Professor, Neuroscience and Psychiatry University of Pittsburgh Phone: (412) 624-5158 Fax: (412) 624-9198 Email: sesack@bns.pitt.edu

Ph.D., Yale University

Research Interests

Monoamine neurons and their prefrontal cortical targets play an important role in the regulation of cognitive functions and have been implicated in the pathophysiology of schizophrenia. Moreover, the prefrontal cortex is the only cortical region with descending projections to the limbic, hypothalamic and brainstem regions that regulate mood, motivation, arousal and attention. Progress toward understanding the neural basis of cognition and emotion as well as the treatment of diseases affecting higher brain function can be made by examining the cellular bases for the physiological actions of monoamines in prefrontal cortical and subcortical regions, as well as the synaptic relationships between the prefrontal cortex and monoamine and other subcortical neurons. Questions regarding synaptic connectivity and neuromodulation are addressed using light and electron microscopic immunocytochemical and tract-tracing methods, as well as in vivo neurophysiological techniques. Subjects currently under investigation include: (1) monoamine afferents to the prefrontal cortex, their synaptic targets, transporter and receptor localization, anatomical substrates for functional interactions, and response to environmental manipulations, (2) neurophysiological responses of brainstem monoamines to intrinsic and extrinsic afferent sources as well as electron microscopic examination of physiologically characterized and intracellularly labeled cells, (3) synaptic mechanisms underlying prefrontal cortical regulation of monoamine cell activity and other prominent limbic structures, such as the amygdala, basal forebrain, hypothalamus and brainstem. Hypotheses regarding cortical-monoamine interactions that are derived from rat studies can also be tested in primate brain before being applied to current network models of cortical function in humans.

Recent Publications

• Omelchenko N, Sesack SR: Glutamate synaptic inputs to ventral tegmental area neurons in the rat derive primarily from subcortical sources. Neuroscience 146: 1259-1274, 2007.
• Day M, Wang Z, Deng J, An X, Ingham CA, Shering AF, Wokosin D, Ilijic E, Sun Z, Sampson AR, Mugnaini E, Deutch AY, Sesack SR, Arbuthnott GW, Surmeier DJ: Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models. Nat Neurosci 9(2): 251-9, 2006.
• Miner LAH, Jedema HP, Moore FW, Blakely RD, Grace AA, Sesack SR: Chronic stress increases the plasmalemmal distribution of the norepinephrine transporter and the co-expression of tyrosine hydroxylase in norepinephrine axons in the prefrontal cortex. J Neorosci 26: 1571-1578, 2006.
• Omelchenko N, Sesack SR: Laterodorsal tegmental afferents to identified cell populations in the rat ventral tegmental area. J Comp Neurol 483: 217-235, 2005.
• Rotaru D. Barrionuevo G, Sesack SR: Mediodorsal thalamic afferents to layer III of the rat prefrontal cortex: synaptic relationships to subclasses of interneurons. J Comp Neurol 490: 220-238, 2005.
• Jankowski M, Sesack SR: Prefrontal cortical projections to the rat dorsal raphe nucleus: associations with serotonin and GABA neurons. J Comp Neurol 468: 518-529, 2004.
• Lipriando LA, Miner LAH, Blakely RD, Lewis DA, Sesack SR: Ultrastructural interactions between terminals and expressing the norepinephrine transporter and dopamine neurons in the rat and mokey ventral tegmental area. Synapse 52: 233-235, 2004.