RT Journal Article
SR Electronic
T1 Whole-Brain Mapping of Direct Inputs to Dopamine D1 and D2 Receptor-Expressing Medium Spiny Neurons in the Posterior Dorsomedial Striatum
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0348-20.2020
DO 10.1523/ENEURO.0348-20.2020
VO 8
IS 1
A1 Jiayi Lu
A1 Yifeng Cheng
A1 Xueyi Xie
A1 Kayla Woodson
A1 Jordan Bonifacio
A1 Emily Disney
A1 Britton Barbee
A1 Xuehua Wang
A1 Mariam Zaidi
A1 Jun Wang
YR 2021
UL http://www.eneuro.org/content/8/1/ENEURO.0348-20.2020.abstract
AB The posterior dorsomedial striatum (pDMS) is mainly composed of medium spiny neurons (MSNs) expressing either dopamine D1 receptors (D1Rs) or D2Rs. Activation of these two MSN types produces opposing effects on addictive behaviors. However, it remains unclear whether pDMS D1-MSNs or D2-MSNs receive afferent inputs from different brain regions or whether the extrastriatal afferents express distinct dopamine receptors. To assess whether these afferents also contained D1Rs or D2Rs, we generated double transgenic mice, in which D1R-expressing and D2R-expressing neurons were fluorescently labeled. We used rabies virus-mediated retrograde tracing in these mice to perform whole-brain mapping of direct inputs to D1-MSNs or D2-MSNs in the pDMS. We found that D1-MSNs preferentially received inputs from the secondary motor, secondary visual, and cingulate cortices, whereas D2-MSNs received inputs from the primary motor and primary sensory cortices, and the thalamus. We also discovered that the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA) contained abundant D2R-expressing, but few D1R-expressing, neurons in a triple transgenic mouse model. Remarkably, although limited D1R or D2R expression was observed in extrastriatal neurons that projected to D1-MSNs or D2-MSNs, we found that cortical structures preferentially contained D1R-expressing neurons that projected to D1-MSNs or D2-MSNs, while the thalamus, substantia nigra pars compacta (SNc), and BNST had more D2R-expressing cells that projected to D2-MSNs. Taken together, these findings provide a foundation for future understanding of the pDMS circuit and its role in action selection and reward-based behaviors.