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GLOBAL IMPACT OF ACTIVATION OF VENTRAL TEGMENTAL AREA DOPAMINE NEURONS

Lohani, Sweyta/SL (2018) GLOBAL IMPACT OF ACTIVATION OF VENTRAL TEGMENTAL AREA DOPAMINE NEURONS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Dopamine neurons in the ventral tegmental area (VTA) are dysregulated in numerous psychiatric disorders, including schizophrenia, addiction, and ADHD. VTA dopamine neurons send strong projections to forebrain areas such as the striatum and the prefrontal cortex (PFC) where they mediate various cognitive and affective processes; these processes range from working memory, attention, decision making, action selection to motivation. Despite the importance of VTA dopamine neurons, we have a limited understanding of how dopamine neuron activity modulates downstream neural activity. The current studies, thus, utilized optogenetics in Th::Cre rats to selectively activate VTA dopamine neurons and investigated how phasic VTA dopamine activity modulates global neural activity. Specifically, these studies examined global forebrain functional magnetic resonance imaging (fMRI) activity and local neural activity within PFC during optogenetic activation of VTA dopamine neurons.

The first study demonstrated that phasic VTA dopamine activity increased fMRI responses in several areas, including VTA-innervated limbic regions such as the ventral striatum. Surprisingly, the most prominent fMRI signal increase was observed in the dorsal striatum, which is not traditionally associated with VTA dopamine neurotransmission. These data suggest that there are more robust functional interactions between mesolimbic and non-limbic basal ganglia dopamine circuits than conventionally described. These findings also provide a potential novel framework for understanding dopamine-dependent functions and interpreting data from human studies that primarily rely on fMRI as a non-invasive measure of neural activity.

The second study revealed that phasic activation of VTA dopamine neurons in freely moving animals elicited heterogeneous patterns of modulation in PFC neuron spiking activity on both transient and sustained timescales. In addition to the modulation of individual unit activity, dopamine stimulation also generated responses at the population level. Furthermore, dopamine neuron activation enhanced the power of PFC high gamma oscillations and phase amplitude coupling between theta and high gamma frequencies in the local field potentials (LFPs). The effects of VTA dopamine activity were also state-dependent as it generated a robust increase in LFP beta but not high gamma oscillations under isoflurane anesthesia. Thus, activation of dopamine neurons elicits diverse effects on PFC network activity that may be relevant for PFC-dependent cognitive processes.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lohani, Sweyta/SLswl9@pitt.eduswl9
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCohen, Marlenecohenm@pitt.educohenm
Committee MemberMoghaddam, Bitabita@ohsu.edubita
Committee MemberGianaros, Petergianaros@pitt.edugianaros
Committee MemberAhmari, Susannesahmari@pitt.edusahmari
Committee MemberSesack, Susansesack@pitt.edusesack
Committee MemberWarden, Melissamrwarden@gmail.com
Date: 31 January 2018
Date Type: Publication
Defense Date: 24 July 2017
Approval Date: 31 January 2018
Submission Date: 22 September 2017
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 231
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: optogenetics;striatum; prefrontal cortex; opto-fMRI; oscillations;
Date Deposited: 31 Jan 2018 18:25
Last Modified: 31 Jan 2018 18:25
URI: http://d-scholarship.pitt.edu/id/eprint/33203

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