Ventral Tegmental Area - CA3 Loop

CA3 Loop

Linking context to reward is important for reward seeking. Recently a group of researchers documented a VTA-CA3 loop that uses the lateral septum as an intermediary. They used a pseudo-rabies virus (PRV) as a transsnyaptic tracer, and injected it into the VTA. They found that unilateral injection into the VTA resulted in bilateral PRV labeling in CA3 beginning 48 hours after injection. Lesions of the caudodorsal lateral septum (cd-LS) prior to VTA PRV injection resulted in significantly less PRV labeled neurons in CA3. Theta wave stimulation of CA3 resulted in increased firing rates for dopamine cells in the VTA, and decreased firing rates for GABA neurons in the VTA. The identity of VTA neurons was confirmed by neurobiotin™ labeling of the recording neuron, and then histological staining for tyrosine hydroxylase (TH). Temporary inactivation of CA3 via GABA agonists prevented context induced reinstatement of lever pressing for intravenous cocaine.

The authors propose a functional circuit loop where activation of glutamatergic cells in CA3 causes activation of GABAergic cells in cd-LS, which inhibits GABA interneurons in the VTA, releasing the dopamine cells from the tonic inhibition, and leading to an increased firing rate for the dopamine cells.