delpech, Valérie; Ihara, Makoto; Coddou, Claudio; Matsuda, Kazuhiko; Sattelle, David B

    2003-11-01

    Nereistoxin (NTX), a natural neurotoxin from the salivary glands of the marine annelid worm Lumbriconereis heteropoda, is highly toxic to insects. Its synthetic analogue, Cartap, was the first commercial insecticide based on a natural product. We have used voltage-clamp electrophysiology to compare the actions of NTX on recombinant nicotinic acetylcholine receptors (nicotinic AChRs) expressed in Xenopus laevis oocytes following nuclear injection of cDNAs. The recombinant nicotinic AChRs investigated were chicken alpha7, chicken alpha4beta2 and the Drosophila melanogaster/chicken hybrid receptors SAD/beta2 and ALS/beta2. No agonist action of NTX (0.1-100 microM) was observed on chicken alpha7, chicken alpha4beta2 and the Drosophila/chicken hybrid nicotinic AChRs. Currents elicited by ACh were reduced in amplitude by NTX in a dose-dependent manner. The toxin was slightly more potent on recombinant Drosophila/vertebrate hybrid receptors than on vertebrate homomeric (alpha7) or heteromeric (alpha4beta2) nicotinic AChRs. Block by NTX of the chicken alpha7, chicken alpha4beta2 and the SAD/beta2 and ALS/beta2 Drosophila/chicken hybrid receptors is in all cases non-competitive. Thus, the site of action on nicotinic AChRs of NTX, to which the insecticide Cartap is metabolised in insects, differs from that of the major nicotinic AChR-active insecticide, imidacloprid.

  10. Neuronal interactions between mentalising and action systems during indirect request processing

    PubMed Central

    Smaragdi, Areti; Rueschemeyer, Shirley-Ann

    2016-01-01

    Human communication relies on the ability to process linguistic structure and to map words and utterances onto our environment. Furthermore, as what we communicate is often not directly encoded in our language (e.g. in the case of irony, jokes or indirect requests), we need to extract additional cues to infer the beliefs and desires of our conversational partners. Although the functional interplay between language and the ability to mentalise has been discussed in theoretical accounts in the past, the neurobiological underpinnings of these dynamics are currently not well understood. Here, we address this issue using functional imaging (fMRI). Participants listened to question-reply dialogues. In these dialogues, a reply is interpreted as a direct reply, an indirect reply or a request for action, depending on the question. We show that inferring meaning from indirect replies engages parts of the mentalising network (mPFC) while requests for action also activate the cortical motor system (IPL). Subsequent connectivity analysis using Dynamic Causal Modelling (DCM) revealed that this pattern of activation is best explained by an increase in effective connectivity from the mentalising network (mPFC) to the action system (IPL). These results are an important step towards a more integrative understanding of the neurobiological basis of indirect speech processing. PMID:27131039

  11. Measuring the quality of neuronal identification in ensemble recordings

    PubMed Central

    Neymotin, Samuel A.; Lytton, William W.; Olypher, Andrey V.; Fenton, André A.

    2011-01-01

    Technological advances in electrode construction and digital signal processing now allow recording simultaneous extracellular action potential discharges from many single neurons, with the potential to revolutionize understanding of the neural codes for sensory, motor and cognitive variables. Such studies have revealed the importance of ensemble neural codes, encoding information in the dynamic relationships amongst the action potential spike trains of multiple single neurons. Although the success of this research depends on the accurate classification of extracellular action potentials to individual neurons, there are no widely used quantitative methods for assessing the quality of the classifications. Here we describe information theoretic measures of action potential waveform isolation applicable to any dataset, that have an intuitive, universal interpretation, and that are not dependent on the methods or choice of parameters for single unit isolation, and that have been validated using a dataset of simultaneous intra- and extracellular neuronal recordings from Sprague-Dawley rats. PMID:22072690

  12. Measuring the quality of neuronal identification in ensemble recordings.

    PubMed

    Neymotin, Samuel A; Lytton, William W; Olypher, Andrey V; Fenton, André A

    2011-11-09

    Technological advances in electrode construction and digital signal processing now allow recording simultaneous extracellular action potential discharges from many single neurons, with the potential to revolutionize understanding of the neural codes for sensory, motor, and cognitive variables. Such studies have revealed the importance of ensemble neural codes, encoding information in the dynamic relationships among the action potential spike trains of multiple single neurons. Although the success of this research depends on the accurate classification of extracellular action potentials to individual neurons, there are no widely used quantitative methods for assessing the quality of the classifications. Here we describe information theoretic measures of action potential waveform isolation applicable to any dataset that have an intuitive, universal interpretation, that are not dependent on the methods or choice of parameters for single-unit isolation, and that have been validated using a dataset of simultaneous intracellular and extracellular neuronal recordings from Sprague Dawley rats.

  13. Estimated cochlear delays in low best-frequency neurons in the barn owl cannot explain coding of interaural time difference.

    PubMed

    Singheiser, Martin; Fischer, Brian J; Wagner, Hermann

    2010-10-01

    The functional role of the low-frequency range (<3 kHz) in barn owl hearing is not well understood. Here, it was tested whether cochlear delays could explain the representation of interaural time difference (ITD) in this frequency range. Recordings were obtained from neurons in the core of the central nucleus of the inferior colliculus. The response of these neurons varied with the ITD of the stimulus. The response peak shared by all neurons in a dorsoventral penetration was called the array-specific ITD and served as criterion for the representation of a given ITD in a neuron. Array-specific ITDs were widely distributed. Isolevel frequency response functions obtained with binaural, contralateral, and ispilateral stimulation exhibited a clear response peak and the accompanying frequency was called the best frequency. The data were tested with respect to predictions of a model, the stereausis model, assuming cochlear delays as source for the best ITD of a neuron. According to this model, different cochlear delays determined by mismatches between the ipsilateral and contralateral best frequencies are the source for the ITD in a binaural neuron. The mismatch should depend on the best frequency and the best ITD. The predictions of the stereausis model were not fulfilled in the low best-frequency neurons analyzed here. It is concluded that cochlear delays are not responsible for the representation of best ITD in the barn owl.

