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.
Rincón-Cortés, M. and Grace, A.A. (2021) Postpartum scarcity-adversity disrupts maternal behavior and induces a hypodopaminergic state in the rat dam and adult female offspring. Neuropsychopharmacology. https://doi.org/10.1038/s41386-021-01210-3.
Uliana, D.L., Gomes, F.V. and Grace, A.A. (2020) Prelimbic medial prefrontal cortex disruption during adolescence increases susceptibility to helpless behavior in adult rats. European Neuropsychopharmacology. https://doi.org/10.1016/j.euroneuro.2020.04.004.
Zhu, X. and Grace, A.A. (2020) Prepubertal environmental enrichment prevents dopamine dyregulation and hippocampal hyperactivity in MAM schizophrenia model rats. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2020.09.023.
Gomes, F., Zhu, X. and Grace, A.A. (2019) The pathophysiological impact of stress on the dopamine system is dependent on the state of the critical period of plasticity. Molecular Psychiatry, 25, 3292-3303. doi: 10.1038/s41380-019-0514-1
Bortz, D.M., Gazo, K.L. and Grace, A.A. (2019) The medial septum enhances reversal learning via actions on ventral tegmental area and substantia nigra dopamine neurons. Neruopsychopharmacology. doi:10.1038/s41386-019-0453-1.
Bortz, D.M. and Grace, A.A. (2018) Medial septum differentially regulates dopamine neuron activity in the ventral tegmental area and substantia nigra via distinct pathways. Neuropsychopharmacology.doi:10.1038/s41386-018-0048-2.
Uliana, D.L., Resstel, L.B.M. and Grace, A.A. (2018) Fear Extinction disruption in a developmental rodent model of schizophrenia correlates with an impairment in basolateral amygdala-medial prefrontal cortex plasticity. Neuropyschopharmacology. doi:10.1038/s41386-018-0128-3.
Grace, A.A. and Gomes, F.V. (2017) The circuitry of dopamine system regulation and its disruption in schizophrenia: Insights into treatment and prevention. Schizophrenia Bulletin. doi:10.1093/schbul/sbx199.
Rincon-Cortes, M. and Grace, A.A. (2017) Sex-dependent effects of stress on immobility behavior and VTA dopamine neuron activity: modulation by ketamine. International Journal of Neuropsychopharmacology, 20, 823-832. DOI: https://doi.org/10.1093/ijnp/pyx048.
Gomes, F.V. and Grace, A.A. (2016) Prefrontal cortex dysfunction increases susceptibility to schizophrenia-like changes induced by adolescent stress exposure. Schizophrenia Bulletin, 43, 592-600. doi: 10.1093/schbul/sbw156. PMCID: PMC4870144