Spontaneous High-Frequency (10–80 Hz) Oscillations during Up States in the Cerebral Cortex In Vitro

Abstract

High-frequency oscillations in cortical networks have been linked to a variety of cognitive and perceptual processes. They have also been recorded in small cortical slices in vitro, indicating that neuronal synchronization at these frequencies is generated in the local cortical circuit. However,in vitro experiments have hitherto necessitated exogenous pharmacological or electrical stimulation to generate robust synchronized activity in the β/γ range. Here, we demonstrate that the isolated cortical microcircuitry generates β and γ oscillations spontaneously in the absence of externally applied neuromodulators or synaptic agonists. We show this in a spontaneously active slice preparation that engages in slow oscillatory activity similar to activity during slow-wave sleep. β and γ synchronization appeared during the up states of the slow oscillation. Simultaneous intracellular and extracellular recordings revealed synchronization between the timing of incoming synaptic events and population activity. This rhythm was mechanistically similar to pharmacologically induced γ rhythms, as it also included sparse, irregular firing of neurons within the population oscillation, predominant involvement of inhibitory neurons, and a decrease of oscillation frequency after barbiturate application. Finally, we show in a computer model how a synaptic loop between excitatory and inhibitory neurons can explain the emergence of both the slow (<1 Hz) and the β-range oscillations in the neocortical network. We therefore conclude that oscillations in the β/γ range that share mechanisms with activity reported in vivo or in pharmacologically activated in vitro preparations can be generated during slow oscillatory activity in the local cortical circuit, even without exogenous pharmacological or electrical stimulation.