Biology subjects

Yonk, A. J.

Publications and source records attributed to Yonk, A. J..

4 recordsLinked to original sources

bioRxiv2025

Neuropathic pain drives time-dependent reorganization of corticostriatal circuits

Chronic pain fundamentally alters sensorimotor integration and motivated behaviors, yet the neural mechanisms underlying this transition remain poorly understood. The striatum, composed of dopamine receptor type 1 (D1)- and type 2 (D2)-expressing spiny projection neurons (SPN), integrates cortical sensory and motor inputs to coordinate movement and motivation, making it a critical candidate for mediating pain-induced behavioral adaptations. Although spinal and cortical pain circuits are well-characterized in limited phases of pain, how corticostriatal pathways and distinct striatal cell populations contribute to the transition from acute to chronic pain states remains unclear. Here we show that neuropathic pain, after spared nerve injury in mice, produces temporally distinct, cell-type-specific changes in striatal SPN activity and corticostriatal plasticity that evolve across acute to chronic pain phases. D1 SPNs exhibit smaller amplitude and slower calcium signals during acute pain stages that persist through early chronic phases, while D2 SPNs show delayed response timing during later chronic stages, but also stimulus-specific alterations in neural activity throughout acute and chronic pain states. Critically, primary somatosensory cortex inputs to D2 SPNs develop depressing synapses specifically during intermediate chronic pain phases ([~]25 days post-injury) that disappear during more severe chronic stages (>3 months), suggesting a failed compensatory mechanism. These findings reveal that striatal circuits undergo dynamic, time-dependent reorganization after peripheral injury, with D1 and D2 pathways contributing distinct temporal signatures to pain-related behavior. The identification of critical windows of striatal plasticity provides new targets for therapeutic interventions that could prevent or reverse chronic pain states by modulating specific corticostriatal circuits during vulnerable transition periods.

neuroscience↗

bioRxiv2024

Role of Posterior Medial Thalamus in the Modulation of Striatal Circuitry and Choice Behavior

The posterior medial (POm) thalamus is heavily interconnected with sensory and motor circuitry and is likely involved in behavioral modulation and sensorimotor integration. POm provides axonal projections to the dorsal striatum, a hotspot of sensorimotor processing, yet the role of POm-striatal projections has remained undetermined. Using optogenetics with slice electrophysiology, we found that POm provides robust synaptic input to direct and indirect pathway striatal spiny projection neurons (D1- and D2-SPNs, respectively) and parvalbumin-expressing fast spiking interneurons (PVs). During the performance of a whisker-based tactile discrimination task, POm-striatal projections displayed learning-related activation correlating with anticipatory, but not reward-related, pupil dilation. Inhibition of POm-striatal axons across learning caused slower reaction times and an increase in the number of training sessions for expert performance. Our data indicate that POm-striatal inputs provide a behaviorally relevant arousal-related signal, which may prime striatal circuitry for efficient integration of subsequent choice-related inputs.

neuroscience↗

bioRxiv2023

Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum

The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and is considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in the strength of their connections with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert an opposing influence on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that SPNs are less innervated by S1 compared to M1, but FSIs receive a similar number of inputs from both M1 and S1. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPNs and FSIs. Notably, clusters of inputs were prevalent in SPNs but not FSIs. Our results suggest that SPNs have stronger functional connectivity to M1 compared to S1 due to a higher density of synaptic inputs. The clustering of M1 and S1 inputs onto SPNs but not FSIs suggest that cortical inputs are integrated through cell-type specific mechanisms and more generally have implications for how sensorimotor integration is performed in the striatum. Significance StatementThe dorsolateral striatum (DLS) is a key brain area involved in sensorimotor integration due to its dense innervation by the primary motor (M1) and sensory cortex (S1). However, the quantity and anatomical distribution of these inputs to the striatal cell population has not been well characterized. In this study we demonstrate that corticostriatal projections from M1 and S1 differentially innervate spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS. S1 inputs innervate SPNs less than M1 and are likely to form synaptic clusters in SPNs but not in FSIs. These findings suggest that sensorimotor integration is partly achieved by differences in the synaptic organization of corticostriatal inputs to local striatal microcircuits.

neuroscience↗

bioRxiv2018

Opposing Influence of Sensory and Motor Cortex on Striatal Circuitry and Choice Behavior

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.

neuroscience↗