First-spike Latency Research Articles

Neonatal di-(2-ethylhexyl)phthalate exposure induces permanent alterations in secretory CRH neuron characteristics in the hypothalamus paraventricular region of adult male rats

Corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) play a critical role in the modulation of the hypothalamic–pituitary–adrenal (HPA) axis. Early-life exposure to di-(2-ethylhexyl) phthalate (DEHP) has been associated with an increased risk of developing psychiatric disorders in adulthood. The present work was designed to explore the impact of neonatal exposure to DEHP on adult PVN CRH neuronal activity. DEHP or vehicle was given to male rat pups from PND16 to PND22. Then, anxiety-like behaviors, serum corticosterone and testosterone, immunohistochemistry, western blotting, fluorescence in situ hybridization and acute ex vivo slice electrophysiological recordings were used to evaluate the influence of DEHP on adult PVN secretory CRH neurons. Neonatal DEHP-exposed rats exhibited enhanced anxiety-like behaviors in adults, with an increase in CORT. Secretory CRH neurons showed higher spontaneous firing activity but could be inhibited by GABAAR blockers. CRH neurons displayed fewer firing spikes, prolonged first-spike latency, depolarizing shifts in GABA reversal potential and strengthened GABAergic inputs, as indicated by increases in the frequency and amplitude of sIPSCs. Enhancement of GABAergic transmission was accompanied by upregulated expression of GAD67 and downregulated expression of GABABR1, KCC2 and GAT1. These findings suggest that neonatal exposure to DEHP permanently altered the characteristics of secretory CRH neurons in the PVN, which may contribute to the development of psychiatric disorders later in life.

Fractional Spiking Neuron: Fractional Leaky Integrate-and-Fire Circuit Described with Dendritic Fractal Model.

As dendrites are essential parts of neurons, they are crucial factors for neuronal activities to follow multiple timescale dynamics, which ultimately affect information processing and cognition. However, in the common SNN (Spiking Neural Networks), the hardware-based LIF (Leaky Integrate-and-Fire) circuit only simulates the single timescale dynamic of soma without relating dendritic morphologies, which may limit the capability of simulating neurons to process information. This study proposes the dendritic fractal model mainly for quantifying dendritic morphological effects containing branch and length. To realize this model, We design multiple analog fractional-order circuits (AFCs) which match their extended structures and parameters with the dendritic features. Then introducing AFC into FLIF (Fractional Leaky Integrate-and-Fire) neuron circuits can demonstrate the same multiple timescale dynamics of spiking patterns as biological neurons, including spiking adaptation, inter-spike variability with power-law distribution, first-spike latency, and intrinsic memory. By contrast, it further enhances the degree of mimicry of neuron models and provides a more accurate model for understanding neural computation and cognition mechanisms.

Impaired Subcortical Processing of Amplitude-Modulated Tones in Mice Deficient for Cacna2d3, a Risk Gene for Autism Spectrum Disorders in Humans.

Temporal processing of complex sounds is a fundamental and complex task in hearing and a prerequisite for processing and understanding vocalization, speech, and prosody. Here, we studied response properties of neurons in the inferior colliculus (IC) in mice lacking Cacna2d3, a risk gene for autism spectrum disorders (ASDs). The α2δ3 auxiliary Ca2+ channel subunit encoded by Cacna2d3 is essential for proper function of glutamatergic synapses in the auditory brainstem. Recent evidence has shown that much of auditory feature extraction is performed in the auditory brainstem and IC, including processing of amplitude modulation (AM). We determined both spectral and temporal properties of single- and multi-unit responses in the IC of anesthetized mice. IC units of α2δ3−/− mice showed normal tuning properties yet increased spontaneous rates compared with α2δ3+/+. When stimulated with AM tones, α2δ3−/− units exhibited less precise temporal coding and reduced evoked rates to higher modulation frequencies (fm). Whereas first spike latencies (FSLs) were increased for only few modulation frequencies, population peak latencies were increased for fm ranging from 20 to 100 Hz in α2δ3−/− IC units. The loss of precision of temporal coding with increasing fm from 70 to 160 Hz was characterized using a normalized offset-corrected (Pearson-like) correlation coefficient, which appeared more appropriate than the metrics of vector strength. The processing deficits of AM sounds analyzed at the level of the IC indicate that α2δ3−/− mice exhibit a subcortical auditory processing disorder (APD). Similar deficits may be present in other mouse models for ASDs.

