Dependence of the spike-triggered average voltage on membrane response properties

The spike-triggered average voltage (STV) is an experimentally measurable quantity that is determined by both the membrane response properties and the statistics of the synaptic drive. Here, the form of the STV is modelled for neurons with three distinct types of subthreshold dynamics; passive decay, h-current sag, and damped oscillations. Analytical expressions for the STV are first obtained in the low-noise limit, identifying how the subthreshold dynamics of the cell affect its form. A second result is then derived that captures the power-law behaviour of the STV near the spike threshold

How adaptation currents change threshold, gain and variability of neuronal spiking

Many types of neurons exhibit spike rate adaptation, mediated by intrinsic slow $\mathrm{K}^+$-currents, which effectively inhibit neuronal responses. How these adaptation currents change the relationship between in-vivo like fluctuating synaptic input, spike rate output and the spike train statistics, however, is not well understood. In this computational study we show that an adaptation current which primarily depends on the subthreshold membrane voltage changes the neuronal input-output relationship (I-O curve) subtractively, thereby increasing the response threshold. A spike-dependent adaptation current alters the I-O curve divisively, thus reducing the response gain. Both types of adaptation currents naturally increase the mean inter-spike interval (ISI), but they can affect ISI variability in opposite ways. A subthreshold current always causes an increase of variability while a spike-triggered current decreases high variability caused by fluctuation-dominated inputs and increases low variability when the average input is large. The effects on I-O curves match those caused by synaptic inhibition in networks with asynchronous irregular activity, for which we find subtractive and divisive changes caused by external and recurrent inhibition, respectively. Synaptic inhibition, however, always increases the ISI variability. We analytically derive expressions for the I-O curve and ISI variability, which demonstrate the robustness of our results. Furthermore, we show how the biophysical parameters of slow $\mathrm{K}^+$-conductances contribute to the two different types of adaptation currents and find that $\mathrm{Ca}^{2+}$-activated $\mathrm{K}^+$-currents are effectively captured by a simple spike-dependent description, while muscarine-sensitive or $\mathrm{Na}^+$-activated $\mathrm{K}^+$-currents show a dominant subthreshold component.Comment: 20 pages, 8 figures; Journal of Neurophysiology (in press

StdpC: a modern dynamic clamp

With the advancement of computer technology many novel uses of dynamic clamp have become possible. We have added new features to our dynamic clamp software StdpC (“Spike timing-dependent plasticity Clamp”) allowing such new applications while conserving the ease of use and installation of the popular earlier Dynclamp 2/4 package. Here, we introduce the new features of a waveform generator, freely programmable Hodgkin–Huxley conductances, learning synapses, graphic data displays, and a powerful scripting mechanism and discuss examples of experiments using these features. In the first example we built and ‘voltage clamped’ a conductance based model cell from a passive resistor–capacitor (RC) circuit using the dynamic clamp software to generate the voltage-dependent currents. In the second example we coupled our new spike generator through a burst detection/burst generation mechanism in a phase-dependent way to a neuron in a central pattern generator and dissected the subtle interaction between neurons, which seems to implement an information transfer through intraburst spike patterns. In the third example, making use of the new plasticity mechanism for simulated synapses, we analyzed the effect of spike timing-dependent plasticity (STDP) on synchronization revealing considerable enhancement of the entrainment of a post-synaptic neuron by a periodic spike train. These examples illustrate that with modern dynamic clamp software like StdpC, the dynamic clamp has developed beyond the mere introduction of artificial synapses or ionic conductances into neurons to a universal research tool, which might well become a standard instrument of modern electrophysiology

Characterizing synaptic conductance fluctuations in cortical neurons and their influence on spike generation

Cortical neurons are subject to sustained and irregular synaptic activity which causes important fluctuations of the membrane potential (Vm). We review here different methods to characterize this activity and its impact on spike generation. The simplified, fluctuating point-conductance model of synaptic activity provides the starting point of a variety of methods for the analysis of intracellular Vm recordings. In this model, the synaptic excitatory and inhibitory conductances are described by Gaussian-distributed stochastic variables, or colored conductance noise. The matching of experimentally recorded Vm distributions to an invertible theoretical expression derived from the model allows the extraction of parameters characterizing the synaptic conductance distributions. This analysis can be complemented by the matching of experimental Vm power spectral densities (PSDs) to a theoretical template, even though the unexpected scaling properties of experimental PSDs limit the precision of this latter approach. Building on this stochastic characterization of synaptic activity, we also propose methods to qualitatively and quantitatively evaluate spike-triggered averages of synaptic time-courses preceding spikes. This analysis points to an essential role for synaptic conductance variance in determining spike times. The presented methods are evaluated using controlled conductance injection in cortical neurons in vitro with the dynamic-clamp technique. We review their applications to the analysis of in vivo intracellular recordings in cat association cortex, which suggest a predominant role for inhibition in determining both sub- and supra-threshold dynamics of cortical neurons embedded in active networks.Comment: 9 figures, Journal of Neuroscience Methods (in press, 2008

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

An axon initial segment is required for temporal precision in action potential encoding by neuronal populations

Central neurons initiate action potentials (APs) in the axon initial segment (AIS), a compartment characterized by a high concentration of voltage-dependent ion channels and specialized cytoskeletal anchoring proteins arranged in a regular nanoscale pattern. Although the AIS was a key evolutionary innovation in neurons, the functional benefits it confers are not clear. Using a mutation of the AIS cytoskeletal protein \beta IV-spectrin, we here establish an in vitro model of neurons with a perturbed AIS architecture that retains nanoscale order but loses the ability to maintain a high NaV density. Combining experiments and simulations we show that a high NaV density in the AIS is not required for axonal AP initiation; it is however crucial for a high bandwidth of information encoding and AP timing precision. Our results provide the first experimental demonstration of axonal AP initiation without high axonal channel density and suggest that increasing the bandwidth of the neuronal code and hence the computational efficiency of network function was a major benefit of the evolution of the AIS.Comment: Title adjusted, no other change

Spike Onset Dynamics and Response Speed in Neuronal Populations

Recent studies of cortical neurons driven by fluctuating currents revealed cutoff frequencies for action potential encoding of several hundred Hz. Theoretical studies of biophysical neuron models have predicted a much lower cutoff frequency of the order of average firing rate or the inverse membrane time constant. The biophysical origin of the observed high cutoff frequencies is thus not well understood. Here we introduce a neuron model with dynamical action potential generation, in which the linear response can be analytically calculated for uncorrelated synaptic noise. We find that the cutoff frequencies increase to very large values when the time scale of action potential initiation becomes short