BISHOP LABORATORY
A Movement Disorder Lab Studying Neuroplasticity in Parkinson's Disease
Recent Research Highlights
Recent Research Highlights
Effects of pedunculopontine nucleus cholinergic lesion on gait and dyskinesia in hemiparkinsonian rats ⬇
Effects of pedunculopontine nucleus cholinergic lesion on gait and dyskinesia in hemiparkinsonian rats ⬇
NE Chambers, M Coyle, J Sergio, K Lanza, C Saito, B Topping, SD Clark, & C Bishop (2020). European Journal of Neuroscience
NE Chambers, M Coyle, J Sergio, K Lanza, C Saito, B Topping, SD Clark, & C Bishop (2020). European Journal of Neuroscience
Pedunculopontine nucleus (PPN) cholinergic neurons are implicated in freezing of gait in Parkinson's disease (PD) and motor stereotypy in normal animals, but the causal role of these neurons on specific gait parameters and treatment‐induced dyskinesia remains speculative. Therefore, we examined whether selective cholinergic lesion of the rostral PPN affects PD motor and gait deficits, L‐DOPA‐induced dyskinesia and motor improvement, and DA‐agonist‐induced dyskinesia. Sprague–Dawley rats were assigned to one unilaterally lesioned group: Sham lesion, PPN cholinergic lesion with diphtheria urotensin II fusion toxin, medial forebrain bundle dopamine lesion with 6‐hydroxydopamine, or dual acetylcholine and dopamine lesion. We used gait analysis and forepaw adjusting steps to examine PD gait and motor deficits. Forepaw adjusting steps were also used to assess motor improvement with L‐DOPA treatment. The abnormal involuntary movements scale measured L‐DOPA and dopamine D1‐ and D2‐receptor agonist‐induced dyskinesia. Lesions, verified via tyrosine hydroxylase and choline acetyltransferase immunohistochemistry reduced an average of 95% of nigral dopamine neurons and 80% of PPN cholinergic neurons, respectively. Rats receiving acetylcholine and dual lesion demonstrated enhanced freezing, and acetylcholine lesioned rats exhibited increased print area and stand index. Dopamine and dual lesion produced similar forepaw adjusting steps task on and off L‐DOPA. Rlative to DA lesioned rats, dual lesioned rats displayed reduced L‐DOPA and DA agonist‐induced dyskinesia at specific time points. Our results indicate that PPN cholinergic neurons affect gait parameters related to postural stability. Therefore, therapeutically targeting PPN cholinergic neurons could reduce intractable postural instability in PD without affecting motor benefits or side effects of L‐DOPA treatment.
Genetic suppression of the dopamine D3 receptor in striatal D1 cells reduces the development of L-DOPA-induced dyskinesia ⬇
Genetic suppression of the dopamine D3 receptor in striatal D1 cells reduces the development of L-DOPA-induced dyskinesia ⬇
K Lanza, A Centner, M Coyle, I Del Priore, FP Manfredsson, & C Bishop (2020). Experimental Neurology
K Lanza, A Centner, M Coyle, I Del Priore, FP Manfredsson, & C Bishop (2020). Experimental Neurology
Parkinson's Disease (PD) is symptomatically managed with L-DOPA but chronic use results in L-DOPA-induced dyskinesia (LID) characterized by abnormal involuntary movements (AIMs). In LID, dopamine D3 receptors (D3R) are upregulated on D1 receptor (D1R)-bearing medium spiny neurons where the can synergistically drive downstream signaling and motor behaviors. Despite evidence implying D1R-D3R cooperativity in LID, the dyskinesiogenic role of D3R has never been directly tested. To this end, we developed a specific cre-dependent microRNA (miRNA) to irreversibly prevent D3R upregulation in D1R striatal cells. D1-Cre rats received unilateral 6-hydroxydopamine lesions. Three weeks later, rats received an adeno-associated virus expressing either D3R miRNA or a scrambled (SCR) miRNA delivered into the striatum. After 4 weeks, rats received chronic L-DOPA (6 mg/kg) or vehicle. AIMs development and motor behaviors were assayed throughout treatment. At the conclusion of the experiment, efficacy and fidelity of the miRNA strategy was analyzed using in situ hybridization (ISH). ISH analyses demonstrated that D1R+/D3R+ cells were upregulated in LID and that the selective D3R miRNA reduced D1R+/D3R+ co-expression. Importantly, silencing of D3R also significantly attenuated LID development without impacting L-DOPA efficacy or other locomotion. These data highlight a dyskinesiogenic role of D3R within D1R cells in LID and highlight aberrant D1R-D3R interactions as targets of LID management.
Recent Lab News
Recent Lab News
Former Bishop lab undergraduate Dr. Anne Taylor has been awarded the Vanderbilt-Fisk Postdoctoral Fellowship.
