Corticostriatal Action Selection in Rats With Opposed Attentional Biases

Abstract

Moving across dynamic surfaces and obstacles requires integrating cues that guide movements, such as turning commands. The ability to detect and effectively integrate these cues, or the failure to do so (termed "misses"), can have severe consequences, leading to life-threatening falls and hospitalization. Prior research has highlighted the pivotal role of cholinergic modulation of fronto-cortical inter- and output neurons in detecting attention-demanding cues. This work hypothesizes that cues are transferred into the striatum via cortico-striatal glutamatergic (GLU) projections to integrate with striatal movement sequencing following cortical detection. The primary aim of this work was to investigate the role of glutamatergic cortico-striatal projections in enabling the initiation, sequencing, and updating of goal-directed actions. We investigated this hypothesis by recording GLU signaling in the striatal projection field of frontal cortical efferents, the dorsomedial striatum (DMS), in rats performing a task involving turn and stop-and-go signals. Leveraging the inherent attentional biases driven by varying cortical cholinergic capacities in goal-trackers (GTs) and sign-trackers (STs), this work aimed to illuminate the significance of corticostriatal glutamatergic signaling in complex movement control guided by cues. Amperometric recordings of GLU were time-locked to task events. Results revealed distinct increases in DMS glutamatergic concentrations, notably dissociated by phenotype and responses to task cues. Specifically, in GTs, detected turn cues evoked sharp, rapid increases in GLU activity, providing evidence of specific dorsomedial glutamate responses preceding and predicting the updating of movement sequences (turns). Conversely, glutamate responses in STs remained indistinguishable across different task responses. We further delved into the role of glutamatergic signaling in cue-triggered turning task (CTTT) performance by manipulating task parameters to increase demands on cue detection. We employed a dual-vector approach to silence corticostriatal projections to confirm the cortical origin of the GLU activity recorded in these experiments. Silencing of this pathway led to cue-triggered turning deficits and attenuated GLU increases in GTs, while STs remained largely unaffected. This discrepancy indicates that STs, characterized by poor attentional control, may compensate for this deficit through bottom-up modulation of GLU release. However, this "replacement" mechanism may prove sufficient for well-practiced, cued movements but is expected to disrupt performance in unfamiliar and dynamic environments. Collectively, these findings shed light on distinct phenotypic variations in cue-guided behavior and have the potential to uncover the underlying neural mechanisms of attentional control in complex movement. Furthermore, delving into the impact of cognitive-motivational styles on corticostriatal glutamatergic signaling may yield invaluable insights into the progression and presentation of various disease states to pave the way for tailored, precise interventions.