Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

Abstract

The striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1-or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry. Results Optogenetic activation of S1 or M1 corticostriatal afferents differentially engage striatal neuronsWe used optogenetic activation of corticostriatal afferents from S1 or M1 with channelrhodopsin-2 (ChR2) combined with ex vivo whole cell current clamp recordings of identified striatal neurons to determine the striatal circuitry engaged by corticostriatal input from different sources ( Figure 1A ). We chose to investigate the anterior dorsal striatum because of prominent overlap between S1 and M1 inputs in this region ( Supplemental Figure 1 ) [3,4] . Striatal D1-SPNs, D2-SPNs and PV interneurons were identified using tdTomato-expressing reporter mice and verified through their intrinsic properties in response to hyperpolarizing and depolarizing current injection (see Methods) ( Figure 1B-D ). We used current clamp recordings in the absence of inhibitory synaptic blockers, as opposed to voltage clamp recordings, to more closely mirror the natural physiological activity of striatal circuitry in response to S1 or M1 inputs. Activation of ChR2-expressing S1 corticostriatal afferents with a single, full-field light pulse (2.5 ms, 460-500 nm; through the 40x microscope objective) induced a depolarizing postsynaptic potential (PSP) in D1-SPNs, D2-SPNs and PV interneurons ( Figure 1E-G ). PSP amplitude was larger in PV interneurons (12.81 ± 2.37 mV, n = 9 neurons from 8 mice) compared to D1-SPNs (2.73 ± 0.71 mV, n = 17 neurons from 10 mice, p = 0.000008) or D2-SPNs (3.23 ± 0.95 mV, n = 10 neurons from 6 mice, p = 0.0001) (F (2, 33) = 17.64, p = 0.000006; Figure 1H ). Suprathreshold responses were sometimes encountered in PV interneurons, but only rarely in D1-or D2-SPNs. Measurable PSPs were found in all recorded neurons, suggesting that S1 innervates D1-, D2-SPNs and PV interneurons with high probability, but tha...

Effects of Optogenetic Stimulation of Primary Somatosensory Cortex and Its Projections to Striatum on Vibrotactile Perception in Freely Moving Rats

“…In contrast, a previous study reported that neurons in somatosensory cortex preferentially targeting D1 direct pathway neurons trigger actions (Wall et al, 2013). However, neurons in whisker-related primary somatosensory cortex innervate parvalbumin (PV)-expressing interneurons as well (Lee et al, 2019), therefore S1FL might have the potential to improve performance by suppressing undesired actions. Additionally, this study found that optogenetic stimulation of S1 corticostriatal afferents led to less responses in the tactile discrimination task, which is different from our results.…”

Multimodal sensorimotor integration of visual and kinaesthetic afferents modulates motor circuits in humans

“…Putative multi-modality neurons [30], [31], [32], [33] in motor-related cortices could take over this task of multisensory-integration projecting to the primary motor cortex. More recently, a significant role in sensorimotor integration has been attributed to the striatum [34]. If kinaesthetic-and visual information are processed in the same way during motor preparation, we proposed above, both, seeing a movement and feeling a passive movement should enhance the corticospinal excitability.…”

Activation of parvalbumin‐expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

“…Previous work has shown strong cortical and thalamic connectivity to PV+ striatal neurons (Arias-García et al, 2018;Assous & Tepper, 2019;Choi et al, 2019;Lee et al, 2019;Melzer et al, 2017;Ramanathan et al, 2002), which are more responsive than SPNs (Gittis et al, 2010;Koós et al, 2004;Mallet et al, 2005;Planert et al, 2010;Tecuapetla et al, 2007). Also, connections between SPNs (Chuhma, Tanaka, Hen, & Rayport, 2011;Czubayko & Plenz, 2002;Tecuapetla et al, 2007;Tunstall, Oorschot, Kean, & Wickens, 2002) whose lateral inhibition (Burke et al, 2017;Dobbs et al, 2016;Guzmán et al, 2003) and their differential responses to afferent inputs, dopamine (DA) and acetylcholine (ACh) may also help to achieve this result (Assous & Tepper, 2019;Dobbs et al, 2016;Flores-Barrera, Vizcarra-Chacón, Bargas, Tapia, & Galarraga, 2011;Flores-Barrera, Vizcarra-Chacón, Tapia, Bargas, & Galarraga, 2010;Garas et al, 2016;García-Vilchis et al, 2019;Gittis et al, 2010;Guzmán et al, 2003;Taverna, Canciani, & Pennartz, 2007;Tecuapetla et al, 2007;Tecuapetla, Koós, Tepper, Kabbani, & Yeckel, 2009).…”