  14. Enhanced Actions of Adenosine in Medial Entorhinal Cortex Layer II Stellate Neurons in Temporal Lobe Epilepsy are Mediated via A1 Receptor Activation

    PubMed Central

    Hargus, Nicholas J.; Jennings, Conor; Perez-Reyes, Edward; Bertram, Edward H.; Patel, Manoj K.

    2011-01-01

    Summary Purpose The adenosinergic system is known to exert an inhibitory affect in the brain and as such adenosine has been considered an endogenous anticonvulsant. Entorhinal cortex (EC) layer II neurons, which serve as the primary input to the hippocampus, are spared in temporal lobe epilepsy (TLE) and become hyperexcitable. Since these neurons also express adenosine receptors, the activity of these neurons may be controlled by adenosine, specifically during seizure activity when adenosine levels are thought to rise. In light of this, we determined if the actions of adenosine on medial EC (mEC) layer II stellate neurons are augmented in TLE and by which receptor subtype. Methods Horizontal brain slices were prepared from rats exhibiting spontaneous seizures (TLE) induced by electrical stimulation and compared with age matched control rats. mEC layer II stellate neurons were visually identified and action potentials (AP) evoked by either a series of depolarizing current injection steps or via presynaptic stimulation of mEC deep layers. The effects of adenosine were compared with actions of adenosine A1 and A2A receptor-specific agonists (CPA and CGS 21680) and antagonists (DPCPX and ZM241385) respectively. Immunohistochemical and qPCR techniques were also employed to assess relative adenosine A1 receptor message and expression. Key Findings mEC layer II stellate neurons were hyper-excitable in TLE, evoking a higher frequency of AP's when depolarized and generating bursts of AP's when synaptically stimulated. Adenosine reduced AP frequency and synaptically evoked AP's in a dose dependent manner (500 nM – 100 μM); however, in TLE, the inhibitory actions of adenosine occurred at concentrations that were without affect in control neurons. In both cases, the inhibitory actions of adenosine were mediated via activation of the A1 and not the A2A receptor subtype. qPCR and immunohistochemical experiments revealed an up-regulation of the adenosine A1 mRNA and an

  15. Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients.

    PubMed

    Osman, Abdullah A; Neskey, David M; Katsonis, Panagiotis; Patel, Ameeta A; Ward, Alexandra M; Hsu, Teng-Kuei; Hicks, Stephanie C; McDonald, Thomas O; Ow, Thomas J; Alves, Marcus Ortega; Pickering, Curtis R; Skinner, Heath D; Zhao, Mei; Sturgis, Eric M; Kies, Merrill S; El-Naggar, Adel; Perrone, Federica; Licitra, Lisa; Bossi, Paolo; Kimmel, Marek; Frederick, Mitchell J; Lichtarge, Olivier; Myers, Jeffrey N

    2015-04-01

    TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC), with mutations occurring in over two thirds of cases; however, the predictive response of these mutations to cisplatin-based therapy remains elusive. In the current study, we evaluate the ability of the Evolutionary Action score of TP53-coding variants (EAp53) to predict the impact of TP53 mutations on response to chemotherapy. The EAp53 approach clearly identifies a subset of high-risk TP53 mutations associated with decreased sensitivity to cisplatin both in vitro and in vivo in preclinical models of HNSCC. Furthermore, EAp53 can predict response to treatment and, more importantly, a survival benefit for a subset of head and neck cancer patients treated with platinum-based therapy. Prospective evaluation of this novel scoring system should enable more precise treatment selection for patients with HNSCC. ©2015 American Association for Cancer Research.

  16. Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions.

    PubMed

    Kaneko, Kentaro; Xu, Pingwen; Cordonier, Elizabeth L; Chen, Siyu S; Ng, Amy; Xu, Yong; Morozov, Alexei; Fukuda, Makoto

    2016-09-13

    The CNS contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD)-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathological changes in the hypothalamus, including diminished cellular leptin sensitivity and increased endoplasmic reticulum (ER) stress and inflammation. Furthermore, pharmacological inhibition of CNS Rap1 signaling normalizes hypothalamic ER stress and inflammation, improves cellular leptin sensitivity, and reduces body weight in mice with dietary obesity. We also demonstrate that Rap1 mediates leptin resistance via interplay with ER stress. Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Amniotic Fluid or Its Fatty Acids Produce Actions Similar to Diazepam on Lateral Septal Neurons Firing Rate

    PubMed Central

    Gutiérrez-García, Ana G.; Vásquez-Hernández, Diana Idania

    2013-01-01

    Human amniotic fluid (AF) contains eight fatty acids (FATs), and both produce anxiolytic-like effects in adult rats and appetitive responses in human newborns. The medial amygdala and lateral septal nucleus function are related to social behavior, but the action of AF or its FATs in this circuit is known. We obtained 267 single-unit extracellular recordings in Wistar rats treated with vehicle (1 mL, s.c.; n = 12), human AF (1 mL, s.c.; n = 12), a FAT mixture (1 mL, s.c.; n = 13), diazepam (1 mg/kg, i.p.; n = 11), and fluoxetine (1 mg/kg, p.o.; n = 12). Compared with the vehicle group, the spontaneous septal firing rate in the AF, FAT mixture, and diazepam groups was the lowest and in the fluoxetine group the highest. Cumulative peristimulus histograms indicated that the significant change in septal firing occurred only in the AF and FAT mixture groups and exclusively in those neurons that increased their firing rate during amygdala stimulation. We conclude that human AF and its FATs produce actions comparable to anxiolytic drugs and are able to modify the responsivity of a circuit involved in social behavior, suggesting facilitation of social recognition processes by maternal-fetal fluids. PMID:23864826

  18. Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task

    PubMed Central

    Wormwood, Benjamin A.; Miller, Rikki L. A.; Gibson, Brett M.; Mair, Robert G.

