Lipid Rafts and Synaptic Signaling
Ligand-Dependent Recruitment of the ErbB4 Signaling Complex into Neuronal Lipid Rafts
Li Ma, Yang Z. Huang, Graham M. Pitcher, Juli G. Valtschanoff, Ying H. Ma, Lin Y. Feng, Bai Lu, Wen C. Xiong, Michael W. Salter, Richard J. Weinberg, and Lin Mei (see pages 3164-3175)
Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and Surface AMPA Receptor Stability
Heike Hering, Chih-Chun Lin, and Morgan Sheng (see pages 3262-3271)
Lipid rafts are plasma membrane microdomains enriched in cholesterol and sphingolipids. A host of signaling molecules has been found recently to congregate within rafts through various post-translational modifications. In this issue, two reports provide new insights into lipid raft functions at neuronal synapses. Ma et al. focus on signaling by neuregulin (NRG), a regulator of synapse formation and plasticity. Neuronal stimulation with NRG recruited its receptor ErbB4 (localized at postsynaptic densities) to the lipid rafts. Disruption of the rafts (through cholesterol sequestration) resulted in the loss of downstream effects of NRG, including Erk activation and NRG-dependent blockade of long-term potentiation. Work by Hering et al. found that the lipid rafts could be separated into distinct components. Several postsynaptic proteins were localized to rafts, including glutamate receptors and their associated proteins. Raft depletion (achieved by disrupting cholesterol and sphingolipid synthesis) led to a loss of stability of AMPA receptors, dendritic spines, and ultimately synapses. In raft-depleted neurons, spine and synapse density was reduced, but the remaining spines were enlarged, perhaps to compensate for the loss. These observations contribute to the growing evidence for a role of lipid rafts as an organizing element in cell signaling, structural integrity, and synaptic communication.
Premature Death of Subplate Neurons
Selective Vulnerability of Subplate Neurons after Early Neonatal Hypoxia-Ischemia
Patrick S. McQuillen, R. Ann Sheldon, Carla J. Shatz, and Donna M. Ferriero (see pages 3308-3315)
Hypoxia-ischemia (H-I) injury during development causes specific types of brain damage and neuronal death. In humans, preterm H-I (thought to be caused by immaturity of the cerebral vasculature) results in damage to subcortical white matter [so-called periventricular leukomalacia (PVL)]. Such babies have abnormal neuronal development and often devastating long-term brain damage. In this issue, McQuillen et al. used a rat model of neonatal H-I to determine whether subplate neurons, a transient cell type sensitive to stage-specific excitotoxicity, are selectively destroyed. As in PVL, H-I in rats (caused by permanent right carotid occlusion on postnatal day 1 or day 2) caused subcortical neuronal death as well as motor deficits. Subplate neurons were indeed killed by H-I, as shown by specific loss of bromodeoxyuridine-labeled neurons. Although subplate neurons are required for the normal development of cortical connections, their premature death in H-I followed the formation of normal thalamocortical connections. Although oligodendrocyte progenitor cells, another transient neuronal cell type with stage-sensitive vulnerability, have been considered a primary victim in developmental H-I, these results suggest that subplate neuronal loss may also contribute to abnormal neuronal development. For example, loss of subplate neurons could prevent the development of mature ocular dominance columns after PVL.
Surround Inhibition in Time and Space
Imaging Spatiotemporal Dynamics of Surround Inhibition in the Barrels Somatosensory Cortex
Dori Derdikman, Rina Hildesheim, Ehud Ahissar, Amos Arieli, and Amiram Grinvald (see pages 3100-3105)
Derdikman et al. selected some of the latest generation of voltage-sensitive dyes to hone in on the spatial and temporal properties of sensory processing in the whisker barrel system of the rat somatosensory cortex. The sensitivity of selected dyes allowed the authors to examine the membrane voltage of many cortical neurons with high resolution, and in real time, after stimulation of single whiskers and the whisker pad. In agreement with previous studies using other methods, the neurons displayed a triphasic pattern. An initial depolarization began in the area of a single cortical barrel but then spread in an asymmetrical oval pattern along rows of the barrel. The third phase consisted of a rebound hyperpolarization associated with 16 Hz oscillations. These experiments illustrate that voltage-sensitive dyes may be particularly useful tools to examine the spatial dynamics of signal processing in small neuronal networks.