Myosin Va and Oligodendrocytes
Jacob A. Sloane and Timothy K. Vartanian
(see pages 11366–11375)
Mutations in myosin Va cause severe neurological abnormalities as manifest in the developmental disorder Griscelli's syndrome type 1 (GSC1). This week, Sloane and Vartanian report that myosin Va-null mice (dilute-lethal) have impaired myelination, suggesting a potential role for oligodendrocytes in the pathophysiology of GSC1. Consistent with this idea, myosin 5a was expressed in wild-type cultured oligodendrocytes at all stages of maturation. Oligodendrocytes transfected with dominant-negative myosin Va had smaller lamellar surface areas, and their processes were reduced in length, number, and branching. Loss of myosin Va did not affect oligodendrocyte maturation or cell death. Vesicle-associated membrane protein 2 (VAMP2) associated with myosin Va in the cytosol of developing oligodendrocytes. As oligodendrocytes began to extend processes, VAMP2 abruptly relocated to lamellas and filopodia, a process that required myosin Va. Disruption of VAMP2 also caused similar cellular defects in oligodendrocyte lamellas and processes.
Activity Dependence of Callosal Projections
Chun-Lei Wang, Lei Zhang, Yang Zhou, Jing Zhou, Xiu-Juan Yang, Shu-min Duan, Zhi-Qi Xiong, and Yu-Qiang Ding
(see pages 11334–11342)
That axonal superhighway, the corpus callosum, sends signals whizzing back and forth between the cerebral hemispheres. Turns out it requires neuronal activity to build and maintain it. Wang et al. labeled these projections by in utero electroporation of a fluorescent marker into cells of the dorsolateral ventricular zone. Some of the labeled cells migrated to layer II/III of the somatosensory cortex and sent projections to layer II/III of the contralateral primary somatosensory cortex (S1). The authors “silenced” these pyramidal cells by overexpressing the inwardly rectifying potassium channel Kir2.1. In these cells, projections were delayed, and axons overextended to terminate in layer I. The results were more drastic after expression of tetanus toxin light chain (TeNT-LC), which prevented synaptic transmission. In this case, projections eventually vanished from the somatosensory cortex altogether. The effects of Kir2.1 and TeNT-LC were additive when they were coexpressed.
Binaural Hearing and Middle Age
Bernhard Ross, Takako Fujioka, Kelly L. Tremblay, and Terence W. Picton
(see pages 11172–11178)
You might be surprised to learn that changes in central auditory processing as well as in peripheral hearing contribute to sensory deterioration as we age. Central processing is important for comprehension of speech, especially in the presence of background noise. This week, Ross et al. used a binaural hearing task to examine age-related changes in human central auditory processing. The authors measured cortical magnetoencephalographic responses to binaural auditory stimuli that had changing interaural phase differences (IPD). The auditory-evoked responses to interaural temporal disparity had an upper frequency limit that declined with age. Young adults responded to shifting IPDs for frequencies up to 1225 Hz, whereas performance in middle-aged subjects suffered above 940 Hz and in older subjects was limited to 760 Hz. The decline in binaural hearing performance was noticeable at middle age before age-related declines in hearing sensation.
Neurobiology of Disease
Histone Methylation and GABAergic Gene Promoters
Hsien-Sung Huang, Anouch Matevossian, Catheryne Whittle, Se Young Kim, Armin Schumacher, Stephen P. Baker, and Schahram Akbarian
(see pages 11254–11262)
Prefrontal cortex (PFC) is center stage for those looking at the neurobiology of schizophrenia. In this week's Journal, Huang et al. start to build a case for developmental or disease-related changes in the regulation of genes in GABAergic neurons in PFC. The mRNA for the GABA synthetic enzyme GAD1 increased until puberty, as measured in human postmortem brain samples. There was an accompanying change in chromatin remodeling, as indicated by increased methylation of histone H3-lysine 4 in the GAD1 promoter region. In tissue from schizophrenic patients, GAD1 expression and H3K4 trimethylation were reduced, particularly in females. H3K4 methylation of the GAD1 promoter also was downregulated in mice heterozygous for a truncated allele of the mixed-leukemia lineage gene Mll1, which encodes a histone methyltransferase expressed in cortical interneurons. In these mice, GAD1 H3K4 trimethylation was increased by the atypical antipsychotic clozapine but not by haloperidol.