Rebound Spikes Research Articles

Bifurcations for counterintuitive post-inhibitory rebound spike related to absence epilepsy and Parkinson disease

Seizures are caused by increased neuronal firing activity resulting from reduced inhibitory effect and enhancement of inhibitory modulation to suppress this activity is used as a therapeutic tool. However, recent experiments have shown a counterintuitive phenomenon that inhibitory modulation does not suppress but elicit post-inhibitory rebound (PIR) spike along with seizure to challenge the therapeutic tool. The nonlinear mechanism to avoid the PIR spike can present theoretical guidance to seizure treatment. This paper focuses on identifying credible bifurcations that underlie PIR spike by modulating multiple parameters in multiple theoretical models. The study identifies a codimension-2 bifurcation called saddle--node homoclinic orbit (SNHOB), which is an intersection between saddle node bifurcation on invariant cycle (SNIC) and other two bifurcations. PIR spike cannot be evoked for the SNIC far from the SNHOB but induced for the SNIC close to the SNHOB, which extends the bifurcation condition for PIR spike from the well-known Hopf to SNIC. Especially, in a thalamic neuron model, increases of conductance of T-type Ca2+ (T Ca) channel induce SNIC bifurcation approaching to the SNHOB to elicit PIR spikes, closely matching experimental results of the absence seizure or Parkinson diseases. Such results imply that, when inhibition is employed to relieve absence seizure and Parkinson diseases related to PIR spike, modulating SNIC to get far from the SNHOB to avoid PIR spike is the principle. The study also addresses the complex roles of T Ca current and comprehensive relationships between PIR spike and nonlinear conceptions such as bifurcation types and shapes of threshold curve.

Spiking Behaviour in Laterally-Coupled Pairs of VCSELs With Applications in Neuromorphic Photonics

We report a theoretical study on laterally-coupled pairs of vertical-cavity surface-emitting lasers (VCSELs) operated under conditions that generate or suppress high-speed optical spiking regimes, and show their potential in exemplar functionalities for use in photonic neuromorphic computing systems. The VCSEL numerical analysis is based on a system of five coupled mode equations, which, for the case of weak coupling, are reduced to a set of three equations that predict the saddle-node stability boundary in terms of device parameters and operating conditions. These results guide numerical simulation to demonstrate multiple neuron-like dynamics, including single- and multiple-spike emission, spiking inhibition, and rebound spiking directly in the optical domain. Importantly, these behaviours are obtained at sub-nanosecond rates, hence multiple orders of magnitude faster than the millisecond timescales of biological neurons. The mechanisms responsible are explained by reference to appropriate phase portraits. The coupled VCSELs model is then used for demonstration of high-speed, all-optical digital-to-spiking encoding and for representation of digital image data using rate-coded spike trains.

Particle-swarm based modelling reveals two distinct classes of CRHPVN neurons.

