Spike and burst coding in thalamocortical relay cells

Abstract

Mammalian thalamocortical relay (TCR) neurons switch their firing activity between a tonic spiking and a bursting regime. In a combined experimental and computational study, we investigated the features in the input signal that single spikes and bursts in the output spike train represent and how this code is influenced by the membrane voltage state of the neuron. Identical frozen Gaussian noise current traces were injected into TCR neurons in rat brain slices as well as in a validated three-compartment TCR model cell. The resulting membrane voltage traces and spike trains were analyzed by calculating the coherence and impedance. Reverse correlation techniques gave the Event-Triggered Average (ETA) and the Event-Triggered Covariance (ETC). This demonstrated that the feature selectivity started relatively long before the events (up to 300 ms) and showed a clear distinction between spikes (selective for fluctuations) and bursts (selective for integration). The model cell was fine-tuned to mimic the frozen noise initiated spike and burst responses to within experimental accuracy, especially for the mixed mode regimes. The information content carried by the various types of events in the signal as well as by the whole signal was calculated. Bursts phase-lock to and transfer information at lower frequencies than single spikes. On depolarization the neuron transits smoothly from the predominantly bursting regime to a spiking regime, in which it is more sensitive to high-frequency fluctuations. The model was then used to elucidate properties that could not be assessed experimentally, in particular the role of two important subthreshold voltage-dependent currents: the low threshold activated calcium current ( I _T ) and the cyclic nucleotide modulated h current ( I _h ). The ETAs of those currents and their underlying activation/inactivation states not only explained the state dependence of the firing regime but also the long-lasting concerted dynamic action of the two currents. Finally, the model was used to investigate the more realistic “high-conductance state”, where fluctuations are caused by (synaptic) conductance changes instead of current injection. Under “standard” conditions bursts are difficult to initiate, given the high degree of inactivation of the T-type calcium current. Strong and/or precisely timed inhibitory currents were able to remove this inactivation.

Author summary

Neurons in the brain respond to (sensory) stimuli by generating electrical pulses called ‘spikes’ or ‘action potentials’. Spikes are organized in different temporal patterns, such as ‘bursts’ in which they occur at a high frequency followed by a period of silence. Bursts are ubiquitous in the nervous system: they occur in different parts of the brain and in different species. Different mechanisms that generate them have been pointed out. Why the nervous system uses bursts in its communication, or what type of information is represented by bursts, remains largely unknown. Here, we looked at bursting in thalamocortical relay (TCR) cells, neurons that form a bridge between early sensory processing and higher-order structures (cortex). These cells fire bursts as a result of the activation of two distinct subthreshold ionic currents: the T-type calcium current and the h-type current. We investigated experimentally and computationally what features in the input makes TCR cells respond with bursts, and what features with single spikes. Bursts are a response to low-frequency slowly increasing input; single spikes are a response to faster fluctuations. Moreover, bursts are rare and highly informative, in line with an earlier hypothesis that bursts could play a ‘wake-up call’ role in the nervous system.