March 31, 2004; 10.1152/jn.00529.2003. In slow neocortical paroxysmal oscillations, the de- and hyperpolarizing envelopes in neocortical neurons are large compared with slow sleep oscillations. Increased local synchrony of membrane potential oscillations during seizure is reflected in larger electroencephalographic oscillations and the appearance of spike- or polyspike-wave complex recruitment at 2-to 3-Hz frequencies. The oscillatory mechanisms underlying this paroxysmal activity were investigated in computational models of cortical networks. The extracellular K � concentration ([K � ] o) was continuously computed based on neuronal K � currents and K � pumps as well as glial buffering. An increase of [K � ] o triggered a transition from normal awake-like oscillations to 2- to 3-Hz seizure-like activity. In this mode, the cells fired periodic bursts and nearby neurons oscillated highly synchronously; in some cells depolarization led to spike inactivation lasting 50–100 ms. A [K � ] o increase, sufficient to

Thalamic reticular (RE) neurons are involved in the genesis of synchronized thalamocottical oscillations, which depend in part on their complex bursting properties. We have investigated the intrinsic properties of RE cells using computational models based on morphological and electrophysiological data. Simulations of a reconstructed RE cell were compared directly with recordings from the same cell to obtain precise values for the passive parameters. In a first series of experiments, the lowthreshold calcium current (ITS) was studied via voltage clamp in acutely dissociated RE cells that lack most of their dendrites. Simulations based on a cell with truncated dendrites and Hodgkin-Huxley kinetics reproduced these recordings with a relatively low density of I,. In a second series of experiments, voltage-clamp recordings obtained in intact RE cells in slices showed a higher amplitude and slower kinetics of I,. These

Abstract. Inhibitory interactions play a crucial role in the synchronization of neuronal activity. Here we investigate the effect of GABAergic PSPs on spike timing in cortical neurons that exhibit an oscillatory modulation of their membrane potential. To this end we combined numerical simulations with in-vitro patch-clamp recordings from layer II/III pyramidal cells of the rat visual cortex. Special emphasis was placed on exploring how the reversal potential of the GABAergic synaptic currents (EGABA) and the phase relations of the PSPs relative to the oscillation cycles affect the timing of spikes riding on the depolarizing peaks of the oscillations. The simulations predicted: (1) With EGABA more negative than the oscillation minima PSPs are hyperpolarizing at all phases and thus delay or prevent spikes. (2) With EGABA being more positive than the oscillation maxima PSPs are depolarizing in a phase-independent way and lead to a phase advance of spikes. (3) In the intermediate case where EGABA lies within oscillation maxima and minima PSPs are either hyper- or depolarizing depending on their phase relations to the Vm oscillations and can therefore either delay or advance spikes. Experiments conducted in this most interesting last configuration with biphasic PSPs agreed with the model predictions. Additional theoretical investigations revealed the effect of these PSP induced shifts in spike timing on synchronization in neuronal circuits. The results suggest that GABAergic mechanisms can assume highly specific timing functions in oscillatory networks.