Spike Firing Research Articles

Targeted Expression of Channelrhodopsin-2 to the Axon Initial Segment Alters the Temporal Firing Properties of Retinal Ganglion Cells.

The axon initial segment (AIS) is essential for initiating action potentials and maintaining neuronal excitability in axon-bearing neurons in the CNS. There is increasing interest in the targeting of optogenetic tools to subcellular compartments, including the AIS, to gain precise control of neuronal activity for basic research and clinical applications. In particular, targeted expression of optogenetic tools in retinal ganglion cells (RGCs) has been explored as an approach for restoring vision after photoreceptor degeneration. Thus, understanding the effects of such targeting on spiking abilities and/or patterns is important. Here, we examined the effects of recombinant adeno-associated virus (rAAV)-mediated targeted expression of channelrhodopsin-2 (ChR2)-GFP with a NaV channel motif in mouse RGCs. We found that this targeted expression disrupted NaV channel clustering at the AIS and converted the spike firing patterns of RGCs from sustained to transient. Our results suggest that the clustering of membrane channels, including NaV channels, at the AIS is important for the ability of RGCs to generate sustained spike firing. Additionally, the targeting of optogenetic tools to the AIS with the NaV channel motif may offer a way to create transient light responses in RGCs for vision restoration.

Effects of bursting dynamic features on the generation of multi-clustered structure of neural network with symmetric spike-timing-dependent plasticity learning rule.

In this paper, the generation of multi-clustered structure of self-organized neural network with different neuronal firing patterns, i.e., bursting or spiking, has been investigated. The initially all-to-all-connected spiking neural network or bursting neural network can be self-organized into clustered structure through the symmetric spike-timing-dependent plasticity learning for both bursting and spiking neurons. However, the time consumption of this clustering procedure of the burst-based self-organized neural network (BSON) is much shorter than the spike-based self-organized neural network (SSON). Our results show that the BSON network has more obvious small-world properties, i.e., higher clustering coefficient and smaller shortest path length than the SSON network. Also, the results of larger structure entropy and activity entropy of the BSON network demonstrate that this network has higher topological complexity and dynamical diversity, which benefits for enhancing information transmission of neural circuits. Hence, we conclude that the burst firing can significantly enhance the efficiency of clustering procedure and the emergent clustered structure renders the whole network more synchronous and therefore more sensitive to weak input. This result is further confirmed from its improved performance on stochastic resonance. Therefore, we believe that the multi-clustered neural network which self-organized from the bursting dynamics has high efficiency in information processing.

Rapid Modulation of Axon Initial Segment Length Influences Repetitive Spike Firing.

SummaryNeurons implement a variety of plasticity mechanisms to alter their function over timescales ranging from seconds to days. One powerful means of controlling excitability is to directly modulate the site of spike initiation, the axon initial segment (AIS). However, all plastic structural AIS changes reported thus far have been slow, involving days of neuronal activity perturbation. Here, we show that AIS plasticity can be induced much more rapidly. Just 3 hr of elevated activity significantly shortened the AIS of dentate granule cells in a calcineurin-dependent manner. The functional effects of rapid AIS shortening were offset by dephosphorylation of voltage-gated sodium channels, another calcineurin-dependent mechanism. However, pharmacological separation of these phenomena revealed a significant relationship between AIS length and repetitive firing. The AIS can therefore undergo a rapid form of structural change over timescales that enable interactions with other forms of activity-dependent plasticity in the dynamic control of neuronal excitability.

Propofol facilitates excitatory inputs of cerebellar Purkinje cells by depressing molecular layer interneuron activity during sensory information processing in vivo in mice.

