Quantitative prediction of vasopressin secretion using a computational population model of rat magnocellular neurons

The goal of this study was to create a realistic and quantitative simulation of vasopressin (AVP) secretion under iso-osmotic and short-term challenged plasma osmolality. The relationship between AVP concentration ([AVP]) and plasma osmolality was computed using a sophisticated and integrated model that chronologically simulates (1) the overall firing rate of the hypothalamus’ magnocellular neuronal (MCN) population, (2) the propagation of the spike activity down the axons, (3) the fatigue and facilitation mechanisms of AVP release at the axon terminals and (4) the [AVP] pharmacodynamics based on the trains of AVP release. This global simulation predicted that the differential MCN sensitivity to dynorphin would be the most critical mechanism underlying the individual variability of MCN firing behaviors (silence, irregular, phasic and continuous firing patterns). However, at the level of the MCN population, the simulation predicted that the dynorphin factor must be combined with the distribution of the resting membrane potentials among the MCNs to obtain a realistic overall firing rate in response to a change in osmolality. Moreover, taking advantage of the integrated model, the simulation predicted that the selective removal of the frequency-dependent facilitation of AVP secretion has a major impact on the overall [AVP]-to-osmolality relationship (mean absolute change of 2.59?pg/ml); the action potential propagation failure, while critical, has a smaller quantitative impact on the overall [AVP] (0.58?pg/ml). The present integrated model (from a single MCN to a quantitative plasma [AVP]) improves our knowledge of the mechanisms underlying overall MCN firing and AVP excitation-secretion coupling.     

Rhythmic activities of hypothalamic magnocellular neurons: Autocontrol mechanisms

Electrophysiological recordings in lactating rats show that oxytocin (OT) and vasopressin (AVP) neurons exhibit specific patterns of activities in relation to peripheral stimuli: periodic bursting firing for OT neurons during suckling, phasic firing for AVP neurons during hyperosmolarity (systemic injection of hypertonic saline). These activities are autocontrolled by OT and AVP released somato-dentritically within the hypothalamic magnocellular nuclei. In vivo, OT enhances the amplitude and frequency of bursts, an effect accompanied with an increase in basal firing rate. However, the characteristics of firing change as facilitation proceeds: the spike patterns become very irregular with clusters of spikes spaced by long silences; the firing rate is highly variable and clearly oscillates before facilitated bursts. This unstable behaviour dramatically decreases during intense tonic activation which temporarily interrupts bursting, and could therefore be a prerequisite for bursting. In vivo, the effects of AVP depend on the initial firing pattern of AVP neurons: AVP excites weakly active neurons (increasing duration of active periods and decreasing silences), inhibits highly active neurons, and does not affect neurons with intermediate phasic activity. AVP brings the entire population of AVP neurons to discharge with a medium phasic activity characterised by periods of firing and silence lasting 20–40 s, a pattern shown to optimise the release of AVP from the neurohypophysis. Each of the peptides (OT or AVP) induces an increase in intracellular Ca²⁺ concentration, specifically in the neurons containing either OT or AVP respectively. OT evokes the release of Ca²⁺ from IP3-sensitive intracellular stores. AVP induces an influx of Ca²⁺ through voltage-dependent Ca²⁺ channels of T-, L- and N-types. We postulate that the facilitatory autocontrol of OT and AVP neurons could be mediated by Ca²⁺ known to play a key role in the control of the patterns of phasic neurons.     

Brainstem control of activity and responsiveness in resting frog tadpoles: tonic inhibition

The hatchling Xenopus laevis tadpole was used to study the brain neurons controlling responsiveness. Tadpoles have reduced motor activity and responsiveness when they hang at rest, attached by cement gland mucus. Afferent input from cement gland mechanosensory neurons has both a phasic role in stopping swimming and a tonic role in reducing responsiveness while tadpoles hang attached. Both these roles depend on GABA_A-mediated inhibition. We provide evidence supporting the hypothesis that long-term reduced responsiveness in attached tadpoles results from tonic activity in the reticulospinal GABAergic pathway mediating the stopping response. Two groups of putative stopping pathway interneurons were recorded in the caudal and rostral hindbrain of immobilised tadpoles. Both groups showed a sustained increase in activity during simulated attachment. This attached activity was irregular and unstructured. We consider whether low-level firing in cement gland afferents (at ~1 Hz) during simulated attachment is sufficient to explain the low-level firing (at ~0.5 Hz) in reticulospinal neurons. We then ask if a small population of these neurons (~20) could produce sufficient inhibition of spinal neurons to reduce the whole tadpoles responsiveness. We conclude that for most of their 1st day of life GABAergic brainstem neurons could produce inhibition continuously while the tadpole is at rest.Abbreviations CV coefficient of variation - EPSP excitatory postsynaptic potential - IPSP inhibitory postsynaptic potential - ISI interspike interval     

