Fast-spiking Neurons Research Articles

Fast Inhibitory Decay Facilitates Adult-like Temporal Processing in Layer 5 of Developing Primary Auditory Cortex.

The protracted maturational process of temporal processing in layer 4 (L4) of primary auditory cortex (A1) has been extensively studied. Accumulating evidences show that layer 5 (L5) receives direct thalamic inputs as well. How the temporal responses in L5 may developmentally emerge remains unclear. Using in vivo loose-patch recordings in rat A1, we found that putative pyramidal (Pyr) neurons in developing L5 exhibited adult-like stimulus-following ability but less bursting shortly after hearing onset. L5 Pyr neurons in adult A1 exhibited phase-locking similar to L4 neurons, while L5 fast-spiking (FS) neurons showed greater phase-locking at 7 and 12.5 pps. In developing L5, whole-cell recordings revealed inhibition with decay constant comparable to that in adult L5, thereby avoiding the summation of inhibition that contributed to the strong adaptation in L4. Given the targets of L5 outputs, the relatively precocious temporal processing in L5 might contribute to temporal response maturation in connected cortical and subcortical areas. Our findings were in agreement with the idea that L5 may be a "hub" for processing cortical inputs and outputs that can operate independently of L4.

SK Channels Regulate Resting Properties and Signaling Reliability of a Developing Fast-Spiking Neuron.

Reliable and precise signal transmission is essential in circuits of the auditory brainstem to encode timing with submillisecond accuracy. Globular bushy cells reliably and faithfully transfer spike signals to the principal neurons of the medial nucleus of the trapezoid body (MNTB) through the giant glutamatergic synapse, the calyx of Held. Thus, the MNTB works as a relay nucleus that preserves the temporal pattern of firing at high frequency. Using whole-cell patch-clamp recordings, we observed a K+ conductance mediated by small-conductance calcium-activated potassium (SK) channels in the MNTB neurons from rats of either sex. SK channels were activated by intracellular Ca2+ sparks and mediated spontaneous transient outward currents in developing MNTB neurons. SK channels were also activated by Ca2+ influx through voltage-gated Ca2+ channels and synaptically activated NMDA receptors. Blocking SK channels with apamin depolarized the resting membrane potential, reduced resting conductance, and affected the responsiveness of MNTB neurons to signal inputs. Moreover, SK channels were activated by action potentials and affected the spike afterhyperpolarization. Blocking SK channels disrupted the one-to-one signal transmission from presynaptic calyces to postsynaptic MNTB neurons and induced extra postsynaptic action potentials in response to presynaptic firing. These data reveal that SK channels play crucial roles in regulating the resting properties and maintaining reliable signal transmission of MNTB neurons.SIGNIFICANCE STATEMENT Reliable and precise signal transmission is required in auditory brainstem circuits to localize the sound source. The calyx of Held synapse in the mammalian medial nucleus of the trapezoid body (MNTB) plays an important role in sound localization. We investigated the potassium channels that shape the reliability of signal transfer across the calyceal synapse and observed a potassium conductance mediated by small-conductance calcium-activated potassium (SK) channels in rat MNTB principal neurons. We found that SK channels are tonically activated and contribute to the resting membrane properties of MNTB neurons. Interestingly, SK channels are transiently activated by calcium sparks and calcium influx during action potentials and control the one-to-one signal transmission from presynaptic calyces to postsynaptic MNTB neurons.

Non-NMDA receptor-mediated vibrotactile responses of neurons from the hindpaw representation in the rat SI cortex

Non-NMDA receptor-mediated vibrotactile responses of neurons from the hindpaw representation were investigated in the rat SI cortex. We recorded single-unit spikes evoked by sinusoidal (duration: 500 ms; frequency: 5, 40, and 250 Hz; amplitude: 100 μm peak-to-peak) stimulation of the glabrous skin. The responses were obtained with microinjection of aCSF (sham), bicuculline, and AMPA near the isolated neurons in anaesthetized rats. Blocking most of the NMDA receptors by ketamine revealed local dynamics differentially modulated by each drug. The responses were generally suppressed after the initial 100-ms period of the 40- and 250-Hz stimulus, but not at 5 Hz. Both drugs increased average firing rates (AFRs) only during vibrotactile stimulation, and increased entrainment as measured by the vector strength (VS) of spike phases. However, bicuculline was more effective on the AFR in the late period particularly at 40 Hz. Complex interactions were found with AMPA; late activity increased only for fast spiking neurons at 40 Hz, and more for regular spiking neurons at 5 Hz. The increase of VS by bicuculline was much higher in layer IV. In addition to thalamocortical feed-forward inhibition, vibrotactile information seems to be suppressed after 100 ms by longer-latency inhibitory networks tuned to mid-frequency inputs. Combined with the presumed AMPA-receptor desensitization, those two inhibitory factors could limit the excitatory flow mostly to lower frequencies. The frequency dependence of the drug effects highlights the role of local cortical dynamics in the hindpaw area.

Mechanisms underlying a thalamocortical transformation during active tactile sensation.

During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain’s ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit.

Transcriptomic immaturity of the hippocampus and prefrontal cortex in patients with alcoholism

Alcoholism, which is defined as the recurring harmful use of alcohol despite its negative consequences, has a lifetime prevalence of 17.8%. Previous studies have shown that chronic alcohol consumption disrupts various brain functions and behaviours. However, the precise mechanisms that underlie alcoholism are currently unclear. Recently, we discovered “pseudo-immature” brain cell states of the dentate gyrus and prefrontal cortex (PFC) in mouse models of psychotic disorders and epileptic seizure. Similar pseudo-immaturity has been observed in patients with psychotic disorders, such as schizophrenia and bipolar disorder. Patients with alcoholism occasionally exhibit similar psychological symptoms, implying shared molecular and cellular mechanisms between these diseases. Here, we performed a meta-analysis to compare microarray data from the hippocampi/PFCs of the patients with alcoholism to data from these regions in developing human brains and mouse developmental data for specific cell types. We identified immature-like gene expression patterns in post-mortem hippocampi/PFCs of alcoholic patients and the dominant contributions of fast-spiking (FS) neurons to their pseudo-immaturity. These results suggested that FS neuron dysfunction and the subsequent imbalance between excitation and inhibition can be associated with pseudo-immaturity in alcoholism. These immaturities in the hippocampi/PFCs and the underlying mechanisms may explain the psychotic symptom generation and pathophysiology of alcoholism.

Increased NRG1-ErbB4 signaling in human symptomatic epilepsy

Previous studies have shown that the neuregulin 1 (NRG1)-ErbB4 signaling pathway may regulate the excitability of fast-spiking neurons in the frontal cortex and participate in primary epilepsy pathogenesis. However, the exact roles and mechanism for NRG1/ErbB4 in human symptomatic epilepsy are still unclear. Using fresh human symptomatic epilepsy tissues, we found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex. In addition, NRG1-ErbB4 signaling suppressed phosphorylation of GluN2B at position 1472 by Src kinase, and decreased levels of phosphorylation level of GluN2B and Src were detected in human symptomatic epilepsy tissues. Our study revealed a critical role of the NRG1-ErbB4 signaling pathway in symptomatic epilepsy, which is different from that in primary epilepsy, and we propose that the NRG1-ErbB4 signaling may act as a homeostasis modulator that protects the brain from aggravation of epileptiform activity.

A Critical Role of Inhibition in Temporal Processing Maturation in the Primary Auditory Cortex.

Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

P186 Prefrontal transcranial direct current stimulation induces polarity-specific changes in resting state electroencephalographic gamma activity

Question The mechanisms underlying transcranial direct current stimulation (tDCS) induced changes of cortical excitability and arousal remain to be fully characterized. In the context of our larger study on the effects of bifrontal tDCS on overnight sleep, we analyzed tDCS-modulated resting state wake EEG data for a better understanding of tDCS’s effects on cortical arousal during wakefulness. Methods We applied a standardized tDCS protocol (1 mA/electrode, 2 × 9 min cathodal, 2 × 13 min anodal, 2 × 11 min sham, with 20 min inter-stimulation interval each) prior to nighttime sleep bilaterally to the prefrontal cortex (electrodes 5 × 7 cm, FP1/FP2; return electrodes 10 × 10 cm, P3/P4 ) of 19 healthy subjects in a randomized crossover design. We conducted 5 min resting state wake EEGs prior to stimulation (T0), after the stimulation (T1) and on the following morning (T2). In a first step of analysis for EEG power differences between conditions at a single frequency, we calculated false discovery rate (FDR) corrected significances, using the Benjamini-Hochberg step-up procedure to assess the significance of the multiple tests. In a second exploratory step, we used uncorrected ANOVAs to further explore tDCS effects on EEG power spectra. Results The FDR-corrected approach did not reveal any significant condition effect. ANOVAs comparing T1 vs. T0 demonstrated a significant decrease in EEG gamma power after cathodal stimulation. A significant main effect for the factor Condition was observed for frequencies of the gamma range. ANOVAs comparing T2 vs. T0 demonstrated a significant increase in EEG gamma power after anodal stimulation and also a significant main effect for the factor Condition for frequencies of the gamma band. Conclusions Exploratory resting state EEG analyses suggested polarity-specific changes in cortical arousal as indexed by resting state EEG power in the gamma frequency range. Cortical gamma activity is considered to emerge from synchronous activity of fast-spiking inhibitory neurons in the cortex and has been linked to the integration of temporally correlated neural events as a prerequisite for attentive wakefulness. It is plausible that depolarization of cortical structures after anodal stimulation facilitates fast-spiking and EEG gamma activity, with reverse effects after cathodal stimulation.

Spike Timing Rigidity Is Maintained in Bursting Neurons under Pentobarbital-Induced Anesthetic Conditions.

Pentobarbital potentiates γ-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission by prolonging the open time of GABAA receptors. However, it is unknown how pentobarbital regulates cortical neuronal activities via local circuits in vivo. To examine this question, we performed extracellular unit recording in rat insular cortex under awake and anesthetic conditions. Not a few studies apply time-rescaling theorem to detect the features of repetitive spike firing. Similar to these methods, we define an average spike interval locally in time using random matrix theory (RMT), which enables us to compare different activity states on a universal scale. Neurons with high spontaneous firing frequency (>5 Hz) and bursting were classified as HFB neurons (n = 10), and those with low spontaneous firing frequency (<10 Hz) and without bursting were classified as non-HFB neurons (n = 48). Pentobarbital injection (30 mg/kg) reduced firing frequency in all HFB neurons and in 78% of non-HFB neurons. RMT analysis demonstrated that pentobarbital increased in the number of neurons with repulsion in both HFB and non-HFB neurons, suggesting that there is a correlation between spikes within a short interspike interval (ISI). Under awake conditions, in 50% of HFB and 40% of non-HFB neurons, the decay phase of normalized histograms of spontaneous firing were fitted to an exponential function, which indicated that the first spike had no correlation with subsequent spikes. In contrast, under pentobarbital-induced anesthesia conditions, the number of non-HFB neurons that were fitted to an exponential function increased to 80%, but almost no change in HFB neurons was observed. These results suggest that under both awake and pentobarbital-induced anesthetized conditions, spike firing in HFB neurons is more robustly regulated by preceding spikes than by non-HFB neurons, which may reflect the GABAA receptor-mediated regulation of cortical activities. Whole-cell patch-clamp recording in the IC slice preparation was performed to compare the regularity of spike timing between pyramidal and fast-spiking (FS) neurons, which presumably correspond to non-HFB and HFB neurons, respectively. Repetitive spike firing of FS neurons exhibited a lower variance of ISI than pyramidal neurons both in control and under application of pentobarbital, supporting the above hypothesis.