Propofol is a rapid-acting sedative-hypnotic medication that has been widely used for the induction and maintenance of anesthesia; it has specific actions on different areas of the brain, such as sensory information transmission in the somatosensory cortex. However, the effects of propofol on the properties of sensory stimulation-evoked responses in cerebellar Purkinje cells (PCs) are currently unclear. In the present study, we studied the effects of propofol on facial stimulation-evoked responses in cerebellar PCs and molecular level interneurons (MLIs) in urethane-anesthetized mice using electrophysiological and pharmacological methods. Our results showed that cerebellar surface perfusion with propofol induced a decrease in the amplitude of the gamma-aminobutyric acid (GABA)-ergic component (P1) in a dose-dependent manner, but induced a significant increase in the amplitude of the excitatory response (N1). The IC50 of propofol-induced inhibition of P1 was 217.3 μM. In contrast, propofol (100 μM) depressed the spontaneous activity and tactile-evoked responses in MLIs. In addition, blocking GABA(A) receptor activity abolished the propofol (300 μM)-induced inhibition of the tactile-evoked inhibitory response and the increase in the sensory stimulation-evoked spike firing rate of PCs. These results indicated that propofol depressed the tactile stimulation-evoked spike firing of MLIs, resulting in a decrease in the amplitude of the tactile-evoked inhibitory response and an increase in the amplitude of the excitatory response in the cerebellar PCs of mice. Our results suggest that propofol modulates sensory information processing in cerebellar cortical PCs and MLIs through the activation of GABA(A) receptors.

Neuronal-glial populations form functional networks in a biocompatible 3D scaffold

Monolayers of neurons and glia have been employed for decades as tools for the study of cellular physiology and as the basis for a variety of standard toxicological assays. A variety of three dimensional (3D) culture techniques have been developed with the aim to produce cultures that recapitulate desirable features of intact. In this study, we investigated the effect of preparing primary mouse mixed neuron and glial cultures in the inert 3D scaffold, Alvetex. Using planar multielectrode arrays, we compared the spontaneous bioelectrical activity exhibited by neuroglial networks grown in the scaffold with that seen in the same cells prepared as conventional monolayer cultures. Two dimensional (monolayer; 2D) cultures exhibited a significantly higher spike firing rate than that seen in 3D cultures although no difference was seen in total signal power (<50Hz) while pharmacological responsiveness of each culture type to antagonism of GABAAR, NMDAR and AMPAR was highly comparable. Interestingly, correlation of burst events, spike firing and total signal power (<50Hz) revealed that local field potential events were associated with action potential driven bursts as was the case for 2D cultures. Moreover, glial morphology was more physiologically normal in 3D cultures. These results show that 3D culture in inert scaffolds represents a more physiologically normal preparation which has advantages for physiological, pharmacological, toxicological and drug development studies, particularly given the extensive use of such preparations in high throughput and high content systems.

Differential participation of pyramidal cells in generation of spontaneous sharp wave-ripples in the mouse subiculum in vitro

Previously stored information in the hippocampus is believed to be replayed during sharp wave-ripple activity thereby serving transfer of information from hippocampal areas CA3 and CA1 to the cortical mantle and memory consolidation. The subiculum represents the main hippocampal output and contains both regular spiking and burst firing neurons that may project to different targets in the CNS. We recorded laminar profiles and intracellular correlates of spontaneous subicular events in mouse horizontal hippocampal slices and investigated involvement of the different subtypes of subicular pyramidal cells. Subicular sharp wave-ripples (SWRs) depend on input from the CA3 and CA1 regions as shown by microdissection experiments between hippocampal subareas. The extracellular subicular waves are associated with multiple unit activity, which varies in form and size. Intracellular recordings reveal that the same pyramidal cell can show different responses to SWRs. In the majority of cases, SWRs cause subthreshold depolarizing potentials. Burster neurons regularly contribute to generation of SWRs by action potential firing, whereas regular-spiking neurons are often inhibited.