    2016-01-01

    To respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays. Combined event-related and video tracking analyses revealed variability in spatial tuning of neurons with similar event-related activity. While all correlated neurons exhibited spatial tuning broadly consistent with relevant task events, for instance reinforcement-related activity concentrated in locations where reinforcement was delivered, some had elevated activity in more specific locations, for instance reinforcement-related activity in one of several locations where reinforcement was delivered. Timing analyses revealed a limited set of distinct response types with activity time-locked to critical behavioral events that represent the temporal organization of dDNMTP trials. Our results suggest that reinforcement-guided decision-making emerges from discrete populations of medial prefrontal neurons that encode information related to planned or ongoing movements and actions and anticipated or actual action-outcomes in conjunction with information about spatial context. PMID:26848579

  19. Calcium-activated potassium conductances contribute to action potential repolarization at the soma but not the dendrites of hippocampal CA1 pyramidal neurons.

    PubMed

    Poolos, N P; Johnston, D

    1999-07-01

    Evidence is accumulating that voltage-gated channels are distributed nonuniformly throughout neurons and that this nonuniformity underlies regional differences in excitability within the single neuron. Previous reports have shown that Ca2+, Na+, A-type K+, and hyperpolarization-activated, mixed cation conductances have varying distributions in hippocampal CA1 pyramidal neurons, with significantly different densities in the apical dendrites compared with the soma. Another important channel mediates the large-conductance Ca2+-activated K+ current (IC), which is responsible in part for repolarization of the action potential (AP) and generation of the afterhyperpolarization that follows the AP recorded at the soma. We have investigated whether this current is activated by APs retrogradely propagating in the dendrites of hippocampal pyramidal neurons using whole-cell dendritic patch-clamp recording techniques. We found no IC activation by back-propagating APs in distal dendritic recordings. Dendritic APs activated IC only in the proximal dendrites, and this activation decayed within the first 100-150 micrometer of distance from the soma. The decay of IC in the proximal dendrites occurred despite AP amplitude, plus presumably AP-induced Ca2+ influx, that was comparable with that at the soma. Thus we conclude that IC activation by action potentials is nonuniform in the hippocampal pyramidal neuron, which may represent a further example of regional differences in neuronal excitability that are determined by the nonuniform distribution of voltage-gated channels in dendrites.

  20. Sharing a task or sharing space? On the effect of the confederate in action coding in a detection task.

    PubMed

    Guagnano, Delia; Rusconi, Elena; Umiltà, Carlo Arrigo

    2010-03-01

    Several studies showed a Simon effect when two participants sit close to each other and perform one of the two halves of a two-choice RT task. That is, each participant perform a go-nogo task. A Simon effect emerges, which instead is absent when the same go-nogo tasks are performed individually. Hence the terms were introduced of "social Simon task" and 'social Simon effect". As of now, the social Simon effect was observed with social Simon tasks that overtly gave the participants the impression of being performing in collaboration with another person. In the present study we show that the social Simon effect was present also when, in the social Simon task, the two participants did not actually collaborate. It is, however, absent when participants perform the social task outside of each other's peripersonal space (i.e., outside arm-reach). We argue that the social Simon effect does not necessarily imply a representation of the other's action, as previously suggested. The presence of an active confederate in peripersonal space might simply provide a reference for coding one's own action in space.

  1. Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study

    PubMed Central

    Zant, Janneke C.; Kim, Tae; Prokai, Laszlo; Szarka, Szabolcs; McNally, James; McKenna, James T.; Shukla, Charu; Yang, Chun; Kalinchuk, Anna V.; McCarley, Robert W.; Brown, Ritchie E.

    2016-01-01

    Understanding the control of sleep–wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep–wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that “selective” stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of “selective” optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons. SIGNIFICANCE STATEMENT Optogenetics is a revolutionary tool to assess the roles of

  2. Antidepressant drugs with differing pharmacological actions decrease activity of locus coeruleus neurons

    PubMed Central

    West, Charles H. K.; Ritchie, James C.; Boss-Williams, Katherine A.; Weiss, Jay M.

    2009-01-01

    Previous studies suggest that all effective antidepressant (AD) drugs decrease activity of locus coeruleus (LC) neurons. However, little data exist regarding blood levels of drug in these studies, and what data do exist suggest blood levels might have been very high. To assess whether decreased LC activity is produced by drugs that selectively block reuptake for either norepinephrine or serotonin at therapeutically relevant blood levels, effects of chronic administration of desipramine, paroxetine, and escitalopram on LC activity were measured across a range of doses and blood levels of drug. Further, effects of a range of doses of mirtazapine were examined; in that mirtazapine blocks α2 adrenergic receptors, it might be anticipated to increase rather than decrease LC activity. Finally, to begin to assess whether the response of LC to ADs was specific to these drugs, effects of four non-AD drugs (single dose) were measured. Drugs were administered via osmotic minipump for 14 d. Electrophysiological recording of LC activity (assessment of both spontaneous firing rate and sensory-evoked ‘burst’ firing) then took place under isoflurane anaesthesia on the last day of drug treatment. The blood level of drugs present at the end of the recording session was also measured. All AD drugs tested decreased LC spontaneous and sensory-evoked ‘burst’ firing, and this was observed across a wide range of blood levels for the drugs. Non-AD drugs did not decrease LC activity. The findings of this investigation continue to support the possibility that all effective AD drugs decrease LC activity. PMID:18950545

  3. Actions of cromakalim on outward currents of CA1 neurones in hippocampal slices.

    PubMed Central

    Erdemli, G; Krnjević, K

    1994-01-01

    1. Membrane effects of cromakalim (Crom; 50-300 microM) were examined in CA1 neurones recorded mainly by intracellular, single-electrode voltage-clamping in slices (from Sprague-Dawley rats) kept in an interface chamber at 33 degrees C. 2. In 14 cells held at -63 +/- 3.5 mV, in the presence of tetrodotoxin, kynurenic acid and (in most cases) bicuculline, bath applied Crom produced no consistent change in holding current (-59 +/- 66 pA) or input conductance (GN) (-3.9 +/- 5.2%). 3. Overall there were no significant changes in instantaneous inward rectification or in Q-current inward relaxations. 4. In 18 out of 22 cells, outward currents, evoked by 0.5 s pulses to voltages > -50 and < -20 mV, were depressed by Crom (by 42 +/- 11%, for n = 22). Because this effect was consistently seen in Ca current-blocking media, containing either Mn and low Ca, or Cd (and also carbachol), the K channels depressed by Crom were probably of the delayed rectifier (IDR) type. 5. The Crom-control difference current (ICrom), obtained with slow depolarizing ramps, had a biphasic character, inward in the voltage (V) range > -50 < -20 mV (where outward currents are depressed by Crom) and tending outward for V > or = -20 mV. 6. In 10 out of 11 cells, Crom potentiated a D-like, slowly-inactivating outward current (by 88 +/- 31%, for n = 11).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7530570

  4. Action-potential duration and the modulation of transmitter release from the sensory neurons of Aplysia in presynaptic facilitation and behavioral sensitization.