Large-scale analysis reveals populational contributions of cortical spike rate and synchrony to behavioural functions.

There have been few systematic population-wide analyses of relationships between spike synchrony within a period of several milliseconds and behavioural functions. In this study, we obtained a large amount of spike data from >23,000 neuron pairs by multiple single-unit recording from deep layer neurons in motor cortical areas in rats performing a forelimb movement task. The temporal changes of spike synchrony in the whole neuron pairs were statistically independent of behavioural changes during the task performance, although some neuron pairs exhibited correlated changes in spike synchrony. Mutual information analyses revealed that spike synchrony made a smaller contribution than spike rate to behavioural functions. The strength of spike synchrony between two neurons was statistically independent of the spike rate-based preferences of the pair for behavioural functions. Spike synchrony within a period of several milliseconds in presynaptic neurons enables effective integration of functional information in the postsynaptic neuron. However, few studies have systematically analysed the population-wide relationships between spike synchrony and behavioural functions. Here we obtained a sufficiently large amount of spike data among regular-spiking (putatively excitatory) and fast-spiking (putatively inhibitory) neuron subtypes (>23,000 pairs) by multiple single-unit recording from deep layers in motor cortical areas (caudal forelimb area, rostral forelimb area) in rats performing a forelimb movement task. After holding a lever, rats pulled the lever either in response to a cue tone (external-trigger trials) or spontaneously without any cue (internal-trigger trials). Many neurons exhibited functional spike activity in association with forelimb movements, and the preference of regular-spiking neurons in the rostral forelimb area was more biased toward externally triggered movement than that in the caudal forelimb area. We found that a population of neuron pairs with spike synchrony does exist, and that some neuron pairs exhibit a dependence on movement phase during task performance. However, the population-wide analysis revealed that spike synchrony was statistically independent of the movement phase and the spike rate-based preferences of the pair for behavioural functions, whereas spike rates were clearly dependent on the movement phase. In fact, mutual information analyses revealed that the contribution of spike synchrony to the behavioural functions was small relative to the contribution of spike rate. Our large-scale analysis revealed that cortical spike rate, rather than spike synchrony, contributes to population coding for movement.

Firing Frequency Maxima of Fast-Spiking Neurons in Human, Monkey, and Mouse Neocortex.

Cortical fast-spiking (FS) neurons generate high-frequency action potentials (APs) without apparent frequency accommodation, thus providing fast and precise inhibition. However, the maximal firing frequency that they can reach, particularly in primate neocortex, remains unclear. Here, by recording in human, monkey, and mouse neocortical slices, we revealed that FS neurons in human association cortices (mostly temporal) could generate APs at a maximal mean frequency (Fmean) of 338 Hz and a maximal instantaneous frequency (Finst) of 453 Hz, and they increase with age. The maximal firing frequency of FS neurons in the association cortices (frontal and temporal) of monkey was even higher (Fmean 450 Hz, Finst 611 Hz), whereas in the association cortex (entorhinal) of mouse it was much lower (Fmean 215 Hz, Finst 342 Hz). Moreover, FS neurons in mouse primary visual cortex (V1) could fire at higher frequencies (Fmean 415 Hz, Finst 582 Hz) than those in association cortex. We further validated our in vitro data by examining spikes of putative FS neurons in behaving monkey and mouse. Together, our results demonstrate that the maximal firing frequency of FS neurons varies between species and cortical areas.

