Physiology, Pharmacology and Topography of Cholinergic Neocortical Oscillations In Vitro. Heath S. Lukatch and M. Bruce MacIver. Stanford Neuroscience Program and Neuropharmacology Laboratory, Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305- 5117.
APStracts 4:0026N, 1997.
ABSTRACT
Rat neocortical brain slices generated rhythmical extracellular field (micro- EEG) oscillations at theta frequencies (3 -12 Hz) when exposed to pharmacological conditions which mimicked endogenous ascending cholinergic and GABAergic inputs. Use of specific receptor agonists and antagonists, carbachol and bicuculline, revealed that simultaneous muscarinic receptor activation, and GABAA-mediated disinhibition were necessary to elicit neocortical oscillations. Rhythmical activity was independent of GABAB receptor activation, but required intact glutamatergic transmission, evidenced by blockade or disruption of oscillations by CNQX and APV, respectively. Multi- site mapping studies showed that oscillations were localized to areas 29d, 18b (Oc2MM) and parts of areas 18a and 17. Peak oscillation amplitudes occurred in layer 2/3, and phase reversals were observed in layers 1 and 5. Current source density analysis revealed large amplitude current sinks and sources in layers 2/3 and 5, respectively. An initial shift in peak inward current density from layer 1 to layer 2/3 indicated that two processes underlie an initial depolarization followed by oscillatory activity. Laminar transections localized oscillation generating circuitry to superficial cortical layers, and sharp-spike generating circuitry to deep cortical layers. Whole cell recordings identified three distinct cell types based on their response properties during rhythmical micro-EEG activity: oscillation-on (theta-on) and -off (theta-off) neurons, and transiently depolarizing glial cells. Theta-on neurons displayed membrane potential oscillations which increased in amplitude with hyperpolarization (from -30 to -90 mV). This, taken together with a glutamate antagonist-induced depression of rhythmical micro-EEG activity, indicated that cholinergically-driven neocortical oscillations require excitatory synaptic transmission. We conclude that under the appropriate pharmacological conditions, neocortical brain slices were capable of producing localized theta frequency oscillations. Experiments examining oscillation physiology, pharmacology and topography demonstrated that neocortical brain slice oscillations share many similarities with the in vivo and in vitro theta EEG activity recorded in other brain regions. 

Received 22 October 1996; accepted in final form 30 December 1996.
APS Manuscript Number J840-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 January 1997