    PubMed

    Hochner, B; Klein, M; Schacher, S; Kandel, E R

    1986-11-01

    Presynaptic facilitation of transmitter release from Aplysia sensory neurons is an important contributor to behavioral sensitization of the gill and siphon withdrawal reflex. The enhanced release is accompanied by reduction of the serotonin-sensitive S current in the sensory neurons and a consequent increase in duration of the presynaptic action potential (ranging from 10% to 30%). We find that changes of similar magnitude in the duration of depolarizing voltage-clamp steps in sensory neurons in intact abdominal ganglia yield increases in synaptic potentials of 45-120%. In dissociated cell culture, these changes lead to increases of 25-60% in the synaptic potential. Prolongation of presynaptic depolarization using voltage clamp or prolongation of the duration of the action potential by K(+)-channel blockers leads to prolongation of the time-to-peak of the synaptic potentials; similar changes in time-to-peak occur during presynaptic facilitation. The time-to-peak is not changed by homosynaptic depression or by changing the Ca(2+) concentration, procedures that alter release without changing the duration of the action potential. Preventing the spike from broadening by voltage clamping the presynaptic neuron substantially reduces or blocks the facilitation. These results suggest that broadening of the action potential during facilitation is a causal factor in the enhancement of transmitter release.

  5. The impact of androgen actions in neurons on metabolic health and disease.

    PubMed

    Morford, Jamie J; Wu, Sheng; Mauvais-Jarvis, Franck

    2017-09-04

    The male hormone testosterone exerts different effects on glucose and energy homeostasis in males and females. Testosterone deficiency predisposes males to visceral obesity, insulin resistance and type 2 diabetes. However, testosterone excess predisposes females to similar metabolic dysfunction. Here, we review the effects of testosterone actions in the central nervous system on metabolic function in males and females. In particular, we highlight changes within the hypothalamus that control glucose and energy homeostasis. We distinguish the organizational effects of testosterone in the programming of neural circuitry during development from the activational effects of testosterone during adulthood. Finally, we explore potential sites where androgen might be acting to impact metabolism within the central nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Neuronal adaptation involves rapid expansion of the action potential initiation site

    PubMed Central

    Scott, Ricardo S.; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P.; Rusakov, Dmitri A.

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma–axon recordings combined with axonal Na+ and Ca2+ imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na+ channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  7. Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies.

    PubMed

    Mika, Joanna; Zychowska, Magdalena; Makuch, Wioletta; Rojewska, Ewelina; Przewlocka, Barbara

    2013-01-01

    The current knowledge of the pharmacological actions of the tricyclic antidepressants (TCAs) has slowly evolved through their over 40-year history. Chronic pain represents one of the most important public health problems, and antidepressants are an essential part of the therapeutic strategy in addition to classical analgesics. This article reviews the available evidence on the efficacy and safety of antidepressants in chronic pain conditions; namely, headaches, low back pain, fibromyalgia, cancer pain and especially neuropathic pain. TCAs are traditionally the main type of depression medication used to treat chronic pain. Recently, new antidepressants were introduced into clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs that are effective for chronic pain belong to the tetracyclic antidepressants (TeCAs) group (amoxapine, maprotiline), the serotonin and noradrenaline reuptake inhibitors (SNRIs) group (duloxetine, venlafaxine, milnacipran) and the atypical antidepressants group (bupropion, trazodone, mirtazapine, nefazodone). In this review, we present the available publications on TCAs (amitriptyline, doxepin, imipramine, desipramine, nortriptyline), TeCAs (amoxapine, maprotiline), selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluoxetine, paroxetine), SNRIs (duloxetine, venlafaxine, milnacipran) and atypical antidepressants (bupropion) for the treatment of neuropathic pain. We also review analgesics acting as both opioid receptor agonists and also acting as aminergic reuptake inhibitors. Existing data are insufficient to conclude which of these new classes of antidepressants has the best clinical profile and will be the most effective in the treatment of neuropathic pain; in addition, a lower incidence of side effects should be considered. Increased experimental and translational research is a key for further improvement of the treatment of chronic pain with antidepressants. However

  8. Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system.

    PubMed

    Liu, Sumei; Gao, Na; Hu, Hong-Zhen; Wang, Xiyu; Wang, Guo-Du; Fang, Xiucai; Gao, Xiang; Xia, Yun; Wood, Jackie D

    2006-01-01

    Immunofluorescence was used to study immunoreactivity (IR) for corticotropin-releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was expressed in both the myenteric and the submucosal plexuses of all regions of the large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve fibers were present in the myenteric and submucosal plexuses, in the circular muscle coat, and surrounding submucosal arterioles. Most of the CRF-IR fibers persisted in the myenteric and submucosal plexuses after 7 days in organotypic culture. CRF-IR was not coexpressed with tyrosine hydroxylase-IR or calcitonin gene-related peptide-IR fibers. The proportions of CRF-IR cell bodies in the myenteric plexus increased progressively from the stomach (0.6%) to the distal colon (2.8%). Most of the CRF-IR myenteric neurons (95%) had uniaxonal morphology; the remainder had Dogiel type II multipolar morphology. CRF-IR cell bodies in the myenteric plexus of the ileum expressed IR for choline acetyltransferase (56.9%), substance P (55.0%), and nitric oxide synthase (37.9%). CRF-IR never colocalized with IR for calbindin, calretinin, neuropeptide Y, serotonin, or somatostatin in the myenteric plexus. CRF-IR cell bodies were more abundant in the submucosal plexus (29.9-38.0%) than in the myenteric plexus. All CRF-IR neurons in submucosal ganglia expressed vasoactive intestinal peptide-IR and were likely to be secretomotor/vasodilator neurons. CRF-IR neurons did not express IR for the CRF(1) receptor. CRF(1)-IR was expressed in neuronal neighbors of those with CRF-IR. Collective evidence suggests that VIPergic secretomotor neurons might provide synaptic input to neighboring cholinergic neurons.

