Behavioral functions of heterogeneous dopaminergic and glutamatergic neuronal subtypes in the ventral tegmental area
Year: 2024
Type: dissertation
Abstract: The ventral tegmental area (VTA) is a region in the midbrain that has a high population of dopaminergic neurons that send projections throughout the brain and have various behavioral and psychological functions. Recent findings have revealed subsets of VTA dopamine neurons are molecularly heterogenous, some of which use complex synaptic architecture to co-release glutamate. This study examined the behavioral functions of molecularly heterogeneous neurons in the VTA and the possibility that their functions are genetically determined by the neurotransmitters being released. It was found that all dopamine neuronal subtypes are involved in signaling reward and reward prediction, but other signaling patterns were cell type specific. Glutamate-only and non-glutamate dopamine neurons were suppressed in reward prediction error, during the omission of reward. Glutamate-dopamine and all-dopamine neurons did not show any significant signaling during reward omission. During the experience of an aversive shock, glutamate-containing neurons (glutamate-only and glutamate-dopamine) increased signaling and non-glutamate dopamine neurons showed suppression, which may have contributed to the unpleasant experience. Signaling patterns during aversive experience were dependent on cell type. Non-glutamate dopamine neuronal activity suppression appeared to signal undesirable experiences related to both reward and aversion. Glutamate-only neurons showed a change in signaling in response to reward prediction and delivery, reward prediction error, and aversive experience. Glutamate-dopamine neurons appeared to function in maintaining motivated behaviors and signaling aversion. All-dopamine neurons were involved in signaling both reward and aversion, though these results may be skewed by the glutamate-dopamine neurons. The results of this investigation provide a more nuanced understanding of previous research regarding dopamine-driven behaviors and unveil the importance of studying dopaminergic neuronal subtypes in the VTA separately. Studying these neuronal subtypes separately allows for improved understanding of the neuronal mechanisms underlying phenomena such as addiction, associative learning, and aversive experience. When applied to the development of therapeutic interventions for psychological disorders, the findings of this study can lead to more targeted treatments with less off-target effects.
Author: Ward, Lucy A
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7111904458