SCN Circadian Output Degrades with Age
Takahiro J. Nakamura, Wataru Nakamura, Shin Yamazaki, Takashi Kudo, Tamara Cutler, et al.
(see pages 10201–10205)
Circadian oscillations of various physiological functions are coordinated by cyclic secretion of neuropeptides by suprachiasmatic nucleus (SCN) neurons, which exhibit endogenous oscillations in gene expression and firing. Circadian rhythms weaken with advancing age, as is evident in sleep patterns: elderly people often sleep less at night and more during the day. Whether circadian disruption results from weaker oscillations in SCN protein levels or neuronal activity or from impaired coordination either among SCN cells or of other regulatory systems (e.g., sleep centers) is unclear. Addressing this question in mice, Nakamura et al. found that older animals were less active overall, and their behavior was fragmented into more bouts. Whereas younger mice had clear circadian oscillations in SCN activity, SCN activity levels fluctuated throughout the day in older animals. Moreover, although the clock gene PER2 showed circadian oscillation in all mice, levels were reduced and cycle periods were more variable in explant cultures from older mice.
Nonpeptidergic Nociceptors Transiently Express TRPV1
Daniel J. Cavanaugh, Alexander T. Chesler, Joao M. Bráz, Nirao M. Shah, David Julius, et al.
(see pages 10119–10127)
Nociception is mediated by myelinated Aδ fibers and small, unmyelinated peptidergic or nonpeptidergic C-fibers. Besides their different patterns of gene expression, C-fibers innervate different skin layers, terminate in different laminae of the dorsal horn, and although generally polymodal, convey different types of nociceptive information: nonpeptidergic neurons primarily signal mechanical pain, whereas peptidergic nociceptors signal noxious heat. Expression of TRPV1 channels likely underlies the heat sensitivity of peptidergic nociceptors, but low levels of TRPV1 expression have also been detected in nonpeptidergic nociceptors. To more definitively assess the distribution of TRPV1 channels, Cavanaugh et al. generated mice that expressed markers either in cells that had expressed TRPV1 at any point during development or only in cells that expressed TRPV1 at the time of the assay. This revealed that during development, TRPV1 is expressed in subsets of both peptidergic and nonpeptidergic nociceptors, but expression subsides in most nonpeptidergic nociceptors during the first two postnatal weeks.
Synchronous Neural Oscillations Reflect Imagined Musical Meter
Sylvie Nozaradan, Isabelle Peretz, Marcus Missal, and André Mouraux
(see pages 10234–10240)
People perceive beat in musical rhythms when periodicity is absent: one can even imagine the beat when the pulse occurs during a pause in the music or when a note is held. Synchronous oscillations in neural activity have been proposed to underlie the perception of beat, but direct evidence for this hypothesis has been lacking. Nozaradan et al. speculated that such oscillations might be detectable with EEG recordings. Indeed, when subjects were presented with an auditory stimulus that was amplitude-modulated to produce a pseudo-periodic beat, the EEG signal amplitude showed periodic peaks at the beat frequency. Moreover, when subjects were instructed to imagine a binary or tertiary substructure (i.e., meter) within the beat structure, the EEG revealed additional peaks consistent with the imagined substructure even though the actual stimuli were identical. These data support the hypothesis that neural activity becomes entrained to the beat frequency and that imagined features are similarly represented.
Neurobiology of Disease
Schwann Cell Mitochondrial Dysfunction Causes Axon Degeneration
Andreu Viader, Judith P. Golden, Robert H. Baloh, Robert E. Schmidt, Daniel A. Hunter, et al.
(see pages 10128–10140)
Neuronal mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Although mitochondrial abnormalities associated with diabetes- and HIV-related neuropathies often occur selectively in Schwann cells, the contribution of glial mitochondrial abnormalities to neuropathy has not been widely investigated. To address this, Viader et al. knocked out the mitochondrial transcription factor Tfam, which is required for transcription of respiratory chain proteins, specifically in Schwann cells. Despite impaired respiratory function, Schwann cells survived and continued to proliferate, and mutant mice developed normally. Nonetheless, adults exhibited progressive peripheral neuropathy characterized by degeneration, first of unmyelinated fibers (bundles of which are normally wrapped by a single Schwann cell) and then of myelinated fibers, resulting in distal weakness and impaired sensory function. This same pattern occurs in diabetic and HIV-associated peripheral neuropathy. Upon nerve injury, Tfam-deficient Schwann cells dedifferentiated and promoted axonal regeneration normally, but the Schwann cells did not redifferentiate, so regenerated axons remained unmyelinated.