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1. MANDELBAUM, GIL. Basal Ganglia Circuitry Controlling Action Selection.
Degree: PhD, 2019, Harvard University
A central goal of neuroscience is to understand how brain circuits integrate diverse streams of information, in order to make optimal future choices. The process of choosing an action, in vertebrate animals, crucially depends on the proper function of the basal ganglia (BG) circuits. However, the precise connectivity in the BG nuclei, as well as the activity patterns that underlie their function in action selection, are currently not well understood. To understand this, one must first identify the functional building blocks of the BG circuits. To this end, we dissected the circuitry of the thalamic Parafascicular Nucleus (PF), an excitatory input to the BG that is omitted from the majority of BG circuit function models. We found that, in mice, PF forms the densest subcortical projection to the striatum. This projection arises from transcriptionally and physiologically distinct classes of PF neurons, which are reciprocally connected with functionally-distinct cortical regions, differentially innervate striatum neurons, and are not synaptically connected in PF. Thus, mouse PF contains heterogeneous neurons that are organized into parallel and independent associative, limbic, and motor circuits. Furthermore, these subcircuits share motifs of cortical-PF-cortical and cortical-PF-striatum organization that allow each PF subregion, via its precise connectivity with cortex, to coordinate diverse inputs to striatum. In order to understand the functional consequences of this circuit organization, we designed a behavioral task in which mice were required to base their next choice on their previous actions and outcomes associations (AOA) in addition to software and hardware for rapid closed-loop optogenetic manipulations triggered off of specific task and behavioral parameters. Optogenetic stimulation of dorsal lateral STR direct and indirect spiny projection neurons during the AOA formation period caused biases in action choice made several seconds later, contraversive and ipsiversive, respectively. Similarly, stimulation during the delay period after the AOA had been formed but prior to reporting the choice caused the same bias. These data suggest that the execution of actions and reinforcement are linked through the dorsolateral striatum. We now seek to further establish this by silencing and recording activity patterns in the PF, STR, and CTX.
Medical SciencesAdvisors/Committee Members: Assad, John A. (advisor), Wilson, Rachel I. (committee member), Born, Richard T. (committee member), Costa, Rui M. (committee member).
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APA (6th Edition):
MANDELBAUM, G. (2019). Basal Ganglia Circuitry Controlling Action Selection. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:41121319
Chicago Manual of Style (16th Edition):
MANDELBAUM, GIL. “Basal Ganglia Circuitry Controlling Action Selection.” 2019. Doctoral Dissertation, Harvard University. Accessed October 27, 2020. http://nrs.harvard.edu/urn-3:HUL.InstRepos:41121319.
MLA Handbook (7th Edition):
MANDELBAUM, GIL. “Basal Ganglia Circuitry Controlling Action Selection.” 2019. Web. 27 Oct 2020.
MANDELBAUM G. Basal Ganglia Circuitry Controlling Action Selection. [Internet] [Doctoral dissertation]. Harvard University; 2019. [cited 2020 Oct 27]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41121319.
Council of Science Editors:
MANDELBAUM G. Basal Ganglia Circuitry Controlling Action Selection. [Doctoral Dissertation]. Harvard University; 2019. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41121319