Similarities in the Biophysical Properties of Spiral-Ganglion and Vestibular-Ganglion Neurons in Neonatal Rats.

The membranes of auditory and vestibular afferent neurons each contain diverse groups of ion channels that lead to heterogeneity in their intrinsic biophysical properties. Pioneering work in both auditory- and vestibular-ganglion physiology have individually examined this remarkable diversity, but there are few direct comparisons between the two ganglia. Here the firing patterns recorded by whole-cell patch-clamping in neonatal vestibular- and spiral ganglion neurons are compared. Indicative of an overall heterogeneity in ion channel composition, both ganglia exhibit qualitatively similar firing patterns ranging from sustained-spiking to transient-spiking in response to current injection. The range of resting potentials, voltage thresholds, current thresholds, input-resistances, and first-spike latencies are similarly broad in both ganglion groups. The covariance between several biophysical properties (e.g., resting potential to voltage threshold and their dependence on postnatal age) was similar between the two ganglia. Cell sizes were on average larger and more variable in VGN than in SGN. One sub-group of VGN stood out as having extra-large somata with transient-firing patterns, very low-input resistance, fast first-spike latencies, and required large current amplitudes to induce spiking. Despite these differences, the input resistance per unit area of the large-bodied transient neurons was like that of smaller-bodied transient-firing neurons in both VGN and SGN, thus appearing to be size-scaled versions of other transient-firing neurons. Our analysis reveals that although auditory and vestibular afferents serve very different functions in distinct sensory modalities, their biophysical properties are more closely related by firing pattern and cell size than by sensory modality.

Bursting in cerebellar stellate cells induced by pharmacological agents: Non-sequential spike adding.

Cerebellar stellate cells (CSCs) are spontaneously active, tonically firing (5-30 Hz), inhibitory interneurons that synapse onto Purkinje cells. We previously analyzed the excitability properties of CSCs, focusing on four key features: type I excitability, non-monotonic first-spike latency, switching in responsiveness and runup (i.e., temporal increase in excitability during whole-cell configuration). In this study, we extend this analysis by using whole-cell configuration to show that these neurons can also burst when treated with certain pharmacological agents separately or jointly. Indeed, treatment with 4-Aminopyridine (4-AP), a partial blocker of delayed rectifier and A-type K+ channels, at low doses induces a bursting profile in CSCs significantly different than that produced at high doses or when it is applied at low doses but with cadmium (Cd2+), a blocker of high voltage-activated (HVA) Ca2+ channels. By expanding a previously revised Hodgkin–Huxley type model, through the inclusion of Ca2+-activated K+ (K(Ca)) and HVA currents, we explain how these bursts are generated and what their underlying dynamics are. Specifically, we demonstrate that the expanded model preserves the four excitability features of CSCs, as well as captures their bursting patterns induced by 4-AP and Cd2+. Model investigation reveals that 4-AP is potentiating HVA, inducing square-wave bursting at low doses and pseudo-plateau bursting at high doses, whereas Cd2+ is potentiating K(Ca), inducing pseudo-plateau bursting when applied in combination with low doses of 4-AP. Using bifurcation analysis, we show that spike adding in square-wave bursts is non-sequential when gradually changing HVA and K(Ca) maximum conductances, delayed Hopf is responsible for generating the plateau segment within the active phase of pseudo-plateau bursts, and bursting can become “chaotic” when HVA and K(Ca) maximum conductances are made low and high, respectively. These results highlight the secondary effects of the drugs applied and suggest that CSCs have all the ingredients needed for bursting.

