Dopamine Neurons That Cotransmit Glutamate, From Synapses to Circuits to Behavior.

Discovered just over 20 years ago, dopamine neurons have the ability to cotransmit both dopamine and glutamate. Yet, the functional roles of dopamine neuron glutamate cotransmission and their implications for therapeutic use are just emerging. This review article encompasses the current body of evidence investigating the functions of dopamine neurons of the ventral midbrain that cotransmit glutamate.

Increased expression of 5-HT₆ receptors in dorsolateral striatum decreases habitual lever pressing, but does not affect learning acquisition of simple operant tasks in rats.

Serotonin-6 (5-HT(6)) receptors are densely expressed in the dorsolateral striatum (DLS), a brain region linked to habits. Medications acting on the serotonergic system, including 5-HT(6) receptors, can diminish habitual and repetitive behaviors associated with clinical syndromes such as obsessive-compulsive disorder, and may have implications for addiction as well. To examine the role of 5-HT(6) receptors in the acquisition and persistence of habitual behavior, we manipulated 5-HT(6) receptor expression in the DLS with herpes simplex virus vectors in combination with different behavioral procedures; control rats received a vector expressing enhanced green fluorescent protein.

Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization.

Dorsal striatum is important for the development of drug addiction; however, a precise understanding of the roles of striatopallidal (indirect) and striatonigral (direct) pathway neurons in regulating behaviors remains elusive. Using viral-mediated expression of an engineered G protein-coupled receptor (hM(4)D), we found that activation of hM(4)D receptors with clozapine-N-oxide (CNO) potently reduced striatal neuron excitability. When hM(4)D receptors were selectively expressed in either direct or indirect pathway neurons, CNO did not change acute locomotor responses to amphetamine, but did alter behavioral plasticity associated with repeated drug treatment.

Increased expression of the 5-HT6 receptor by viral mediated gene transfer into posterior but not anterior dorsomedial striatum interferes with acquisition of a discrete action-outcome task.

Serotonin plays a role in reinforcement learning; however, it is not known which serotonin receptors mediate these effects. Serotonin 6 (5-HT(6)) receptors are abundant in the striatum, a brain area that is involved in reinforcement learning. We previously found that 5-HT(6) receptors in the dorsomedial striatum (DMS) affect reinforcement learning or consolidation over several days.