Concurrent activation of striatal direct and indirect pathways during action initiation

Abstract

Summary The basal ganglia are subcortical nuclei that control voluntary actions, and are affected by a number of debilitating neurological disorders1–4. The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum5,6 - the so-called direct and indirect pathways - have opposing effects on movement: while activity of direct-pathway SPNs purportedly facilitates movement, activity of indirect-pathway SPNs inhibits movement1,2. This model has been difficult to test due to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals. We developed a novel in-vivo method that allowed us to specifically measure direct- and indirect-pathway SPN activity using Cre-dependent viral expression of the genetically encoded calcium indicator (GECI) GCAMP3 in the dorsal striatum of D1-Cre (direct-pathway specific6,7) and A2A-Cre (indirect-pathway specific8,9) mice10. Using fiber optics and time-correlated single photon counting (TCSPC) in mice performing an operant task, we observed transient increases in neural activity in both direct- and indirect-pathway SPNs when animals initiated actions, but not when they were inactive. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements, and predicted the occurrence of specific movements within 500 ms. These observations challenge the classical view of basal ganglia function, and may have implications for understanding the origin of motor symptoms in basal ganglia disorders.

Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice

“…other deep networks, and are thought to represent network firing bursts (24)(25)(26). Using simultaneous electrical recordings and GCaMP6s imaging from the same GAD65 LH -GCaMP6s cells in vitro, we confirmed that GCaMP6s linearly reports spike firing rate (Fig.…”

Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

“…This interpretation is congruous with the canonical view of the basal ganglia in the generation of motoric responses (Albin et al, 1989;DeLong, 1990), a theory that received recent validation using modern neuroscientific and computational techniques (Dreyer et al, 2010;Kravitz et al, 2012; but see Cui et al, 2013). According to this theory, high concentration surges in dopamine release activate striatal medium spiny neurons comprising the direct pathway to promote directed action sequences (eg, reinforcement-directed active lever response), whereas moderate dopamine concentrations activate striatal medium spiny neurons comprising the indirect pathway to inhibit directed action sequences, and possibly switch the motivational drive of the animal to seek out alternative options (Dreyer et al, 2010;Kravitz et al, 2012).…”

Action, time and the basal ganglia

“…A velocity reference signal enters the basal ganglia circuit which then generates opponent configuration reference signals that are sent to the level below. One possible neural implementation is suggested by the anatomy: the excitatory input to the striatum activates both the striatonigral and striatopallidal pathways [61], and the intrinsic organization of these two pathways transforms the uniform excitation into a pair of signals, one increasing and the other decreasing from a common mode signal. And finally, a time integral can be produced in the basal ganglia transforming a given magnitude of velocity error into a rate of change in the reference signal for body configuration control.…”