A heterogeneous population of ventral tegmental area neurons project to the central amygdala
Publication Date
July 2019
Location
LSU Health Medical Education Building
Document Type
Abstract
Start Date
26-7-2019 9:00 AM
End Date
26-7-2019 12:00 PM
Description
Alcohol Use Disorder (AUD) is a disorder characterized by alcohol dependence that affects around 16 million Americans. While the neural adaptations that occur in individuals with AUD are not entirely understood, they may involve alterations in stress and reward circuitry. Here, we focused on a connection between the ventral tegmental area (VTA) and the central amygdala (CeA), a circuit that possibly plays a role in alcohol dependence-associated behaviors. The CeA is a region of the brain that is primarily associated with feelings of stress and alcohol dependence-associated behaviors. The VTA, however, is associated with more positive emotions and is sometimes referred to as the “reward center” of the brain. Previous work from our lab has demonstrated increased activity of CeA-projecting VTA neurons in the alcohol dependent rat relative to naïve controls. Our overarching hypotheses are that following the induction of alcohol dependence, this circuit becomes activated and contributes to alcohol dependence-associated behaviors. However, this circuit is largely under-characterized, even in the naïve brain. Previous work in our lab has determined that only about 30% of CeA-projecting VTA neurons are dopaminergic, suggesting a substantial population of putative glutamatergic or GABAergic neurons. Electrophysiological studies from our lab indicate that stimulation of VTA terminals in the CeA can elicit excitatory postsynaptic currents, suggesting that at least some of these neurons are capable of glutamate release. The goal of this research is to better characterize this circuit in alcohol-naïve rats by examining the expression profiles of CeA-projecting VTA neurons. We hypothesized that there would be a substantial portion of glutamatergic CeAprojecting VTA neurons. This hypothesis was tested using retrograde tracing and in situ hybridization on tissue sections of alcohol-naïve. VTA-containing tissue sections were imaged and analyzed to determine if the CeA-projecting neurons contained vesicular glutamate transporter 2 (vGluT2), which would indicate that neuron is glutamatergic, or tyrosine hydroxylase (TH), which would indicate that neuron is dopaminergic. Of the CeA-projecting neurons analyzed, some were found to have projected from the substantia nigra (SNc), a neighboring brain region to the VTA. In both the CeA-projecting VTA neurons and the CeA-projecting SNc neurons, there was a substantial amount of neurons that contained neither vGluT2 or TH, indicating they were neither glutamatergic or dopaminergic (putative GABAergic). In the substantia nigra, a large percent of the neurons were found to be only glutamatergic while a smaller percent were found to be able to express both vGluT2 and TH. In the VTA, there was an even amount of dopaminergic and glutamatergic neurons while none were able to co-express vGluT2 and TH. These findings are important for better characterizing the expression profile of CeA-projecting neurons and will help to show how they affect the CeA downstream. Future research will extend this analysis to include expression profiles of GABAergic CeA-projecting neurons, as well as determining how these neurons are altered in the alcohol dependent brain. Ultimately, characterization of this circuit could provide useful targets in the treatment of individuals with AUD.
Recommended Citation
Constans, Michael J., "A heterogeneous population of ventral tegmental area neurons project to the central
amygdala" (2019). Summer Research Internship Program. 7.
https://digitalscholar.lsuhsc.edu/srip/2019/undergrad/7
A heterogeneous population of ventral tegmental area neurons project to the central amygdala
LSU Health Medical Education Building
Alcohol Use Disorder (AUD) is a disorder characterized by alcohol dependence that affects around 16 million Americans. While the neural adaptations that occur in individuals with AUD are not entirely understood, they may involve alterations in stress and reward circuitry. Here, we focused on a connection between the ventral tegmental area (VTA) and the central amygdala (CeA), a circuit that possibly plays a role in alcohol dependence-associated behaviors. The CeA is a region of the brain that is primarily associated with feelings of stress and alcohol dependence-associated behaviors. The VTA, however, is associated with more positive emotions and is sometimes referred to as the “reward center” of the brain. Previous work from our lab has demonstrated increased activity of CeA-projecting VTA neurons in the alcohol dependent rat relative to naïve controls. Our overarching hypotheses are that following the induction of alcohol dependence, this circuit becomes activated and contributes to alcohol dependence-associated behaviors. However, this circuit is largely under-characterized, even in the naïve brain. Previous work in our lab has determined that only about 30% of CeA-projecting VTA neurons are dopaminergic, suggesting a substantial population of putative glutamatergic or GABAergic neurons. Electrophysiological studies from our lab indicate that stimulation of VTA terminals in the CeA can elicit excitatory postsynaptic currents, suggesting that at least some of these neurons are capable of glutamate release. The goal of this research is to better characterize this circuit in alcohol-naïve rats by examining the expression profiles of CeA-projecting VTA neurons. We hypothesized that there would be a substantial portion of glutamatergic CeAprojecting VTA neurons. This hypothesis was tested using retrograde tracing and in situ hybridization on tissue sections of alcohol-naïve. VTA-containing tissue sections were imaged and analyzed to determine if the CeA-projecting neurons contained vesicular glutamate transporter 2 (vGluT2), which would indicate that neuron is glutamatergic, or tyrosine hydroxylase (TH), which would indicate that neuron is dopaminergic. Of the CeA-projecting neurons analyzed, some were found to have projected from the substantia nigra (SNc), a neighboring brain region to the VTA. In both the CeA-projecting VTA neurons and the CeA-projecting SNc neurons, there was a substantial amount of neurons that contained neither vGluT2 or TH, indicating they were neither glutamatergic or dopaminergic (putative GABAergic). In the substantia nigra, a large percent of the neurons were found to be only glutamatergic while a smaller percent were found to be able to express both vGluT2 and TH. In the VTA, there was an even amount of dopaminergic and glutamatergic neurons while none were able to co-express vGluT2 and TH. These findings are important for better characterizing the expression profile of CeA-projecting neurons and will help to show how they affect the CeA downstream. Future research will extend this analysis to include expression profiles of GABAergic CeA-projecting neurons, as well as determining how these neurons are altered in the alcohol dependent brain. Ultimately, characterization of this circuit could provide useful targets in the treatment of individuals with AUD.
Comments
Mentor: Dr. Nicholas Gilpin, Department of Physiology