Electrophysiological recordings can provide detailed information of single neurons' dynamical features and shed light on their response to stimuli. Unfortunately, rapidly modelling electrophysiological data for inferring network-level behaviours remains challenging. Here, we investigate how modelled single neuron dynamics leads to network-level responses in the paraventricular nucleus of the hypothalamus (PVN), a critical nucleus for the mammalian stress response. Recordings of corticotropin releasing hormone neurons from the PVN (CRHPVN ) were performed using whole-cell current-clamp. These, neurons, which initiate the endocrine response to stress, were rapidly and automatically fit to a modified adaptive exponential integrate-and-fire model (AdEx) with particle swarm optimization (PSO). All CRHPVN neurons were accurately fit by the AdEx model with PSO. Multiple sets of parameters were found that reliably reproduced current-clamp traces for any single neuron. Despite multiple solutions, the dynamical features of the models such as the rheobase, fixed points, and bifurcations, were shown to be stable across fits. We found that CRHPVN neurons can be divided into two subtypes according to their bifurcation at the onset of firing: CRHPVN -integrators and CRHPVN -resonators. The existence of CRHPVN -resonators was then directly confirmed in a follow-up patch-clamp hyperpolarization protocol which readily induced post-inhibitory rebound spiking in 33% of patched neurons. We constructed networks of CRHPVN model neurons to investigate the network level responses of CRHPVN neurons. We found that CRHPVN -resonators maintain baseline firing in networks even when all inputs are inhibitory. The dynamics of a small subset of CRHPVN neurons may be critical to maintaining a baseline firing tone in the PVN. KEY POINTS: Corticotropin-releasing hormone neurons (CRHPVN ) in the paraventricular nucleus of the hypothalamus act as the final neural controllers of the stress response. We developed a computational modelling platform that uses particle swarm optimization to rapidly and accurately fit biophysical neuron models to patched CRHPVN neurons. A model was fitted to each patched neuron without the use of dynamic clamping, or other procedures requiring sophisticated inputs and fitting algorithms. Any neuron undergoing standard current clamp step protocols for a few minutes can be fitted by this procedure The dynamical analysis of the modelled neurons shows that CRHPVN neurons come in two specific 'flavours': CRHPVN -resonators and CRHPVN -integrators. We directly confirmed the existence of these two classes of CRHPVN neurons in subsequent experiments. Network simulations show that CRHPVN -resonators are critical to retaining the baseline firing rate of the entire network of CRHPVN neurons as these cells can fire rebound spikes and bursts in the presence of strong inhibitory synaptic input.

Multiple and complex codimension-2 bifurcations underlying post-inhibitory rebound spike and excitability transition

Neuron exhibits nonlinear dynamics such as excitability transition and post-inhibitory rebound (PIR) spike related to bifurcations, which are associated with information processing, locomotor modulation, or brain disease. PIR spike is evoked by inhibitory stimulation instead of excitatory stimulation, which presents a challenge to the threshold concept. In this paper, 7 codimension-2 or degenerate bifurcations related to 10 codimension-1 bifurcations are acquired in a neuronal model, which presents the bifurcations underlying the excitability transition and PIR spike. Type I excitability corresponds to saddle-node bifurcation on an invariant cycle (SNIC) bifurcation, and type II excitability to saddle-node (SN) bifurcation or sub-critical Hopf (SubH) bifurcation or sup-critical Hopf (SupH) bifurcation. The excitability transition from type I to II corresponds to the codimension-2 bifurcation, Saddle-Node Homoclinic orbit (SNHO) bifurcation, via which SNIC bifurcation terminates and meanwhile big homoclinic orbit (BHom) bifurcation and SN bifurcation emerge. A degenerate bifurcation via which BHom bifurcation terminates and limit point of cycle (LPC) bifurcation emerges is responsible for spiking transition from type I to II, and the roles of other codimension-2 bifurcations (Cusp, Bogdanov-Takens, and Bautin) are discussed. In addition, different from the widely accepted viewpoint that PIR spike is mainly evoked near Hopf bifurcation rather than SNIC bifurcation, PIR spike is identified to be induced near SNIC or BHom or LPC bifurcations, and threshold curves resemble that of Hopf bifurcation. The complex bifurcations present comprehensive and deep understandings of excitability transition and PIR spike, which are helpful for the modulation to neural firing activities and physiological functions.

Geometric characterization of dynamical structure for neural firing activities induced by inhibitory pulse.

