Patrick Sheets Adjunct Assistant Professor
My laboratory uses a multifaceted approach to elucidate the functional organization of neural circuitry involved in pain processing. Our major objective is to understand the mechanisms by which neuropathic and inflammatory pain alter the morphology, intrinsic physiology, neuromodulation, and connectivity of circuitry encompassing the medial prefrontal cortex (mPFC), periaqueductal gray (PAG), and amygdala. Importantly, circuits comprising the mPFC are essential in processing emotional components of our everyday experiences, and therefore, are implicated in the affective component, or unpleasantness, of pain. Additionally, mPFC circuits are associated with depression and anxiety which are common co-morbidities of neuropathic pain. The PAG is a link in the primary pain-modulating network essential for endogenous analgesia and autonomic response to pain. In humans, the mPFC-PAG pathway is associated with emotional modulation of pain. The amygdala serves as a key node that integrates information essential for connecting pain and emotion. Signaling of reciprocal pathways between the PAG and amygdala is critical for neuronal processing involved in nociception. However, virtually nothing is known regarding 1) the functional organization of local or long-range inputs of mPFC-PAG-amygdala circuits and 2) the specific mechanisms by which neuropathic pain alters the neurophysiology and synaptic function of mPFC-PAG-amygdala circuitry. These are critical unknowns that need to be resolved for understanding the mechanisms that drive dysfunction of neural activity in neuropathic and inflammatory pain. Our lab is currently using multiple techniques (retrograde labeling, slice electrophysiology, laser scanning photostimulation, high resolution imaging, optogenetics, behavior) to resolve these critical unknowns. The rationale for our work is that identifying the neural mechanisms through which neuropathic pain alters circuit function in cognitive and emotional networks of the brain (specifically mPFC-PAG-amygdala) will produce critical knowledge regarding the affective and emotional dimensions of pain. Such an understanding can lead to novel strategies for therapeutic intervention.
- Assistant Professor in Pharmacology and Toxicology, IUSM-South Bend
- Adjunct Assistant Professor in Biological Sciences, University of Notre Dame
- Postdoctoral fellow, Northwestern University, Department of Physiology
- Ph.D., Indiana University School of Medicine (Pharmacology) 2007
- M.S., Purdue University (Toxicology) 2003
- B.S., Purdue University (Health Sciences) 2001
- Ploplis, V. A., Donahue, D. L., Sandoval-Cooper, M. J., MorenoCaffaro, M., Sheets, P., Thomas, S. G., ... & Castellino, F. J. (2014). Systemic platelet dysfunction is the result of local dysregulated coagulation and platelet activation in the brain in a rat model of isolated traumatic brain injury. Journal of neurotrauma, 31(19), 1672-1675.
- Balsara, R. D., Ferreira, A. N., Donahue, D. L., Castellino, F. J., & Sheets, P. L. (2014). Probing NMDA receptor GluN2A and GluN2B subunit expression and distribution in cortical neurons. Neuropharmacology, 79, 542-549.
- Yasvoina, M. V., Genç, B., Jara, J. H., Sheets, P. L., Quinlan, K. A., Milosevic, A., ... & Özdinler, P. H. (2013). eGFP expression under UCHL1 promoter genetically labels corticospinal motor neurons and a subpopulation of degeneration-resistant spinal motor neurons in an ALS mouse model. The Journal of Neuroscience, 33(18), 7890-7904.
- Brittain, M. K., Brustovetsky, T., Sheets, P. L., Brittain, J. M., Khanna, R., Cummins, T. R., & Brustovetsky, N. (2012). Delayed calcium dysregulation in neurons requires both the NMDA receptor and the reverse Na+/Ca 2+ exchanger. Neurobiology of disease, 46(1), 109-117.