Propofol-induced spike firing suppression is more pronounced in pyramidal neurons than in fast-spiking neurons in the rat insular cortex

Propofol is a major intravenous anesthetic that facilitates GABAA receptor-mediated inhibitory synaptic currents and modulates inward current (Ih), K+, and voltage-gated Na+ currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation. We conducted multiple whole-cell patch-clamp recordings from pyramidal neurons and from GABAergic neurons, which were classified into fast-spiking (FS), low threshold spike (LTS), late-spiking (LS), and regular-spiking nonpyramidal (RSNP) neurons. We found that 100μM propofol hyperpolarized the resting membrane potential and decreased input resistance in all types of neurons tested. Propofol also potently suppressed, and in most cases eliminated, repetitive spike firing in all these neurons. However, the potency of the propofol-induced changes in membrane and firing properties is particularly prominent in pyramidal neurons. Using a low concentration of propofol clarified this tendency: 30μM propofol decreased the firing of pyramidal neurons but had little effect on GABAergic neurons. Pre-application of a GABAA receptor antagonist, picrotoxin (100μM), diminished the propofol-induced suppression of neural activities in both pyramidal and FS neurons. These results suggest that GABAergic neurons, especially FS neurons, are less affected by propofol than are pyramidal neurons and that propofol-induced modulation of the intrinsic membrane properties and repetitive spike firing are principally mediated by GABAA receptor-mediated tonic currents

Myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK) is caused by heterozygous KCNC1 mutations.

Progressive myoclonus epilepsy (PME) is a distinct group of seizure disorders characterized by gradual neurological decline with ataxia, myoclonus and recurring seizures. There are several forms of PME, among which the most recently described is MEAK - myoclonus epilepsy and ataxia due to potassium channel mutation. This particular subtype is caused by a recurrent de novo heterozygous mutation (c.959G>A, p.Arg320His) in the KCNC1 gene, which maps to chromosome 11 and encodes for the Kv3.1 protein (a subunit of the Kv3 subfamily of voltage-gated potassium channels). Loss of Kv3 function disrupts the firing properties of fast-spiking neurons, affects neurotransmitter release and induces cell death. Specifically regarding Kv3.1 malfunctioning, the most affected neurons include inhibitory GABAergic interneurons and cerebellar neurons. Impairment of the former cells is believed to contribute to myoclonus and seizures, whereas dysfunction of the latter to ataxia and tremor. Phenotypically, MEAK patients generally have a normal early development. At the age of 6 to 14 years, they present with myoclonus, which tends to progressively worsen with time. Tonic-clonic seizures may or may not be present, and some patients develop mild cognitive impairment following seizure onset. Typical electroencephalographic features comprise generalized epileptiform discharges and, in some cases, photosensitivity. Brain imaging is either normal or shows cerebellar atrophy. The identification of MEAK has both expanded the phenotypic and genotypic spectra of PME and established an emerging role for de novo mutations in PME.

Perineuronal Nets Enhance the Excitability of Fast-Spiking Neurons.

Perineuronal nets (PNNs) are specialized complexes of extracellular matrix molecules that surround the somata of fast-spiking neurons throughout the vertebrate brain. PNNs are particularly prevalent throughout the auditory brainstem, which transmits signals with high speed and precision. It is unknown whether PNNs contribute to the fast-spiking ability of the neurons they surround. Whole-cell recordings were made from medial nucleus of the trapezoid body (MNTB) principal neurons in acute brain slices from postnatal day 21 (P21) to P27 mice. PNNs were degraded by incubating slices in chondroitinase ABC (ChABC) and were compared to slices that were treated with a control enzyme (penicillinase). ChABC treatment did not affect the ability of MNTB neurons to fire at up to 1000 Hz when driven by current pulses. However, f-I (frequency-intensity) curves constructed by injecting Gaussian white noise currents superimposed on DC current steps showed that ChABC treatment reduced the gain of spike output. An increase in spike threshold may have contributed to this effect, which is consistent with the observation that spikes in ChABC-treated cells were delayed relative to control-treated cells. In addition, parvalbumin-expressing fast-spiking cortical neurons in >P70 slices that were treated with ChABC also had reduced excitability and gain. The development of PNNs around somata of fast-spiking neurons may be essential for fast and precise sensory transmission and synaptic inhibition in the brain.

Effects of Hypocretin/Orexin and Major Transmitters of Arousal on Fast Spiking Neurons in Mouse Cortical Layer 6B

Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells.

