Studies in the Seal laboratory are focused on delineating the neural circuitry that drives behavior normally and in disease. We aim to discover fundamental principals and mechanisms of the nervous system as well as identify novel treatment strategies for nervous system disorders. Our laboratory is currently studying: 1) peripheral and central pain circuits, 2) motor circuits affected by Parkinson’s disease and 3) peripheral and central auditory circuits
Auditory Circuits: Cochlear outer hair cell glutamate release.Cochlear outer hair cells are important for normal hearing as they amplify sound transmitted through inner hair cells as well as sharpen the frequency-tuning curve. The electro-motility or movement of the hair cell in response to sound underlies these outer hair cell functions. Interestingly, like inner hair cells, outer hair cells also release vesicular glutamate. but the role of the glutamate signaling is not known. We are using genetic mouse models to study the role of glutamate signaling by these cells in hearing. We are also interested in the functional connectivity of outer hair cells to cochlear nucleus neurons. Mapping the connectivity will provide additional insight into function.
Selected Recent Publications (last 5 years)
Layer- and Cell type-Selective Co-transmission by a Basal Forebrain Cholinergic Projection to the Olfactory Bulb. Case DT, Burton SD, Gedeon JY, Williams S-PG, Urban NN, Seal RP Nat Comm (2017) 8:652
Neural Pain Circuits: recent advances and current views. Peirs C, Seal RP. Science (2016) 354(6312):578-584. Review.
Illuminating the Gap: Neuronal Cross-Talk within Sensory Ganglia and Persistent Pain. Seal RP. Neuron (2016) 91: 950-951
Do the Distinct Synaptic Properties of VGLUTs Shape Pain? Seal RP. Neurochem Int.(2016) 98:82-88. Review
Ensuring Transparency and Minimization of Methodologic Bias in Preclinical Pain Research: PPRECISE Considerations. Andrews NA, Latrémolière A, Basbaum AI, Mogil JS, Porreca F, Rice AS, Woolf CJ, Currie GL, Dworkin RH, Eisenach JC, Evans S, Gewandter JS, Gover TD, Handwerker H, Huang W, Iyengar S, Jensen MP, Kennedy JD, Lee N, Levine J, Lidster K, Machin I, McDermott MP, McMahon SB, Price TJ, Ross SE, Scherrer G, Seal RP, Sena ES, Silva E, Stone L, Svensson CI, Turk DC, Whiteside G. Pain (2016) 157(4):901-9.
Affective Touch and the Neurophysiology of CT Afferents. Seal RP and Lumpkin EA.(2016) Cell Biology of Tactile Afferents. (Springer) Book Chapter In press
Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson’s Disease. Divito CB, Steece-Collier K, Case DT, Williams SP, Stancati JA, Zhi L, Rubio ME, Sortwell CE, Collier TJ, Sulzer D, Edwards RH, Zhang H, Seal RP. J Neurosci. (2015) 35(45):14983-99.
Targeting Toll-like receptors to treat chronic pain. Peirs C, Seal RP. Nat Med. (2015) 21(11):1251-2.
Dorsal Horn Circuits for Persistent Mechanical Pain. Peirs C, Williams SPG, Zhao X, Walsh CE, Gedeon JY, Cagle NE, Goldring AC, Hioki H, Liu Z, Marell PS, Seal RP. Neuron. 87(4):797-812.
VGLUT3-independent Communication from Cochlea to Brain Detects Tissue-damaging Noise. Flores EN, Madathany T, Hogan AK, Kumar G, Seal RP, Edwards RH, Liberman MC, and Garcia-Anoveros J. Curr. Biol. 25(5): 606-612.
Presynaptic Inhibition of Optogenetically Identified VGluT3+ Sensory Fibres by Opioids and Baclofen. Honsek S, Seal RP, and Sandkühler J. Pain 156(2): 243-251.
A Glutamatergic Reward Input from the Dorsal Raphe to Ventral Tegmental Area Dopamine Neurons. Qi J, Zhang S, Wang HL, Wang H, Aceves Buendia J, Hoffman A, Lupica C, Seal RP, and Morales M. Nat. Comm. 5 (5390).
An Unconventional Glutamatergic Circuit in the Retina Formed by vGluT3 Amacrine Cells. Lee S*, Chen L*, Chen M*, Ye M, Seal RP, and Zhou ZJ. Neuron 84(4): 1-8.
A Novel Population of Glomerular Neurons Controls Sensory Information Transfer in the Mouse Olfactory Bulb. Tatti R*, Bhaukaurally K*, Gschwend O*, Seal RP, Edwards RH, Rodriguez I, and Carleton A. Nat. Comm. 5: 3791.
Striatal Cholinergic Neurotransmission Requires VGLUT3. Nelson AB, Bussert TG, Kreitzer AC, Seal RP. J Neurosci. 34(26):8772-7.
Striatal cholinergic interneurons drive GABA release from dopamine terminals. Nelson AB, Hammack N, Yang CF, Shah NM, Seal RP, Kreitzer AC. Neuron.82(1):63-70.
TAFA4, a Chemokine-Like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice. Delfini MC, Mantilleri A, Gaillard S, Hao J, Reynders A, Malapert P, Alonso S, Francois A, Barrere C, Seal R, Landry M, Eschallier A, Alloui A, Bourinet E, Delmas P, Le Feuvre Y, Moqrich A. Cell Rep. 5(2): 378-388.
Transcript Expression of Vesicular Glutamate Transporters in Lumbar Dorsal Root Ganglia and the Spinal Cord of Mice-Effects of Peripheral Axotomy or Hindpaw Inflamation. Malet M, Vieytes CA, Lundgren KH, Seal RP, Tomasella E, Seroogy KB, Hökfelt T, Gebhart GF, Brumovsky PR. Neuroscience. 248C: 95-111.
Expression of Vesicular Glutamate Transporters in Sensory and Autonomic Neurons Innervating the Mouse Bladder. Brumovsky PR, Seal RP, Lundgren KH, Seroogy KB, Watanabe M, Gebhart GF. J Urol. 89(6): 2342-2349.
Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy. Akil O, Seal RP, Burke K, Wang C, Alem A, During MJ, Edwards RH, Lustig LR. Neuron. 75(2):283-93.
NA(v)1.8 expression is not restricted to noiceptors in mouse peripheral nervous system. Shields SD, Ahn HS, Yang Y, Han C, Seal RP, Wood JN, Waxman SG and Dib-Hajj SD. Pain 153 (10): 2017-2030..