Neurophysiology of basal ganglia system related to psychiatric disorders.
Dr. Grace's research interests lie at the interface of neurobiology and psychiatry. Experiments conducted in his laboratory combine in vivo and in vitro electrophysiological recordings of identified neurons with behavioral and neuroanatomical techniques to study central dopaminergic systems, with the ultimate goal of determining the neurobiological correlates of mental disorders and the modes of action of psychotherapeutic drugs. Ongoing studies into the neurobiology of schizophrenia involve study of the interaction of the prefrontal cortex and antipsychotic drugs with subcortical dopamine systems, and examining the impact of developmental disruption on limbic system function, as a model for the pathophysiological changes underlying schizophrenia in humans. The mechanism of deep brain stimulation in treatment of obsessive compulsive disorder and the impact of stress on drug abuse are also investigated in anesthetized and awake animals.
The techniques employed in these analyses include: 1) recordings of identified neurons and local field potentials using intracellular and extracellular electrophysiological techniques, 2) anatomical studies of identified neurons and neurotransmitter pathways, 3) producing neurochemically specific lesions of neurons and selective disruptions of neuronal development, and 4) behavioral measures that correlate with electrophysiological studies. Through this approach, the basic neurobiological processes that contribute to psychiatric disorders may be elucidated, and insight may be gained into more effective therapeutic strategies for treating these diseases in humans.
Chang, C.-h. and Grace, A.A. (2014) Amygdala-ventral pallidum pathway modulates the down-regulation of dopamine activity following unpredictable chronic mild stress in rats. Biological Psychiatry doi:10.1016/j.biopsych.2013.09.020. PMID: 24209776
Du, Y. and Grace, A.A. (2013) Peripubertal diazepam prevents the emergence of dopamine hyper-responsivity in the MAM model of schizophrenia. Neuropsychopharmacology 38:1881-1888. PMC3746684
Ewing, S.G. and Grace, A.A. (2013) Chronic high frequency deep brain stimulation of the nucleus accumbens drives time-dependent changes in functional connectivity in the rodent limbic system. Brain Stimulation 6: 274-285. PMC3536888
Ungless, M.A. and Grace, A.A. (2012) Are you or aren’t you? Challenges associated with physiologically identifying dopamine neurons. Trends in Neurosciences 35: 422-430. PMCID: 3383926
Grace, AA (2012) Dopamine system dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. Neuropharmacology 62: 1342-1348. PMC3179528
Gill, K.M., Lodge, D.J., Cook, J.M., Aras, S. and Grace, A.A. (2011) A novel a5GABAAR positive allosteric modulator reverses hyperactivation of the dopamine system in the MAM model of schizophrenia. Neuropsychopharmacology 36: 1903-1911. PMC3154109