Insights Into Spinal Dorsal Horn Circuit Function and Dysfunction Using Optical Approaches.

Erika K Harding,Samuel Wanchi Fung,Robert P Bonin

doi:10.3389/fncir.2020.00031

Erika K Harding, Samuel Wanchi Fung + Show 1 more

Open Access

https://doi.org/10.3389/fncir.2020.00031

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Abstract

Somatosensation encompasses a variety of essential modalities including touch, pressure, proprioception, temperature, pain, and itch. These peripheral sensations are crucial for all types of behaviors, ranging from social interaction to danger avoidance. Somatosensory information is transmitted from primary afferent fibers in the periphery into the central nervous system via the dorsal horn of the spinal cord. The dorsal horn functions as an intermediary processing center for this information, comprising a complex network of excitatory and inhibitory interneurons as well as projection neurons that transmit the processed somatosensory information from the spinal cord to the brain. It is now known that there can be dysfunction within this spinal cord circuitry in pathological pain conditions and that these perturbations contribute to the development and maintenance of pathological pain. However, the complex and heterogeneous network of the spinal dorsal horn has hampered efforts to further elucidate its role in somatosensory processing. Emerging optical techniques promise to illuminate the underlying organization and function of the dorsal horn and provide insights into the role of spinal cord sensory processing in shaping the behavioral response to somatosensory input that we ultimately observe. This review article will focus on recent advances in optogenetics and fluorescence imaging techniques in the spinal cord, encompassing findings from both in vivo and in vitro preparations. We will also discuss the current limitations and difficulties of employing these techniques to interrogate the spinal cord and current practices and approaches to overcome these challenges.

Highlights

Our physical connection to the world through sensation is essential for our health and wellbeing
One study found that stimulating the anterior cingulate cortex resulted in potentiation of the calcium response in over 50% of pinch-responding neurons in the dorsal horn, indicating rapid descending modulation of spinal cord neuron excitability (Chen et al, 2018). These initial results will be incredibly interesting to investigate further through combination with optogenetic stimulation, or with the labeling of genetically distinct neuronal populations, to begin to delineate which spinal cord cell types contribute to the processing of different sensory modalities
Given the complexity of the circuitry involved in the processing of somatosensory information, these tools promise to aid in unraveling how somatosensory information is encoded and integrated within the spinal cord, and how these processes change in conditions such as pathological pain

Summary

INTRODUCTION

Our physical connection to the world through sensation is essential for our health and wellbeing. Peripheral stimulation is the most cost-effective and straightforward method for optogenetic stimulation of spinal cord circuitry and can be accomplished without the need for surgical intervention, depending on the method of opsin expression Using this technique, the role of different primary afferent populations in various modalities of somatosensation is beginning to be understood and has demonstrated the capacity for light-activated primary afferent stimulation to induce central sensitization within the spinal cord. To dissect out these roles, opsins can be selectively expressed in the spinally-projecting brainstem or brain neurons Using this technique, a novel basolateral amygdala—medial prefrontal cortex—PAG—spinal cord pathway has been identified, that when optogenetically activated, inhibits nocifensive behaviors in mice with a pathological pain condition (Huang et al, 2019). Challenges to Achieving Freely Behaving in vivo Calcium Imaging in the Spinal Cord Effective calcium imaging requires precise spatial and temporal resolution, which can be difficult to achieve in vivo in the spinal

Method of opsin

Findings

SUMMARY AND OUTLOOK