Lamina‐specific population encoding of cutaneous signals in the spinal dorsal horn using multi‐electrode arrays

Abstract

Key points Traditional, widely used in vivo electrophysiological techniques for the investigation of spinal processing of somatosensory information fail to account for the diverse functions of each lamina.To overcome this oversimplification, we have used multi‐electrode arrays, in vivo, to simultaneously record neuronal activity across all laminae of the spinal dorsal horn.Multi‐electrode arrays are sensitive enough to detect lamina‐ and region‐specific encoding of different subtypes of afferent fibres and to detect short‐lived changes in synaptic plasticity as measured by the application of cutaneous electrical stimulation of varying intensity and frequency.Differential encoding of innocuous and noxious thermal and mechanical stimuli were also detected across the laminae with the technique, as were the effects of the application of capsaicin.This new approach to the study of the dorsal spinal cord produces significantly more information per experiment, permitting accelerated research whilst also permitting the effects of pharmacological tools to modulate network responses. AbstractThe dorsal horn (DH) of the spinal cord is a complex laminar structure integrating peripheral signals into the central nervous system. Spinal somatosensory processing is commonly measured electrophysiologically in vivo by recording the activity of individual wide‐dynamic‐range neurons in the deep DH and extrapolating their behaviour to all cells in every lamina. This fails to account for the specialized processes that occur in each lamina and the considerable heterogeneity in cellular phenotype within and between laminae. Here we overcome this oversimplification by employing linear multi‐electrode arrays (MEAs) in the DH of anaesthetized rats to simultaneously measure activity across all laminae. The MEAs, comprising 16 channels, were inserted into the lumbar dorsal horn and peripheral neurons activated electrically via transcutaneous electrodes and ethologically with von Frey hairs (vFHs) or an aluminium heating block. Ascending electrical stimuli showed fibre thresholds with distinct dorsoventral innervation profiles. Wind up was observed across the DH during the C‐fibre and post‐discharge latencies following 0.5 Hz stimulation. Intrathecal application of morphine (5 ng/50 μl) significantly reduced Aδ‐ and C‐fibre‐evoked activity in deep and superficial DH. Light vFHs (≤10 g) predominantly activated intermediate and deep laminae whereas noxious vFHs (26 g) also activated the superficial laminae. Noxious heat (55°C) induced significantly greater activity in the superficial and deep laminae than the innocuous control (30°C). The application of these arrays produced the first description of the processing of innocuous and noxious stimuli throughout the intact DH.

Methodology for quantifying excitability of identified projection neurons in the dorsal horn of the spinal cord, specifically to study spinal cord stimulation paradigms

“…Many in vivo electrophysiologists are now using electrodes with multiple contacts to record from more than one neuron during a protocol, with a single probe containing 384 recording channels (Jun et al, 2017) or being inserted into multiple lamina within the spinal cord (Greenspon et al, 2018).…”

Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain

“…The final window timings for each stimulation paradigm are displayed in table 1. Previous studies have reported a sustained elevated response to thermal stimulation after cessation of the stimulus [50,51]; we therefore also analysed a second window for noxious thermal responses from the end of the stimulus response window (1.5 s post-stimulus onset) to the end of our recording block (4.5 s post-stimulus onset). For this condition, as we did not have 3 s of pre-stimulus data, a 1 s pre-stimulus window was used and spike counts were multiplied by 3.…”

The Effect of Pre-Electroacupuncture on Nociceptive Discharges of Spinal Wide Dynamic Range Neurons in Rat

“…A feedback-controlled heating blanket (ALC-HTP, Shanghai Alcott Biotech Co., People's Republic of China) was used to monitor and maintain core body temperature at 37.0 ± 0.5°C. 22 Extracellular Recording of the SDH Neurons Extracellular recording of SDH neurons was performed at L4-6 segments through a 5 MΩ parylene-coated tungsten microelectrode 23 (575,500, A-M Systems, Sequim, WA, United States) or a microelectrode array 24 (ASSY, Lotus Biochips, United States) (Figure 1A and B). After surgery, recording electrodes were inserted perpendicularly into the SDH at a depth of approximately 600-1400 μm from the dorsal surface and 0.3 mm lateral to the central vessel by a micromanipulator (DMA-1510, Narishige, Japan).…”