Parkinson’s disease (PD) is a debilitating neurodegenerative disorder that is characterized by progressive motor deficits including tremor, rigidity, bradykinesia, and postural instability and is caused by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc). In a recent study, we reported that mice lacking the vesicular glutamate transporter (VGLUT) 3 do not show motor deficits in a model of PD (Divito et al, J. Neurosci, 2015).
Our work is now focused on:
• Determining how loss of VGLUT3 improves motor function in Parkinson’s disease.
• Investigating mechanisms of striatal plasticity and changes to thalamostriatal and corticostriatal signaling that shape motor output in Parkinson’s disease.
• Identifying novel therapeutic strategies to treat Parkinson’s disease.
• Determining the population of VGLUT3 neurons that modulates DA neuron activity.
Strategies we use to test our hypotheses: • Optogenetics • Chemogenics • Retrograde tracing • High-resolution imaging • Whole-cell patch clamp recordings • Cyclic voltammetry • Immunohistochemistry • Transgenic rodents • In vivo viral expression • Rodent behavior
Loss of VGLUT3 Produces Circadian-dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and L-dopa mediated Dyskinesias in a Model of Parkinson’s Disease. (2015) Divito CB, Steece-Collier K, Case DT, Williams S-PG, Stancati JA, Zhi L, Rubio ME, Sortwell CE, Collier TJ, Sulzer D, Edwards RH, Zhang H and Seal RP. J. Neurosci. 35(45): 14983-14999.
Striatal Cholinergic Interneurons Drive GABA Release from Dopamine Terminals. (2014) Nelson AB, Hammack N, Yang CF, Shah N, Seal RP and Kreitzer AC. Neuron 82(1): 63-70.
Cholinergic Neurotransmission in the Striatum Requires VGLUT3. (2014) Nelson AB, Bussert TG, Kreitzer AC, and Seal RP. (2014) J. Neurosci. 34(26) 8772-8777.