Local interneurons and information processing in the olfactory glomeruli of the moth Manduca sexta

Intracellular recordings were made from the major neurites of local interneurons in the moth antennal lobe. Antennal nerve stimulation evoked 3 patterns of postsynaptic activity: (i) a short-latency compound excitatory postsynaptic potential that, based on electrical stimulation of the antennal nerve and stimulation of the antenna with odors, represents a monosynaptic input from olfactory afferent axons (71 out of 86 neurons), (ii) a delayed activation of firing in response to both electrical- and odor-driven input (11 neurons), and (iii) a delayed membrane hyperpolarization in response to antennal nerve input (4 neurons).Simultaneous intracellular recordings from a local interneuron with short-latency responses and a projection (output) neuron revealed unidirectional synaptic interactions between these two cell types. In 20% of the 30 pairs studied, spontaneous and current-induced spiking activity in a local interneuron correlated with hyperpolarization and suppression of firing in a projection neuron. No evidence for recurrent or feedback inhibition of projection neurons was found. Furthermore, suppression of firing in an inhibitory local interneuron led to an increase in firing in the normally quiescent projection neuron, suggesting that a disinhibitory pathway may mediate excitation in projection neurons. This is the first direct evidence of an inhibitory role for local interneurons in olfactory information processing in insects. Through different types of multisynaptic interactions with projection neurons, local interneurons help to generate and shape the output from olfactory glomeruli in the antennal lobe.Abbreviations AL antennal lobe - EPSP excitatory postsynaptic potential - GABA -aminobutyric acid - IPSP inhibitory postsynaptic potential - LN local interneuron - MGC macroglomerular complex - OB olfactory bulb - PN projection neuron - TES N-tris[hydroxymethyl]methyl-2-aminoethane-sulfonic acid     

Intracellular activity in cricket neurons during generation of song patterns

Summary During production of song patterns by the semi-isolated CNS of Gryllus campestris, intracellullar recordings were made in fibers of the mesothoracic ganglion, including synaptic areas of identified wing opener and closer motor neurons. The normal calling song pattern and some transitional songs toward courtship and toward aggression were generated by the CNS in the absence of any phasic sensory timing (Figs. 1, 4). Intracellular activity of the opener motor neurons was characterized by an absence of events in the interchirp interval, an EPSP underlying each burst, and an IPSP following the burst if the closer motor neurons were to be activated (Fig. 1). Intracellular activity of the closer motor neurons was characterized by an absence of events in the interchirp interval, an IPSP immediately following the onset of the opener motor neuron burst, and an EPSP after the IPSP (Figs. 2, 3). Units were found which fired in a burst during the period when both the opener and closer motor neurons were inhibited (Fig. 5). Complementary sets of units were found which displayed an oscillation of activity at the chirp rhythm but not at the pulse rhythm (Fig. 6). Gaps in the calling song were observed whose characteristics indicated that motor neuron activity was neither required for, nor effective in, resetting the chirp timing oscillator (Fig. 8). A possible model for the song generating mechanism is outlined.     

Intracellular responses of primary auditory cortical neurons to tones of different frequencies and to electrical stimulation of spiral ganglion fibers in cat

Experiments on cats anesthetized with pentobarbital showed that, depending on the intensity and frequency of acoustic stimulation, neurons in auditory area AI give responses of EPSP, EPSP-spike-IPSP, EPSP-IPSP, and IPSP type. Presentation of a tone of characteristic or near-characteristic frequency and above-threshold intensity, and also electrical stimulation of nerve fibers of the spiral ganglion, innervating the central zone of the receptive field of the neuron, evoke in most cases a response of EPSP-spike-IPSP type. Tone differing considerably in frequency from the characteristic, and electrical stimulation of peripheral zones of the receptive field, evoked responses of EPSP-IPSP or IPSP type. The range of frequencies of tones to which, at threshold intensity, an action potential is generated by the neuron is considerably narrower than the range of frequencies of tones evoking an EPSP and IPSP. Above the intensity of tone threshold IPSP is an invariable component of the response of most neurons in area AI. The appearance of an IPSP in the neuron is accompanied by depression of spontaneous activity and the neuronal response to testing stimulation. Two types of IPSP were distinguished: One type is a component of the EPSP-spike-IPSP response and arises during excitation of auditory receptors located in the central part of the receptive field of the neuron, the other arises during excitation of receptors located at the periphery of the field, and which project to neurons with other characteristic frequencies. The former arise after spike excitation of the neuron, the latter after EPSP or primarily.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 123–131, January–February, 1984.     

Intracellular electrophysiology of mammalian peptidergic neurons in rat hypothalamic slices

The magnocellular neuropeptidergic cells (MNCs) of the paraventricular and supraoptic nuclei have been a model for biochemical and physiological studies of peptidergic neurons in the mammalian brain, but nearly all the electrophysiological studies of these vasopressinergic and oxytocinergic neuroendocrine cells are based on extracellular recordings. This paper reviews recent literature on electrophysiological properties of neurons in the magnocellular nuclei in which the rat in vitro slice preparation and intracellular recording were used. Spontaneously occurring action potentials and synaptic potentials (excitatory and inhibitory) have been observed in hypothalamic slices. The spike patterns have included slow and irregular firing, short rapid bursts of inactivating spikes, and slow phasic discharge with prolonged active and silent periods. Some studies have shown that increased osmolality causes neuronal firing, but this area is controversial. Intracellular injections of lucifer yellow have shown that some MNCs are dye-coupled and electron microscopic observations with the freeze-fracture technique have revealed occasional gap junctions, thus suggesting that some MNCs are electrotonically coupled. Both excitatory and inhibitory postsynaptic potentials have been evoked with extracellular stimulation. Therefore, action potentials, synaptic potentials, burst discharges, and probably electrotonic coupling have been found with intracellular recording in mammalian neuroendocrine cells. Future studies with intracellular recording and staining followed by immunohistochemical identification of cells should provide significant new information on the membrane physiology and synaptic pharmacology of vasopressinergic and oxytocinergic cells.     

Slope-Based Stochastic Resonance: How Noise Enables Phasic Neurons to Encode Slow Signals

Fundamental properties of phasic firing neurons are usually characterized in a noise-free condition. In the absence of noise, phasic neurons exhibit Class 3 excitability, which is a lack of repetitive firing to steady current injections. For time-varying inputs, phasic neurons are band-pass filters or slope detectors, because they do not respond to inputs containing exclusively low frequencies or shallow slopes. However, we show that in noisy conditions, response properties of phasic neuron models are distinctly altered. Noise enables a phasic model to encode low-frequency inputs that are outside of the response range of the associated deterministic model. Interestingly, this seemingly stochastic-resonance (SR) like effect differs significantly from the classical SR behavior of spiking systems in both the signal-to-noise ratio and the temporal response pattern. Instead of being most sensitive to the peak of a subthreshold signal, as is typical in a classical SR system, phasic models are most sensitive to the signal''s rising and falling phases where the slopes are steep. This finding is consistent with the fact that there is not an absolute input threshold in terms of amplitude; rather, a response threshold is more properly defined as a stimulus slope/frequency. We call the encoding of low-frequency signals with noise by phasic models a slope-based SR, because noise can lower or diminish the slope threshold for ramp stimuli. We demonstrate here similar behaviors in three mechanistic models with Class 3 excitability in the presence of slow-varying noise and we suggest that the slope-based SR is a fundamental behavior associated with general phasic properties rather than with a particular biological mechanism.     

A biologically motivated and analytically soluble model of collective oscillations in the cortex

. Feature linking and pattern separation are shown to be performed as simultaneous processes by a highly connected auto-associative network of spiking neurons (spike response model). In principle, many (e.g., with nine) patterns can be separated, but with a biological set of parameters the number is limited to four. The patterns have been learned by an asymmetric hebbian rule that can handle a low activity which may vary from pattern to pattern (in a range between 4% and 7%). Spikes are generated by a threshold process and – with some delay – transmitted to postsynaptic neurons. There they evoke an excitatory or inhibitory postsynaptic potential (EPSP or IPSP). Spike emission is followed by an absolute refractory period (1 ms) and activates an inhibitory delay loop that prevents continuous firing. Three different network topologies are discussed, i.e., a structureless fully connected system, a network composed of two ‘hemispheres’, and finally a hierarchical network with four subsystems that represent different ‘functions’ and interact via feedforward and feedback connections. Functional feedback turns out to be essential for context-sensitive binding. The coherence between the two hemispheres is dependent on the interhemispheric delays. If these are on average too large, the two hemispheres oscillate coherently by themselves but phase-shifted by half a period with respect to each other. Received: 16 June 1993/Accepted in revised form: 24 March 1994     

Computational simulation of the input-output relationship in hippocampal pyramidal cells

The precise mapping of how complex patterns of synaptic inputs are integrated into specific patterns of spiking output is an essential step in the characterization of the cellular basis of network dynamics and function. Relative to other principal neurons of the hippocampus, the electrophysiology of CA1 pyramidal cells has been extensively investigated. Yet, the precise input-output relationship is to date unknown even for this neuronal class. CA1 pyramidal neurons receive laminated excitatory inputs from three distinct pathways: recurrent CA1 collaterals on basal dendrites, CA3 Schaffer collaterals, mostly on oblique and proximal apical dendrites, and entorhinal perforant pathway on distal apical dendrites. We implemented detailed computer simulations of pyramidal cell electrophysiology based on three-dimensional anatomical reconstructions and compartmental models of available biophysical properties from the experimental literature. To investigate the effect of synaptic input on axosomatic firing, we stochastically distributed a realistic number of excitatory synapses in each of the three dendritic layers. We then recorded the spiking response to different stimulation patterns. For all dendritic layers, synchronous stimuli resulted in trains of spiking output and a linear relationship between input and output firing frequencies. In contrast, asynchronous stimuli evoked non-bursting spike patterns and the corresponding firing frequency input-output function was logarithmic. The regular/irregular nature of the input synaptic intervals was only reflected in the regularity of output inter-burst intervals in response to synchronous stimulation, and never affected firing frequency. Synaptic stimulations in the basal and proximal apical trees across individual neuronal morphologies yielded remarkably similar input-output relationships. Results were also robust with respect to the detailed distributions of dendritic and synaptic conductances within a plausible range constrained by experimental evidence. In contrast, the input-output relationship in response to distal apical stimuli showed dramatic differences from the other dendritic locations as well as among neurons, and was more sensible to the exact channel densities. Action Editor: Alain Destexhe     

Sensitivity of transformed (phasic to tonic) motor neurons to the neuromodulator 5-HT

Long-term adaptation resulting in a 'tonic-like' state can be induced in phasic motor neurons of the crayfish, Procambarus clarkii, by daily low-frequency stimulation [Lnenicka, G.A., Atwood, H.L., 1985b. Long-term facilitation and long-term adaptation at synapses of a crayfish phasic motoneuron. J. Neurobiol. 16, 97-110]. To test the hypothesis that motor neurons undergoing adaptation show increased responses to the neuromodulator serotonin (5-HT), phasic motor neurons innervating the deep abdominal extensor muscles of crayfish were stimulated at 2.5 Hz, 2 h/day, for 7 days. One day after cessation of conditioning, contralateral control and conditioned motor neurons of the same segment were stimulated at 1 Hz and the induced excitatory post-synaptic potentials (EPSPs) were recorded from DEL(1) muscle fibers innervated by each motor neuron type. Recordings were made in saline without and with 100 nM 5-HT. EPSP amplitudes were increased by 5-HT exposure in all cases. Conditioned muscles exposed to 5-HT showed a 2-fold higher percentage of increase in EPSP amplitude than did control muscles. Thus, the conditioned motor neurons behaved like intrinsically tonic motoneurons in their response to 5-HT. While these results show that long-term adaptation (LTA) extends to 5-HT neuromodulation, no phenotype switch could be detected in the postsynaptic muscle. Protein isoform profiles, including the myosin heavy chains, do not change after 1 week of conditioning their innervating motor neurons.     

Some well-kept hypothalamic secrets disclosed

The magnocellular neuropeptidergic cells of the supraoptic and paraventricular nuclei comprise much of what is known as the hypothalamoneurohypophyseal system and is involved in several functions, including body fluid balance, parturition, and lactation. In vivo experiments have not produced a clear understanding of some of the crucial features associated with the functioning of this system. In particular, questions relating to the osmosensitivity of magnocellular neurons and the mechanisms(s) by which their characteristic firing patterns are generated have not been answered by using the older approaches. Electrophysiological studies with brain slices present direct evidence for osmosensitivity, and perhaps even osmoreceptivity, of magnocellular neurons. Other evidence is reviewed indicating that the phasic bursting patterns of activity associated with vasopressin-releasing neurons: 1) occur in the absence of patterned chemical synaptic input, 2) are probably influenced by localized changes in extracellular K+ concentrations, 3) may be modulated by electrotonic conduction across gap junctions connecting magnocellular neurons, and 4) are likely to be generated by endogenous membrane currents.     

