Distinct mechanisms of signal processing by lamina I spino-parabrachial neurons

Abstract

Lamina I spino-parabrachial neurons (SPNs) receive peripheral nociceptive input, process it and transmit to the supraspinal centres. Although responses of SPNs to cutaneous receptive field stimulations have been intensively studied, the mechanisms of signal processing in these neurons are poorly understood. Therefore, we used an ex-vivo spinal cord preparation to examine synaptic and cellular mechanisms determining specific input-output characteristics of the neurons. The vast majority of the SPNs received a few direct nociceptive C-fiber inputs and generated one spike in response to saturating afferent stimulation, thus functioning as simple transducers of painful stimulus. However, 69% of afferent stimulation-induced action potentials in the entire SPN population originated from a small fraction (19%) of high-output neurons. These neurons received a larger number of direct Aδ- and C-fiber inputs, generated intrinsic bursts and efficiently integrated a local network activity via NMDA-receptor-dependent mechanisms. The high-output SPNs amplified and integrated the nociceptive input gradually encoding its intensity into the number of generated spikes. Thus, different mechanisms of signal processing allow lamina I SPNs to play distinct roles in nociception.

Spinoparabrachial projection neurons form distinct classes in the mouse dorsal horn

“…This suggests functionally discrete LI SPBN subpopulations exist to play different roles in relaying sensory signals to the brain as has been recently highlighted. 15 Examples of correspondence between the LI SPBN clusters and other classifications based on afferent responsiveness 1 and modality selectivity 26 reinforce the heterogeneity of these important spinal cord output neurons. We also provide the first data on intrinsic and synaptic properties of deeper LIII-V SPBNs and show they are electrophysiologically distinct from their more superficial counterparts in lamina I.…”

“…This aligns with recent work in rat describing 3 functionally distinct PN groups, distinguishable on AP spiking evoked by dorsal root (afferent) input. 1 High-output PNs responded with extended AP discharge, low-output PNs responded with a single AP, and a small proportion of PNs exhibited intermediate responses. Among other features, burst firing during depolarising current injections was prominent in the high-output subpopulation.…”

“… 44 Rat lamina I projection neuron spiking has also been characterised after single dorsal root stimuli, distinguishing high, medium, and low responders based on the degree of spiking. 1 Projection neuron characterisation in the mouse is less common but recent work has identified distinct projection neuron populations encoding various intensities and modalities of sensory stimuli in labelled ascending lines for perception. 15 Given that lamina I projection neurons display a range of electrophysiological and modality coding properties, it is highly likely that these underlie distinct roles played by functionally defined subpopulations in sensory experience.…”

Excitatory and Inhibitory Neurons of the Spinal Cord Superficial Dorsal Horn Diverge in Their Somatosensory Responses and Plasticityin Vivo

“…Congruently, nearly all the excitatory and inhibitory neurons identified in our temperature studies were also mechanosensitive. This multimodality of SDH neurons argues against strict labeled lines in somatosensory coding (Ma, 2010;Prescott et al, 2014) but in turn raises interesting questions about how population coding can convey distinct qualities of somatosensation and differentiate innocuous and noxious stimuli, especially as information must pass through broadly tuned projection neurons before reaching higher pain centers (Agashkov et al, 2019).…”

Presynaptic Interactions between Trigeminal and Cervical Nociceptive Afferents Supplying Upper Cervical Lamina I Neurons

“…The afferent-driven presynaptic inhibition of the dorsal horn neuronal network, that is seen as an overall reduction of the monosynaptic and polysynaptic EPSC components, further shapes input to convergent neurons. This mechanism could have a substantial impact on the long-lasting discharge of spinoparabrachial Lamina I neurons that is driven by strong polysynaptic inputs (Agashkov et al, 2019). Interestingly, C2 SN conditioning completely abolished the polysynaptic input from the TN in cervical-specific neurons, thus preventing them from being excited by the trigeminal afferent volley.…”