  9. Multiple excitatory actions of orexins upon thalamo-cortical neurons in dorsal lateral geniculate nucleus - implications for vision modulation by arousal.

    PubMed

    Chrobok, Lukasz; Palus-Chramiec, Katarzyna; Chrzanowska, Anna; Kepczynski, Mariusz; Lewandowski, Marian Henryk

    2017-08-09

    The orexinergic system of the lateral hypothalamus plays a crucial role in maintaining wakefulness and mediating arousal in a circadian time-dependent manner. Due to the extensive connections of orexinergic neurons, both orexins (OXA and OXB) exert mainly excitatory effects upon remote brain areas, including the thalamus. The dorsal lateral geniculate nucleus (DLG) is a relay thalamic centre for the visual system. Its thalamo-cortical (TC) neurons convey photic information from the retina to the primary visual cortex. The present study shows that orexins are powerful modulators of neuronal activity in the DLG. OXA directly depolarised the majority of neurons tested, acting predominately on postsynaptic OX2 receptors. Moreover, OXA was found to increase excitability and enhance neuronal responses to both glutamate and γ-aminobutyric acid (GABA). Mechanistic studies showed the involvement of voltage-gated calcium currents and GIRK channels in the observed depolarisations. Immunohistochemical staining showed sparse orexinergic innervation of the DLG during the light phase, with increased density at night. We hypothesise that the depolarising effects of orexins upon DLG neurons may facilitate signal transmission through the visual thalamo-cortical pathway during behavioural arousal. Thus, the action of orexin on DLG TC neurons may underlie the circadian/behavioural modulation of vision.

  10. Assessing the Electrode-Neuron Interface with the Electrically Evoked Compound Action Potential, Electrode Position, and Behavioral Thresholds.

    PubMed

    DeVries, Lindsay; Scheperle, Rachel; Bierer, Julie Arenberg

    2016-06-01

    Variability in speech perception scores among cochlear implant listeners may largely reflect the variable efficacy of implant electrodes to convey stimulus information to the auditory nerve. In the present study, three metrics were applied to assess the quality of the electrode-neuron interface of individual cochlear implant channels: the electrically evoked compound action potential (ECAP), the estimation of electrode position using computerized tomography (CT), and behavioral thresholds using focused stimulation. The primary motivation of this approach is to evaluate the ECAP as a site-specific measure of the electrode-neuron interface in the context of two peripheral factors that likely contribute to degraded perception: large electrode-to-modiolus distance and reduced neural density. Ten unilaterally implanted adults with Advanced Bionics HiRes90k devices participated. ECAPs were elicited with monopolar stimulation within a forward-masking paradigm to construct channel interaction functions (CIF), behavioral thresholds were obtained with quadrupolar (sQP) stimulation, and data from imaging provided estimates of electrode-to-modiolus distance and scalar location (scala tympani (ST), intermediate, or scala vestibuli (SV)) for each electrode. The width of the ECAP CIF was positively correlated with electrode-to-modiolus distance; both of these measures were also influenced by scalar position. The ECAP peak amplitude was negatively correlated with behavioral thresholds. Moreover, subjects with low behavioral thresholds and large ECAP amplitudes, averaged across electrodes, tended to have higher speech perception scores. These results suggest a potential clinical role for the ECAP in the objective assessment of individual cochlear implant channels, with the potential to improve speech perception outcomes.

  11. Nitrous oxide directly inhibits action potential-dependent neurotransmission from single presynaptic boutons adhering to rat hippocampal CA3 neurons.

    PubMed

    Wakita, Masahito; Kotani, Naoki; Yamaga, Toshitaka; Akaike, Norio

    2015-09-01

    We evaluated the effects of N2O on synaptic transmission using a preparation of mechanically dissociated rat hippocampal CA3 neurons that allowed assays of single bouton responses evoked from native functional nerve endings. We studied the effects of N2O on GABAA, glutamate, AMPA and NMDA receptor-mediated currents (IGABA, IGlu, IAMPA and INMDA) elicited by exogenous application of GABA, glutamate, (S)-AMPA, and NMDA and spontaneous, miniature, and evoked GABAergic inhibitory and glutamatergic excitatory postsynaptic current (sIPSC, mIPSC, eIPSC, sEPSC, mEPSC and eEPSC) in mechanically dissociated CA3 neurons. eIPSC and eEPSC were evoked by focal electrical stimulation of a single bouton. Administration of 70% N2O altered neither IGABA nor the frequency and amplitude of both sIPSCs and mIPSCs. In contrast, N2O decreased the amplitude of eIPSCs, while increasing failure rates (Rf) and paired-pulse ratios (PPR) in a concentration-dependent manner. On the other hand, N2O decreased IGlu, IAMPA and INMDA. Again N2O did not change the frequency and amplitude of either sEPSCs of mEPSCs. N2O also decreased amplitudes of eEPSCs with increased Rf and PPR. The decay phases of all synaptic responses were unchanged. The present results indicated that N2O inhibits the activation of AMPA/KA and NMDA receptors and also that N2O preferentially depress the action potential-dependent GABA and glutamate releases but had little effects on spontaneous and miniature releases.

  12. Prolonged acetylsalicylic-acid-supplementation-induced gastritis affects the chemical coding of the stomach innervating vagal efferent neurons in the porcine dorsal motor vagal nucleus (DMX).

