Brief synaptic inhibition can overwhelm a nearly coincident suprathreshold excitatory input to preclude spike generation. Surprisingly, a brief inhibitory event that occurs in a favorable time window preceding an otherwise subthreshold excitation can facilitate spiking. Such postinhibitory facilitation (PIF) requires that the inhibition has a short (decay) time constant tauinh. The timescale ranges of tauinh and of the window (width and timing) for PIF depend on the rates of neuronal subthreshold dynamics. The mechanism for PIF is general, involving reduction by hyperpolarization of some excitability-suppressing factor that is partially recruited at rest. Here we illustrate and analyze PIF, experimentally and theoretically, using brain stem auditory neurons and a conductance-based five-variable model. In this auditory case, PIF timescales are in the sub- to few millisecond range and the primary mechanistic factor is a low-threshold potassium conductance gKLT. Competing dynamic influences create the favorable time window: hyperpolarization that moves V away from threshold and hyperexcitability resulting from reduced gKLT. A two-variable reduced model that retains the dynamics only of V and gKLT displays a similar time window. We analyze this model in the phase plane; its geometry has generic features. Further generalizing, we show that PIF behavior may occur even in a very reduced model with linear subthreshold dynamics, by using an integrate-and-fire model with an accommodating voltage-dependent threshold. Our analyses of PIF provide insights for fast inhibition's facilitatory effects in longer trains. Periodic subthreshold excitatory inputs can lead to firing, even one for one, if brief inhibitory inputs are interleaved within a range of favorable phase lags. The temporal specificity of inhibition's facilitating effect could play a role in temporal processing, in sensitivity to inhibitory and excitatory temporal patterning, in the auditory and other neural systems.
We study the existence and stability of phase-locked patterns and amplitude death states in a closed chain of delay coupled identical limit cycle oscillators that are near a supercritical Hopf bifurcation. The coupling is limited to nearest neighbors and is linear. We analyze a model set of discrete dynamical equations using the method of plane waves. The resultant dispersion relation, which is valid for any arbitrary number of oscillators, displays important differences from similar relations obtained from continuum models. We discuss the general characteristics of the equilibrium states including their dependencies on various system parameters. We next carry out a detailed linear stability investigation of these states in order to delineate their actual existence regions and to determine their parametric dependence on time delay. Time delay is found to expand the range of possible phase-locked patterns and to contribute favorably toward their stability. The amplitude death state is studied in the parameter space of time delay and coupling strength. It is shown that death island regions can exist for any number of oscillators N in the presence of finite time delay. A particularly interesting result is that the size of an island is independent of N when N is even but is a decreasing function of N when N is odd.
Deister CA, Dodla R, Barraza D, Kita H, Wilson CJ. Firing rate and pattern heterogeneity in the globus pallidus arise from a single neuronal population. J Neurophysiol 109: 497-506, 2013. First published October 31, 2012 doi:10.1152/jn.00677.2012.-Intrinsic heterogeneity in networks of interconnected cells has profound effects on synchrony and spike-time reliability of network responses. Projection neurons of the globus pallidus (GPe) are interconnected by GABAergic inhibitory synapses and in vivo fire continuously but display significant rate and firing pattern heterogeneity. Despite being deprived of most of their synaptic inputs, GPe neurons in slices also fire continuously and vary greatly in their firing rate (1-70 spikes/s) and in regularity of their firing. We asked if this rate and pattern heterogeneity arises from separate cell types differing in rate, local synaptic interconnections, or variability of intrinsic properties. We recorded the resting discharge of GPe neurons using extracellular methods both in vivo and in vitro. Spike-to-spike variability (jitter) was measured as the standard deviation of interspike intervals. Firing rate and jitter covaried continuously, with slow firing being associated with higher variability than faster firing, as would be expected from heterogeneity arising from a single physiologically distinct cell type. The relationship between rate and jitter was unaffected by blockade of GABA and glutamate receptors. When the firing rate of individual neurons was altered with constant current, jitter changed to maintain the rate-jitter relationship seen across neurons. Long duration (30 -60 min) recordings showed slow and spontaneous bidirectional drift in rate similar to the acrosscell heterogeneity. Paired recordings in vivo and in vitro showed that individual cells wandered in rate independently of each other. Input conductance and rate wandered together, in a manner suggestive that both were due to fluctuations of an inward current.
