Event Abstract Back to Event Parkinsonian brain activity patterns in urethane-anesthetized VMAT2-deficient mice Jeremy R. Edgerton1* and Dieter Jaeger1 1 Emory University, Faculty of Electrical Engineering and Computing, United States Parkinson's disease (PD) is a devastating neurological disorder involving the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). SNc neurons project principally to the striatum and other regions of the basal ganglia, and the loss of dopaminergic modulation in this circuit results in akinesia, rigidity and tremor - the movement symptoms that are the hallmarks of PD. In addition to the motor symptoms of PD, there are a number of non-motor symptoms that typically do not respond as well to dopamine replacement therapy. It has been proposed that these non-motor symptoms may involve the noradrenergic and serotonergic neurotransmitter systems, which also show significant degeneration in PD. In support of this hypothesis, a recent study found that mice expressing only 5% of the normal level of the vesicular monoamine transporter 2 (VMAT2 LO mice), resulting in severely depleted levels of DA, NE and 5-HT, display both an age-dependent motor phenotype and several of the non-motor symptoms of PD [1]. Neurophysiological studies of dopamine-depleted primate and rodent models of PD have found altered neuronal firing rates and patterns at multiple basal ganglia sites including the output nuclei. Three pattern changes have been emphasized as consistent features of Parkinsonian brain activity: increased burst firing, abnormal 8 - 45 Hz oscillations, and elevated synchrony between neurons. To determine the neurophysiological correlates of the Parkinsonian phenotype observed in VMAT2 LO mice, we have compared local field potential and single-unit activity between these mice and wild-type controls. We recorded simultaneously from three brain regions: the substantia nigra pars reticulata (SNr), which is a major basal ganglia output nucleus composed of GABAergic projection neurons; the ventral medial thalamus (VM), which is one of the principal targets of the SNr in mice; and motor cortex, which is reciprocally connected with VM and also a major source of input to the basal ganglia circuit. Preliminary results show markedly increased oscillatory power at about 10 Hz in the VMAT2 LO mice under urethane anesthesia. The 10 Hz oscillations were highly coherent between motor cortex, SNr and VM, consistent with increased synchrony across the cortico-basal ganglia network. The elevated oscillations were not observed under isoflurane anesthesia, and were observed under urethane only during periods of cortical activation induced by a toe-pinch stimulus. These results indicate that VMAT2 LO mice show some of the same neuronal activity pattern abnormalities that are characteristic of more established animal models of PD.