Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information

Abstract

Summary An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information, and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior.

Striatal synapses, circuits, and Parkinson's disease

“…How these cellular and network adaptations dictate behavior remains unanswered, but the rapid evolution of in vivo recording techniques that can be applied to awake, unanesthetized animals is sure to provide new insights in the near future. Although it was believed for decades that direct and indirect pathways had opposing effects on behavioral output, a rapidly growing body of evidence suggests that this model is oversimplified — coordinated activity and spatiotemporal organization of neuronal ensembles of both pathways are critical to behavior [90*,91–93]. It would be invaluable to determine how these additional dimensions are altered in parkinsonian state.…”

Striatal Local Circuitry: A New Framework for Lateral Inhibition

“…Recent work in the dorsal striatum using calcium imaging with fiber photometry (Cui et al, 2014; Tecuapetla et al, 2014), deep brain calcium imaging (Barbera et al, 2016), and in vivo electrophysiology in which SPN subtypes were identified with optogenetic tagging (Jin et al, 2014) or post hoc in situ hybridization (Isomura et al, 2013), have all demonstrated that both dSPNs and iSPNs are more active when an animal is performing a task or freely moving and less active when the animal is not moving or engaged in a task (though dSPNs and iSPNs have differing activity patterns). These data imply that iSPNs and dSPNs are coactive during action initiation and that the direct and indirect pathways are both necessary to facilitate actions.…”

“…An important question then is how to reconcile the findings from optogenetic stimulation experiments suggesting that iSPN activation inhibits movement (Kravitz et al, 2010) with those from calcium dynamics showing iSPN activation during action initiation and behavior (Barbera et al, 2016; Cui et al, 2014; Natsubori et al, 2017). The most parsimonious explanation is that during behavior, dSPNs facilitate the desired behavior, while iSPNs act simultaneously to inhibit all other competing undesirable behaviors (see more in section 3).…”

“…Other groups have visualized SPN network activity using calcium indicators both in vitro and in vivo to provide evidence that SPNs are organized into neuronal clusters based on synchronized activation that might represent functional ensembles (Barbera et al, 2016; Carrillo-reid et al, 2008; Carrillo-Reid et al, 2011). In light of this, many computational models have attempted to explain how feedforward inhibition, mediated by PV cells, and lateral inhibition, mediated by SPN collaterals, could generate these ensembles and thereby transform information flow through the striatum (Humphries et al, 2010, 2009; Moyer et al, 2014; Ponzi and Wickens, 2012, 2010, 2013; Yim et al, 2011).…”

Skin suturing and cortical surface viral infusion improves imaging of neuronal ensemble activity with head-mounted miniature microscopes

“…This technique usually requires the insertion of a small graded-index (GRIN) optical lens inside the brain, and has been successfully used to study the function of deep brain structures such as the hippocampus (Okuyama et al, 2016; Ziv et al, 2013), amygdala (Grewe et al, 2017), striatum (Barbera et al, 2016) and hypothalamus (Jennings et al, 2015). However, the cerebral cortex located at the top of the brain has not yet been extensively studied through this technique (Pinto and Dan, 2015).…”