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

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.

Dorsal column and root stimulation at Aβ-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations

“… 66 , 67 The mouse spinal cord is well-suited for optical techniques given its size and expanding understanding of the molecularly defined populations processing somatosensation. 19 , 68 , 69 We imaged activity-evoked changes in intracellular calcium using GCaMP6s and deconvolved activity using spike-inference algorithms built into the software CaImAn, an established methodology. 24 , 26 , 70 A recent imaging study demonstrated that calcium responses faithfully encode action potentials in lamina I in mice.…”

Experimental Protocols and Analytical Procedures for Studying Synaptic Transmission in Rodent Spinal Cord Dorsal Horn

“…The identification of the site of modulation (pre‐ versus postsynaptic) is difficult because of the complexity of the system. Several complementary approaches have been used for this purpose, including electrophysiological and analytical procedures, optical recording, and opto‐ or chemogenetic stimulation of specific synaptic inputs (reviewed in Harding, Fung, & Bonin, 2020). The methods described in this article can help address this issue.…”

Differential modulation of thermal preference after sensitization by optogenetic or pharmacological activation of heat-sensitive nociceptors

“…Indeed, selective primary afferent innervation of excitatory and inhibitory interneurons in the spinal dorsal horn allow for varied integration of incoming signals from the periphery. 67 Additionally, artificial single channel driven neuronal activation fails to recapitulate physiological neuronal firing and the change in thermal preference likely requires a host of other changes beyond an increase in the excitability of TrpV1 + afferents.…”