Holly Moore, PhD
Associate Professor of Clinical Neurobiology (in Psychiatry)
Research in the Moore laboratory falls into two inter-related areas: 1) ontogeny of connectivity and function of limbic basal forebrain circuits and ascending monoaminergic systems, and 2) rodent models of neural circuit dysfunction in schizophrenia-related disorders.
The first line of research characterizes developmental changes in connectivity within limbic-related circuits, and the functional significance of these changes. For the second line of research, we use "rodent disease models" relevant to schizophrenia. We use genetic manipulations in the mouse to to model cortical interneuron deficits or dysfunction, or dysregulation of dopamine neurotransmission. We then use these models to understand links between these neural systems and specific behavioral or cognitive abnormalities in schizophrenia.
Trainees will have the opportunity to study anatomical, behavioral and neurophysiological development as it relates to limbic or frontal corticostriatal circuits in these models using multiple sophisticated behavioral techniques, anatomical techniques such as immunohistochemistry combined with stereology and in vivo neurophysiological recordings from the single-cell to EEG level.
Limbic-related cortical regions, including hippocampus, parahippocampal, medial prefrontal and cingulate cortices, and the nuclei in the basal forebrain, midbrain and hindbrain that are innervated by these regions, regulate cognitive and behavioral processes that provide the animal what it needs (e.g. food, water, sex, avoidance or escape from threatening situations). One of the goals of our research is to study how interactions between environmental factors and limbic-related circuits can lead to the pathophysiology and behavioral symptoms of schizophrenia and depression.
Our general approach is to expose the animal to a physiological or psychological stressor, then study the behavioral, neurochemical and neurophysiological effects that persist after the stressor is removed. As part of the Lieber Center for Schizophrenia Research, we study the impact of altered DNA methylation on the development of the cerebral cortex and cortical-to-subcortical circuits that mediate cognition and motivation. We have found that a disruption of DNA methylation, occurring early in development, leads to abnormal physiology of limbic cortical and related subcortical neurons in the mature animal.
Moreover, animals with early disruption of limbic cortical development show cognitive and motivational behavioral abnormalities that correlate with the neurophysiological abnormalities. We also study the effects of stress on the physiology of limbic cortical-subcortical circuits and the behaviors mediated by these circuits. Our collaboration with other laboratories in the training program provides us with opportunities to study the impact of specific genes on limbic brain circuits.