Feedback enhances feedforward figure-ground segmentation by changing firing mode

In the visual cortex, feedback projections are conjectured to be crucial in figure-ground segregation. However, the precise function of feedback herein is unclear. Here we tested a hypothetical model of reentrant feedback. We used a previous developed 2-layered feedforward spiking network that is able to segregate figure from ground and included feedback connections. Our computer model data show that without feedback, neurons respond with regular low-frequency (～9 Hz) bursting to a figure-ground stimulus. After including feedback the firing pattern changed into a regular (tonic) spiking pattern. In this state, we found an extra enhancement of figure responses and a further suppression of background responses resulting in a stronger figure-ground signal. Such push-pull effect was confirmed by comparing the figure-ground responses with the responses to a homogenous texture. We propose that feedback controls figure-ground segregation by influencing the neural firing patterns of feedforward projecting neurons.     

A model for repetitive firing in neurons

This paper describes a model for the generation of repetitive firing patterns in single neurons to be used as a module in large-scale network simulation studies. The model is based on the combination of extended versions of Hill's model for accomodation and of Kernell's model for adaptation. Both digital computer and electronic circuit realizations of the model are presented. The model is shown to produce strength-duration curves for accomodation which are compatible with available data from real neurons. Both “high ceiling” and “low ceiling” cell types can be matched by adjusting parameters in the model. An equation relating steady-state firing rate to amplitude of applied steady current is presented which includes the accumulation of potassium conductance changes with repetitive firing. The occurence of phasic and tonic responses to step stimulation is mapped in the parameter space of the model. Several representative response patterns to irregular inputs are presented.     

Firing patterns in the adaptive exponential integrate-and-fire model

For simulations of large spiking neuron networks, an accurate, simple and versatile single-neuron modeling framework is required. Here we explore the versatility of a simple two-equation model: the adaptive exponential integrate-and-fire neuron. We show that this model generates multiple firing patterns depending on the choice of parameter values, and present a phase diagram describing the transition from one firing type to another. We give an analytical criterion to distinguish between continuous adaption, initial bursting, regular bursting and two types of tonic spiking. Also, we report that the deterministic model is capable of producing irregular spiking when stimulated with constant current, indicating low-dimensional chaos. Lastly, the simple model is fitted to real experiments of cortical neurons under step current stimulation. The results provide support for the suitability of simple models such as the adaptive exponential integrate-and-fire neuron for large network simulations.     

Cortical network modeling: analytical methods for firing rates and some properties of networks of LIF neurons.

The circuitry of cortical networks involves interacting populations of excitatory (E) and inhibitory (I) neurons whose relationships are now known to a large extent. Inputs to E- and I-cells may have their origins in remote or local cortical areas. We consider a rudimentary model involving E- and I-cells. One of our goals is to test an analytic approach to finding firing rates in neural networks without using a diffusion approximation and to this end we consider in detail networks of excitatory neurons with leaky integrate-and-fire (LIF) dynamics. A simple measure of synchronization, denoted by S(q), where q is between 0 and 100 is introduced. Fully connected E-networks have a large tendency to become dominated by synchronously firing groups of cells, except when inputs are relatively weak. We observed random or asynchronous firing in such networks with diverse sets of parameter values. When such firing patterns were found, the analytical approach was often able to accurately predict average neuronal firing rates. We also considered several properties of E-E networks, distinguishing several kinds of firing pattern. Included were those with silences before or after periods of intense activity or with periodic synchronization. We investigated the occurrence of synchronized firing with respect to changes in the internal excitatory postsynaptic potential (EPSP) magnitude in a network of 100 neurons with fixed values of the remaining parameters. When the internal EPSP size was less than a certain value, synchronization was absent. The amount of synchronization then increased slowly as the EPSP amplitude increased until at a particular EPSP size the amount of synchronization abruptly increased, with S(5) attaining the maximum value of 100%. We also found network frequency transfer characteristics for various network sizes and found a linear dependence of firing frequency over wide ranges of the external afferent frequency, with non-linear effects at lower input frequencies. The theory may also be applied to sparsely connected networks, whose firing behaviour was found to change abruptly as the probability of a connection passed through a critical value. The analytical method was also found to be useful for a feed-forward excitatory network and a network of excitatory and inhibitory neurons.     

