Opponent control of reinforcement by striatal dopamine and serotonin.

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT) powerfully regulate associative learning. Similarities in the activity and connectivity of these neuromodulatory systems have inspired competing models of how DA and 5HT interact to drive the formation of new associations. However, these hypotheses have not been tested directly because it has not been possible to interrogate and manipulate multiple neuromodulatory systems in a single subject.

Intercalated Amygdala Dysfunction Drives Avoidance Extinction Deficits in the Sapap3 Mouse Model of Obsessive-Compulsive Disorder.

Background: The avoidance of aversive stimuli through negative reinforcement learning, which demands dynamic responding to both positive and negative stimuli that often conflict with each other, is critical for survival in real-world environments. Individuals with obsessive-compulsive disorder commonly exhibit impaired negative reinforcement and extinction, perhaps involving deficits in amygdala functioning. The intercalated nuclei of the amygdala (ITC) is an amygdala subregion of particular interest that has been linked to negative reinforcement and extinction, with distinct clusters mediating separate aspects of behavior.

5-HT receptors in the nucleus accumbens constrain the rewarding effects of MDMA.

MDMA is a promising adjunct to psychotherapy and has well-known abuse liability, although less than other amphetamine analogs. While the reinforcing dopamine (DA)-releasing properties of MDMA are on par with methamphetamine (METH), MDMA is a far more potent serotonin (5-HT) releaser, via the 5-HT transporter (SERT). MDMA-mediated 5-HT release in a major reward center, the nucleus accumbens (NAc), drives prosocial behaviors via 5-HTR activation.

Cross-species brain-wide mapping reveals a conserved and coordinated network engaged by NAc DBS.

Nucleus accumbens (NAc) deep brain stimulation (DBS) has been increasingly explored as a treatment modality for refractory neuropsychiatric disorders. Uncovering the accumbens network that is engaged by DBS is a critical step forward in understanding how modulating this important node impacts the broader mesocorticolimbic circuit. Using whole-brain clearing and unbiased, brain-wide neural activity mapping, we found that NAc DBS increases neural activity in a coordinated mesocorticolimbic network in mice.

Myelin plasticity in the ventral tegmental area is required for opioid reward.

All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance-use disorders. Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behaviour. Here we explore the role of myelin plasticity in dopaminergic circuitry and reward learning.