In general, inhibitory stimuli are thought to inhibit neuronal firing, but they may actually enhance firing sometimes, such as post-inhibitory rebound spike (PIR spike) and post-inhibitory facilitation (PIF) phenomena, which play an important role in human neuronal activities. We study responses to inhibitory pulse in a classical neuron model (Quartic adaptive Integrate-and-fire model) well known to reproduce a number of biologically realistic behaviors. The three phenomena that we study are PIR, in which a neuron fires after an inhibitory pulse, and PIF, in which a subthreshold excitatory input can induce a spike if it is applied with proper timing after an inhibitory pulse, as well as period firing after inhibitory pulse. When the system features focus and saddle two equilibriums, the three phenomena will be occurred under the inhibitory pulse, while all three phenomena will not be induced when the system features node and saddle two equilibriums. Using dynamical systems theory, we explain the threshold mechanism of enhancement of neural firing response induced by inhibitory pulse and analyze the origin of these phenomena from several factors. We also describe the geometric characterization of dynamical structures of these three phenomena. This study therefore enrich the paradoxical phenomena that induced by inhibitory input and advance our understanding of its role.

Negative self-feedback induced enhancement and transition of spiking activity for class-3 excitability

Post-inhibitory rebound (PIR) spike, which has been widely observed in diverse nervous systems with different physiological functions and simulated in theoretical models with class-2 excitability, presents a counterintuitive nonlinear phenomenon in that the inhibitory effect can facilitate neural firing behavior. In this study, a PIR spike induced by inhibitory stimulation from the resting state corresponding to class-3 excitability that is not related to bifurcation is simulated in the Morris–Lecar neuron. Additionally, the inhibitory self-feedback mediated by an autapse with time delay can evoke tonic/repetitive spiking from phasic/transient spiking. The dynamical mechanism for the PIR spike and the tonic/repetitive spiking is acquired with the phase plane analysis and the shape of the quasi-separatrix curve. The result extends the counterintuitive phenomenon induced by inhibition to class-3 excitability, which presents a potential function of inhibitory autapse and class-3 neuron in many neuronal systems such as the auditory system.

Post inhibitory rebound spike related to nearly vertical nullcline for small homoclinic and saddle-node bifurcations

<abstract><p>A spike induced by inhibitory stimulation instead of excitatory stimulation, called post-inhibitory rebound (PIR) spike, has been found in multiple neurons with important physiological functions, which presents counterintuitive behavior mainly related to focus near Hopf bifurcation. In the present paper, the condition for the PIR spike is extended to small homoclinic orbit (SHom) and saddle-node (SN) bifurcations, and the underlying mechanism is acquired in a neuron model. Firstly, PIR spike is evoked from a stable node near the SHom or SN bifurcation by a strong inhibitory stimulation. Then, the dynamics of threshold curve for a spike, vector fields, and nullcline of recovery variable are used to well explain the cause for the PIR spike. The shape of threshold curve for the node resembles that of focus. The nullcline plays an important role in forming PIR spike, which is analytically identified at last. Besides, a sufficient condition is acquired from the integration to a differential equation, and the range of parameters for the PIR spike is presented. The extended bifurcation types and the underlying mechanisms for the PIR spike such as the nullcline present comprehensive and deep understandings for the PIR spike, which also provides potential strategy to modulate the PIR phenomenon and even related physiological functions of neurons.</p></abstract>

Opto-vTrap, an optogenetic trap for reversible inhibition of vesicular release, synaptic transmission, and behavior

Spatiotemporal control of brain activity by optogenetics has emerged as an essential tool to study brain function. For silencing brain activity, optogenetic probes, such as halorhodopsin and archaerhodopsin, inhibit transmitter release indirectly by hyperpolarizing membrane potentials. However, these probes cause an undesirable ionic imbalance and rebound spikes. Moreover, they are not applicable to use in non-excitable glial cells. Here we engineered Opto-vTrap, a light-inducible and reversible inhibition system to temporarily trap the transmitter-containing vesicles from exocytotic release. Light activation of Opto-vTrap caused full vesicle clusterization and complete inhibition of exocytosis within 1min, which recovered within 30min after light off. We found a significant reduction in synaptic and gliotransmission upon activation of Opto-vTrap in acute brain slices. Opto-vTrap significantly inhibited hippocampus-dependent memory retrieval with full recovery within an hour. We propose Opto-vTrap as a next-generation optogenetic silencer to control brain activity and behavior with minimal confounding effects.

A Synaptic Story of Working Memory

Paradoxical phenomena such as synchronization and post inhibitory rebound spike induced by the inhibitory effects are important for both nonlinear science and neuroscience. In the present paper, a novel paradoxical example for the bursting activity modulated by the negative self-feedback of the inhibitory autapse and the dynamical mechanism are acquired in a theoretical model. As the inhibitory autaptic conductance increases, the burst duration becomes wide or the spike number per burst becomes large, which is different from the common viewpoint that the burst duration should become narrow or the spike number should become small. Meanwhile, the bursting patterns exhibit the transition from “fold/homoclinic” type, to “fold cycle/homoclinic” type, and to “point-point” type, which shows that the paradoxical phenomenon is not a special case for a specific bursting but a universal phenomenon for multiple bursting patterns. Furthermore, the paradoxical enhancement of bursting activity is well explained with the nonlinear dynamics such as the bifurcations of the fast subsystem, the amplitude of the stable limit cycle, and the eigenvalues of the stable focus. The results enrich the contents of nonlinear science and present a potential strategy to enhance the bursting activity of neuron with inhibitory autapse.

The role of rebound spikes in the maintenance of self-sustained neural spiking activity

In general, the mechanisms that maintain the activity of neural systems after a triggering stimulus has been removed are not well understood. Different mechanisms involving at the cellular and network levels have been proposed. In this work, based on analysis of a computational model of a spiking neural network, it is proposed that the spike that occurs after a neuron is inhibited (the rebound spike) can be used to sustain the activity in a recurrent inhibitory neural circuit after the stimulation has been removed. It is shown that, in order to sustain the activity, the neurons participating in the recurrent circuit should fire at low frequencies. It is also shown that the occurrence of a rebound spike depends on a combination of factors including synaptic weights, synaptic conductances and the neuron state. We point out that the model developed here is minimalist and does not aim at empirical accuracy. Its purpose is to raise and discuss theoretical issues that could contribute to the understanding of neural mechanisms underlying self-sustained neural activity.

Basal ganglia and cortical control of thalamic rebound spikes.

Movement-related decreases in firing rate have been observed in basal ganglia output neurons. They may transmit motor signals to the thalamus, but the effect of these firing rate decreases on downstream neurons in the motor thalamus is not known. One possibility is that they lead to thalamic post-inhibitory rebound spikes. However, it has also been argued that the physiological conditions permitting rebound spiking are pathological, and primarily present in Parkinson's disease. As in Parkinson's disease neural activity becomes pathologically correlated, we investigated the impact of correlations in basal ganglia output on the transmission of motor signals using a Hodgkin-Huxley model of thalamocortical neurons. We found that such correlations disrupt the transmission of motor signals via rebound spikes by decreasing the signal-to-noise ratio and increasing the trial-to-trial variability. We further examined the role of sensory responses in basal ganglia output neurons and the effect of cortical excitation of motor thalamus in modulating rebound spiking. Interestingly, both could either promote or suppress the generation of rebound spikes depending on their timing relative to the motor signal. Finally, we determined parameter regimes, such as levels of excitation, under which rebound spiking is feasible in the model, and confirmed that the conditions for rebound spiking are primarily given in pathological regimes. However, we also identified specific conditions in the model that would allow rebound spiking to occur in healthy animals in a small subset of thalamic neurons. Overall, our model provides novel insights into differences between normal and pathological transmission of motor signals.

Fast A-type currents shape a rapidly adapting form of delayed short latency firing of excitatory superficial dorsal horn neurons that express the neuropeptide Y Y1 receptor.

Neuropeptide Y Y1 receptor-expressing neurons in the dorsal horn of the spinal cord contribute to chronic pain. For the first time, we characterized the firing patterns of Y1-expressing neurons in Y1eGFP reporter mice. Under hyperpolarized conditions, most Y1eGFP neurons exhibited fast A-type potassium currents and delayed, short-latency firing (DSLF). Y1eGFP DSLF neurons were almost always rapidly adapting and often exhibited rebound spiking, characteristics of spinal pain neurons under the control of T-type calcium channels. These results will inspire future studies to determine whether tissue or nerve injury downregulates the channels that underlie A-currents, thus unmasking membrane hyperexcitability in Y1-expressing dorsal horn neurons, leading to persistent pain. Neuroanatomical and behavioural evidence indicates that neuropeptide Y Y1 receptor-expressing interneurons (Y1-INs) in the superficial dorsal horn (SDH) are predominantly excitatory and contribute to chronic pain. Using an adult ex vivo spinal cord slice preparation from Y1eGFP reporter mice, we characterized firing patterns in response to steady state depolarizing current injection of GFP-positive cells in lamina II, the great majority of which expressed Y1 mRNA (88%). Randomly sampled (RS) and Y1eGFP neurons exhibited five firing patterns: tonic, initial burst, phasic, delayed short-latency <180ms (DSLF) and delayed long-latency >180ms (DLLF). When studied at resting membrane potential, most RS neurons exhibited delayed firing, while most Y1eGFP neurons exhibited phasic firing. A preconditioning membrane hyperpolarization produced only subtle changes in the firing patterns of RS neurons, but dramatically shifted Y1eGFP neurons to DSLF (46%) and DLLF (24%). In contrast to RS DSLF neurons, which rarely exhibited spike frequency adaptation, Y1eGFP DSLF neurons were almost always rapidly adapting, a characteristic of nociceptive-responsive SDH neurons. Rebound spiking was more prevalent in Y1eGFP neurons (6% RS vs. 32% Y1eGFP), indicating enrichment of T-type calcium currents. Y1eGFP DSLF neurons exhibited fast A-type potassium currents that are known to delay or limit action potential firing and exhibited smaller current density as compared to RS DSLF neurons. Our results will inspire future studies to determine whether tissue or nerve injury downregulates channels that contribute to A-currents, thus potentially unmasking T-type calcium channel activity and membrane hyperexcitability in Y1-INs, leading to persistent pain.

Theta Oscillations Gate the Transmission of Reliable Sequences in the Medial Entorhinal Cortex.

Stability and precision of sequential activity in the entorhinal cortex (EC) is crucial for encoding spatially guided behavior and memory. These sequences are driven by constantly evolving sensory inputs and persist despite a noisy background. In a realistic computational model of a medial EC (MEC) microcircuit, we show that intrinsic neuronal properties and network mechanisms interact with theta oscillations to generate reliable outputs. In our model, sensory inputs activate interneurons near their most excitable phase during each theta cycle. As the inputs change, different interneurons are recruited and postsynaptic stellate cells are released from inhibition. This causes a sequence of rebound spikes. The rebound time scale of stellate cells, because of an h–current, matches that of theta oscillations. This fortuitous similarity of time scales ensures that stellate spikes get relegated to the least excitable phase of theta and the network encodes the external drive but ignores recurrent excitation. In contrast, in the absence of theta, rebound spikes compete with external inputs and disrupt the sequence that follows. Further, the same mechanism where theta modulates the gain of incoming inputs, can be used to select between competing inputs to create transient functionally connected networks. Our results concur with experimental data that show, subduing theta oscillations disrupts the spatial periodicity of grid cell receptive fields. In the bat MEC where grid cell receptive fields persist even in the absence of continuous theta oscillations, we argue that other low frequency fluctuations play the role of theta.

Enhancement of coherence resonance induced by inhibitory autapse in Hodgkin–Huxley model

Inhibitory effect often suppresses electronic activities of the nervous system. In this paper, the inhibitory autapse is identified to enhance the degree of coherence resonance (CR) induced by noise in the Hodgkin–Huxley (HH) model with Hopf bifurcation from resting state to spiking with nearly fixed period [Formula: see text]. Without noise, the inhibitory autapse can induce a post inhibitory rebound (PIR) spike from the resting state at time delay approximating [Formula: see text] and can inhibit a spike of spiking at time delay approximating [Formula: see text]. In the presence of noise, CR characterized by maximal value of power spectrum of spike trains appears in a wide range of both time delay and conductance of autapse. With increasing autaptic conductance, CR degree becomes stronger for time delay approximating [Formula: see text] plus integer (from 0) multiples of [Formula: see text], because the inhibitory autaptic current pulses can induce more PIR spikes. The decrease of CR degree at time delay approximating integer (from 1) multiples of [Formula: see text] can be explained by the inhibition effect. The promotion of coherence resonance degree and the underlying PIR mechanism induced by inhibitory self-feedback extends the paradoxical phenomenon of inhibitory autapse to stochastic system and presents potential measures to modulate CR degree and information processing.

Paradoxical enhancement of neuronal bursting response to negative feedback of autapse and the nonlinear mechanism

Abstract Paradoxical phenomena such as synchronization and post inhibitory rebound spike induced by the inhibitory effects are important for both nonlinear science and neuroscience. In the present paper, a novel paradoxical example for the bursting activity modulated by the negative self-feedback of the inhibitory autapse and the dynamical mechanism are acquired in a theoretical model. As the inhibitory autaptic conductance increases, the burst duration becomes wide or the spike number per burst becomes large, which is different from the common viewpoint that the burst duration should become narrow or the spike number should become small. Meanwhile, the bursting patterns exhibit the transition from “fold/homoclinic” type, to “fold cycle/homoclinic” type, and to “point-point” type, which shows that the paradoxical phenomenon is not a special case for a specific bursting but a universal phenomenon for multiple bursting patterns. Furthermore, the paradoxical enhancement of bursting activity is well explained with the nonlinear dynamics such as the bifurcations of the fast subsystem, the amplitude of the stable limit cycle, and the eigenvalues of the stable focus. The results enrich the contents of nonlinear science and present a potential strategy to enhance the bursting activity of neuron with inhibitory autapse.

Changes in Excitability Properties of Ventromedial Motor Thalamic Neurons in 6-OHDA Lesioned Mice.

The activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions has not be investigated at the cellular level. Such changes may well be expected because of homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-hydroxydopamine hydrochloride (6-OHDA)-treated adult mice. At a minimum of one month after 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily because of a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in the BG thalamocortical network in Parkinson’s disease.

Big homoclinic orbit bifurcation underlying post-inhibitory rebound spike and a novel threshold curve of a neuron

&lt;p style='text-indent:20px;'&gt;Post-inhibitory rebound (PIR) spike induced by the negative stimulation, which plays important roles and presents counterintuitive nonlinear phenomenon in the nervous system, is mainly related to the Hopf bifurcation and hyperpolarization-active caution (&lt;inline-formula&gt;&lt;tex-math id="M1"&gt;$ I_h $&lt;/tex-math&gt;&lt;/inline-formula&gt;) current. In the present paper, the emerging condition for the PIR spike is extended to the bifurcation of the big homoclinic (BHom) orbit in a model without &lt;inline-formula&gt;&lt;tex-math id="M2"&gt;$ I_h $&lt;/tex-math&gt;&lt;/inline-formula&gt; current. The threshold curve for a spike evoked from a mono-stable or coexisting steady state surrounds the steady state from left, to below, and to right, because the BHom orbit is big enough to surround the steady state. The right part of the threshold curve coincides with the stable manifold of the saddle and acts the threshold for the spike induced by the positive stimulation, resembling that of the saddle-node bifurcation on an invariant cycle, and the left part acts the threshold for the PIR spike, resembling that of the Hopf bifurcation. The bifurcation curve and a codimension-2 bifurcation point related to the BHom orbit are acquired in the two-parameter plane. The results present a comprehensive viewpoint to the dynamics near the BHom orbit bifurcation, which presents a novel threshold curve and extends the conditions for the PIR spike.&lt;/p&gt;

