Activation of the dopaminergic pathway from VTA to the medial olfactory tubercle generates odor-preference and reward.

Odor-preferences are usually influenced by life experiences. However, the neural circuit mechanisms remain unclear. The medial olfactory tubercle (mOT) is involved in both reward and olfaction, whereas the ventral tegmental area (VTA) dopaminergic (DAergic) neurons are considered to be engaged in reward and motivation. Here, we found that the VTA (DAergic)-mOT pathway could be activated by different types of naturalistic rewards as well as odors in DAT-cre mice. Optogenetic activation of the VTA-mOT DAergic fibers was able to elicit preferences for space, location and neutral odor, while pharmacological blockade of the dopamine receptors in the mOT fully prevented the odor-preference formation. Furthermore, inactivation of the mOT-projecting VTA DAergic neurons eliminated the previously formed odor-preference and strongly affected the Go-no go learning efficiency. In summary, our results revealed that the VTA (DAergic)-mOT pathway mediates a variety of naturalistic reward processes and different types of preferences including odor-preference in mice.

Whole-Brain Mapping of the Inputs and Outputs of the Medial Part of the Olfactory Tubercle.

The medial part of the olfactory tubercle (OT) is a brain structure located at the interface of the reward and olfactory system. It is closely related to pheromone-rewards, natural reinforcement, addiction and many other behaviors. However, the structure of the anatomic circuitry of the medial part of the OT is still unclear. In the present study, the medial part of the OT was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool. In order to further investigate the detailed connections for specific neurons, another tracing tool - rabies virus was utilized for D1R-cre and D2R-cre mice. The D1R and D2R neurons in the medial part of the OT were both preferentially innervated by the olfactory areas, especially the piriform cortex, and both had similar direct input patterns. With the help of the adeno-associated virus labeling, it was found that the two subpopulations of neurons primarily innervate with the reward related brain regions, with slightly less axons projecting to the olfactory areas. Thus, the whole-brain input and output circuitry structures for specific types of neurons in the medial part of the OT were systematically investigated, and the results revealed many unique connecting features. This work could provide new insights for further study into the physiological functions of the medial part of the OT.