Evidence for spatial modules mediated by temporal synchronization of carbachol-induced gamma rhythm in medial entorhinal cortex

Abstract

Fast (γ) oscillations in the cortex underlie the rapid temporal coordination of large-scale neuronal assemblies in the processing of sensory stimuli. Cortical γ rhythm is modulated in vivo by cholinergic innervation from the basal forebrain and can be generated in vitro after exogenous cholinergic stimulation. Using the isolated guinea pig brain, an in vitro preparation that allows for the study of an intact cerebrum, we studied the spatial features of γ activity evoked by the cholinomimetic carbachol (CCh) in the medial entorhinal cortex (mEC). γ activity induced by either arterial perfusion or intraparenchymal application of CCh showed a phase reversal across mEC layer II and was reduced or abolished in a spatially localized region by focal infusions of atropine, bicuculline, and CNQX. In addition, a spatially restricted zone of γ activity could be induced by passive diffusion of CCh from a recording pipette. Finally, γ oscillations recorded at multiple sites across the surface of the-mEC using army electrodes during arterial perfusion of CCh demonstrated a decline in synchronization (coherence) as the interelectrode distance increased. This effect was independent of the signal amplitude and was specific for γ as opposed to theta-like activity induced by CCh in the same experiments. These results suggest that CCh-induced γ oscillations in the mEC are mediated through direct muscarinic excitation of a highly localized reciprocal inhibitory-excitatory network located in superficial layers. We propose that functional cortical modules of highly synchronous γ oscillations may organize incoming (cortical) and outgoing (hippocampal) information in the mEC.