Computational modeling of epileptiform activities in medial temporal lobe epilepsy combined with <Emphasis Type="Italic">in vitro</Emphasis> experiments

Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson’s disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.     

Role of excitatory amino acid receptors in synaptic transmission in area CA1 of rat hippocampus

The new antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which blocks responses to kainate and quisqualate, has been used in conjunction with D-2-amino-5-phosphonovalerate (APV), which blocks selectively responses to N-methyl-D-aspartate (NMDA), to determine the role of excitatory amino acid receptors in synaptic transmission. An excitatory postsynaptic potential (EPSP)-inhibitory postsynaptic potential (IPSP) sequence was evoked in CA1 neurons by stimulation of the Schaffer collateral-commissural pathway in rat hippocampal slices. CNQX (10 microM) substantially reduced the EPSP without having any effect on input resistance or membrane potential. The IPSP was also reduced provided that the stimulating electrode was place approximately 1 mm from the recording electrode. The EPSP that remained in the presence of CNQX had characteristics of an NMDA receptor-mediated potential; it had a slow timecourse, summated at high frequencies, was blocked reversibly by APV, increased greatly in size in Mg2+-free medium, and showed an anomalous voltage dependence in Mg2+-containing medium. In the presence of CNQX, an APV-sensitive polysynaptic GABAergic IPSP could be evoked, indicating that NMDA receptors can mediate suprathreshold EPSPS in inhibitory interneurons. It is suggested that either NMDA or non-NMDA receptors can, under different circumstances, mediate the synaptic excitation of pyramidal neurons and inhibitory interneurons in area CA1 of the hippocampus.     

Short-latency unit responses of the lateral geniculate body to electrical stimulation of the optic tract in rats

Short-latency responses of single relay neurons of the lateral geniculate body to electrical stimulation of the optic tract were studied. The response of many neurons was complex and could consist of a series of (1–3) spikes with fixed latent periods. Each spike of such a response can be recorded on the EPSP in the absence of other spikes, preserving its latent period. The fixed latent periods of different relay neurons may vary from one to another. In the intervals between spikes with these latent periods active inhibition (IPSP) takes place. The series of spikes, EPSP, and IPSP is completed, as a rule, by a long IPSP.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 5, No. 1, pp. 28–32, January–February, 1973.     

In vivo conditions induce faithful encoding of stimuli by reducing nonlinear synchronization in vestibular sensory neurons

Previous studies have shown that neurons within the vestibular nuclei (VN) can faithfully encode the time course of sensory input through changes in firing rate in vivo. However, studies performed in vitro have shown that these same VN neurons often display nonlinear synchronization (i.e. phase locking) in their spiking activity to the local maxima of sensory input, thereby severely limiting their capacity for faithful encoding of said input through changes in firing rate. We investigated this apparent discrepancy by studying the effects of in vivo conditions on VN neuron activity in vitro using a simple, physiologically based, model of cellular dynamics. We found that membrane potential oscillations were evoked both in response to step and zap current injection for a wide range of channel conductance values. These oscillations gave rise to a resonance in the spiking activity that causes synchronization to sinusoidal current injection at frequencies below 25 Hz. We hypothesized that the apparent discrepancy between VN response dynamics measured in in vitro conditions (i.e., consistent with our modeling results) and the dynamics measured in vivo conditions could be explained by an increase in trial-to-trial variability under in vivo vs. in vitro conditions. Accordingly, we mimicked more physiologically realistic conditions in our model by introducing a noise current to match the levels of resting discharge variability seen in vivo as quantified by the coefficient of variation (CV). While low noise intensities corresponding to CV values in the range 0.04-0.24 only eliminated synchronization for low (<8 Hz) frequency stimulation but not high (>12 Hz) frequency stimulation, higher noise intensities corresponding to CV values in the range 0.5-0.7 almost completely eliminated synchronization for all frequencies. Our results thus predict that, under natural (i.e. in vivo) conditions, the vestibular system uses increased variability to promote fidelity of encoding by single neurons. This prediction can be tested experimentally in vitro.