Gamma oscillations induced by kainate receptor activation in the entorhinal cortex in vitro

Gamma frequency (30-80 Hz) oscillations are recordable from human and rodent entorhinal cortex. A number of mechanisms used by neuronal networks to generate such oscillations in the hippocampus have been characterized. However, it is as yet unclear as to whether these mechanisms apply to other anatomically disparate brain regions. Here we show that the medial entorhinal cortex (mEC) in isolation in vitro generates gamma frequency oscillations in response to kainate receptor agonists. Oscillations had the same horizontal and laminar spatiotemporal distribution as seen in vivo and in the isolated whole-brain preparation. Oscillations occurred in the absence of input from the hippocampal formation and did not spread to lateral entorhinal regions. Pharmacological similarities existed between oscillations in the hippocampus and mEC in that the latter were also sensitive to GABAA receptor blockade, barbiturates, AMPA receptor blockade, and reduction in gap junctional conductance. Stellate and pyramidal neuron recordings revealed a large GABAergic input consisting of gamma frequency IPSP trains. Fast spiking interneurons in the superficial mEC generated action potentials at gamma frequencies phase locked to the local field. Stellate cells also demonstrated a subthreshold membrane potential oscillation at theta frequencies that was temporally correlated with a theta-frequency modulation in field gamma power. Disruption in this stellate theta frequency oscillation by the hyperpolarisation activated current (Ih) blocker ZD7288 also disrupted theta modulation of field gamma frequency oscillations. We propose that similar cellular and network mechanisms to those seen in the hippocampus generate and modulate persistent gamma oscillations in the entorhinal cortex.