Mapping Thalamo-striatal Neuronal Circuits Underlying Motivational Drive

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Motivational drive is an adaptive process that helps individuals overcome obstacles to obtain essential needs and hence ensure survival. Motivation is composed of two major components. The first component is the directionality of motivation (the orientation of goal-oriented behavior), such as seek food/shelter or avoid pain. The second is the activational motivation (the energizing of goal-oriented behaviors) such as increase vigor, and persistence of these actions. Impairments in these components of motivation are common characteristic among individuals who suffer from psychiatric disorders. However, the underlying mechanisms controlling different components of motivational drive have yet to be conclusively identified. It is known that the nucleus accumbens (NAc) mediates different components of motivation through different subregions, the NAc shell (NAcshell) and the NAc core (NAccore). Indeed, the NAcshell facilitates the directionality of motivation through suppression of goal-irrelevant behaviors; whereas the NAccore is known to mediate the activational, or invigorating aspects, of motivational drive. However, NAc neurons rely on glutamatergic extra-striatal inputs to initiate and maintain goal-oriented behavior and motivation. The paraventricular nucleus of the thalamus (PVT) integrates visceroceptive signals (originating from the brainstem and hypothalamus) to promote adaptive responses via projections to the NAc. Previous research and my preliminary data show that the PVT has two major distinct subpopulations of neurons, Type1PVT and Type2PVT, which differ on their genetic identity, connectional features, and functionality. Particularly, Type1PVT neurons send strong inputs to the NAccore and are activated during the activational components of motivational drive. Whereas, Type2PVT neurons project almost exclusively to the NAcshell and are active during omissions of expected rewards. However, despite this evidence, the contribution of PVT inputs to the NAc in mediation of goal-oriented behavior and motivation remain largely unknown. My central hypothesis is that Type1PVT–NAccore and Type2PVT–NAcshell neurons are part of independent but complementary thalamo-striatal pathways and they each play a distinct role in motivation. Specifically, Type1PVT-NAccore neurons are critical for the activational component of motivational drive, while Type2PVT–NAcshell neurons facilitate the directionality of motivation by suppression of goal-irrelevant behaviors. Using a multidisciplinary approach that includes a combination of anatomical, imaging, optogenetic, and behavioral techniques, I will characterize PVT-NAc connectivity with anatomical and functional precision. Thereafter, I will then establish the role of Type1PVT–NAccore neurons and Type2PVT–NAcshell neurons in mediating the activational and directionality components of motivated behavior. These findings will advance our understanding of the contributions of thalamo-striatal circuits promoting motivational drive that can create fundamental insights to develop novel approaches for individuals suffering from motivational deficits.