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

Abstract

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.

Neurochemical organization of the ventral striatum’s olfactory tubercle

“…DAergic neurons from the ventral tegmental area (VTA), which form the mesolimbic projection pathway, project to the OT as well as the nucleus accumbens (Del‐Fava, Hasue, Ferreira, & Shammah‐Lagnado, ; Mingote et al, ; Watabe‐Uchida, Zhu, Ogawa, Vamanrao, & Uchida, ; Zhang, Liu, et al, ). These fibers begin to innervate the OT as early as mouse embryonic day 13, and progressively arborize from layer 3 to layer 1 in an ‘inside‐out’ gradient (Martin‐Lopez et al, ).…”

“…Consistent with DA’s role in learning and reinforcement in other brain regions, OT DA is associated with the formation of learned odor preferences (Zhang, Liu, et al, ). In addition, DAergic neuronal ablation in the medial OT via 6‐OHDA microinjections reduces the preference of sexually naïve female mice to investigate male urinary odors, while having no effect on the ability to discriminate between the odors (DiBenedictis, Olugbemi, Baum, & Cherry, ).…”

“…(Mingote et al, 2015), in contrast to CINs which included an NMDAR component (Wieland et al, 2014). Vamanrao, & Uchida, 2012;Zhang, Liu, et al, 2017a). These fibers begin to innervate the OT as early as mouse embryonic day 13, and progressively arborize from layer 3 to layer 1 in an 'inside-out' gradient (Martin-Lopez et al, 2019).…”

Phasic dopamine enhances the distinct decoding and perceived salience of stimuli

“…1a). The OTu provides the main direct access of olfactory information to the limbic reward system (35) and shares functions in reinforcement and salience with nucleus accumbens (34)(35)(36). In the first instance, we examined how neuronal representations are modified during a reversal learning go/no-go task.…”

“…Mesolimbic dopamine in the ventral striatum is critical to reinforcement learning (30,31) and the incentive salience hypothesis of dopamine function in reward suggests that dopaminergic neurotransmission in the ventral striatum modulates the attribution of salience to conditioned cues that anticipate reward (25). While the behavioral sufficiency of dopamine to render stimuli more salient is well established (32)(33)(34), it is not clear in how far pDA modifies directly the neuronal population encoding of stimuli in ventral striatal networks. We therefore tested in awake animals whether pDA release itself is sufficient to induce plasticity to the population encoding of initially neutral stimuli to generate distinct stimulus representations with increased perceived salience.…”