Our work is focused on neural circuits that mediate two neurological conditions: Pain and Parkinson’s disease. We are also developing novel therapies to treat these conditions.
The Seal laboratory studies the neural circuitry that drives behavior in health and disease. We are currently focused on the following circuits: i) peripheral and central pain circuits, ii) motor circuits affected by Parkinson’s disease iii) glutamate and GABA co-release by forebrain cholinergic neurons and iv) peripheral and central auditory circuits. We aim to discover fundamental principals and mechanisms of the nervous system as well as identify novel treatment strategies for nervous system disorders.
Experimental Approach: We use mice as a model system and techniques such as virally-mediated designer receptors (DREADDs) to selectively activate or inhibit neurons, virally-mediated anterograde and retrograde tools to trace circuits, slice electrophysiology with optogenetic stimulation, confocal and 2-photon microscopy, molecular biology, histology, biochemistry and behavior.
Outer hair cell glutamate signaling through type II spiral ganglion afferents activates neurons in the cochlear nucleus in response to non-damaging sounds. Catherine J.C. Weisz*, Sean-Paul G. Williams, Chad S. Eckard, Christopher B. Divito, David W. Ferreira, Kristen N. Fantetti, Shenin A. Dettwyler, Hou-Ming Cai, Maria E. Rubio†, Karl Kandler and Rebecca P. Seal*† J. Neurosci epub 2021. Download here.
Mechanical allodynia circuitry in the dorsal horn is defined by the nature of the injury. Peirs, C, Williams, SPG, Zhao, X, Arokiaraj, CM, Ferreira, D, Noh, M, Smith, KM, Halder, P, Corrigan, K, Gideon, J, Lee, SJ, Gatto, G, Chi, D, Ross, SE, Goulding, M, Seal, RP. Neuron epub 2020 Nov 11. Download here.
A functional topographic map for spinal sensorimotor reflexes. Gatto, G, Bourane, S, Ren, X, Fenton, P, Halder, P, Seal, RP, Goulding M. Neuron epub 2020 Nov 11
Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission. Cunha C, Smiley JF, Chuhma N, Shah R, Bleiwas C, Menezes EC, Seal RP, Edwards RH, Rayport S, Ansorge MS, Castellanos FX, Teixeira CM. Mol Psychiatry. 2020 May 12. doi: 10.1038/s41380-020-0763-z. Online ahead of print. PMID: 32398719
Moehring, F. Halder P, Seal RP, Stucky CL. Uncovering the Cells and Circuits of Touch in Normal and Pathological Settings. Neuron (2018), 100(2) 349-360.
Megat, S., S. Shiers, JK Moy, P. Barragan-Iglesias, G. Pradhan, Seal RP, G. Dussor and TJ Price. A Critical Role for Dopamine D5 Receptors in Pain Chronicity in Male Mice.J. Neurosci. (2018), 38(2): 379-397. Download Article
Case DT, Burton SD, Gedeon JY, Williams S-PG, Urban NN, Seal RP. Layer- and Cell type-Selective Co-transmission by a Basal Forebrain Cholinergic Projection to the Olfactory Bulb.Nat Comm (2017), 8:652. Download Article
Peirs C, Seal RP. Neural Pain Circuits: recent advances and current views. Science (2016), 354(6312):578-584. Review. Download Article
Seal RP. Illuminating the Gap: Neuronal Cross-Talk within Sensory Ganglia and Persistent Pain. Neuron (2016), 91: 950-951. Download Article