Medial septum modulates hippocampal gamma activity and prepulse inhibition in an N-methyl-d-aspartate receptor antagonist model of schizophrenia.
L Stan Leung, Jingyi Ma
Schizophrenia Research August 1, 2018 DOI: 10.1016/j.schres.2017.07.053 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Animal model (rats or mice, implied by typical use of such models) |
| Interventions | MK-801 inactivation or lesion of GABAergic neurons in the medial septum deep brain stimulation of the medial septum or nucleus accumbens positive modulation of GABAB receptors |
| Topics | Ketamine |
| Keywords | Auditory gating Hippocampal gamma activity Hyperactivity Nmda receptor antagonist Prepulse inhibition |
| Key findings | High-amplitude hippocampal gamma oscillations are closely associated with psychosis-relevant behaviors including prepulse inhibition loss, behavioral hyperactivity, and loss of auditory gating in an NMDA receptor antagonist animal model of schizophrenia. |
Abstract
We reviewed the participation of the septohippocampal system in an animal model of schizophrenia that was acutely induced by systemic injection of an N-methyl-d-aspartate (NMDA) receptor antagonist such as phencyclidine, MK-801 and ketamine. The NMDA receptor antagonist-induced model of schizophrenia is characterized by behavioral and electrophysiological disruptions, including a decrease in prepulse inhibition of the acoustic startle response (PPI), hyperlocomotion, decrease in gating of hippocampal auditory evoked potentials and robust increase in hippocampal gamma (30-100Hz) oscillations. Similar disruptions were also induced by a single electrographic seizure in the hippocampus. The behavioral and electrophysiological disruptions induced by an NMDA receptor antagonist can be reduced by inactivation or lesion of GABAergic neurons in the medial septum, deep brain stimulation of the medial septum or nucleus accumbens, or positive modulation of GABAB receptors. Our results suggest a close association between high-amplitude hippocampal gamma oscillations and psychosis-relevant behaviors including PPI loss, behavioral hyperactivity and loss in auditory gating. Abnormal electrophysiology suggests a disruption of somatic and apical dendritic inhibition in the hippocampus, resulting in distorted sensory integration, and impaired cognitive and memory processing. The hippocampus is suggested to be a hub in a brain network that participates in psychosis-relevant behaviors, through its direct projection to the nucleus accumbens, or through indirect connections via the entorhinal, cingulate and prefrontal cortices.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 10
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Ketamine activates psychosis and alters limbic blood flow in schizophrenia Neuroreport April 1, 1995
- Ketamine alters oscillatory coupling in the hippocampus Scientific Reports August 2, 2013
- Effects of GABA-B receptor positive modulator on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in freely moving rats. Psychopharmacology October 2017
and 5 more in the library