Ventral cochlear nucleus bushy cells encode hyperacusis in guinea pigs

Psychophysical studies characterize hyperacusis as increased loudness growth over a wide-frequency range, decreased tolerance to loud sounds and reduced behavioral reaction time latencies to high-intensity sounds. While commonly associated with hearing loss, hyperacusis can also occur without hearing loss, implicating the central nervous system in the generation of hyperacusis. Previous studies suggest that ventral cochlear nucleus bushy cells may be putative neural contributors to hyperacusis. Compared to other ventral cochlear nucleus output neurons, bushy cells show high firing rates as well as lower and less variable first-spike latencies at suprathreshold intensities. Following cochlear damage, bushy cells show increased spontaneous firing rates across a wide-frequency range, suggesting that they might also show increased sound-evoked responses and reduced latencies to higher-intensity sounds. However, no studies have examined bushy cells in relationship to hyperacusis. Herein, we test the hypothesis that bushy cells may contribute to the neural basis of hyperacusis by employing noise-overexposure and single-unit electrophysiology. We find that bushy cells exhibit hyperacusis-like neural firing patterns, which are comprised of enhanced sound-driven firing rates, reduced first-spike latencies and wideband increases in excitability.

Frequency response areas of neurons in the mouse inferior colliculus. III. Time-domain responses: Constancy, dynamics, and precision in relation to spectral resolution, and perception in the time domain.

The auditory midbrain (central nucleus of inferior colliculus, ICC) receives multiple brainstem projections and recodes auditory information for perception in higher centers. Many neural response characteristics are represented in gradients (maps) in the three-dimensional ICC space. Map overlap suggests that neurons, depending on their ICC location, encode information in several domains simultaneously by different aspects of their responses. Thus, interdependence of coding, e.g. in spectral and temporal domains, seems to be a general ICC principle. Studies on covariation of response properties and possible impact on sound perception are, however, rare. Here, we evaluated tone-evoked single neuron activity from the mouse ICC and compared shapes of excitatory frequency-response areas (including strength and shape of inhibition within and around the excitatory area; classes I, II, III) with types of temporal response patterns and first-spike response latencies. Analyses showed covariation of sharpness of frequency tuning with constancy and precision of responding to tone onsets. Highest precision (first-spike latency jitter < 1 ms) and stable phasic responses throughout frequency-response areas were the quality mainly of class III neurons with broad frequency tuning, least influenced by inhibition. Class II neurons with narrow frequency tuning and dominating inhibitory influence were unsuitable for time domain coding with high precision. The ICC center seems specialized rather for high spectral resolution (class II presence), lateral parts for constantly precise responding to sound onsets (class III presence). Further, the variation of tone-response latencies in the frequency-response areas of individual neurons with phasic, tonic, phasic-tonic, or pauser responses gave rise to the definition of a core area, which represented a time window of about 20 ms from tone onset for tone-onset responding of the whole ICC. This time window corresponds to the roughly 20 ms shortest time interval that was found critical in several auditory perceptual tasks in humans and mice.

Activation of GABAB receptors results in excitatory modulation of calyx terminals in rat semicircular canal cristae.

Previous studies have found GABA in vestibular end organs. However, existence of GABA receptors or possible GABAergic effects on vestibular nerve afferents has not been investigated. The current study was conducted to determine whether activation of GABAB receptors affects calyx afferent terminals in the central region of the cristae of semicircular canals. We used patch-clamp recording in postnatal day 13-18 (P13-P18) Sprague-Dawley rats of either sex. Application of GABAB receptor agonist baclofen inhibited voltage-sensitive potassium currents. This effect was blocked by selective GABAB receptor antagonist CGP 35348. Application of antagonists of small (SK)- and large-conductance potassium (BK) channels almost completely blocked the effects of baclofen. The remaining baclofen effect was blocked by cadmium chloride, suggesting that it could be due to inhibition of voltage-gated calcium channels. Furthermore, baclofen had no effect in the absence of calcium in the extracellular fluid. Inhibition of potassium currents by GABAB activation resulted in an excitatory effect on calyx terminal action potential firing. While in the control condition calyces could only fire a single action potential during step depolarizations, in the presence of baclofen they fired continuously during steps and a few even showed repetitive discharge. We also found a decrease in threshold for action potential generation and a decrease in first-spike latency during step depolarization. These results provide the first evidence for the presence of GABAB receptors on calyx terminals, showing that their activation results in an excitatory effect and that GABA inputs could be used to modulate calyx response properties.NEW & NOTEWORTHY Using in vitro whole cell patch-clamp recordings from calyx terminals in the vestibular end organs, we show that activation of GABAB receptors result in an excitatory effect, with decreased spike-frequency adaptation and shortened first-spike latencies. Our results suggest that these effects are mediated through inhibition of calcium-sensitive potassium channels.

