Sensory input plays critical roles in the development of the somatosensory cortex during the neonatal period. This early sensory input may involve: (1) stimulation arising from passive interactions with the mother and littermates and (2) sensory feedback arising from spontaneous infant movements. The relative contributions of these mechanisms under natural conditions remain largely unknown, however. Here, we show that, in the whisker-related barrel cortex of neonatal rats, spontaneous whisker movements and passive stimulation by the littermates cooperate, with comparable efficiency, in driving cortical activity. Both tactile signals arising from the littermate's movements under conditions simulating the littermates' position in the litter, and spontaneous whisker movements efficiently triggered bursts of activity in barrel cortex. Yet, whisker movements with touch were more efficient than free movements. Comparison of the various experimental conditions mimicking the natural environment showed that tactile signals arising from the whisker movements with touch and stimulation by the littermates, support: (1) a twofold higher level of cortical activity than in the isolated animal, and (2) a threefold higher level of activity than in the deafferented animal after the infraorbital nerve cut. Together, these results indicate that endogenous (self-generated movements) and exogenous (stimulation by the littermates) mechanisms cooperate in driving cortical activity in newborn rats and point to the importance of the environment in shaping cortical activity during the neonatal period.SIGNIFICANCE STATEMENTSensory input plays critical roles in the development of the somatosensory cortex during the neonatal period. However, the origins of sensory input to the neonatal somatosensory cortex in the natural environment remain largely unknown. Here, we show that in the whisker-related barrel cortex of neonatal rats, spontaneous whisker movements and passive stimulation by the littermates cooperate, with comparable efficiency, in driving cortical activity during the critical developmental period.

Isoflurane and other volatile anesthetics are widely used in children to induce deep and reversible coma, but they may also exert neurotoxic actions. The effects of volatile anesthetics on the immature brain activity remain elusive, however. The effects of isoflurane on spontaneous and sensory-evoked activity were explored using intracortical extracellular field potential and multiple unit recordings in the rat barrel cortex from birth to adulthood. During the first postnatal week, isoflurane suppressed cortical activity in a concentration-dependent manner. At surgical anesthesia levels (1.5–2%), isoflurane completely suppressed the electroencephalogram and silenced cortical neurons. Although sensory potentials evoked by the principal whisker deflection persisted, sensory-evoked early gamma and spindle-burst oscillations were completely suppressed by isoflurane. Isoflurane-induced burst-suppression pattern emerged during the second postnatal week and matured through the first postnatal month. Bursts in adolescent and adult rats were characterized by activation of entire cortical columns with a leading firing of infragranular neurons, and were triggered by principal and adjacent whiskers stimulation, and by auditory and visual stimuli, indicating an involvement of horizontal connections in their generation and horizontal spread. The effects of isoflurane on cortical activity shift from total suppression of activity to burst-suppression pattern at the end of the first postnatal week. Developmental emergence of bursts likely involves a development of the intracortical short- and long-range connections. We hypothesize that complete suppression of cortical activity under isoflurane anesthesia during the first postnatal week may explain neuronal apoptosis stimulated by volatile anesthetics in the neonatal rats.

Trigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the TRPV1 agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters) were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish ‘responder’ (65%) from ‘non-responder’ clusters (35%). Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at spinal cord level. Almost all spikes were suppressed by TTX suggesting an involvement of the TTX-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing) and long-lasting (slowly desensitizing,) responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine.