Concurrent Activation of Striatal Direct and Indirect Pathways During Action Initiation

By Guo-fang Cui, S. Jun, Xin Jin, Michael D. Pham, Steven S. Vogel, D. Lovinger, Rui M. Costa. Nature, 2013

1,156 citations recorded by the source corpus.

The basal ganglia are subcortical nuclei that control voluntary actions, and they are affected by a number of debilitating neurological disorders. The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum—the so-called direct and indirect pathways—have opposing effects on movement: activity of direct-pathway SPNs is thought to facilitate movement, whereas activity of indirect-pathway SPNs is presumed to inhibit movement. This model has been difficult to test owing to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals. Here we develop a novel in vivo method 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-specific) and A2A-Cre (indirect-pathway-specific) mice. Using fibre 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.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/8b3f9269f926472aa982c8cfdb521580f087b46b

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Citations in the corpus

A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain (2018, background): “…with canonical SPNs suggests eSPNs have been molecularly “camouflaged,” including in studies using mice that have employed Drd1 and Adora2a driven – transgenes to label and manipulate dSPNs or iSPNs (Cui et al., 2014; Kozorovitskiy et al., 2012; Kravitz et al., 2010; Oldenburg and Sabatini, 2015).”
The Neuroscience of Drug Reward and Addiction. (2019, neutral): “For example, studies have shown that in the dorsal striatum both D1R-MSNs (direct) and D2R-MSNs (indirect) are activated when initiating an action (75).”
Schizophrenia, Dopamine and the Striatum: From Biology to Symptoms (2019, result): “Moreover, recent findings indicate that neural activity in both pathways increases when animals initiate behaviour, in contrast to the classical accelerator/ brake model [33,34].”
Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors (2018, background): “Much work has been devoted to determining how neural representations of behavioral states are encoded in the firing patterns of neuromodulatory neurons (4–9), but very little is known about how the precise release of neuromodulators alters the function of their target circuits (10, 11).”
Neural Circuit Motifs in Valence Processing (2018, neutral): “More often than not, the neurons that diverge from a given region may locally interact and therefore show coordinated activation during natural behaviors (Beyeler et al., 2018; Calhoon et al., 2018; Cui et al., 2013).”
A Sensorimotor Circuit in Mouse Cortex for Visual Flow Predictions. (2017, neutral): “The other is that this hemispheric bias is a consequence of a general bias of neural activity to the laterality of themovement, which has been described in motor cortex (Li et al., 2015) and the striatum (Cui et al., 2013).”