Auditory DUM neurons in a bush-cricket: inhibited inhibitors

Thoracic ganglia of many hearing insects house the first level of auditory processing. In bush-crickets, the largest population of local auditory neurons in the prothoracic processing centre are dorsal unpaired median (DUM) neurons. It has been suggested that DUM neurons are inhibitory using γ-aminobutyric acid (GABA) as transmitter. Immunohistochemistry reveals a population of about 35–50 GABA-positive somata in the posterior medial cluster of the prothoracic ganglion. Only very few small somata in this cluster remain unstained. At least 10 neurites from 10 neurons can be identified. Intracellularly stained auditory DUM neurons have their soma in the cluster of median GABA positive cells and most of them exhibit GABA-immunoreactivity. Responses of certain DUM neurons show obvious signs of inhibition. Application of picrotoxin (PTX), a chloride-channel blocker in insects, changes the responses of many DUM neurons. They become broader in frequency tuning and broader or narrower in temporal pattern tuning. Furthermore, inhibitory postsynaptic potentials (IPSPs) may be replaced by excitatory postsynaptic potentials. Loss of an IPSP in the rising graded potential after PTX-application leads to a significant reduction of first-spike latency. Therefore, auditory DUM neurons receive effective inhibition and are the best candidates for inhibition in DUM neurons and other auditory interneurons.

Periodicity Pitch Perception.

This study presents a computational model to reproduce the biological dynamics of “listening to music.” A biologically plausible model of periodicity pitch detection is proposed and simulated. Periodicity pitch is computed across a range of the auditory spectrum. Periodicity pitch is detected from subsets of activated auditory nerve fibers (ANFs). These activate connected model octopus cells, which trigger model neurons detecting onsets and offsets; thence model interval-tuned neurons are innervated at the right interval times; and finally, a set of common interval-detecting neurons indicate pitch. Octopus cells rhythmically spike with the pitch periodicity of the sound. Batteries of interval-tuned neurons stopwatch-like measure the inter-spike intervals of the octopus cells by coding interval durations as first spike latencies (FSLs). The FSL-triggered spikes synchronously coincide through a monolayer spiking neural network at the corresponding receiver pitch neurons.

Self-similar network model for fractional-order neuronal spiking: implications of dendritic spine functions

Fractional-order derivatives have been widely used to describe the spiking patterns of neurons, without considering their self-similar dendritic structures. In this study, a self-similar resistor–capacitor network is proposed to relate the spiny dendritic structure with fractional spiking properties. In order to achieve this goal, two types of networks comprising recursively staggered resistors and capacitors were developed to model the functional properties of smooth and spiny dendrites, respectively. Their overall electrotonic properties can be described by fractional order temporal operators derived by Heaviside operational calculus. According to this operator method, spiking patterns of spiny dendrites were controlled by the standard 0.5-order derivative, whereas an exponential modulation term was added in the governing fractional operator of the smooth dendrites. The application of these fractional operators in a leaky integrate-and-fire model reveals that the dendritic spine plays an important role in alternations of the spiking properties, including first-spike latency, firing rate adaptation, and afterhyperpolarization conductance. Further, the multilevel assembly of this network indicates that the fractional spiking behaviors of spiny neurons might originate from their hierarchical substructures, thereby highlighting possible functional consequences of alterations to dendritic self-similarity.

Switching in Cerebellar Stellate Cell Excitability in Response to a Pair of Inhibitory/Excitatory Presynaptic Inputs: A Dynamical System Perspective

