Pathway-Specific Striatal Substrates for Habitual Behavior

Abstract

The dorsolateral striatum (DLS) is implicated in habit formation. However, the DLS circuit mechanisms underlying habit remain unclear. A key role for DLS is to transform sensorimotor cortical input into firing of output neurons that project to the mutually antagonistic direct and indirect basal ganglia pathways. Here we examine whether habit alters this input-output function. By imaging cortically-evoked firing in large populations of pathway-defined striatal projection neurons (SPNs), we identify features that strongly correlate with habitual behavior on a subject-by-subject basis. Habitual behavior correlated with strengthened DLS output to both pathways as well as a tendency for action-promoting direct pathway SPNs to fire before indirect pathway SPNs. In contrast, habit suppression correlated solely with a weakened direct pathway output. Surprisingly, all effects were broadly distributed in space. Together, these findings indicate that the striatum imposes broad, pathway-specific modulations of incoming activity to render learned motor behaviors habitual.

Parvalbumin Interneurons Modulate Striatal Output and Enhance Performance during Associative Learning

“…The DLS is innervated by glutamatergic afferents from sensorimotor cortical areas (Hintiryan et al, 2016; McGeorge and Faull, 1989; Pennartz et al, 2009). The experience-dependent increase in MSN activity which was observed here, and in other studies (Barnes et al, 2005; Jin and Costa, 2010; Jog et al, 1999; Kimchi et al, 2009; Miyachi et al, 2002; Thorn et al, 2010; Yin et al, 2009), is consistent with an enhancement of corticostriatal coupling that accompanies some forms of learning (Koralek et al, 2013; O’Hare et al, 2016; Xiong et al, 2015). Thus, our results suggest that PV interneurons regulate MSN firing rate by a relatively fixed amount across all stages of training, compared to other inputs whose strength increases as animals gain experience.…”

Increased Metabotropic Glutamate Receptor 5 Signaling Underlies Obsessive-Compulsive Disorder-like Behavioral and Striatal Circuit Abnormalities in Mice

“…To elucidate how the various consequences of elevated striatal mGluR5 signaling ultimately integrate within the striatal microcircuit to affect SPN firing, we used an approach we recently established that measures striatal output while preserving the influence of local circuit features (28). With the use of multiphoton laser vector-line scan microscopy of the calcium indicator dye, Fura-2, to visualize APs, we evoked SPN Firing by electrical stimulation of excitatory afferents (28) (Figure 2A–C).…”

“…(28). Briefly, acute parasagittal (300 µm) slices, corresponding to tissue approximately 300–900 µm medial to the first visible lateral aspect of dorsal striatum, were bulk loaded with the calcium indicator dye, Fura-2 AM (F-1221; Thermo Fisher Scientific, Waltham, MA) (Supplement).…”

Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex Regulation and Interplay with Memory and Decision Processes

“…Here we showed that modulation of the relative weights of the BG pathways could effectively modulate the SSRT, which provides a possible source for individual difference of the SSRT. Recently, goal directed or habitual behavior in rodents was associated with latency changes for the activation of direct and indirect pathways striatal neurons (O’Hare et al, 2016). It has been found that in goal directed response the indirect pathway striatal neurons showed a shorter latency than the direct pathway neurons.…”