Electrophysiological and firing properties of neurons: Categorizing soloists and choristers in primary visual cortex

Visual processing in the cortex involves various aspects of neuronal properties such as morphological, electrophysiological and molecular. In particular, the neural firing pattern is an important indicator of dynamic circuitry within a neuronal population. Indeed, in microcircuits, neurons act as soloists or choristers wherein the characteristical activity of a ‘soloist’ differs from the firing pattern of a ‘chorister’. Both cell types correlate their respective firing rate with the global populational activity in a unique way. In the present study, we sought to examine the relationship between the spike shape (thin spike neurons and broad spike neurons) of cortical neurons recorded from V1, their firing levels and their propensity to act as soloists or choristers. We found that thin spike neurons, which exhibited higher levels of firing, generally correlate their activity with the neuronal population (choristers). On the other hand, broad spike neurons showed lower levels of firing and demonstrated weak correlations with the assembly (soloists). A major consequence of the present study is: estimating the correlation of neural spike trains with their neighboring population is a predictive indicator of spike waveforms and firing level. Indeed, we found a continuum distribution of coupling strength ranging from weak correlation-strength (attributed to low-firing neurons) to high correlation-strength (attributed to high-firing neurons). The tendency to exhibit high- or low-firing is conducive to the spike shape of neurons. Our results offer new insights into visual processing by showing how high-firing rate neurons (mostly thin spike neurons) could modulate the neuronal responses within cell-assemblies.

Developmental remodeling of relay cells in the dorsal lateral geniculate nucleus in the absence of retinal input

BackgroundThe dorsal lateral geniculate nucleus (dLGN) of the mouse has been an important experimental model for understanding thalamic circuit development. The developmental remodeling of retinal projections has been the primary focus, however much less is known about the maturation of their synaptic targets, the relay cells of the dLGN. Here we examined the growth and maturation of relay cells during the first few weeks of life and addressed whether early retinal innervation affects their development. To accomplish this we utilized the math5 null (math5−/−) mouse, a mutant lacking retinal ganglion cells and central projections.ResultsThe absence of retinogeniculate axon innervation led to an overall shrinkage of dLGN and disrupted the pattern of dendritic growth among developing relay cells. 3-D reconstructions of biocytin filled neurons from math5−/− mice showed that in the absence of retinal input relay cells undergo a period of exuberant dendritic growth and branching, followed by branch elimination and an overall attenuation in dendritic field size. However, math5−/− relay cells retained a sufficient degree of complexity and class specificity, as well as their basic membrane properties and spike firing characteristics.ConclusionsRetinal innervation plays an important trophic role in dLGN development. Additional support perhaps arising from non-retinal innervation and signaling is likely to contribute to the stabilization of their dendritic form and function.

Local Circuits for Contrast Normalization and Adaptation Investigated with Two-Photon Imaging in Cat Primary Visual Cortex.

Neurons in the primary visual cortex (V1) respond near instantaneously over a limited range of contrasts but can also shift their operating range according to the average contrast of the scene. This "contrast adaptation" takes 5-10 s and ensures that a full range of contrasts can be encoded in V1, while remaining sensitive to small changes in local contrast. By optically recording many layer 2 neurons simultaneously, we discovered that networks of neurons collectively code for a much wider range of contrasts. Whereas most neurons responded to sustained increases in contrast by decreasing their spike firing rates, two types of inhibitory neurons in the cat's visual cortex paradoxically increased their firing rates and so could inhibit other neurons to produce contrast adaptation.

What the fly’s nose tells the fly’s brain

The fly olfactory system has a three-layer architecture: The fly's olfactory receptor neurons send odor information to the first layer (the encoder) where this information is formatted as combinatorial odor code, one which is maximally informative, with the most informative neurons firing fastest. This first layer then sends the encoded odor information to the second layer (decoder), which consists of about 2,000 neurons that receive the odor information and "break" the code. For each odor, the amplitude of the synaptic odor input to the 2,000 second-layer neurons is approximately normally distributed across the population, which means that only a very small fraction of neurons receive a large input. Each odor, however, activates its own population of large-input neurons and so a small subset of the 2,000 neurons serves as a unique tag for the odor. Strong inhibition prevents most of the second-stage neurons from firing spikes, and therefore spikes from only the small population of large-input neurons is relayed to the third stage. This selected population provides the third stage (the user) with an odor label that can be used to direct behavior based on what odor is present.