Former Bishop lab undergraduate Dr. Anne Taylor has been awarded the Vanderbilt-Fisk Postdoctoral Fellowship.
These fellowships are designed to offer opportunities for recent Vanderbilt Ph.D. graduates to build their teaching and scholarship portfolios. is a neuroscientist studying addiction. Her goal in this research is to uncover the neurophysiological mechanisms of short- and long-term drug use and its relation to negative affective behaviors. She wants to use her work to create and disseminate educational tools for the broader community. She believes, as part of her duty as a scientist, that she should enrich the lives of individuals who have experienced adversity to minimize their risk for future negative health outcomes. Taylor completed her undergraduate degree at Binghamton University, where she completed a research project with Dr. Christopher Bishop that was published in Neuroscience. She was awarded a National Institute on Drug Abuse fellowship, which allowed her to continue research during the summer of 2016 in Dr. Paul Meyer’s lab at the University of Buffalo. The experience with Meyer encouraged Taylor to apply for graduate school to pursue a career in the field of addiction research. Taylor completed her doctorate June 2023. She aspires to be a leading expert in her field, with a particular focus on the plasticity mechanisms that underly the transition from alcohol use to abuse. She is committed to creating a supporting and inclusive learning environment and instill a love of lifelong learning in the students she teaches and mentors. To read more, click here.
These fellowships are designed to offer opportunities for recent Vanderbilt Ph.D. graduates to build their teaching and scholarship portfolios. is a neuroscientist studying addiction. Her goal in this research is to uncover the neurophysiological mechanisms of short- and long-term drug use and its relation to negative affective behaviors. She wants to use her work to create and disseminate educational tools for the broader community. She believes, as part of her duty as a scientist, that she should enrich the lives of individuals who have experienced adversity to minimize their risk for future negative health outcomes. Taylor completed her undergraduate degree at Binghamton University, where she completed a research project with Dr. Christopher Bishop that was published in Neuroscience. She was awarded a National Institute on Drug Abuse fellowship, which allowed her to continue research during the summer of 2016 in Dr. Paul Meyer’s lab at the University of Buffalo. The experience with Meyer encouraged Taylor to apply for graduate school to pursue a career in the field of addiction research. Taylor completed her doctorate June 2023. She aspires to be a leading expert in her field, with a particular focus on the plasticity mechanisms that underly the transition from alcohol use to abuse. She is committed to creating a supporting and inclusive learning environment and instill a love of lifelong learning in the students she teaches and mentors. To read more, click here.
SUNY Chancellor announces nearly $200K in Technology Accelerator Fund (TAF) grants, vongratulates Bishop Lab
SUNY Chancellor announces nearly $200K in Technology Accelerator Fund (TAF) grants, vongratulates Bishop Lab
In a press release, SUNY Chancellor Jim Maltras announced grants to three SUNY campuses to fund groundbreaking technologies to treat serious illnesses and to protect our environment. Among the congratulated recipients are Christopher Bishop and Fredric Manfredsson, who are repurposing an FDA-approved drug previously approved for depression to prevent the emergence of L-DOPA-Induced dyskinesia. To read more, click here.
In a press release, SUNY Chancellor Jim Maltras announced grants to three SUNY campuses to fund groundbreaking technologies to treat serious illnesses and to protect our environment. Among the congratulated recipients are Christopher Bishop and Fredric Manfredsson, who are repurposing an FDA-approved drug previously approved for depression to prevent the emergence of L-DOPA-Induced dyskinesia. To read more, click here.
Bishop Lab Showcased in BU Student Newspaper, Pipe Dream
Bishop Lab Showcased in BU Student Newspaper, Pipe Dream
“We hope to advance this project on two fronts. First, by understanding how our drugs work, we can gain a better understanding of the basic neurobiology of Parkinson’s disease. Second, we hope to partner with [the] industry to repurpose safe, FDA-approved drugs for improved treatment of Parkinson’s disease patients.” - Dr. Chris Bishop
To read more, click here
Principal Investigator
Principal Investigator
Dr. Christopher Bishop
Dr. Christopher Bishop
Chris completed his doctoral and postdoctoral work at Wayne State University in the Departments of Psychology and Anatomy and Cell Biology, respectively. In 2005 he joined the Behavioral Neuroscience Program within the Department of Psychology at Binghamton University, a doctoral-granting institution of the State University of New York. Throughout this research, Dr. Bishop has focused on pre-clinical models of Parkinson’s disease with particular interest in translational approaches for improved treatment of motor and non-motor symptoms.
Bishop Movement Disorders Lab
Bishop Movement Disorders Lab
For Inquiries: Email: cbishop@binghamton.eduMail: Binghamton University4400 Vestal Pkwy E,Science 4, Room 175Binghamton, NY 13905United StatesPhone: 607-777-3410