Stress may lead to many pathological conditions such as anxiety disorders, post traumatic stress disorder, and addiction. The extended amygdala is a region that is known to be involved in stress, anxiety and addiction related behaviors and receives substantial dopamine input. Although, dopamine is classically regarded as a reward neurotransmitter, there is evidence that dopamine neurons play a role in the stress response. Therefore, delineating the role the dopamine system plays in stress may be extremely important for the development of new therapeutics. Approximately half of the dopaminergic projection to the extended amygdala arises from a group of dopamine neurons termed the A10 dorsocaudal (A10dc) neurons, in addition to the more classically studied ventral tegmental area (VTA) dopamine group. The A10dc group consists of dopamine neurons located within the periaqueductal gray (PAG) and the rostral and caudal linear nuclei of the raphe (RLi and CLi). This group of dopamine neurons remains largely unstudied regarding stress, anxiety, and addiction related behaviors. However, there is evidence that these cells play a key role in opiate reward behaviors and are activated during stress. The A10dc group receives a substantial norepinephrine input from the locus coeruleus. Since norepinephrine is released during times of stress, we hypothesize that norepinephrine recruits the A10dc neurons during stress. We have sought out a genetic reporter mouse model that expresses enhanced green fluorescent protein under control of the tyrosine hydroxylase promoter to allow accurate identification of the sparse population of A10dc neurons for electrophysiological analyses. We propose to use this model to determine how stress and norepinephrine modulate glutamatergic transmission and excitability of the A10dc neurons.
Stress is an everyday experience that can lead to devastating pathological consequences including post traumatic stress disorder, anxiety disorders, and addiction. This project investigates an understudied area of the brain, a unique group of dopamine neurons, which may play important roles in mediating the stress response. This work will provide insights into the pathways mediating stress and anxiety with the goal of determining novel targets for therapeutics for diseases that may arise due to an imbalance in the appropriate stress response.
|Williams, Megan A; Li, Chia; Kash, Thomas L et al. (2014) Excitatory drive onto dopaminergic neurons in the rostral linear nucleus is enhanced by norepinephrine in an ?1 adrenergic receptor-dependent manner. Neuropharmacology 86:116-24|