Memory and attention deficits in schizophrenia may be due to abnormal structure and function of dopamine and glutamate neurons in the frontal cortex of the brain. Members of the Finlay Lab are exploring whether dysfunction of dopamine nerve terminals and glutamate NMDA receptors sustained in the developing rodent result in behavioral and neurochemical disruptions in the adult organism that are reminiscent of those associated with schizohrenia.
Disruption of dopamine nerve terminals is induced by local administration of a neurotoxin into the frontal cortex. Disruption of NMDA receptors is induced by local knock-out of a portion of a gene encoding for a protein subunit (the NR1 subunit) required for proper function of the receptor.
The behavioral consequences of impaired dopamine nerve terminal and NMDA receptor function are quantified by examining performance in a variety of memory and attention tasks including T-maze delayed response, random-foraging, spatial win-shift, social interaction, and 5-choice visual sustained attention tasks.
The effects of dopamine nerve terminal and NMDA receptor dysfunction on neurotransmitter release in the frontal cortex are assessed using in vivo microdialysis combined with high-pressure liquid chromatography for assay of extracellular neurotransmitter concentrations.