This dissertation focuses on the role of striatal microcircuits and how afferents from cortex and globus pallidus externa (GPe) play a role in striatal activity and behavioral output. In the first chapter I summarize the role of striatal subregions in behavioral selection and initiation and elaborate on how striatal activity in output neurons (SPNs) and fast-spiking interneurons (FSIs) has been associated with behavioral initiations.
Chapter 2 highlights the capacity of an FSI-specific pallidostriatal projection for controlling the activity of SPNs, particularly under dopamine depletion conditions. These data suggest that GPe may provide bursts of inhibition to FSIs, allowing SPNs a disinhibition window of time in which to fire without strong regulation from FSIs.
In Chapter 3 I investigate abnormalities in cortical input to central striatum (CS) of Sapap3-KO mice. I demonstrate that LOFC inputs to CS are reduced onto SPNs in Sapap3-KOs. In contrast, M2 inputs, which are weak in WTs, are strengthened in KOs. These data suggest a potential increase in motor control over CS in KOs, possibly contributing to the repetitive behavior observed in these mice.
Chapter 4 presents work investigating the role of the M2-CS circuit in grooming behavior. I first describe data from the lab showing that CS is hyperactive at the start of a grooming bout in Sapap3-KOs. I then show that there is grooming-related activity in both M2 and terminals in CS, but that this activity doesn’t differ by genotype; this suggests that ex vivo post-synaptic strengthening may lead to a post-synaptic potentiation of M2 signals in CS. I then demonstrate the sufficiency of this circuit in grooming behavior by stimulating CS or M2 terminals in CS and showing evoked grooming behavior.
In the final chapter I discuss what my data may suggest about the role of corticostriatal circuits in behavioral initiations. Based on data that cortical terminal stimulation doesn’t cause immediate evoked behavior but CS stimulation does, I propose that the site of grooming initiation signals is in striatum. I describe a model in which CS integrates inputs from cortex and GPe to overcome hyperpolarized membrane potentials and generate activity to initiate grooming.
|Advisor:||Ahmari, Susanne E., Gittis, Aryn H.|
|Commitee:||Turner, Robert S., Sesack, Susan R., Strick, Peter L., Rothwell, Patrick|
|School:||University of Pittsburgh|
|Department:||School of Medicine|
|School Location:||United States -- Pennsylvania|
|Source:||DAI-B 81/7(E), Dissertation Abstracts International|
|Keywords:||Behavioral selection, Compulsive behavior, Cortex, Pallidus, Striatum|
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