Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

Suppression of Gap Junctional Activity Attenuates Pathological Beta Oscillations in the Basal Ganglia of the Parkinsonian Rat

Investigator: Sujoy Phookan, Albany Medical College

Co-Investigators: Jeremy Butz, Autumn Smith, Megan Calos, Lauren Mueller, Matthew Berk, Alexander Sutton, Wilson Yu, Dr. Julie Pilitsis, and Dr. Damian Shin

Mentor: Dr. Damian Shin, MSc, PhD, Center for Neuropharmacology and Neuroscience, Albany Medical College

Oscillations in the brain are important for normal physiological processes. However, dominant oscillations in the beta frequency (12-35 Hz) are commonly reported in Parkinson’s disease (PD) patients and animal models of PD in the basal ganglia (BG) and are considered pathological since they coincide with akinesia and bradykinesia. At present, the mechanism(s) that mediate or propagate beta oscillations in PD remain ill-defined. Here, we hypothesize that gap junctions (GJs) electrically couple and synchronize BG neuronal activity at the beta frequency in PD. To test this, we anesthetized rats made PD (with 6-hydroxydopamine) and treated them with 200 mg/kg carbenoxolone (CBX), a GJ inhibitor, either systemically (intraperitoneal injection) or directly into the globus pallidus pars externa (GPe); a BG nucleus that exhibits dominant beta oscillations in PD. Extracellular local field potentials were obtained in the GPe before and after CBX treatment. Systemic delivery of CBX decreased beta activity in the GPe from 6.10 ± 1.29 A.U. (arbitrary units; pre-injection) to 2.48 ± 0.87 A.U.; peak attenuation occurred 90.00 ± 20.50 minutes post CBX-injection; similar effects were observed with octanol, another GJ inhibitor. Direct injection of CBX into the GPe in PD rats attenuated beta activity from 1.85 ± 0.45 A.U. to 0.76 ± 0.23 A.U. 52.0 ± 22.08 minutes after injection. Interestingly, direct injection of trimethylamine (TMA), a GJ activator, into the GPe of non-PD rats increased beta activity. Lastly, PD rats that were systemically injected with CBX exhibited improved forelimb function in the stepping test . Overall, our data shows that GJs may underlie the generation and/or propagation of beta frequency activity in the BG of PD rats. However, further work is needed to validate our proof-of-concept that GJ inhibition may represent an innovative approach for treating PD patients.

Updated on November 8, 2012.


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