Hippocampus-Mediated Activation of Superficial and Deep Layer Neurons in the Medial Entorhinal Cortex of the Isolated Guinea Pig Brain

The entorhinal cortex (EC) is regarded as the structure that regulates information flow to and from the hippocampus. It is commonly assumed that superficial and deep EC neurons project to and receive from the hippocampal formation, respectively. Anatomical evidences suggest that both the hippocampal output and deep EC neurons also project to superficial EC layers. To functionally characterize the interlaminar synaptic EC circuit entrained the by hippocampal output, we performed simultaneous intracellular recordings and laminar profile analysis in the medial EC (m-EC) of the in vitro isolated guinea pig brain after polysynaptic hippocampal activation by lateral olfactory tract (LOT) stimulation. Optical imaging of voltage-generated signals confirmed that the LOT-evoked hippocampus-mediated response is restricted to the m-EC. The hippocampal output generated an extracellular current sink in layers V–VI, coupled with an EPSP in deep neurons. Deep neuron firing was terminated by a biphasic IPSP. The earliest response observed in superficial layer neurons was characterized by a feedforward IPSP of circa 100 ms (–69 ± 1.3 mV reversal potential) abolished by local application of 1 mm bicuculline. The feedforward IPSP was followed by a delayed EPSP blocked by AP-5 (100 μm), presumably mediated by deep-to-superficial m-EC connections. Our findings demonstrate that superficial m-EC cells are inhibited by the hippocampal output via a feedforward pathway that prevents activity reverberation in the hippocampal–EC–hippocampal loop. We propose that such inhibition could serve as a protective mechanism to prevent epileptic hyperexcitability.

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