The O'Donnell lab
at the Department
of Anatomy & Neurobiology and Program in Neuroscience
|
Electrophysiology of the Prefrontal Cortex (Are interneurons altered in schizophrenia models?) |
Funded by NIH grant R01 MH57683 |
One of the most replicated findings when brains from people with schizophrenia are assessed post-mortem is a set of changes that indicate loss of function in a subset of cortical inhibitory interneurons, the parvalbumin-containing, fast-spiking GABA interneurons. We have shown that the modulation of this cell population by dopamine changes dramatically during adolescence, providing a late critical period in cortical development. We are testing whether this late developmental maturation is affected in several different animal models of schizophrenia. Rats with a Neonatal Ventral Hippocampal Lesion (NVHL), the most extensively studied and validated developmental model, indeed exhibit loss of GABA interneuron function. This loss of function is evidenced with electrophysiological recordings in brain slices, in anesthetized animals, and in awake freely moving rats (The figure illustrates increased PFC firing ald loss of interneuron-dependent beta oscillations during a behavioral epoch with high dopaminec). We are testing whether fast-spiking inteneurons are affected in a pharmacological model (rats treated with NMDA antagonists) and a few genetic models. Mice with a dominant-negative DISC1 gene that resembles the truncated DISC1 gene observed in a Scottish family with extremely high incidence of major psychiatric disorders also exhibit deficits in GABA interneuron function.