Retrograde Mapping of Inputs to Direct-and Indirect-pathway Neurons in the Posterior Dorsomedial Striatum
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The dorsomedial striatum (DMS) is crucial for goal-directed learning and heavily implicated in drug and alcohol addiction. The posterior DMS (pDMS) receives multiple inputs and contains medium spiny neurons (MSNs) expressing dopamine D1 receptors (D1Rs) or D2Rs. These neurons exhibit abnormal synaptic plasticity after excessive alcohol consumption. However, the different sources of the afferent inputs to pDMS D1- vs. D2-MSNs are unclear. To identify the presynaptic neurons projecting to specific neuronal types, we used a state-of-the-art monosynaptic retrograde tracing technology to label these presynaptic neurons in the whole mouse brain. Then, we determined the extent to which those presynaptic cells projecting to pDMS D1-MSNs (or D2-MSNs) also contain D1Rs (or D2Rs). We found abundant projecting neurons in the different cortical regions, amygdala, thalamus, and midbrain. Interestingly, we found that most D1-MSN-projecting neurons did not express D1Rs; most D2-MSN-projecting neurons did not express D2Rs. We only observed a few D1-MSN-projecting neurons in the cortex and thalamus contained D1Rs; a few D2-MSN-projecting neurons in the cortex, thalamus, and midbrain neurons expressed D2Rs. These results suggest that connected corticostriatal and thalamostriatal neurons do not express the same type of dopamine receptors, which is an important question in the addiction field that has not been addressed before. Understanding these connections will also improve our knowledge of the pDMS circuit in drug addiction.
Barbee, Britton Rae (2017). Retrograde Mapping of Inputs to Direct-and Indirect-pathway Neurons in the Posterior Dorsomedial Striatum. Undergraduate Research Scholars Program. Available electronically from