Cerebellar stellate cells form inhibitory synapses with Purkinje cells, the sole output of the cerebellum. Upon stimulation by a pair of varying inhibitory and fixed excitatory presynaptic inputs, these cells do not respond to excitation (i.e., do not generate an action potential) when the magnitude of the inhibition is within a given range, but they do respond outside this range. We previously used a revised Hodgkin-Huxley type of model to study the nonmonotonic first-spike latency of these cells and their temporal increase in excitability in whole cell configuration (termed run-up). Here, we recompute these latency profiles using the same model by adapting an efficient computational technique, the two-point boundary value problem, that is combined with the continuation method. We then extend the study to investigate how switching in responsiveness, upon stimulation with presynaptic inputs, manifests itself in the context of run-up. A three-dimensional reduced model is initially derived from the original six-dimensional model and then analyzed to demonstrate that both models exhibit type 1 excitability possessing a saddle-node on an invariant cycle (SNIC) bifurcation when varying the amplitude of . Using slow-fast analysis, we show that the original model possesses three equilibria lying at the intersection of the critical manifold of the fast subsystem and the nullcline of the slow variable (the inactivation of the A-type K channel), the middle equilibrium is of saddle type with two-dimensional stable manifold (computed from the reduced model) acting as a boundary between the responsive and non-responsive regimes, and the (ghost of) SNIC is formed when the -nullcline is (nearly) tangential to the critical manifold. We also show that the slow dynamics associated with (the ghost of) the SNIC and the lower stable branch of the critical manifold are responsible for generating the nonmonotonic first-spike latency. These results thus provide important insight into the complex dynamics of stellate cells.

Low-frequency Stimulation Decreases Hyperexcitability Through Adenosine A1 Receptors in the Hippocampus of Kindled Rats.

Introduction:In this study, the role of A1 adenosine receptors in improving the effect of Low-Frequency Electrical Stimulation (LFS) on seizure-induced hyperexcitability of hippocampal CA1 pyramidal neurons was investigated.Methods:A semi-rapid hippocampal kindling model was used to induce seizures in male Wistar rats. Examination of the electrophysiological properties of CA1 pyramidal neurons of the hippocampus using whole-cell patch-clamp recording 48 h after the last kindling stimulation revealed that the application of LFS as two packages of stimulations at a time interval of 6 h for two consecutive days could significantly restore the excitability CA1 pyramidal neurons evidenced by a decreased in the of the number of evoked action potentials and enhancement of amplitude, maximum rise slope and decay slope of the first evoked action potential, rheobase, utilization time, adaptation index, first-spike latency, and post-AHP amplitude. Selective locked of A1 receptors by the administration of 8-Cyclopentyl-1,3-dimethylxanthine (1 μM, 1 μl, i.c.v.) before applying each LFS package, significantly reduced LFS effectiveness in recovering these parameters.Results:On the other hand, selective activation of A1 receptors by an injection of N6-cyclohexyladenosine (10 μM, 1 μl, i.c.v.), instead of LFS application, could imitate LFS function in improving these parameters.Conclusion:It is suggested that LFS exerts its efficacy on reducing the neuronal excitability, partially by activating the adenosine system and activating its A1 receptors.

Capsaicin-Induced Impairment of Functional Network Dynamics in Mouse Hippocampus via a TrpV1 Receptor-Independent Pathway: Putative Involvement of Na+/K+-ATPase

The vanilloid compound capsaicin (Cp) is best known to bind to and activate the transient receptor potential vanilloid receptor-1 (TrpV1). A growing number of studies use capsaicin as a tool to study the role of TrpV1 in the central nervous system (CNS). Although most of capsaicin’s CNS effects have been reported to be mediated by TrpV1 activation, evidence exists that capsaicin can also trigger functional changes in hippocampal activity independently of TrpV1. Recently, we have reported that capsaicin induces impairment in hippocampal gamma oscillations via a TrpV1-independent pathway. Here, we dissect the underlying mechanisms of capsaicin-induced alterations to functional network dynamics. We found that capsaicin induces a reduction in action potential (AP) firing rate and a subsequent loss of synchronicity in pyramidal cell (PC) spiking activity in hippocampus. Moreover, capsaicin induces alterations in PC spike-timing since increased first-spike latency was observed after capsaicin treatment. First-spike latency can be regulated by the voltage-dependent potassium current D (ID) or Na+/K+-ATPase. Selective inhibition of ID via low 4-AP concentration and Na+/K+-ATPase using its blocker ouabain, we found that capsaicin effects on AP spike timing were completely inhibited by ouabain but not with 4-AP. In conclusion, our study shows that capsaicin in a TrpV1-independent manner and possibly involving Na+/K+-ATPase activity can impair cognition-relevant functional network dynamics such as gamma oscillations and provides important data regarding the use of capsaicin as a tool to study TrpV1 function in the CNS.

