Distinct Roles of Ventromedial versus Ventrolateral Striatal Medium Spiny Neurons in Reward-Oriented Behavior

Abstract

The ventral striatum (VS) is a key brain center regulating reward-oriented behavior [1-4]. The VS can be anatomically divided into medial (VMS) and lateral (VLS) portions based on cortical input patterns. The VMS receives inputs from medial pallium-originated limbic structures (e.g., the medial prefrontal cortex [mPFC]), and the VLS receives inputs from the lateral pallium-originated areas (e.g., the insula) [5, 6]. This anatomical feature led us to hypothesize a functional segregation within the VS in terms of the regulation of reward-oriented behavior. Here, we engineered a fiber photometry system [4] and monitored population-level Ca activities of dopamine D2-receptor-expressing medium spiny neurons (D2-MSNs), one of the major cell types in the striatum, during a food-seeking discrimination task. We found that VLS D2-MSNs were activated at the time of cue presentation. In stark contrast, VMS D2-MSNs were inhibited at this time point. Optogenetic counteraction of those changes in the VLS and VMS impaired action initiation and increased responding toward non-rewarded cues, respectively. During lever-press reversal training, VMS inhibition at the time of cue presentation temporarily ceased and optogenetic activation of VMS D2-MSNs facilitated acquisition of the new contingency. These data indicate that the opposing inhibition and excitation in VMS and VLS are important for selecting and initiating a proper action in a reward-oriented behavior. We propose distinct subregional roles within the VS in the execution of successful reward-oriented behavior.

Acute stress enhances associative learning via dopamine signaling in the ventral lateral striatum

“…2C). Stress did not alter the time to approach to the food tray, as the latency from the CS onset to the first tray entry did not differ between groups (treatment effect F(1, 35)=0.80, p=0.38; Fig. 2D).…”

“…3D). Dopamine release to the US decayed with training (session effect F(2.5, 43.9)=8.02, p=.0005; Fig 3E) Increasing evidence highlights that the ventral lateral striatum (VLS) contributes to reward-related behaviors 35,40,41 . Furthermore, aversive experience increases excitatory transmission to dopamine neurons projecting to the VLS 42 .…”

“…2D). The number of tray entries during the intertrial interval was unaffected by stress exposure, indicating no change in overall activity (treatment effect F(1, 35)=1.03, p=0.32; Fig. 2E).…”

“…Conditioned responding was elevated in stressed rats relative to controls (treatment effect F(1, 35)=8.22, p=0.007; n=16 control, 21 stress; Fig. 2C).…”

“…given the involvement of the VMS in reward-related behaviors 34,35 . Consistent with prior studies 36,37 , dopamine release in the VMS was time-locked to both the CS and the US ( Fig.…”