bioRxiv
January 18, 2023
Cristina Delgado-Sallent, Thomas Gener, Pau Nebot et al.
preprint
In mice with NMDAR hypofunction induced by subchronic phencyclidine (PCP), memory and auditory perception impairments are linked to disrupted connectivity between the medial prefrontal cortex and the dorsal hippocampus. Short-term memory relies on high gamma connectivity from the prefrontal cortex to the hippocampus, while long-term memory retrieval depends on theta connectivity from the hippocampus to the prefrontal cortex. Subchronic PCP impairs both short-term and long-term memory, increases prefrontal activity, decreases hippocampal activity, and disrupts this connectivity. Two weeks of daily risperidone rescues memory deficits, attenuates hippocampal desynchronization, and also ameliorates auditory perception impairments and their neural correlates.
Frontiers in cellular neuroscience
January 1, 2023
Cristina Delgado-Sallent, Thomas Gener, Pau Nebot et al.
Blocking NMDA receptors with phencyclidine (PCP) in mice impairs short-term and long-term object recognition memory and disrupts auditory processing, modeling cognitive deficits in schizophrenia. Memory impairments were linked to increased theta oscillations in the medial prefrontal cortex, decreased gamma oscillations and theta-gamma coupling in the dorsal hippocampus, and disrupted communication between the two regions. The atypical antipsychotic risperidone, given daily for two weeks after PCP, rescued memory deficits and partly normalized hippocampal activity but did not fully restore prefrontal cortex or circuit connectivity. Auditory processing deficits were also partially reversed. The findings suggest that NMDA receptor hypofunction disconnects prefrontal-hippocampal circuits, and risperidone may improve cognition by acting on this circuitry.
Cristina Delgado-Sallent, Pau Nebot, Thomas Gener et al.
preprint
Psychosis induced by the NMDAR antagonist phencyclidine in mice causes hypersynchronization and disrupted communication between the prefrontal cortex and hippocampus, including increased oscillatory power at delta, high gamma, and high frequencies, aberrant cross-frequency coupling, enhanced cross-regional coupling and phase coherence, and a reversal of the direction of theta-frequency information flow from hippocampus-to-prefrontal-cortex to delta rhythms traveling in the opposite direction. Three antipsychotic drugs—haloperidol, clozapine, and risperidone—rescued most of these changes, suggesting common cellular mechanisms. Selective serotonin receptor agents rescued power, coupling, and phase coherence but not the directionality, indicating additional targets are needed.