    PubMed

    Gańko, Marta; Całka, Jarosław

    2014-01-01

    The main goal of our research was to study the possible alterations of the chemical coding of the dorsal motor vagal nucleus (DMX) neurons projecting to the porcine stomach prepyloric region following prolonged acetylsalicylic acid supplementation. Fast Blue (FB) was injected into the studied area of the stomach. Since the seventh day following the FB injection, acetylsalicylic acid (ASA) was given orally to the experimental gilts. All animals were euthanized on the 28th day after FB injection. Medulla oblongata sections were then processed for double-labeling immunofluorescence for choline acetyltransferase (ChAT), pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), galanin (GAL), substance P (SP), leu enkephalin (LENK), and cocaine- and amphetamine-regulated transcript (CART). In the control DMX, only PACAP was observed in 30.08 ± 1.97 % of the FB-positive neurons, while VIP, NOS, GAL, SP, LENK, and CART were found exclusively in neuronal processes running between FB-labeled perikarya. In the ASA DMX, PACAP was revealed in 49.53 ± 5.73 % of traced vagal perikarya. Moreover, we found de novo expression of VIP in 40.32 ± 7.84 %, NOS in 25.02 ± 6.08 %, and GAL in 3.37 ± 0.85 % of the FB-labeled neurons. Our results suggest that neuronal PACAP, VIP, NOS, and GAL are mediators of neural response to aspirin-induced stomach inflammatory state.

  13. Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

    PubMed

    Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

    2016-05-01

    High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS

  14. Long-term treatment with antidepressant drugs reduces the sensitivity of cortical cholinergic neurons to the activating actions of stress and the anxiogenic drug FG 7142.

    PubMed

    Dazzi, L; Vacca, G; Ladu, S; Pisu, M G; Serra, M; Biggio, G

    2001-08-01

    Certain antidepressant drugs exert an anxiolytic action in both humans and rodents. The effects of long-term treatment with imipramine or mirtazapine, two antidepressant drugs with different mechanisms of action, on the response of cortical cholinergic neurons to foot-shock stress or to the anxiogenic drug FG 7142 were investigated in freely moving rats. Chronic treatment with imipramine or mirtazapine reduced the increase in cortical acetylcholine output induced by foot-shock stress by approximately 50%. The same treatment also reduced the sensitivity of cortical cholinergic neurons to the stimulatory effect of acute administration of FG 7142. In contrast, the administration of a single dose of either antidepressant 40 min before foot shock or FG 7142 injection failed to increase the threshold of excitability of cortical cholinergic neurons. These results demonstrate that long-term treatment with either imipramine or mirtazapine reduces the sensitivity of cortical cholinergic neurons to stress or to an anxiogenic drug with an efficacy similar to that of acute administration of benzodiazepines. The neurochemical mechanism responsible for regulation of cholinergic neuron sensitivity might contribute to the modulation of cognitive function associated with emotional and affective disorders.

  15. Rapid Signaling Actions of Environmental Estrogens in Developing Granule Cell Neurons Are Mediated by Estrogen Receptor β

    PubMed Central

    Le, Hoa H.; Belcher, Scott M.

    2010-01-01

    Estrogenic endocrine disrupting chemicals (EDCs) constitute a diverse group of man-made chemicals and natural compounds derived from plants and microbial metabolism. Estrogen-like actions are mediated via the nuclear hormone receptor activity of estrogen receptor (ER)α and ERβ and rapid regulation of intracellular signaling cascades. Previous study defined cerebellar granule cell neurons as estrogen responsive and that granule cell precursor viability was developmentally sensitive to estrogens. In this study experiments using Western blot analysis and pharmacological approaches have characterized the receptor and signaling modes of action of selective and nonselective estrogen ligands in developing cerebellar granule cells. Estrogen treatments were found to briefly increase ERK1/2-phosphorylation and then cause prolonged depression of ERK1/2 activity. The sensitivity of granule cell precursors to estrogen-induced cell death was found to require the integrated activation of membrane and intracellular ER signaling pathways. The sensitivity of granule cells to selective and nonselective ER agonists and a variety of estrogenic and nonestrogenic EDCs was also examined. The ERβ selective agonist DPN, but not the ERα selective agonist 4,4′,4′-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol or other ERα-specific ligands, stimulated cell death. Only EDCs with selective or nonselective ERβ activities like daidzein, equol, diethylstilbestrol, and bisphenol A were observed to induce E2-like neurotoxicity supporting the conclusion that estrogen sensitivity in granule cells is mediated via ERβ. The presented results also demonstrate the utility of estrogen sensitive developing granule cells as an in vitro assay for elucidating rapid estrogen-signaling mechanisms and to detect EDCs that act at ERβ to rapidly regulate intracellular signaling. PMID:20926581

  16. Associative pairing enhances action potential back-propagation in radial oblique branches of CA1 pyramidal neurons

    PubMed Central

    Gasparini, Sonia; Losonczy, Attila; Chen, Xixi; Johnston, Daniel; Magee, Jeffrey C

    2007-01-01

    Back-propagating action potentials (bAPs) are involved in associative synaptic plasticity and the modulation of dendritic excitability. We have used high-speed confocal and two-photon imaging to measure calcium and voltage signals associated with action potential propagation into oblique branches of CA1 pyramidal neurons in adult hippocampal slices. The spatial profile of the bAP-associated Ca2+ influx was biphasic, with an initial increase in the proximity of the branch point followed by a progressive decrease. Voltage imaging in the branches showed that bAP amplitude was initially constant and then steadily declined with distance from the soma. To determine the role of transient K+ channels in this profile, we used external Ba2+ (150 μm) as a channel blocker, after characterizing its effect on A-type K+ channels in the apical trunk. Bath application of Ba2+ significantly reduced the A-type K+ current in outside-out patches and nearly eliminated the distance-dependent decrease in bAP amplitude and its associated Ca2+ signal. Finally, small amplitude bAPs at more distal oblique branch locations could be boosted by simultaneous branch depolarization, such that the paired Ca2+ signal became nearly the same for proximal and distal oblique dendrites. These data suggest that dendritic K+ channels regulate the amplitude of bAPs to create a dendritic Ca2+ signal whose magnitude is inversely related to the electrotonic distance from the soma when bAPs are not associated with a significant amount of localized synaptic input. This distance-dependent Ca2+ signal from bAPs, however, can be amplified and a strong associative signal is produced once the proper correlation between synaptic activation and AP output is achieved. We hypothesize that these two signals may be involved in the regulation of the expression and activity of dendritic voltage- and ligand-gated ion channels. PMID:17272353

  17. Neuronal representation of task performance in the medial frontal cortex undergoes dynamic alterations dependent upon the demand for volitional control of action.