Energy consumption in Hodgkin–Huxley type fast spiking neuron model exposed to an external electric field

Summary This paper evaluates the change in metabolic energy required to maintain the signalling activity of neurons in the presence of an external electric field. We have analysed the Hodgkin–Huxley type conductance based fast spiking neuron model as electrical circuit by changing the frequency and amplitude of the applied electric field. The study has shown that, the presence of electric field increases the membrane potential, electrical energy supply and metabolic energy consumption. As the amplitude of applied electric field increases by keeping a constant frequency, the membrane potential increases and consequently the electrical energy supply and metabolic energy consumption increases. On increasing the frequency of the applied field, the peak value of membrane potential after depolarization gradually decreases as a result electrical energy supply decreases which results in a lower rate of hydrolysis of ATP molecules.

A Phenomenological Synapse Model for Asynchronous Neurotransmitter Release.

Neurons communicate with each other via synapses. Action potentials cause release of neurotransmitters at the axon terminal. Typically, this neurotransmitter release is tightly time-locked to the arrival of an action potential and is thus called synchronous release. However, neurotransmitter release is stochastic and the rate of release of small quanta of neurotransmitters can be considerably elevated even long after the ceasing of spiking activity, leading to asynchronous release of neurotransmitters. Such asynchronous release varies for tissue and neuron types and has been shown recently to be pronounced in fast-spiking neurons. Notably, it was found that asynchronous release is enhanced in human epileptic tissue implicating a possibly important role in generating abnormal neural activity. Current neural network models for simulating and studying neural activity virtually only consider synchronous release and ignore asynchronous transmitter release. Here, we develop a phenomenological model for asynchronous neurotransmitter release, which, on one hand, captures the fundamental features of the asynchronous release process, and, on the other hand, is simple enough to be incorporated in large-size network simulations. Our proposed model is based on the well-known equations for short-term dynamical synaptic interactions and includes an additional stochastic term for modeling asynchronous release. We use experimental data obtained from inhibitory fast-spiking synapses of human epileptic tissue to fit the model parameters, and demonstrate that our model reproduces the characteristics of realistic asynchronous transmitter release.

A stochastic version of the Potjans-Diesmann cortical column model

Event Abstract Back to Event A stochastic version of the Potjans-Diesmann cortical column model Vinicius L. Cordeiro1, Renan O. Shimoura1, Nilton L. Kamiji1, Osame Kinouchi1 and Antonio C. Roque1* 1 Universidade de São Paulo, Departamento de Física, Brazil Experimental evidence suggests that neurons and neural circuits display stochastic variability [1] and, therefore, it is important to have neural models that capture this stochasticity. There are basically two types of noise model for a neuron [2]: (1) spike generation is modeled deterministically and noise enters the dynamics via additional stochastic terms; or (2) spike generation is directly modeled as a stochastic process. Recently, Galves and Löcherbach [3] introduced a neural model of the latter type in which the firing of a neuron at a given time t is a random event with probability given by a monotonically increasing function of its membrane potential V. The model of Galves and Löcherbach (GL) has as one of its components a graph of interactions between neurons. In this work we consider that this graph has the structure of the Potjans and Diesmann network model of a cortical column [4]. The model of Potjans and Diesmann has four layers and two neuron types, excitatory and inhibitory, so that there are eight cell populations. The population-specific neuron densities and connectivity are taken from comprehensive anatomical and electrophysiological studies [5-6], and the model has approximately 80,000 neurons and 300,000,000 synapses. We adjusted the parameters of the firing probability of the GL model to reproduce the firing behavior of regular (excitatory) and fast (inhibitory) spiking neurons [7]. Then, we replaced the leaky integrate-and-fire neurons of the original Potjans-Diesmann model by these stochastic neurons to obtain a stochastic version of the Potjans-Diesmann model. The parameters of the model are the weights we and wi of the excitatory and inhibitory synaptic weights of the GL model [3]. We studied the firing patterns of the eight cell populations of the stochastic model in the absence of external input and characterized their behavior in the two-dimensional diagram spanned by the excitatory and inhibitory synaptic weights. For a balanced case in which the network activity is asynchronous and irregular the properties of the stochastic model are similar to the properties of the original Potjans-Diesmann model. Different neural populations have different firing rates and inhibitory neurons have higher firing rates than excitatory neurons. In particular, the stochastic model emulates the very low firing rates of layer 2/3 observed in the original model and also experimentally [4]. We also submitted the network to random input spikes applied to layers 4 and 6 to mimic thalamic inputs, as done by Potjans and Diesmann [4], and studied the propagation of activity across layers. In conclusion, the stochastic version of the Potjans-Diesmann model can be a useful replacement for the original Potjans-Diesmann model in studies that require a comparison between stochastic and deterministic models. Acknowledgements This article was produced as part of the activities of FAPESP Research, Innovation and Dissemination Center for Neuromathematics (grant 2013/07699-0), S.Paulo Research Foundation). VLC is supported by a CNPq-PIBIC grant. NLK is supported by a FAPESP postdoctorate grant (2016/03855-5). OK receives support from CNAIPS-USP. ACR is supported by a CNPq research grant (306251/2014-0).