Propofol depresses cerebellar Purkinje cell activity via activation of GABAA and glycine receptors in vivo in mice

Propofol is an intravenous sedative-hypnotic agen, which causes rapid and reliable loss of consciousness. Under in vitro conditions, propofol activates GABAA and glycine receptors in spinal cord, hippocampus and hypothalamus neurons. However, the effects of propofol on the cerebellar neuronal activity under in vivo conditions are currently unclear. In the present study, we examined the effects of propofol on the spontaneous activity of Purkinje cells (PCs) in urethane-anesthetized mice by cell-attached recording and pharmacological methods. Our results showed that cerebellar surface perfusion of propofol (10–1000μM) induced depression of the PC simple spike (SS) firing rate in a dose-dependent manner, but without significantly changing the properties of complex spikes (CS). The IC50 of propofol for inhibiting SS firing of PCs was 144.5μM. Application of GABAA receptor antagonist, SR95531 (40μM) or GABAB receptor antagonist, saclofen (20μM), as well as glycine receptor antagonist, strychnine (10μM) alone failed to prevent the propofol-induced inhibition of PCs spontaneous activity. However, application the mixture of SR95531 (40μM) and strychnine (10μM) completely blocked the propofol-induced inhibition of PC SS firing. These data indicated that cerebellar surface application of propofol depressed PC SS firing rate via facilitation of GABAA and functional glycine receptors activity in adult cerebellar PCs under in vivo conditions. Our present results provide a new insight of the anesthetic action of propofol in cerebellar cortex, suggesting that propofol depresses the SS outputs of cerebellar PCs which is involved in both GABAA and glycine receptors activity.

Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic subdivisions of the mPFC in behaving rats. These conditioning-induced changes in mPFC firing were mitigated by systemic administration of propranolol (10 mg/kg, i.p.), a β-noradrenergic receptor antagonist. Moreover, propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning. These findings suggest that β-adrenoceptors mediate stress-induced changes in mPFC spike firing that contribute to extinction impairments. Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma.

Sensory transduction at the frog semicircular canal: how hair cell membrane potential controls junctional transmission.

At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs), due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot be studied at the intact semicircular canal. To circumvent the problem, we combined patch-clamp recordings at the isolated hair cell and electrophysiological recordings at the cytoneural junction in the intact preparation. At isolated hair cells, the K channel blocker tetraethylammonium (TEA) is shown to block a fraction of total voltage-dependent K-conductance (IKD) that depends on TEA concentration but not on membrane potential (Vm). Considering the bioelectric properties of the hair cell, as previously characterized by this lab, a fixed fractional block of IKD is shown to induce a relatively fixed shift in Vm, provided it lies in the range −30 to −10 mV. The same concentrations of TEA were applied to the intact labyrinth while recording from single afferent fibers of the posterior canal, at rest and during mechanical stimulation. At the peak of stimulation, TEA produced increases in mEPSP rate that were linearly related to the shifts produced by the same TEA concentrations (0.1–3 mM) in hair cell Vm (0.7–5 mV), with a slope of 29.8 Hz/mV. The membrane potential of the hair cell is not linearly related to receptor conductance, so that the slope of quantal release vs. receptor conductance depends on the prevailing Vm (19.8 Hz/nS at −20 mV; 11 Hz/nS at −10 mV). Changes in mEPSP peak size were negligible at rest as well as during stimulation. Since ample spatial summation of mEPSPs occurs at the afferent terminal and threshold-governed spike firing is intrinsically nonlinear, the observed increases in mEPSP frequency, though not very large, may suffice to trigger afferent spike discharge.

Facial stimulation induces long-term depression at cerebellar molecular layer interneuron-Purkinje cell synapses in vivo in mice.

