Activation But Not Inhibition of the Indirect Pathway Disrupts Choice Suppression in a Freely Moving, Multiple Choice Foraging Task

Prepubertal ovariectomy alters dorsomedial striatum indirect pathway neuron excitability and explore/exploit balance in female mice

“…The DMS has been implicated in action selection and determining choice policy, and previous studies have found evidence that estrous cycle modulates the intrinsic excitability of striatal SPNs. Furthermore, several lines of evidence suggest that D2R(+) iSPNs: 1) are modulated by ovarian hormones (Le Saux and Di Paolo, 2005; Le Saux et al, 2006; Krentzel et al, 2019) and 2) can influence explore/exploit balance during decision making (Kwak et al, 2014; Lee et al, 2015; Delevich et al, 2020b). We therefore investigated whether changes in the intrinsic excitability of D2R(+) SPNs within DMS may contribute to sham vs. pOVX differences in choice policy during reversal learning.…”

“…The DMS is implicated in the regulation of goal-directed action selection (Tai et al, 2012; Nonomura et al, 2018; Matamales et al, 2020; Peak et al, 2020) and choice policy (Collins and Frank, 2014), and recent work suggests that enhancing the activity of D2R(+) SPNs in the dorsal striatum biases choice behavior to be more exploratory (Lee et al, 2015; Delevich et al, 2020b) but see (Verharen et al, 2019a). While nuclear estrogen receptors are notably absent from the dorsal striatum in adulthood (Krentzel et al, 2021), extranuclear estrogen receptors (ERα, ERβ, and GPER1) localize to SPNs, glia, and the presynaptic terminals of striatal GABAergic and cholinergic interneurons of adult female rats (Almey et al, 2012).…”