Abstracts

High-frequency spike bursts have been recorded in neocortical pyramidal neurons [italic]in vivo[/italic]. Burst firing may promote epileptic discharges by increasing firing rate, synchronizing firing at high frequencies, and increasing neurotransmitter release at facilitating synapses. It is unclear whether bursts primarily reflect the pattern of synaptic input or intrinsic cellular properties. In some pyramidal neurons repetitive bursting occurs during direct current (DC) stimulation, but in most bursting is absent or appears only at the onset of current steps. In order to determine how intrinsic cellular properties shape firing patterns of layer 2/3 pyramidal neurons during input with rapid fluctuations characteristic of [italic]in vivo[/italic] synaptic excitation, we applied broadband noise stimuli., Coronal slices of rat sensorimotor cortex were superfused with artificial cerebrospinal fluid (34[deg]C) containing blockers of ionotropic glutamate and GABA receptors. Intracellular recordings were obtained from 21 regular-spiking neurons in layer 2/3 using sharp microelectrodes filled with 2.7 M KCl and 1% biocytin. The location and pyramidal morphology of most cells were confirmed by biocytin histochemistry. Neurons were stimulated with broadband current noise (1 ms exponential relaxation) in combination with a DC offset that was usually set near spike threshold., All of the neurons tested fired regularly during DC stimuli, without repetitive bursting. However, 19 / 21 cells generated a mixture of single spikes and bursts of two or more spikes during noise stimuli. Raising the noise amplitude or the DC offset increased burst frequency, while the mean duration of intra-burst intervals remained nearly constant at approximately 10 milliseconds. The interval-dependent firing probability (hazard function) during high-noise stimulation roughly corresponded to the post-spike voltage trajectory, which is shaped by a fast afterhyperpolarization (fAHP), a fast afterdepolarization (fADP), and a medium-duration afterhyperpolarization (mAHP). Increasing the fAHP conductance by spike-triggered dynamic current clamp had little effect on regular spiking to DC stimuli but strongly reduced stochastic bursting., Our results suggest that intrinsic properties of layer 2/3 pyramidal neurons, including their small fAHP and prominent fADP, create an intrinsic resonance that is usually subthreshold during firing to DC stimuli but promotes bursting with an intra-burst frequency of approximately 100 Hz during noisy excitation. This frequency is similar to that of ripples observed in extracellular and EEG recordings during neocortical seizures, suggesting that high-frequency resonance in regular-spiking pyramidal neurons may contribute to epileptic discharges., (Supported by a Veterans Affairs Merit Review to W.J.S.)