Cerebellar long-term synaptic plasticity has been proposed to provide a cellular mechanism for motor learning. Numerous studies have demonstrated the induction and mechanisms of synaptic plasticity at parallel fiber–Purkinje cell (PF–PC), parallel fiber–molecular layer interneurons (PF–MLI) and mossy fiber–granule cell (MF–GC) synapses, but no study has investigated sensory stimulation-evoked synaptic plasticity at MLI–PC synapses in the cerebellar cortex of living animals. We studied the expression and mechanism of MLI–PC GABAergic synaptic plasticity induced by a train of facial stimulation in urethane-anesthetized mice by cell-attached recordings and pharmacological methods. We found that 1 Hz, but not a 2 Hz or 4 Hz, facial stimulation induced a long-term depression (LTD) of GABAergic transmission at MLI–PC synapses, which was accompanied with a decrease in the stimulation-evoked pause of spike firing in PCs, but did not induce a significant change in the properties of the sensory-evoked spike events of MLIs. The MLI–PC GABAergic LTD could be prevented by blocking cannabinoid type 1 (CB1) receptors, and could be pharmacologically induced by a CB1 receptor agonist. Additionally, 1 Hz facial stimulation delivered in the presence of a metabotropic glutamate receptor 1 (mGluR1) antagonist, JNJ16259685, still induced the MLI–PC GABAergic LTD, whereas blocking N-methyl-D-aspartate (NMDA) receptors during 1 Hz facial stimulation abolished the expression of MLI–PC GABAergic LTD. These results indicate that sensory stimulation can induce an endocannabinoid (eCB)-dependent LTD of GABAergic transmission at MLI–PC synapses via activation of NMDA receptors in cerebellar cortical Crus II in vivo in mice. Our results suggest that the sensory stimulation-evoked MLI–PC GABAergic synaptic plasticity may play a critical role in motor learning in animals.

Expression of KCNH2-3.1 mRNA is increased in small neurons in the dorsolateral prefrontal cortex in patients with schizophrenia

Background and Objectives: Abnormalities in neuronal firing, controlled and organised by a series of voltage-gated ion channels, may contribute to the pathogenesis of schizophrenia. KCNH2, encoding the voltage-gated potassium channel Kv11.1, has been identified as a potential risk gene for schizophrenia. Single nucleotide polymorphisms (SNPs) in the second intron promote the expression of a brain-specific isoform, KCNH2-3.1, which exhibits altered gating kinetics and results in less adaptation of firing rate in response to prolonged stimulation. To determine the pathophysiological consequence of these altered gating properties, we need to know in which cells KCNH2-3.1 is expressed and how this is affected by genotype and/or diagnosis. Methods: We performed SNP analysis and in-situ hybridization on brain tissue from 37 healthy controls and schizophrenia (n = 30)/schizoaffective (n = 7) patients to investigate expression levels and cellular distribution of KCNH2-3.1 mRNA in the dorsolateral prefrontal cortex (DLPFC). Results: KCNH2-3.1 mRNA is expressed in all six layers of the DLPFC. It is expressed in both pyramidal and interneuron-like cells, with significantly higher expression in small neurons in layer III and IV in schizophrenia patients compared to controls. Schizophrenia/schizoaffective patients who carry risk alleles at rs11763131 and/or rs3807373 show significantly higher expression in layer IV compared to schizophrenia/schizoaffective patients who are non-risk allele carriers. Conclusions: We have anatomically localized an increase in KCNH2-3.1 to putative interneurons in schizophrenia/schizoaffective. Our results demonstrate that the risk alleles are likely to be preferentially associated with higher KCNH2-3.1 mRNA expression, which would be expected to result in increased spike frequency and firing in layer IV interneurons. (Grants: NHMRC Fellowships)

Rhythmic Firing of Pedunculopontine Tegmental Nucleus Neurons in Monkeys during Eye Movement Task.