We report a facilitatory role of inhibitory synaptic input that can enhance a neuron's firing rate, in contrast to the conventional belief that inhibition suppresses firing. We study this phenomenon using the Hodgkin-Huxley model of spike generation with random Poisson trains of subthreshold excitatory and inhibitory inputs. Enhancement occurs when, by chance, brief inhibition leads excitation with a favorable timing and counterintuitively induces a reduction of the spike threshold. The basic mechanism is also illustrated with the phase-plane analysis of a two variable model. [12] and temporal sensitivity to coincident inputs [13]. In the classical view, an inhibitory input hyperpolarizes the membrane away from its spike threshold resulting in a reduction of the spike probability. Thus inhibition has conventionally been viewed as a suppressor of neuronal response [14][15][16][17], and, in particular, causing either divisive or subtractive effect on the output firing rate [14]. But inhibition playing a facilitatory role was recognized about 50 years ago [18,19], to the best of our knowledge, in the form of postinhibitory rebound [PIR] and is thought to play a major role in central pattern generator networks [20]. In PIR a neuron fires after being released from a long-lasting hyperpolarizing input. Here we report a facilitatory mechanism by which brief inhibitory inputs can, in contrast to the conventional belief, enhance firing probability during ongoing stimulation by trains of brief excitatory inputs. Unlike PIR, this mechanism does not require that an inhibitory input by itself leads to a rebound spike. In our case both the excitatory and inhibitory single inputs are subthreshold in magnitude.We study this phenomenon using a Hodgkin-Huxley model neuron [21] with external excitatory and inhibitory input conductances. The inputs are subthreshold α functions timed at random independent Poisson intervals. For pure excitatory driving, the neuron responds with a finite output rate due to temporal summation of nearly coincident inputs. When inhibitory inputs are included some spikes are lost but other ones are added. With respect to the onset time of these evoked spikes, inhibitory events form a temporally localized distribution leading ahead of a similar distribution of excitatory events. The leading inhibition can transiently reduce the spike threshold, and a well timed brief subthreshold excitation can utilize this to evoke a spike. We term this phenomenon as the postinhibitory facilitation (PIF) [22]. The enhanced output response could also consist of inhibitory events that are paired with another set of inhibitory events displaying PIR for temporally brief inputs. Our result stresses the importance of the timing of the prespike input events rather than postspike [23,24] or the diffusion process response [25] of the membrane. NIH Public Access
Many auditory neurons possess low-threshold potassium currents ( I(KLT)) that enhance their responsiveness to rapid and coincident inputs. We present recordings from gerbil medial superior olivary (MSO) neurons in vitro and modeling results that illustrate how I(KLT) improves the detection of brief signals, of weak signals in noise, and of the coincidence of signals (as needed for sound localization). We quantify the enhancing effect of I(KLT) on temporal processing with several measures: signal-to-noise ratio (SNR), reverse correlation or spike-triggered averaging of input currents, and interaural time difference (ITD) tuning curves. To characterize how I(KLT), which activates below spike threshold, influences a neuron's voltage rise toward threshold, i.e., how it filters the inputs, we focus first on the response to weak and noisy signals. Cells and models were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the "noise"), together with a larger but still subthreshold postsynaptic conductance, EPSG (the "signal"). Reduction of I(KLT) decreased the SNR, mainly due to an increase in spontaneous firing (more "false positive"). The spike-triggered reverse correlation indicated that I(KLT) shortened the integration time for spike generation. I(KLT) also heightened the model's timing selectivity for coincidence detection of simulated binaural inputs. Further, ITD tuning is shifted in favor of a slope code rather than a place code by precise and rapid inhibition onto MSO cells (Brand et al. 2002). In several ways, low-threshold outward currents are seen to shape integration of weak and strong signals in auditory neurons.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.