Neuroscience
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During development, Purkinje axons elongate along precise trajectories and acquire stereotypic branching patterns to innervate targets in the deep nuclei and cerebellar cortex. These processes are accomplished through cell-intrinsic mechanisms, whose operation is regulated by environmental signaling cues. Here, we show that Anosmin-1, the protein defective in the X-linked form of Kallmann syndrome, is one among such cues. ⋯ Comparable results are obtained by administering the protein or the blocking antibodies to organotypic cultures of postnatal (P0) rat cerebellum. In P10 cerebellar slices, Anosmin-1 does not enhance the spontaneous regenerative capabilities of severed Purkinje axons, but promotes the terminal outgrowth of injured neurites into embryonic neocortical explants apposed to the axotomy site. Although Anosmin-1 is unable to change the overall intrinsic growth competence of Purkinje cells, it exerts a powerful stimulatory action on the budding and extension of collateral branches and terminal plexus, contributing to the patterning of Purkinje axons.
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CD226, a member of cell adhesion molecules, has been widely studied in the immune system; however, its expression in the CNS remains unknown. In our present study, we detected CD226 mRNA and protein in the mouse hippocampus and cerebellum by RT-PCR and Western blotting, respectively. ⋯ During postnatal development, CD226 could not be detected at its adult locations until postnatal day 12; however, it was temporally expressed in the somata of neighboring or distant nuclei associated with its adult location. These results showed the diverse localization of CD226 in the mouse hippocampus and cerebellum for the first time and suggested its potential role in the CNS.
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Glutamatergic signaling has been exceptionally well characterized in the brain's gray matter, where it underlies fast information processing, learning and memory, and also generates the neuronal damage that occurs in pathological conditions such as stroke. The role of glutamatergic signaling in the white matter, an area until recently thought to be devoid of synapses, is less well understood. Here we review what is known, and highlight what is not known, of glutamatergic signaling in the white matter. We focus on how glutamate is released, the location and properties of the receptors it acts on, the interacting molecules that may regulate trafficking or signaling of the receptors, the possible functional roles of glutamate in the white matter, and its pathological effects including the possibility of treating white matter disorders with glutamate receptor blockers.
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Axonal action potentials initiate the cycle of synaptic communication that is key to our understanding of nervous system functioning. The field has accumulated vast knowledge of the signature action potential waveform, firing patterns, and underlying channel properties of many cell types, but in most cases this information comes from somatic intracellular/whole-cell recordings, which necessarily measure a mixture of the currents compartmentalized in the soma, dendrites, and axon. Because the axon in many neuron types appears to be the site of lowest threshold for action potential initiation, the channel constellation in the axon is of particular interest. ⋯ Recent studies have developed and applied single-fiber extracellular recording, direct intracellular recording, and optical recording techniques from axons toward understanding the behavior of the axonal action potential. We are starting to understand better how specific channels and other cellular properties shape action potential threshold, waveform, and timing: key elements contributing to downstream transmitter release. From this increased scrutiny emerges a theme of axons with more computational power than in traditional conceptualizations.
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Ampa receptors mediate the majority of excitatory synaptic transmission in the brain. Thus, the mechanisms that control the developmental and activity-dependent changes in the functional synaptic expression of AMPA receptors are of fundamental importance. Here we focus on the role of GluR2 subunit in synaptic function and plasticity.