Modeling excitability in cerebellar stellate cells: Temporal changes in threshold, latency and frequency of firing

Cerebellar stellate cells are inhibitory molecular interneurons that regulate the firing properties of Purkinje cells, the sole output of cerebellar cortex. Recent evidence suggests that these cells exhibit temporal increase in excitability during whole-cell patch-clamp configuration in a phenomenon termed runup. They also exhibit a non-monotonic first-spike latency profile as a function of the holding potential in response to a fixed step-current. In this study, we use modeling approaches to unravel the dynamics of runup and categorize the firing behavior of cerebellar stellate cells as either type I or type II oscillators. We then extend this analysis to investigate how the non-monotonic latency profile manifests itself during runup. We employ a previously developed, but revised, Hodgkin–Huxley type model to show that stellate cells are indeed type I oscillators possessing a saddle node on an invariant cycle (SNIC) bifurcation. The SNIC in the model acts as a “threshold” for tonic firing and produces a slow region in the phase space called the ghost of the SNIC. The model reveals that (i) the SNIC gets left-shifted during runup with respect to Iapp=Itest in the current-step protocol, and (ii) both the distance from the stable limit cycle along with the slow region produce the non-monotonic latency profile as a function of holding potential. Using the model, we elucidate how latency can be made arbitrarily large for a specific range of holding potentials close to the SNIC during pre-runup (post-runup). We also demonstrate that the model can produce transient single spikes in response to step-currents entirely below ISNIC, and that a pair of dynamic inhibitory and excitatory post-synaptic inputs can robustly evoke action potentials, provided that the magnitude of the inhibition is either low or high but not intermediate. Our results show that the topology of the SNIC is the key to explaining such behaviors.

First spike latency of ON/OFF neurons in the optic tectum of pigeons.

Some shallow and middle optic tectum (OT) neurons have stable, asymmetric full-screen ON and OFF stimulus response properties, which makes them candidates for delay encoding. In this paper, we investigated the delay encoding mechanism for the neuronal clusters in the OT region of pigeons and determined the mechanism of delay coding in the OT region. By analyzing the responses of the neuron cluster under full-screen switch-on and switch-off stimulation, we found that the delay coding was widespread in the OT region where the ON/OFF stimulation time difference was 4-6 ms. Information theory analysis under grating stimulation and experiments based on single-neuron character reconstruction of neurons showed that OT neuron clusters use the first spike latency (FSL) for the rapid transfer of spatial structure information. Furthermore, 4 models were used to predict the first spike latency of these OT neurons. The best simulation results were obtained using an architecture where the ON and OFF paths of multiple retinal ganglion cells (RGCs) were integrated and summed, respectively.

Inhibitory effect of 980-nm laser on neural activity of the rat's cochlear nucleus.

.Near-infrared radiation (NIR) has been described as one of the highest-resolution tools for neuromodulation. However, the poor tissue penetration depth of NIR has limited its further application on some of the deeper layer neurons in vivo. A 980-nm short-wavelength NIR (SW-NIR) with high penetration depth was employed, and its inhibitory effect on neurons was investigated in vivo. In experiments, SW-NIR was implemented on the rat’s cochlear nucleus (CN), the auditory pathway was activated by pure-tones through the rat’s external auditory canal, and the neural responses were recorded in the inferior colliculus by a multichannel electrode array. Neural firing rate (FR) and the first spike latency (FSL) were analyzed to evaluate the optically induced neural inhibition. Meanwhile, a two-layered finite element, consisting of a fluid layer and a gray matter layer, was established to model the optically induced temperature changes in CN; different stimulation paradigms were used to compare the inhibitory efficiency of SW-NIR. Results showed that SW-NIR could reversibly inhibit acoustically induced CN neural activities: with the increase of laser radiant exposures energy, neural FR decreased significantly and FSL lengthened steadily. Significant inhibition occurred when the optical pulse stimulated prior to the acoustic stimulus. Results indicated that the inhibition relies on the establishment time of the temperature field. Moreover, our preliminary results suggest that short-wavelength infrared could regulate the activities of neurons beyond the neural tissues laser irradiated through neural networks and conduction in vivo. These findings may provide a method for accurate neuromodulation in vivo.

