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Synaptic dysfunction and adaptation after NMDA receptor ablation in the mouse medial prefrontal cortex - PubMed

6 hours ago
  • #Prefrontal Cortex
  • #Schizophrenia
  • #NMDAR
  • NMDARs in the prefrontal cortex (PFC) regulate neuronal excitability, synaptic plasticity, and cognitive function.
  • Disruptions in NMDAR function mimic schizophrenia symptoms, supporting the glutamate hypothesis of schizophrenia.
  • Schizophrenia is associated with abnormal NMDAR expression and decreased dendritic spine density in the PFC.
  • Genetic manipulation of NMDARs alters spine density and synaptic transmission.
  • Study used in vivo genome editing to ablate Grin1 gene in adolescent mice PFC neurons.
  • NMDAR ablation led to an initial decrease in basilar dendritic spine density, followed by a rebound and increased AMPAR-mediated synaptic transmission.
  • Effects of pan-neuronal NMDAR ablation were not observed with specific excitatory neuron manipulation.
  • Findings suggest NMDAR ablation triggers reorganization of PFC networks, possibly involving compensatory processes impaired in disease states.