Disruption of rat deep cerebellar perineuronal net alters eyeblink conditioning and neuronal electrophysiology

The perineuronal net (PNN) is a specialized type of extracellular matrix found in the central nervous system. The PNN forms on fast spiking neurons during postnatal development but the ontogeny of PNN development has yet to be elucidated. By studying the development and prevalence of the PNN in the juvenile and adult rat brain, we may be able to understand the PNN’s role in development and learning and memory. We show that the PNN is fully developed in the deep cerebellar nuclei (DCN) of rats by P18. By using enzymatic digestion of the PNN with chondroitinase ABC (ChABC), we are able to study how digestion of the PNN affects cerebellar-dependent eyeblink conditioning in vivo and perform electrophysiological recordings from DCN neurons in vitro. In vivo degradation of the PNN resulted in significant differences in eyeblink conditioning amplitude and area. Female animals in the vehicle group demonstrated higher levels of conditioning as well as significantly higher post-probe conditioned responses compared to males in that group, differences not present in the ChABC group. In vitro, we found that DCN neurons with a disrupted PNN following exposure to ChABC had altered membrane properties, fewer rebound spikes, and decreased intrinsic excitability. Together, this study further elucidates the role of the PNN in cerebellar learning in the DCN and is the first to demonstrate PNN degradation may erase sex differences in delay conditioning.

Inhibitory autapses enhance coherence resonance of a neuronal network

The counterintuitive phenomenon that inhibitory autapses enhance coherence resonance (CR) is investigated in a Hodgkin–Huxley neuronal network, which can be well interpreted by post-inhibitory rebound (PIR) spikes. Noise can induce CR in the network with excitatory coupling. After introducing inhibitory autapses, multiple CRs induced by noise appear at multiple time delays of inhibitory autapses. The degree of CRs can be enhanced by inhibitory autapses with time delays approximating to 10 ms or the sum of 10 ms and multiples of the firing period. For these time delays, each delayed inhibitory current pulse can induce a PIR spike, which is a signature of the stable focus near the Hopf bifurcation. The degree of CRs can be reduced by inhibitory autapses for time delays nearly equaling multiples of the firing period, because the inhibitory autaptic current pulses take effect near the spikes, resulting in the reduced irregularity of the spikes. More detailed dynamics of CR is investigated in planes composed of every two parameters out of the noise intensity, the autaptic strength, and the time delay. The counterintuitive phenomenon that inhibitory autapses can enhance the CR degree is in contrast to the conventional notion that inhibitory effects suppress the neuronal activities, which not only enriches the content of nonlinear dynamics, but also provides an approach to modulate CR or the firing regularity of neuronal networks.

Modeling Reveals Human-Rodent Differences in H-Current Kinetics Influencing Resonance in Cortical Layer 5 Neurons.

While our understanding of human neurons is often inferred from rodent data, inter-species differences between neurons can be captured by building cellular models specifically from human data. This includes understanding differences at the level of ion channels and their implications for human brain function. Thus, we here present a full spiking, biophysically detailed multi-compartment model of a human layer 5 (L5) cortical pyramidal cell. Model development was primarily based on morphological and electrophysiological data from the same human L5 neuron, avoiding confounds of experimental variability. Focus was placed on describing the behavior of the hyperpolarization-activated cation (h-) channel, given increasing interest in this channel due to its role in pacemaking and differentiating cell types. We ensured that the model exhibited post-inhibitory rebound spiking considering its relationship with the h-current, along with other general spiking characteristics. The model was validated against data not used in its development, which highlighted distinctly slower kinetics of the human h-current relative to the rodent setting. We linked the lack of subthreshold resonance observed in human L5 neurons to these human-specific h-current kinetics. This work shows that it is possible and necessary to build human-specific biophysical neuron models in order to understand human brain dynamics.