The pedunculopontine tegmental nucleus (PPTN) has been thought to be involved in the control of behavioral state. Projections to the entire thalamus and reciprocal connections with the basal ganglia nuclei suggest a potential role for the PPTN in the control of various rhythmic behaviors, including waking/sleeping and locomotion. Recently, rhythmic activity in the local field potentials was recorded from the PPTN of patients with Parkinson's disease who were treated with levodopa, suggesting that rhythmic firing is a feature of the functioning PPTN and might change with the behaving conditions even within waking. However, it remains unclear whether and how single PPTN neurons exhibit rhythmic firing patterns during various behaving conditions, including executing conditioned eye movement behaviors, seeking reward, or during resting. We previously recorded from PPTN neurons in healthy monkeys during visually guided saccade tasks and reported task-related changes in firing rate, and in this paper, we reanalyzed these data and focused on their firing patterns. A population of PPTN neurons demonstrated a regular firing pattern in that the coefficient of variation of interspike intervals was lower than what would be expected of theoretical random and irregular spike trains. Furthermore, a group of PPTN neurons exhibited a clear periodic single spike firing that changed with the context of the behavioral task. Many of these neurons exhibited a periodic firing pattern during highly active conditions, either the fixation condition during the saccade task or the free-viewing condition during the intertrial interval. We speculate that these task context-related changes in rhythmic firing of PPTN neurons might regulate the monkey's attentional and vigilance state to perform the task.

An implantable microelectrode array for simultaneous L-glutamate and electrophysiological recordings in vivo

L-glutamate, the most common excitatory neurotransmitter in the mammalian central nervous system (CNS), is associated with a wide range of neurological diseases. Because neurons in CNS communicate with each other both electrically and chemically, dual-mode (electric and chemical) analytical techniques with high spatiotemporal resolution are required to better understand glutamate function in vivo. In the present study, a silicon-based implantable microelectrode array (MEA) composed of both platinum electrochemical and electrophysiological microelectrodes was fabricated using micro-electromechanical system. In the MEA probe, the electrophysiological electrodes have a low impedance of 0.018 MΩ at 1 kHz, and the electrochemical electrodes show a sensitivity of 56 pA µM−1 to glutamate and have a detection limit of 0.5 µM. The MEA probe was used to monitor extracellular glutamate levels, spikes and local field potentials (LFPs) in the striatum of anaesthetised rats. To explore the potential of the MEA probe, the rats were administered to KCl via intraperitoneal injection. K+ significantly increases extracellular glutamate levels, LFP low-beta range (12–18 Hz) power and spike firing rates with a similar temporal profile, indicating that the MEA probe is capable of detecting dual-mode neuronal signals. It was concluded that the MEA probe can help reveal mechanisms of neural physiology and pathology in vivo. Abnormal transmission of L-glutamate can cause neurological disorders such as Parkinson's disease, stroke and epilepsy. In their search for effective treatments, researchers are deploying extensive efforts to understand this key neurotransmitter, which regulates receptors located at chemical synapses. However, their attempts often fail to analyze the syntrophic complexity of biochemical and electrical events occurring in neurons. Now, Xinxia Cai and co-workers from the Institute of Electronics, Chinese Academy of Sciences, Beijing, China, have developed a silicon-based probe that simultaneously measures L-glutamate levels and electrical activity at various locations in the brain with high spatial and temporal resolution. The implantable array combines electrochemical and electrophysiological microelectrodes created through MEMS and nanotechnology. The team expects it to provide insight into physiological and pathological pathways in live brain tissue, paving the way to new diagnostic and therapeutic approaches.

Impairment of cognitive function by chemotherapy: association with the disruption of phase-locking and synchronization in anterior cingulate cortex.

