(1) Mechanisms of neurodegeneration and structural plasticity in Parkinson’s disease.
(2) Role of the amygdala in substance abuse.
Our work is focused on the mechanisms that underlie structural plasticity in basal ganglia circuits following manipulation of dopaminergic pathways or their receptors. Disease-related destruction of the dopaminergic system or drug-induced changes in dopamine transmission are implicated in numerous neurological and psychiatric disorders. The diversity of these disorders is related to two important features of the dopaminergic systems: i) differential signaling at dopaminergic receptors and ii) the structural consequences of changing dopamine neurotransmission. Our investigations focus on the mechanisms underlying dopamine-mediated cell death and structural change, especially examining the factors responsible for synapse stabilization and plasticity. Our work is carried out at light and electron microscopic levels, and includes the use of tracing molecules to elucidate pathways, single, dual and triple label immunocytochemistry (fluorescent, particulate and gold labels), and the intracellular filling of neurons in fixed slices. Routinely we carry out studies employing the reconstruction of of intracellularly-filled neurons, design-based stereology, and in situ hybrization using 35S-labeled oligonucleotide probes (films and dipped slides). All work is in animal models or with human material. Our work on substance abuse is funded by the National Institute on Drug Abuse.
Kathy Steece-Collier, PhD
David Rademacher, PhD
D. James Surmeier, PhD