Phenotype-dependent Ca(2+) dynamics in single boutons of various anatomically identified GABAergic interneurons in the rat hippocampus.

Interneurons (INs) of the hippocampus exert versatile inhibition on pyramidal cells by silencing the network at different oscillation frequencies. Although IN discharge can phase‐lock to various rhythms in the hippocampus, under high‐frequency axon firing, the boutons may not be able to follow the fast activity. Here, we studied Ca2+ responses to action potentials (APs) in single boutons using combined two‐photon microscopy and patch clamp electrophysiology in three types of INs: non‐fast‐spiking (NFS) neurons showing cannabinoid 1 receptor labelling and dendrite targeting, fast‐spiking partially parvalbumin‐positive cells synapsing with dendrites (DFS), and parvalbumin‐positive cells with perisomatic innervation (PFS). The increase in [Ca2+]i from AP trains was substantially higher in NFS boutons than in DFS or PFS boutons. The decay of bouton Ca2+ responses was markedly faster in DFS and PFS cells compared with NFS neurons. The bouton‐to‐bouton variability of AP‐evoked Ca2+ transients in the same axon was surprisingly low in each cell type. Importantly, local responses were saturated after shorter trains of APs in NFS cells than in PFS cells. This feature of fast‐spiking neurons might allow them to follow higher‐frequency gamma oscillations for a longer time than NFS cells. The function of NFS boutons may better support asynchronous GABA release. In conclusion, we demonstrate several neuron‐specific Ca2+ transients in boutons of NFS, PFS and DFS neurons, which may serve differential functions in hippocampal networks.

Mechanisms of cortical high-gamma activity (60-200 Hz) investigated with computational modeling

High-gamma activity (HGA) at frequencies 60-200 Hz have been observed during task-related cortical activation in humans [1] and in animals [2], and have been used to map normal brain function and to decode commands in brain-computer interfaces. To understand the role that HGA plays in both normal and pathological brain states, deeper insights into its generating mechanisms are essential. Because the neural populations recorded by LFPs and EEG cannot be comprehensively recorded at scales that are likely to be relevant, we used a biologically based computational model of a cortical network to investigate the mechanisms generating HGA. The computational model included excitatory pyramidal regular-spiking and inhibitory fast-spiking neurons described by Hodgkin - Huxley dynamics. We compared activity generated by this model with HGA that was observed in LFP recorded in monkey somatosensory cortex during vibrotactile stimulation. Increase of firing rate and broadband HGA responses in LFP signals generated by the model were in agreement with experimental results (see Figure ​Figure11). Figure 1 Comparison of high-gamma observed in vivo (AB) and simulated in the model (CD) during sensory stimulation for different stimulus amplitudes denoted G1, G2, G5 and G10. AC: average firing rate of neurons. BD: time - frequency maps of LFP signals.