Distinct Age-Dependent C Fiber-Driven Oscillatory Activity in the Rat Somatosensory Cortex

Abstract

When skin afferents are activated, the sensory signals are transmitted to the spinal cord and eventually reach the primary somatosensory cortex (SI), initiating the encoding of the sensory percept in the brain. While subsets of primary afferents mediate specific somatosensory information from an early age, the subcortical pathways that transmit this information undergo striking changes over the first weeks of life, reflected in the gradual emergence of specific sensory behaviours. We therefore hypothesised that this period is associated with differential changes in the encoding of incoming afferent volleys in SI. To test this, we compared SI responses to A fibre skin afferent stimulation and A+C skin afferent fibre stimulation in lightly anaesthetised male rats at postnatal day (P) 7, 14, 21 and 30. Differences in SI activity following A and A+C fibre stimulation changed dramatically over this period. At P30, A+C fibre stimulation evoked significantly larger gamma, beta and alpha energy increases compared to A fibre stimulation alone. At younger ages, the changes in S1 oscillatory activity evoked by the two afferent volleys were not significantly different. Silencing TRPV1+ C fibres with QX-314 significantly reduced the gamma and beta SI oscillatory energy increases evoked by A+C fibres, at P30 and P21, but not at younger ages. Thus, C fibres differentially modulate SI oscillatory activity only from the third postnatal week, well after the functional maturation of the somatosensory cortex. This age-related change in afferent evoked S1 oscillatory activity may underpin the maturation of sensory discrimination in the developing brain. Significance Statement Behavioural responses to sensory stimulation of the skin undergo major developmental changes over the first postnatal weeks. Here we show that this is accompanied by a shift in the differential frequency encoding of sensory A fibre and C fibre afferent inputs into the developing rat somatosensory cortex. The results demonstrate major postnatal changes in the ability of the cortex to differentiate between afferent sensory inputs arriving in the mammalian brain.

Premature infants display discriminable behavioral, physiological, and brain responses to noxious and nonnoxious stimuli

“…An important next step is to investigate the development of the spatial organization of the noxious-related brain activity in preterm infants using techniques such as fMRI, which have successfully been used in term infants ( Goksan et al 2015 ; Williams et al 2015 ; Duff et al 2020 ). Importantly, the emergence of remarkably similar patterns of noxious-evoked activity have also been observed in rat pups after sensory fiber stimulation ( Chang et al 2020 ), facilitating the translation between laboratory and clinical investigations.…”

Widespread nociceptive maps in the human neonatal somatosensory cortex

“…In rodents, at every level of the developing somatosensory central nervous system, tactile processing matures before nociceptive processing ( Fitzgerald, 2005 ; Koch and Fitzgerald, 2013 ; Chang et al, 2016 ; Chang et al, 2020 ; Verriotis et al, 2016a ) consistent with a delayed refinement of a cortical nociceptive map. Widespread nociceptive cortical maps are consistent with infant pain behaviour, characterised by exaggerated and disorganised nociceptive reflexes in both rodent pups and human neonates ( Fitzgerald, 2005 ; Fitzgerald, 2015 ), and which can fail to remove a body part from the source of pain ( Waldenström et al, 2003 ).…”

Early life pain experience changes adult functional pain connectivity in the rat somatosensory and the medial prefrontal cortex

“…In humans, gamma-band oscillations in the primary somatosensory cortex correlate with subjective pain perception (Zhang et al, 2012; Heid et al, 2020) and in mice they are specifically strengthened, independently of any motor component, in the S1 cortex during nociception and are elevated during pain hypersensitivity (Tan et al, 2019). Nociceptive C fibre stimulation drives gamma activity in adult rat S1 (Chang et al, 2020b) and gamma oscillations generated by optogenetic activation of parvalbumin-expressing inhibitory interneurons in the S1 cortex enhance nociceptive sensitivity and induce aversive avoidance behaviour, while activating a network of prefrontal cortical and subcortical centres including descending serotonergic facilitatory pathways (Tan et al, 2021). Recent evidence suggests that gamma oscillations reflect strongly coupling of neural activity with fast spiking interneurons in the superficial layers of the S1 contralateral to the stimulated side (Yue et al, 2020).…”

“…To address whether ELP impacts upon cortical function from the sensory-discriminative and emotional/cognitive perspectives, the S1 and mPFC are attractive targets (Tan and Kuner, 2021). S1 is a functionally defined part of the somatosensory and nociceptive system and processes sensory nociceptive information about pain from an early age in both rodents and humans (Chang et al, 2016, 2020b; Jones et al, 2021). S1 encodes nociceptive intensity and perceived pain intensity (Mancini et al, 2012) and gamma-band oscillations in this area correlate with subjective pain perception (Ong et al, 2019).…”