Dynamic modulation of excitation and inhibition during stimulation at gamma and beta frequencies in the CA1 hippocampal region

Fast oscillations at gamma and beta frequency are relevant to cognition. Du ring this activity, excitatory and inhibitory postsynaptic potentials (EPSP s and IPSPs) are generated rhythmically and synchronously and are thought t o play an essential role in pacing the oscillations. The dynamic changes oc curring to excitatory and inhibitory synaptic events during repetitive acti vation of synapses are therefore relevant to fast oscillations. To cast lig ht on this issue in the CA1 region of the hippocampal slice, we used a trai n of stimuli, to the pyramidal layer, comprising 1 s at 40 Hz followed by 2 -3 s at 10 Hz, to mimic the frequency pattern observed during fast oscillat ions. Whole cell current-clamp recordings from CA1 pyramidal neurons reveal ed that individual stimuli at 40 Hz produced EPSPs riding on a slow biphasi c hyperpolarizing-depolarizing waveform. EPSP amplitude initially increased ; it then decreased concomitantly with the slow depolarization and with a l arge reduction in membrane resistance. During the subsequent 10-Hz train: t he cells repolarized, EPSP amplitude and duration increased to above contro l, and no IPSPs were detected. In the presence of GABA, receptor antagonist s, the slow depolarization was blocked, and EPSPs of constant amplitude wer e generated by 10-Hz stimuli. Altering pyramidal cell membrane potential af fected the time course of the slow depolarization, with the peak being reac hed earlier at more negative potentials. Glial recordings revealed that the trains were associated with extracellular potassium accumulation, but the time course of this event was slower than the neuronal depolarization. Nume rical simulations showed that intracellular chloride accumulation (due to m assive GABAergic activation) can account for these observations. We conclud e that synchronous activation of inhibitory synapses at gamma frequency cau ses a rapid chloride accumulation in pyramidal neurons, decreasing the effi cacy of inhibitory potentials. The resulting transient disinhibition of the local network leads to a short-lasting facilitation of polysynaptic EPSPs. These results set constraints on the role that synchronous, rhythmic IPSPs may play in pacing oscillations at gamma frequency in the CA1 hippocampal region.