David Wirtshafter, PhD
My research interests have focused on the neural substrates of motivation, that is, the neural circuitry underlying the selection and activation of behavior. My laboratory has primarily concentrated on the role of two major brain structures, the median raphe nucleus in the midbrain and the basal ganglia, using a multlidisciplinary combination of behavioral, pharmacological, anatomical and gene expression approaches.
Median Raphe Nucleus (MR). The MR is a midline structure located in the midbrain tegmentum, and is best known as one of the major sources of serotonin containing projections to the forebrain. Serotonergic cells, however, make up only a small proportion of the total neuronal population of the MR, and relatively little is known about the anatomy or functional role of the remaining cell types. We have found that suppression of MR activity leads to a remarkable potentiation of a variety of behaviors including locomotor activity, feeding and drinking, suggesting that this structure exerts a major inhibitory influence on behavioral activation. Strikingly, these effects do not appear to be mediated primarily through the nonserotonergic cells found in this nucleus. Our current efforts are directed towards understanding the circuitry underlying the uniquely powerful influence of the MR on motivational mechanisms.
Basal Ganglia. Our recent work on this complex group of structures has focused on what can be referred to as the "ventral striatopallidal system," that is the nucleus accumbens and a closely associated nucleus to which it sends inhibitory projections, the ventral pallidum. Current dogma holds that these structures are part of the brain's "reward system." We, and others, have shown however, that large and highly selective increases in food intake can be produced either by inhibition of the medial shell region of the accumbens or by excitation of the ventral pallidum. Further, we have shown that both of these effects are mediated by alterations in the activity of cells in the lateral hypothalamus. We have recently found that excitation of the ventral pallidum preferentially increases fat intake, raising the possibility that it might play a role in certain forms of human obesity. Our current work is aimed at understanding the pathways through which these effects are produced and the way in which they are related to the presumed role of these structures in more general "reward" processes.
Wirtshafter, D. & Stratford, T.R. Chemogenetic inhibition of cells in the paramedian midbrain tegmentum increases locomotor activity in rats. Brain Res. 1632: 98-106 (2016). (PDF)
Covelo, I.R., Patel, Z.I., Luviano, J.A., Stratford, T.R. &Wirtshafter, D. Manipulation of GABA in the ventral pallidum, but not the nucleus accumbens, induces intense, preferential, fat consumption in rats. Behav. Brain Res. 270:316-325 (2014). (PDF)
Shim, I.S., Stratford, T.R. & Wirtshafter, D. Dopamine is differentially involved in the locomotor hyperactivity produced by manipulations of opioid, GABA and glutamate receptors in the median raphe nucleus. Behav. Brain. Res. 261: 65-70 (2014). (PDF)
Stratford,T.R. & Wirtshafter, D. Lateral hypothalamic involvement in feeding elicited from the ventral pallidum. Eur. J. Neurosci. 37(4): 648-653 (2013). (PDF)
Wirtshafter, D., Covelo, I.R. Salija, I. & Stratford, T.R. Effects of Muscimol in the Nucleus Accumbens Shell on Salt Appetite and Sucrose Intake: A Microstructural Study with a Comment on the Sensitization of Salt Intake. Behav. Neurosci. 126(5):699-709 (2012). (PDF)
Wirtshafter, D. & Stratford, T.R. Evidence for motivational effects elicited by activation of GABA-A or dopamine receptors within the nucleus accumbens shell. Pharmacol. Biochem. Behav. 96: 342-346 (2010). (PDF)
Wirtshafter, D. & Osborn, C.V. The distribution of m4 acetycholine receptors in the islands of Calleja and striatum of rats and Cynomolgus monkeys. J. Chem.Neuroanat. 28: 107–116( 2004). (PDF)
Wirtshafter, D. & Sheppard, A. Localization of GABA-B receptors on monoamine containing neurons in the midbrain. Brain Res. Bull., 56:1-5 (2001). (PDF)
Wirtshafter, D. The control of ingestive behavior by the median raphe nucleus. Appetite 36: 99-105 (2000). (PDF)
Stratford, T.R. & Wirtshafter, D. Ascending dopaminergic projections from the dorsal raphe nucleus in the rat. Brain Res., 511, 173-176 (1990). (PDF)
Wirtshafter, D. & J.D. Davis. Set points, settling points, and the control of body weight. Physiol. Behav., 19: 75-78 (1977). (PDF)
PhD, University of Illinois at Chicago, 1982