Effect of sound pressure level on contralateral inhibition underlying duration-tuned neurons in the mammalian inferior colliculus.

Duration tuning in the mammalian inferior colliculus (IC) is created by the interaction of excitatory and inhibitory synaptic inputs. We used extracellular recordings and paired tone stimulation to measure the strength and time course of the contralateral inhibition underlying duration-tuned neurons (DTNs) in the IC of the awake bat. The onset time of a short, best duration (BD), excitatory probe tone set to +10 dB (re threshold) was varied relative to the onset of a longer-duration, nonexcitatory (NE) suppressor tone whose sound pressure level (SPL) was varied. Spikes evoked by the roving BD tone were suppressed when the stationary NE tone amplitude was at or above the BD tone threshold. When the NE tone was increased from 0 to +10 dB, the inhibitory latency became shorter than the excitatory first-spike latency and the duration of inhibition increased, but no further changes occurred at +20 dB (re BD tone threshold). We used the effective duration of inhibition as a function of the NE tone amplitude to obtain suppression-level functions that were used to estimate the inhibitory half-maximum SPL (ISPL50). We also measured rate-level functions of DTNs with single BD tones varied in SPL and modeled the excitatory half-maximum SPL (ESPL50). There was a correlation between the ESPL50 and ISPL50, and the dynamic range of excitation and inhibition were similar. We conclude that the strength of inhibition changes in proportion to excitation as a function of SPL, and this feature likely contributes to the amplitude tolerance of the responses of DTNs. NEW & NOTEWORTHY Duration-tuned neurons arise from excitatory and inhibitory synaptic inputs offset in time. We measured the strength and time course of inhibition to changes in sound level. The onset of inhibition shortened while its duration lengthened as the stimulus level increased from 0 to +10 dB re threshold; however, no further changes were observed at +20 dB. Excitatory rate-level and inhibitory suppression-level response functions were strongly correlated, suggesting a mechanism for level tolerance in duration tuning.

Functional Development of Principal Neurons in the Anteroventral Cochlear Nucleus Extends Beyond Hearing Onset.

Sound information is transduced into graded receptor potential by cochlear hair cells and encoded as discrete action potentials of auditory nerve fibers. In the cochlear nucleus, auditory nerve fibers convey this information through morphologically distinct synaptic terminals onto bushy cells (BCs) and stellate cells (SCs) for processing of different sound features. With expanding use of transgenic mouse models, it is increasingly important to understand the in vivo functional development of these neurons in mice. We characterized the maturation of spontaneous and acoustically evoked activity in BCs and SCs by acquiring single-unit juxtacellular recordings between hearing onset (P12) and young adulthood (P30) of anesthetized CBA/J mice. In both cell types, hearing sensitivity and characteristic frequency (CF) range are mostly adult-like by P14, consistent with rapid maturation of the auditory periphery. In BCs, however, some physiological features like maximal firing rate, dynamic range, temporal response properties, recovery from post-stimulus depression, first spike latency (FSL) and encoding of sinusoid amplitude modulation undergo further maturation up to P18. In SCs, the development of excitatory responses is even more prolonged, indicated by a gradual increase in spontaneous and maximum firing rates up to P30. In the same cell type, broadly tuned acoustically evoked inhibition is immediately effective at hearing onset, covering the low- and high-frequency flanks of the excitatory response area. Together, these data suggest that maturation of auditory processing in the parallel ascending BC and SC streams engages distinct mechanisms at the first central synapses that may differently depend on the early auditory experience.

All-optical inhibitory dynamics in photonic neuron based on polarization mode competition in a VCSEL with an embedded saturable absorber.

An all-optical spike inhibition scheme based on polarization-mode competition (PMC) in a vertical-cavity surface-emitting laser (VCSEL) with an embedded saturable absorber is proposed and investigated numerically. The inhibitory dynamics is characterized by spike amplitude and first-spike latency (FSL) for the first time, to the best of our knowledge. The effects of time differences between inhibitory and excitatory inputs, inputs strengths, bias current, as well as noise on the spike amplitude and FSL are examined. The results show that a spike can be triggered in the y-polarization mode by excitatory input and can be inhibited in the presence of inhibitory input due to PMC.