Functional neuroanatomy of cortical and brainstem monoamine systems.
Dr. Sesack’s research focuses on the monoamine and cortical systems that regulate cognitive and emotional behaviors. These systems have been implicated in the pathophysiology of mental and affective disorders and represent the circuitry that is disrupted by substance abuse. Progress toward the understanding and treatment of diseases that affect higher brain function depends on a detailed knowledge of the synaptic and extrasynaptic actions of monoamines on the cortical and subcortical circuits that regulate behavior. The research in Dr. Sesack’s laboratory focuses mainly on the organization of brainstem dopamine, and norepinephrine neurons and their interactions with the cerebral cortex. Questions regarding synaptic connectivity, receptor and transporter localization, and alterations in morphology due to environmental manipulations are addressed using light and electron microscopic immunocytochemical and tract-tracing methods. Subjects currently under investigation in the laboratory include: (1) synaptic inputs to different populations of midbrain dopamine neurons, (2) multiple substrates for prefrontal cortical regulation of brainstem monoamine cells, (3) anatomical localization by light and electron microscopy of receptors and transporters for monoamines, and (4) alterations of normal brain structure and receptor or transporter expression caused by chronic antidepressant drug treatment, chronic stress, or selective brain lesions. The results of research in the Sesack laboratory provide important connectivity data for models of brain function and insight into how experience alters brain anatomy.
Erickson, S.L., Gandhi, A.R., Asafu-Adjei, J.K., Sampson, A.R., Miner, L.A., Blakely, R.D. and Sesack, S.R. Chronic desipramine treatment alters tyrosine hydroxylase but not norepinephrine transporter immunoreactivity in norepinephrine axons in the rat prefrontal cortex. Int J Neuropsychopharm, in press, 2010.
Balcita-Pedicino, J.J., Omelchenko, N., Bell, R. and Sesack, S.R. The inhibitory influence of the lateral habenula on midbrain dopamine cells: ultrastructural evidence for indirect mediation via the rostromedial mesopontine tegmental nucleus. J Comp Neurol in press, 2010.
Holmstrand, E., Asafu-Adjei, J., Sampson, A.R., Blakely, R.D. and Sesack, S.R. Ultrastructural localization of high-affinity choline transporter in the rat anteroventral thalamus and ventral tegmental area: differences in axon morphology and transporter distribution. J Comp Neurol 518: 1908-1924, 2010.
Omelchenko, N. and Sesack, S.R. Ultrastructural analysis of local collaterals of rat ventral tegmental area neurons: GABA phenotype and synapses onto dopamine and GABA cells. Synapse 63: 895-906, 2009
Omelchenko, N., Bell, R. and Sesack, S.R. Lateral habenula projections to dopamine and GABA neurons the rat ventral tegmental area. Eur J Neurosci 30: 1239-1250, 2009.
Pinto, A. and Sesack, S.R. Ultrastructural analysis of prefrontal cortical inputs to the rat amygdala: spatial relationships to presumed dopamine axons and D1 and D2 receptors, Brain Structure and Function 213: 159-175, 2008.
Salahpour, A., Medvedev, I.O., Ramsey, A.J., Kile, B., Sotnikova, T.D., Holmstrand, E., Ghisi, V., Wong, L., Murphy, K., Sesack, S.R., Wightman, M.R., Gainetdinov, R.R. and Caron, M.G. Increased amphetamine-induced hyperactivity and reward in mice over-expressing the dopamine transporter. Proc Natl Acad Sci, 105: 4405-4410, 2008.