Journal of neurophysiology
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Neuroimaging studies have demonstrated that the right temporoparietal junction (TPJ) is activated during detection of salient stimuli, including pain, in the sensory environment. Right TPJ damage more often produces spatial neglect than left TPJ damage. We recently reported a right lateralized system of white matter connectivity of the TPJ. ⋯ Dual regression revealed this network was more strongly connected with right TPJ than left TPJ. Seed-based functional connectivity analysis showed 1) negative connectivity the TPJ bilaterally with the "default mode network"; 2) positive connectivity of TPJ bilaterally with the salience/ventral attention network; 3) stronger connectivity between right TPJ compared with left TPJ with regions within the salience/ventral attention network and mid-insula, S2, and temporal/parietal opercula (implicated in pain); and 4) stronger connectivity of left TPJ compared with right TPJ with the "executive control network," including the dorsomedial/medial PFC, inferior frontal gyrus, and cerebellum (crus I/II). Our findings build on classic lesion and neuroimaging studies, demonstrating a complex spatial network organization of lateralization in TPJ functional connectivity in the absence of an overt stimulus.
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The tyrosine kinases of Src family play an important role in the central sensitization following peripheral inflammation. However, whether the Src family in the arcuate nucleus (ARC) of mediobasal hypothalamus is involved in central sensitization remains unknown. The aim of this study was to investigate the role and mechanisms of tyrosine kinases of Src family in N-methyl-d-aspartate (NMDA) receptor activity in the ARC following peripheral inflammation. ⋯ Peripheral inflammation also increased the association of NR2B protein with p-Src protein in the ARC. Administration of PP2 blocked the upregulation of NR2B phosphorylation induced by CFA injection. Taken together, our present results suggest that the arcuate Src activation-induced tyrosine phosphorylation of NR2B NMDA subunit may contribute to inflammatory pain.
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Mammalian peripheral cold thermoreceptors respond to cooling of their sensory endings with an increase in firing rate and modification of their discharge pattern. We recently showed that cultured trigeminal cold-sensitive (CS) neurons express a prominent hyperpolarization-activated current (I(h)), mainly carried by HCN1 channels, supporting subthreshold resonance in the soma without participating in the response to acute cooling. However, peripheral pharmacological blockade of I(h), or characterization of HCN1(-/-) mice, reveals a deficit in acute cold detection. ⋯ The firing pattern of nerve endings from HCN1(-/-) mice was also affected by ZD7288, which we attribute to the presence of HCN2 channels in the place of HCN1. Mathematical modeling shows that the firing phenotype of CS nerve endings from HCN1(-/-) mice can be reproduced by replacing HCN1 channels with the slower HCN2 channels rather than by abolishing I(h). We propose that I(h) carried by HCN1 channels helps tune the frequency of the oscillation and the length of bursts underlying regular spiking in cold thermoreceptors, having important implications for neural coding of cold sensation.