Layer-specific pain relief pathways originating from primary motor cortex.

The primary motor cortex (M1) is involved in the control of voluntary movements and is extensively mapped in this capacity. Although the M1 is implicated in modulation of pain, the underlying circuitry and causal underpinnings remain elusive. We unexpectedly unraveled a connection from the M1 to the nucleus accumbens reward circuitry through a M1 layer 6-mediodorsal thalamus pathway, which specifically suppresses negative emotional valence and associated coping behaviors in neuropathic pain. By contrast, layer 5 M1 neurons connect with specific cell populations in zona incerta and periaqueductal gray to suppress sensory hypersensitivity without altering pain affect. Thus, the M1 employs distinct, layer-specific pathways to attune sensory and aversive-emotional components of neuropathic pain, which can be exploited for purposes of pain relief.

Higher-Order Thalamic Encoding of Somatosensory Patterns and Bilateral Events.

The function of the higher-order sensory thalamus remains unclear. Here, the posterior medial (POm) nucleus of the thalamus was examined by in vivo extracellular recordings in anesthetized rats across a variety of contralateral, ipsilateral, and bilateral whisker sensory patterns. We found that POm was highly sensitive to multiwhisker stimuli involving diverse spatiotemporal interactions. Accurate increases in POm activity were produced during the overlapping time between spatial signals reflecting changes in the spatiotemporal structure of sensory patterns. In addition, our results showed for first time that POm was also able to respond to tactile stimulation of ipsilateral whiskers. This finding challenges the notion that the somatosensory thalamus only computes unilateral stimuli. We found that POm also integrates signals from both whisker pads and described how this integration is generated. Our results showed that ipsilateral activity reached one POm indirectly from the other POm and demonstrated a transmission of sensory activity between both nuclei through a functional POm-POm loop formed by thalamocortical, interhemispheric, and corticothalamic projections. The implication of different cortical areas was investigated revealing that S1 plays a central role in this POm-POm loop. Accordingly, the subcortical and cortical inputs allow POm but not the ventral posteromedial thalamic nucleus (VPM) to have sensory information from both sides of the body. This finding is in agreement with the higher-order nature of POm and can be considered to functionally differentiate and classify these thalamic nuclei. A possible functional role of these higher-order thalamic patterns of integrated activity in brain function is discussed.

Tactile response adaptation to whisker stimulation in the lemniscal somatosensory pathway of rats.

Response adaptation is associated with attenuation of neural responses as the result of different mechanisms. However, the main function of adaptation may be to enhance the flow of relevant information transmission in sensory pathways. To study tactile response adaptation in the somatosensory pathway, unit recordings were performed in the principal trigeminal nucleus, ventro postero-medial thalamic nucleus and barrel cortex by means of tungsten microelectrodes in urethane anesthetized rats. Tactile stimuli consisted in 20 ms duration whisker deflections at different frequencies (0.5-10 Hz). Presumably pyramidal cortical neurons showed response adaptation at frequencies >2 Hz while putative inhibitory cortical neurons did not show response adaptation at 0.5, 5 or 10 Hz. Inhibitory activity was increased by muscimol application into the cortex (8mM, 0.1 µl); in this condition cortical adaptation was not affected, suggesting that adaptation was not due to an increase of inhibitory mechanisms. Adaptation was also observed in subcortical structures although the response attenuation was lesser than in the barrel cortex. Adaptation remained in subcortical structures after reversible cortical inactivation by cooling the barrel cortex. Acetylcholine application (10 µM; 0.1 µl) into the barrel cortex reduced response adaptation through the activation of muscarinic receptors because the effect was blocked by intraperitoneal injection of atropine (1mg/kg), suggesting that adaptation may change according to the cortical Ach level. Results indicate that response adaptation increases along the somatosensory pathway probably to alter the sensitivity of neurons in order to encode sensory stimuli more efficiently and to enhance the detectability of rare stimuli.