    PubMed

    Matsuzaka, Yoshiya; Akiyama, Tetsuya; Mushiake, Hajime

    2013-09-01

    Neural network contributing to forelimb task performance in the frontal cortex is dynamically reorganized by the necessity for volitional control of action. Neurons in the posterior medial prefrontal cortex (pmPFC) exhibit clear activity modulation when monkeys volitionally select the correct response tactic from multiple choices, but such activity disappears if selection of a tactic is unnecessary. Prompted by these results, we studied how the requirement to select an appropriate tactic affects the neural representation of action in downstream cortical areas. Two monkeys performed a spatial arm-reaching task with either left or right targets. The task required the monkeys to reach either toward (concordant trials) or away from (discordant trials) an illuminated target. Under the dual-tactic condition, concordant and discordant trials were randomly intermixed, requiring the selection of a response tactic. Under the single-tactic condition, only concordant trials were presented, allowing the monkeys to use the same tactic. Neurons in the pmPFC exhibited clear activity related to task performance under the former condition, but such activity disappeared under the latter condition. In contrast, neurons related to task performance were present under both conditions in supplementary motor area (SMA) and presupplementary motor area (pre-SMA). However, the efficacy of action representation by SMA but not pre-SMA neurons dramatically improved under the single-tactic condition. These results suggest that selection of the appropriate response tactic reorganizes neural circuits in specific motor areas in the medial frontal cortex, in addition to the pmPFC.

  18. Excitability and Burst Generation of AVPV Kisspeptin Neurons Are Regulated by the Estrous Cycle Via Multiple Conductances Modulated by Estradiol Action123

    PubMed Central

    Wang, Luhong

    2016-01-01

    Abstract The preovulatory secretory surge of gonadotropin-releasing hormone (GnRH) is crucial for fertility and is regulated by a switch of estradiol feedback action from negative to positive. GnRH neurons likely receive estradiol feedback signals via ERα-expressing afferents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV) are thought to be critical for estradiol-positive feedback induction of the GnRH surge. We examined the electrophysiological properties of GFP-identified AVPV kisspeptin neurons in brain slices from mice on the afternoon of diestrus (negative feedback) and proestrus (positive feedback, time of surge). Extracellular recordings revealed increased firing frequency and action potential bursts on proestrus versus diestrus. Whole-cell recordings were used to study the intrinsic mechanisms of bursting. Upon depolarization, AVPV kisspeptin neurons exhibited tonic firing or depolarization-induced bursts (DIB). Both tonic and DIB cells exhibited bursts induced by rebound from hyperpolarization. DIB occurred similarly on both cycle stages, but rebound bursts were observed more often on proestrus. DIB and rebound bursts were both sensitive to Ni2+, suggesting that T-type Ca2+ currents (ITs) are involved. IT current density was greater on proestrus versus diestrus. In addition to IT, persistent sodium current (INaP) facilitated rebound bursting. On diestrus, 4-aminopyridine-sensitive potassium currents contributed to reduced rebound bursts in both tonic and DIB cells. Manipulation of specific sex steroids suggests that estradiol induces the changes that enhance AVPV kisspeptin neuron excitability on proestrus. These observations indicate cycle-driven changes in circulating estradiol increased overall action potential generation and burst firing in AVPV kisspeptin neurons on proestrus versus diestrus by regulating multiple intrinsic currents. PMID:27280155

  19. Action Research of a Color-Coded, Onset-Rime Decoding Intervention: Examining the Effects with First Grade Students Identified as at Risk

    ERIC Educational Resources Information Center

    Wall, Candace A.; Rafferty, Lisa A.; Camizzi, Mariya A.; Max, Caroline A.; Van Blargan, David M.

    2016-01-01

    Many students who struggle to obtain the alphabetic principle are at risk for being identified as having a reading disability and would benefit from additional explicit phonics instruction as a remedial measure. In this action research case study, the research team conducted two experiments to investigate the effects of a color-coded, onset-rime,…

  20. Action Research of a Color-Coded, Onset-Rime Decoding Intervention: Examining the Effects with First Grade Students Identified as at Risk

    ERIC Educational Resources Information Center

    Wall, Candace A.; Rafferty, Lisa A.; Camizzi, Mariya A.; Max, Caroline A.; Van Blargan, David M.

    2016-01-01

    Many students who struggle to obtain the alphabetic principle are at risk for being identified as having a reading disability and would benefit from additional explicit phonics instruction as a remedial measure. In this action research case study, the research team conducted two experiments to investigate the effects of a color-coded, onset-rime,…

  1. A Role for Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α in Nucleus Accumbens Neuron Subtypes in Cocaine Action.

    PubMed

    Chandra, Ramesh; Engeln, Michel; Francis, T Chase; Konkalmatt, Prasad; Patel, Dipal; Lobo, Mary Kay

    2017-04-01

    Molecules critically involved in cocaine behavioral plasticity are known to regulate and interact with peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). In addition, the PGC-1α promoter has binding sites for early growth response 3 (Egr3), which plays a dynamic role in cocaine action in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 (D1-MSN) versus D2 (D2-MSN). However, the role of PGC-1α in NAc in cocaine action is unknown. PGC-1α messenger RNA and protein were examined in NAc after repeated cocaine exposure. Binding of Egr3 to and histone methylation at the PGC-1α promoter was examined in NAc using chromatin immunoprecipitation after repeated cocaine. PGC-1α ribosome-associated messenger RNA in MSN subtypes was assessed after repeated cocaine using D1-Cre-RiboTag and D2-Cre-RiboTag lines. Finally, PGC-1α was expressed in NAc D1-MSNs versus D2-MSNs using a Cre-inducible adeno-associated virus and Cre lines during cocaine conditioned place preference and cocaine-induced locomotion. Repeated cocaine increased PGC-1α levels and increased Egr3 binding and H3K4me3 at the PGC-1α promoter in NAc. Increased PGC-1α occurred in D1-MSNs, while D2-MSNs showed reduced levels. Viral-mediated expression of PGC-1α in D1-MSNs enhanced behavioral responses to cocaine, while expression in D2-MSNs blunted these behaviors. We demonstrate a novel role for PGC-1α in NAc in cocaine action. PGC-1α is enhanced in NAc D1-MSNs, specifically after cocaine exposure. These data are consistent with increased active methylation and Egr3 binding at the PGC-1α promoter. Finally, we demonstrate a bidirectional role for PGC-1α in mediating behavioral plasticity to cocaine through D1-MSNs versus D2-MSNs. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons

    PubMed Central

    Crunelli, Vincenzo

    2017-01-01

    Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca2+-imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that “tonic”' and low-threshold-spike (LTS) “burst” APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level

  3. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

    PubMed

    Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

    2017-05-24

    Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca(2+)-imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons.SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of

  4. From muscles synergies and individual goals to interpersonal synergies and shared goals: Mirror neurons and interpersonal action hierarchies. Comment on "Grasping synergies: A motor-control approach to the mirror neuron mechanism" by D'Ausilio et al.

    NASA Astrophysics Data System (ADS)

    Candidi, Matteo; Sacheli, Lucia Maria; Aglioti, Salvatore Maria

    2015-03-01

    D'Ausilio et al. [28] must be praised for bringing attention to the important question of how human Mirror Neurons (MNs) may contribute to action perception, prediction and understanding [1] and for linking their role with the granularity of the motor system as conceptualized in the domain of action control theories. Although we think that the Authors are right in saying that the granularity of the motor system constrains the granularity of the MN system, we speculate that the contribution of MNs to action perception, prediction and understanding is also constrained by the connections between MNs and other cortical and subcortical regions, and by the identity of MNs, i.e. whether they are interneurons or pyramidal cells [2]. In other words, the functional contribution of MS depends on whether they are connected to sensory, emotional and cognitive networks for the service of action perception, prediction and understanding.

  5. Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons.

    PubMed

    Colbert, C M; Magee, J C; Hoffman, D A; Johnston, D

    1997-09-01

    Na+ action potentials propagate into the dendrites of pyramidal neurons driving an influx of Ca2+ that seems to be important for associative synaptic plasticity. During repetitive (10-50 Hz) firing, dendritic action potentials display a marked and prolonged voltage-dependent decrease in amplitude. Such a decrease is not apparent in somatic action potentials. We investigated the mechanisms of the different activity dependence of somatic and dendritic action potentials in CA1 pyramidal neurons of adult rats using whole-cell and cell-attached patch-clamp methods. There were three main findings. First, dendritic Na+ currents decreased in amplitude when repeatedly activated by brief (2 msec) depolarizations. Recovery was slow and voltage-dependent. Second, Na+ currents decreased much less in somatic than in dendritic patches. Third, although K+ currents remained constant during trains, K+ currents were necessary for dendritic action potential amplitude to decrease in whole-cell experiments. These results suggest that regional differences in Na+ and K+ channels determine the differences in the activity dependence of somatic and dendritic action potential amplitudes.

  6. Breaking the Neural Code

    DTIC Science & Technology

    2015-05-21

    SECURITY CLASSIFICATION OF: This seedling proposed to use advanced imaging techniques to break the neuronal code that links the firing of neurons in...Report: Breaking the Neural Code Report Title This seedling proposed to use advanced imaging techniques to break the neuronal code that links the...generating a closed-loop on-line experimental platform. We have completed all proposed tasks of the seedling and successfully completed preliminary

  7. Auditory Distance Coding in Rabbit Midbrain Neurons and Human Perception: Monaural Amplitude Modulation Depth as a Cue

    PubMed Central

    Zahorik, Pavel; Carney, Laurel H.; Bishop, Brian B.; Kuwada, Shigeyuki

    2015-01-01

    Mechanisms underlying sound source distance localization are not well understood. Here we tested the hypothesis that a novel mechanism can create monaural distance sensitivity: a combination of auditory midbrain neurons' sensitivity to amplitude modulation (AM) depth and distance-dependent loss of AM in reverberation. We used virtual auditory space (VAS) methods for sounds at various distances in anechoic and reverberant environments. Stimulus level was constant across distance. With increasing modulation depth, some rabbit inferior colliculus neurons increased firing rates whereas others decreased. These neurons exhibited monotonic relationships between firing rates and distance for monaurally presented noise when two conditions were met: (1) the sound had AM, and (2) the environment was reverberant. The firing rates as a function of distance remained approximately constant without AM in either environment and, in an anechoic condition, even with AM. We corroborated this finding by reproducing the distance sensitivity using a neural model. We also conducted a human psychophysical study using similar methods. Normal-hearing listeners reported perceived distance in response to monaural 1 octave 4 kHz noise source sounds presented at distances of 35–200 cm. We found parallels between the rabbit neural and human responses. In both, sound distance could be discriminated only if the monaural sound in reverberation had AM. These observations support the hypothesis. When other cues are available (e.g., in binaural hearing), how much the auditory system actually uses the AM as a distance cue remains to be determined. PMID:25834060

  8. The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials in the central neuron of snail, Achatina fulica Ferussac.

    PubMed

    Lin, Chia-Hsien; Tsai, Ming-Cheng

    2005-05-01

    The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials were studied on the RP1 central neuron of giant African snails (Achatina fulica Ferussac). Extra-cellular application of d-amphetamine or procaine reversibly elicited bursts of potential (BoP). Prazosin, propranolol, atropine or d-tubocurarine did not alter the BoP elicited by either d-amphetamine or procaine. KT-5720 or H89 (protein kinase A inhibitors) blocked d-amphetamine-elicited BoP, whereas they did not block the procaine-elicited BoP. U73122, neomycin (phospholipase C inhibitors) blocked the procaine-elicited BoP, whereas they did not block the d-amphetamine-elicited BoP in the same neuron. These results suggest that BoP elicited by d-amphetamine or procaine were associated with protein kinase A and phospholipase C activity in the neuron.

  9. Speech Coding in the B