Synchronous firing of dorsal horn neurons at the origin of dorsal root reflexes in naïve and paw-inflamed mice

Abstract

Spinal interneurons located in the dorsal horn induce primary afferent depolarization (PAD) controlling the excitability of the afferent’s terminals. Following inflammation, PAD may reach firing threshold contributing to maintain inflammation and pain. Our aim was to study the collective behavior of dorsal horn neurons, its relation to backfiring of primary afferents and the effects of a peripheral inflammation in this system. Experiments were performed on slices of spinal cord obtained from naïve adult mice or mice that had suffered an inflammatory pretreatment. Simultaneous recordings from groups of dorsal horn neurons and primary afferents were obtained and machine-learning methodology was used to analyze effective connectivity between them. Dorsal horn recordings showed grouping of spontaneous action potentials from different neurons in “population bursts.” These occurred at irregular intervals and were formed by action potentials from all classes of neurons recorded. Compared to naïve, population bursts from treated animals concentrated more action potentials, had a faster onset and a slower decay. Population bursts were disrupted by perfusion of picrotoxin and held a strong temporal correlation with backfiring of afferents. Effective connectivity analysis allowed pinpointing specific neurons holding pre- or post-synaptic relation to the afferents. Many of these neurons had an irregular fast bursting pattern of spontaneous firing. We conclude that population bursts contain action potentials from neurons presynaptic to the afferents which are likely to control their excitability. Peripheral inflammation may enhance synchrony in these neurons, increasing the chance of triggering action potentials in primary afferents and contributing toward central sensitization.

Spike inference from mouse spinal cord calcium imaging data

“…Since in vivo ground truth recordings in spinal cord during behavior are hardly feasible, due to the general difficulty of access and due to prominent motion artifacts (Johannssen and Helmchen, 2010;Nelson et al, 2019;Sullivan and Sdrulla, 2022), our ground truth recordings represent a compromise that matches the natural conditions as much as possible. In our ground truth recordings, spike patterns included both bursts and more regular spiking patterns, which is in agreement with observations in vitro and in vivo across multiple species both for spontaneous and stimulus-evoked patterns (Kumazawa and Perl, 1978;Lucas-Romero et al, 2022Medrano et al, 2016;Sandkühler and Eblen-Zajjur, 1994). A caveat to keep in mind is that there are diverging definitions of specific spike patterns across fields.…”

“…5). We would like to clarify that both event types overlap but do not coincide with the definition of "bursty" spike patterns defined in previous studies on the spinal cord (Lucas-Romero et al, 2022. Irrespective of these definitions, our dataset (>70,000 action potentials over 7.4 hours of recording) includes a diversity of firing patterns and can therefore be seen as the best available dataset to train a supervised algorithm for spike inference for spinal cord neurons.…”

Neural population dynamics reveal that motor-targeted intraspinal microstimulation preferentially depresses nociceptive transmission in spinal cord injury-related neuropathic pain

“…Second, it is possible that ISMS promoted different neuronal discharge states across animals with SCI-NP and those without. WDR neurons have the capacity to manifest at least 3 discharge states: tonic firing (i.e., effectively tracking synaptic input 1-to-1), plateau potentials, and intrinsic bursting (Derjean et al, 2003), for example; motoneurons and other interneurons can likewise inhabit different firing states (Bandres et al, 2021;Dougherty and Chen, 2016;Lucas-Romero et al, 2022;Lucas-Romero et al, 2018;Steedman and Zachary, 1990;Stein et al, 2005). Each of these states has implications for the fidelity of information transfer through the cell.…”

Ca2+-Permeable AMPA Receptors Contribute to Changed Dorsal Horn Neuronal Firing and Inflammatory Pain

“…Peripheral inflammation triggered by locally released inflammatory mediators and signalling molecules causes an increased firing of primary nociceptive afferents [28]-peripheral sensitization [7,29]-those transfer action potential (AP) patterns to the DH of the spinal cord. There was reported an increased level of pro-inflammatory mediators within the spinal cord [30,31] and changes in some of the intrinsic properties of the superficial (lamina I-II) DH neurons, such as decreased input resistance [32], augmented spontaneous activity [5], and synchronous burst firing [33]. The lamina I-II DH neurons are in their majority interneurons, which make the first-order synapses with the nociceptive afferents and are primarily involved in computing incoming sensory inputs before conveying the output signals to the higher central pathways.…”