Zimmerman, Eric
(2017)
CIRCUIT DYNAMICS UNDERLYING CONTROL OF DOPAMINE NEURON ACTIVITY BY THE NUCLEUS REUNIENS OF THE MIDLINE THALAMUS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
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Abstract
The circuitry mediating top-down control of dopamine (DA) neurons in the ventral tegmental area (VTA) is exceedingly complex. Characterizing these networks will be critical to our understanding of fundamental behaviors, such as motivation and reward processing, as well as several disease states. Previous work suggests that the medial prefrontal cortex (mPFC) exerts a profound influence on VTA DA neuron firing. Recently, our group reported that inhibition of the infralimbic subdivision of the medial prefrontal cortex (ilPFC) increases the proportion of VTA DA neurons that are spontaneously active (i.e., “population activity”) and that this effect depends on activity in the ventral subiculum of the hippocampus (vSub). However, there is no direct projection from the mPFC to the vSub. Anatomical evidence suggests that communication between the two structures is mediated by the nucleus reuniens of the midline thalamus (RE). The work presented in this dissertation aims to determine if RE controls VTA DA neuron firing and to describe the circuits underlying ilPFC-RE communication. In Chapter 2, we present findings demonstrating that RE can drive VTA DA neuron firing by engaging vSub. In addition, we show that ilPFC opposes this effect, likely via input to RE in the form of feedforward inhibition from TRN. In Chapter 3, we present findings that characterize the diverse array of RE neuron firing patterns in an intact preparation and describe the circuit dynamics underlying projections from ilPFC to RE. These studies suggest that ilPFC exerts control of RE neuron firing pattern through direct, monosynaptic connections and via the thalamic reticular nucleus (TRN). Overall, the studies described in this dissertation reveal a novel role for a corticothalamic circuit including the ilPFC, RE, and vSub in controlling VTA DA neuron firing and confirm that corticothalamic input from ilPFC to RE can modulate RE neuron firing pattern in nuanced and complex ways. In addition, these findings provide a plausible circuit basis for various behavioral phenomena observed in schizophrenia, and could help inform the development of novel treatments.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Ahmari, Susanne | | | | | Committee Member | Kellendonk, Christoph | | | | | Committee Member | Sweet, Robert | | | | | Committee Member | Sesack, Susan | | | | | Committee Member | Volk, David | | | | | Committee Member | Grace, Anthony | | | |
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| Date: |
28 September 2017 |
| Date Type: |
Publication |
| Defense Date: |
27 July 2017 |
| Approval Date: |
28 September 2017 |
| Submission Date: |
31 July 2017 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
132 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Neuroscience |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Dopamine, Neuroscience, VTA, Thalamus |
| Date Deposited: |
29 Sep 2017 01:27 |
| Last Modified: |
29 Sep 2017 01:27 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/33110 |
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