Population analysis of the striatum during voluntary movement
Romano, Michael Francis
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The basal ganglia are primitive brain structures important for learning, decision making, and locomotion. Though the striatum is central for basal ganglia functions, it remains largely unknown how different types of neurons in the striatum support diverse behaviors. We here deployed two-color, wide-field calcium imaging and examined the distinct contributions of MSNs and interneuron subtypes during voluntary movement. First, to promote the use of scientific complementary metal-oxide semiconductor (sCMOS) cameras in wide-field calcium imaging at high spatiotemporal resolution, we developed a Teensy 3.2 microcontroller-based interface capable of integrating novel behavioral paradigms with sCMOS cameras. We quantified the performance of the Teensy interface in a locomotion experiment and in a trace-conditioning experiment. We show that this Teensy interface provides flexibility in integrating sCMOS cameras into diverse experimental designs with high temporal precision. In parallel, we utilized two-color wide-field calcium imaging, labelling striatal neurons with the green calcium indicator GCaMP6f (fast), while additionally targeting two interneuron classes, parvalbumin-positive (PV) and cholinergic interneurons (CHIs) using red fluorophores in two transgenic mice. We found that PVs are highly correlated with motor output and precipitate a decrease in MSN-MSN (medium-spiny neuron) coactivity. In contrast, CHI activation elicits a decrease in locomotion and precipitates an increase in MSN coactivity. These results provide the first experimental evidence for the distinct contribution of striatal interneuron subtypes during locomotion. Finally, we performed a cluster analysis to examine the relationship of MSN networks with motor output upon pharmacological elevation of striatal cholinergic tone or dopaminergic tone. We found that striatal activity becomes uncoupled from motor output in both conditions, and individual MSN clusters become less correlated and less predictive of motor output. These results suggest that balanced levels of acetylcholine and dopamine in the striatum are important for striatal encoding of motor function. In this dissertation we extend our knowledge about how the striatum coordinates locomotion and improve upon existing neurotechnologies to study the striatum. Future studies might extend such findings to build a more intricate network model of the striatum to better understand its function in normal locomotion or in disease conditions.
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