Symposium
Session Room 219
Wednesday, June 18, 10:50 AM – 12:05 PM
Symposium 15: Neural Circuits of Dorsal Striatum and Amygdala in Addictive Behaviors
The striatum and amygdala are implicated in addictive behaviors. Two morphologically indistinguishable but functionally counteracting populations of medium spiny neurons (MSNs), direct (dMSNs) or indirect (iMSNs) medium spiny neurons, comprise over 90% of the neurons in the striatum. Dr. Choi and Dr. Citri will discuss the role of striatal dMSNs and iMSNs in alcohol-seeking and cocaine-elicited behaviors. While dysfunction of striatal iMSNs, expressing the dopamine D2 receptor (D2R), contributes to compulsive alcohol-seeking, compartmentalized activation of this population alleviates cocaine-induced stereotypic behaviors. Dr. Baik will discuss the role of amygdala D2R-expressing neurons in the development of compulsive eating. Our symposium will update the current understanding of dopamine-modulated neural circuits in addiction-related behaviors for food, alcohol and cocaine.

Dr. Choi from Mayo Clinic in the USA, will present a striatal neural circuit on compulsive alcohol-seeking behavior. His team investigated the role of the iMSNs in the dorsolateral striatum using optogenetic manipulations and caspase-dependent circuit ablation. First, they found that optogenetic inhibition of the GPe projection of the DLS iMSNs circuit increases reward-seeking behaviors. Next, they found that ablation of this circuit increases compulsive alcohol-seeking behavior, indicating that disinhibition of iMSNs promotes pathological drug-seeking.

Dr. Citri from Hebrew University in Israel, will present unpublished work describing the robust development of stereotypic orofacial actions following repeated exposure to cocaine. To study these actions, the Citri lab developed a novel deep-learning framework for behavioral annotation (termed STEREO). Using this framework, Citri’s group uncovered a dominant role for dMSNs in the ventrolateral aspect of the dorsal striatum (VLS) in driving stereotypic actions, while VLS iMSNs prominently limit the expression of orofacial stereotypies. Further probing the circuit, they identified enriched VLS iSPNs from the anterior insular cortex (aINS). Intriguingly, these inputs are acutely inhibited by exposure to cocaine. Optogenetic stimulation of the insular inputs, negating the inhibition induced by cocaine, delays the development of orofacial stereotypies. Thus, these results indicate that VLS iSPNs gate the expression of orofacial action and stereotypes. Repeated cocaine exposure reduces the drive from the insula onto VLS iSPNs, opening the gate and enhancing the probability of exhibiting orofacial stereotypes.

Dr. Baik from Korea University in South Korea, will present recent findings obtained in her laboratory on the role of the dopamine system in compulsive eating. Motivation toward palatable food involves reward learning and conditioning processes, and pathological overeating is linked to dysregulation of reward-related behavioral components such as impulsivity and compulsivity. Dysfunctional dopaminergic neurotransmission, especially involving the dopamine D2 receptor (D2R), has been proposed to be a mechanism underlying these maladaptive behaviors. Dr. Baik's laboratory observed that D2R knockout mice consumed significant amounts of palatable food in an aversive context, displaying compulsive eating behavior. They further demonstrated that D2R–expressing neurons from the central nucleus of the amygdala critically contribute to regulating impulsive and compulsive eating behavior. These studies provide a basis for developing new approaches to managing neuropsychiatric and metabolic disorders associated with maladaptive eating behaviors.