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Investigating Basal Ganglia Circuitry and Function using Silicon Microprobes and Optogenetic Techniques


The basal ganglia are a system of subcortical nuclei that are known to be involved in movement, reward processing, associative learning, and some forms of memory. Basal ganglia disorders, such as Parkinson’s disease and Huntington’s disease, cause a wide range of severe motor impairments. In addition, the basal ganglia have been implicated in a multitude of neuropsychiatric disorders, including obsessive-compulsive disorder, Tourette syndrome, and even depression and addiction. Progress has been made in the last century to map out basal ganglia circuitry, identify its inputs and outputs, and elucidate its functions. However, due to its complexity, many questions remain. Here we aimed to study the basal ganglia by exploring interactions between nuclei and important input structures, examining neural activity in the most prominent nucleus during movement generation, and investigating the role of inputs during reward-guided behaviors. Chapter one discusses the development of a three-dimensional silicon microprobe capable of simultaneously recording extracellular activity from hundreds of neurons spatially distributed throughout the basal ganglia and input structures such as the cortex and ventral tegmental area. Chapter two examines activity of the direct and indirect pathways, the two major pathways from basal ganglia input to output. It describes coordinated activation of optogenetically identified cells measured in the striatum during motivated movement initiation. Chapter three describes optogenetic manipulation of dopaminergic signaling during reward-guided behavior and provides strong causal evidence that phasic dopamine responses to rewarding stimuli are necessary and sufficient for associative learning. Taken together these findings have significant implications for basal ganglia function.

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