In vivo cortical neurons are known to exhibit highly irregular spike patterns. Because the intervals between successive spikes fluctuate greatly, irregular neuronal firing makes it difficult to estimate instantaneous firing rates accurately. If, however, the irregularity of spike timing is decoupled from rate modulations, the estimate of firing rate can be improved. Here, we introduce a novel coding scheme to make the firing irregularity orthogonal to the firing rate in information representation. The scheme is valid if an interspike interval distribution can be well fitted by the gamma distribution and the firing irregularity is constant over time. We investigated in a computational model whether fluctuating external inputs may generate gamma process-like spike outputs, and whether the two quantities are actually decoupled. Whole-cell patch-clamp recordings of cortical neurons were performed to confirm the predictions of the model. The output spikes were well fitted by the gamma distribution. The firing irregularity remained approximately constant regardless of the firing rate when we injected a balanced input, in which excitatory and inhibitory synapses are activated concurrently while keeping their conductance ratio fixed. The degree of irregular firing depended on the effective reversal potential set by the balance between excitation and inhibition. In contrast, when we modulated conductances out of balance, the irregularity varied with the firing rate. These results indicate that the balanced input may improve the efficiency of neural coding by clamping the firing irregularity of cortical neurons. We demonstrate how this novel coding scheme facilitates stimulus decoding. Key words: firing irregularity; neural code; balanced synaptic input; brain-machine interface; gamma distribution; information geometry

Previous work has established that stellate cells of the medial entorhinal cortex produce prominent intrinsic subthreshold oscillations in the voltage response concentrated within the theta range (3–7 Hz). It has been speculated that these oscillations play an important role in vivo in establishing network behavior both in the entorhinal cortex and hippocampus. Consequently, it is important to investigate under what conditions theta oscillations in stellate cells can be generated and whether the spike-train power spectral density (PSD) also carries power at theta. We investigated the ability of stellate cells to generate theta oscillations in the presence of generic in vivo-like patterns of stimulation. Inputs were Poisson process-driven excitatory and inhibitory synaptic conductances or currents, introduced via dynamic clamp. We analyzed the subthreshold membrane oscillations and spike-train behavior in the presence of comparable synaptic conductance- or current-mediated membrane fluctuations. In the presence of conductance-based synapses, subthreshold oscillations are highly attenuated or entirely eliminated. Conversely, with current-based synapses stellate cells retain their ability to generate subthreshold oscillations in the theta band. These results also extend into the spiking regime, where only under current-based synapses does the PSD of the spike train show a prominent peak at theta. Furthermore, the peak in the spike-train PSD and spike clustering results from anincreasedprobabilityoffiringafteraspikeafterhyperpolarizationandnotdirectlyfromsubthresholdoscillatorydynamicsashasbeen previously suggested. Our results suggest that subthreshold oscillations may contribute less to in vivo response properties than has been hypothesized. Key words: membrane conductance; medial entorhinal cortex; theta; oscillations; dynamic clamp; AHP

In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, agility in motor systems has received little attention. Here we analyze how intense synaptic activity affects integration time in spinal motoneurons during functional motor activity and report a 10-fold decrease. As a result, action potentials can only be predicted from the membrane potential within 10 ms of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory and excitatory synaptic activity. By shortening the effective integration time, this intense synaptic input may serve to facilitate the generation of rapid changes in movements.