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Susan R. Sesack, PhD
- Professor, Neuroscience and Psychiatry
Education & TrainingPhD, Yale University (1988)
A210 Langley Hall
One-Line Research DescriptionFunctional 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.
Bagalkot TR, Block ER, Bucchin K, Balcita Pedicino JJ, Calderon M, Sesack SR, and Sorkin A (2021) Dopamine transporter localization in medial forebrain bundle axons indicates its long range transport primarily by membrane diffusion with a limited contribution of vesicular traffic on retromer positive compartments. Journal of Neuroscience, 41: 234-250. https://pubmed.ncbi.nlm.nih.gov/33234607/
Dong Y, Wang J, Holt LM, Huang HH, Sesack SR, Nestler EJ (2021) Astrocytes in cocaine addiction and beyond. Molecular Psychiatry, published online. https://pubmed.ncbi.nlm.nih.gov/33837268/
Wang J, Li K-L, Shukla A, Beroun A, Ishikawa M, Huang X, Wang Y, Wang YQ, Yang Y, Bastola ND, Huang HH, Kramer LE, Chao T, Huang YH, Sesack SR, Nestler EJ, Schlüter OM, Dong Y (2021) Cocaine triggers astrocyte mediated synaptogenesis. Biological Psychiatry, 89: 386-397. https://pubmed.ncbi.nlm.nih.gov/33069367/
Xia S-H, Yu J, Huang X, Sesack SR, Huang YH, Schlüter OM, Cao J-L, Dong Y (2020) Cortical and thalamic interaction with amygdala to accumbens synapses. Journal of Neuroscience, 40: 7119 7132. https://pubmed.ncbi.nlm.nih.gov/32763909/
Neumann PA, Wang Y, Yan Y, Wang Y, Ishiwaka M, Cui R, Huang YH, Sesack SR, Schlüter OM, Dong Y (2016) Cocaine induced synaptic alterations in thalamus to nucleus accumbens projection. Neuropsychopharmacology 41: 2399-2410. https://pubmed.ncbi.nlm.nih.gov/27074816/
Neumann, P., Wang, Y., Yan, Y. et al. Cocaine-Induced Synaptic Alterations in Thalamus to Nucleus Accumbens Projection. Neuropsychopharmacol 41, 2399–2410 (2016). https://doi.org/10.1038/npp.2016.52
Omelchenko, N., Roy, P., Balcita-Pedicino, J.J. et al. Impact of prenatal nicotine on the structure of midbrain dopamine regions in the rat. Brain Struct Funct 221, 1939–1953 (2016). https://doi.org/10.1007/s00429-015-1014-y
Block E, Nuttle J, Balcita Pedicino JJ, Caltagarone J, Sesack SR, Sorkin A (2015) Brain region specific trafficking of the dopamine transporter. Journal of Neuroscience, 35: 12845 12858. https://pubmed.ncbi.nlm.nih.gov/26377471/
Omelchenko N, Roy P, Balcita-Pedicino JJ, Poloyac S, Sesack SR (2015) Impact of prenatal nicotine on the structure of midbrain dopamine regions in the rat. Brain Structure & Function, 221: 1939 1953, published online 1-15. https://pubmed.ncbi.nlm.nih.gov/25716298/
Ethan R. Block, Jacob Nuttle, Judith Joyce Balcita-Pedicino, John Caltagarone, Simon C. Watkins, Susan R. Sesack and Alexander Sorkin. Journal of Neuroscience 16 September 2015, 35 (37) 12845-12858; DOI: https://doi.org/10.1523/JNEUROSCI.1391-15.2015
Ma YY, Lee BR, Wang X, Guo C, Liu L, Cui R, Lan Y, Balcita-Pedicino JJ, Wolf ME, Sesack SR, Shaham Y, Schlüter OM, Huang YH, Dong Y. Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections. Neuron. 83: 1453-67 (2014). PMID 25199705 DOI: 10.1016/j.neuron.2014.08.023
Bourdy, R., Sánchez-Catalán, M., Kaufling, J. et al. Control of the Nigrostriatal Dopamine Neuron Activity and Motor Function by the Tail of the Ventral Tegmental Area. Neuropsychopharmacol 39, 2788–2798 (2014). https://doi.org/10.1038/npp.2014.129
Lee BR, Ma YY, Huang YH, Wang X, Otaka M, Ishikawa M, Neumann PA, Graziane NM, Brown TE, Suska A, Guo C, Lobo MK, Sesack SR, Wolf ME, Nestler EJ, et al. Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving. Nature Neuroscience. 16: 1644-51. PMID 24077564 DOI: 10.1038/nn.3533
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.