Medial septum modulates hippocampal gamma activity and prepulse inhibition in an N-methyl-d-aspartate receptor antagonist model of schizophrenia.
Schizophrenia research August 1, 2018 L Stan Leung, Jingyi Ma
In an animal model of schizophrenia induced by NMDA receptor antagonists like phencyclidine, MK-801, and ketamine, the septohippocampal system plays a key role. These drugs cause behavioral and electrophysiological disruptions, including reduced prepulse inhibition of the acoustic startle response, hyperlocomotion, impaired auditory gating, and increased hippocampal gamma oscillations. A single hippocampal seizure produces similar effects. Inactivating or lesioning GABAergic neurons in the medial septum, deep brain stimulation of the medial septum or nucleus accumbens, or positive modulation of GABAB receptors can reduce these disruptions. The findings indicate a close link between high-amplitude hippocampal gamma oscillations and psychosis-relevant behaviors, suggesting the hippocampus acts as a hub in a brain network underlying these symptoms.