BackgroundPatients following prolonged cancer chemotherapy are at high risk of emotional and cognitive deficits. Research indicates that the brain neuronal temporal coding and synaptic long-term potentiation (LTP) are critical in memory and perception. We studied the effects of cisplatin on induction of LTP in the basolateral amygdala (BLA)-anterior cingulate cortex (ACC) pathway, characterized the coordination of spike timing with local theta oscillation, and identified synchrony in the BLA-ACC network integrity.ResultsIn the study presented, the impacts of cisplatin on emotional and cognitive functions were investigated by elevated plus-maze test, Morris water maze test, and rat Iowa gambling task (RGT). Electrophysiological recordings were conducted to study long-term potentiation. Simultaneous recordings from multi-electrodes were performed to characterize the neural spike firing and ongoing theta oscillation of local field potential (LFP), and to clarify the synchronization of large scale of theta oscillation in the BLA-ACC pathway. Cisplatin-treated rats demonstrated anxiety- like behavior, exhibited impaired spatial reference memory. RGT showed decrease of the percentage of good decision-makers, and increase in the percentage of maladaptive behavior (delay-good decision-makers plus poor decision-makers). Cisplatin suppressed the LTP, and disrupted the phase-locking of ACC single neural firings to the ongoing theta oscillation; further, cisplatin interrupted the synchrony in the BLA-ACC pathway.ConclusionsWe provide the first direct evidence that the cisplatin interrupts theta-frequency phase-locking of ACC neurons. The block of LTP and disruption of synchronized theta oscillations in the BLA-ACC pathway are associated with emotional and cognitive deficits in rats, following cancer chemotherapy.

Modelling the Effects of Electrical Coupling between Unmyelinated Axons of Brainstem Neurons Controlling Rhythmic Activity.

Gap junctions between fine unmyelinated axons can electrically couple groups of brain neurons to synchronise firing and contribute to rhythmic activity. To explore the distribution and significance of electrical coupling, we modelled a well analysed, small population of brainstem neurons which drive swimming in young frog tadpoles. A passive network of 30 multicompartmental neurons with unmyelinated axons was used to infer that: axon-axon gap junctions close to the soma gave the best match to experimentally measured coupling coefficients; axon diameter had a strong influence on coupling; most neurons were coupled indirectly via the axons of other neurons. When active channels were added, gap junctions could make action potential propagation along the thin axons unreliable. Increased sodium and decreased potassium channel densities in the initial axon segment improved action potential propagation. Modelling suggested that the single spike firing to step current injection observed in whole-cell recordings is not a cellular property but a dynamic consequence of shunting resulting from electrical coupling. Without electrical coupling, firing of the population during depolarising current was unsynchronised; with coupling, the population showed synchronous recruitment and rhythmic firing. When activated instead by increasing levels of modelled sensory pathway input, the population without electrical coupling was recruited incrementally to unpatterned activity. However, when coupled, the population was recruited all-or-none at threshold into a rhythmic swimming pattern: the tadpole “decided” to swim. Modelling emphasises uncertainties about fine unmyelinated axon physiology but, when informed by biological data, makes general predictions about gap junctions: locations close to the soma; relatively small numbers; many indirect connections between neurons; cause of action potential propagation failure in fine axons; misleading alteration of intrinsic firing properties. Modelling also indicates that electrical coupling within a population can synchronize recruitment of neurons and their pacemaker firing during rhythmic activity.

An astrocyte neuromorphic circuit that influences neuronal phase synchrony.

Neuromorphic circuits are designed and simulated to emulate the role of astrocytes in phase synchronization of neuronal activity. We emulate, to a first order, the ability of slow inward currents (SICs) evoked by the astrocyte, acting on extrasynaptic N-methyl-D-aspartate receptors (NMDAR) of adjacent neurons, as a mechanism for phase synchronization. We run a simulation test incorporating two small networks of neurons interacting with astrocytic microdomains. These microdomains are designed using a resistive and capacitive ladder network and their interactions occur through pass transistors. Upon enough synaptic activity, the astrocytic microdomains interact with each other, generating SIC events on synapses of adjacent neurons. Since the amplitude of SICs is several orders of magnitude larger compared to synaptic currents, a SIC event drastically enhances the excitatory postsynaptic potential (EPSP) on adjacent neurons simultaneously. This causes neurons to fire synchronously in phase. Phase synchrony holds for a duration of time proportional to the time constant of the SIC decay. Once the SIC decay has completed, the neurons are able to go back to their natural phase difference, inducing desynchronization of their firing of spikes. This paper incorporates some biological aspects observed by recent experiments showing astrocytic influence on neuronal synchronization, and intends to offer a circuit view on the hypothesis of astrocytic role on synchronous activity that could potentially lead to the binding of neuronal information.