Kinesin super family protein 2A (KIF2A), an ATP-dependent microtubule (MT) destabilizer, regulates cell migration, axon elongation, and pruning in the developing nervous system. KIF2A mutations have recently been identified in patients with malformed cortical development. However, postnatal KIF2A is continuously expressed in the hippocampus, in which new neurons are generated throughout an individual's life in established neuronal circuits. In this study, we investigated KIF2A function in the postnatal hippocampus by using tamoxifen-inducible conditional knockout (-cKO) mice. Despite exhibiting no significant defects in neuronal proliferation or migration, -cKO mice showed signs of an epileptic hippocampus. In addition to mossy fiber sprouting, the -cKO dentate granule cells (DGCs) showed , leading to the growth of many aberrant overextended dendrites that eventually developed axonal properties. These results suggested that postnatal KIF2A is a key length regulator of DGC developing neurites and is involved in the establishment of precise postnatal hippocampal wiring.
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http://dx.doi.org/10.7554/eLife.30935 | DOI Listing |
Exp Physiol
January 2025
Department of Physiology, School of Medicine, University College Cork, Cork, Ireland.
Absence of the structural protein, dystrophin, results in the neuromuscular disorder Duchenne Muscular Dystrophy (DMD). In addition to progressive skeletal muscle dysfunction, this multisystemic disorder can also result in cognitive deficits and behavioural changes that are likely to be consequences of dystrophin loss from central neurons and astrocytes. Dystrophin-deficient mdx mice exhibit decreases in grey matter volume in the hippocampus, the brain region that encodes and consolidates memories, and this is exacerbated with ageing.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address:
Background: Fabry disease (FD) patients are known to be at high risk of developing neuropsychiatric symptoms such as anxiety, depression and cognitive deficits. Despite this, they are underdiagnosed and inadequately treated. It is unknown whether these symptoms arise from pathological glycosphingolipid deposits or from cerebrovascular abnormalities affecting neuronal functions in the central nervous system.
View Article and Find Full Text PDFJ Neurosci
December 2024
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA
Excitatory synapses and the actin-rich dendritic spines on which they reside are indispensable for information processing and storage in the brain. In the adult hippocampus, excitatory synapses must balance plasticity and stability to support learning and memory. However, the mechanisms governing this balance remain poorly understood.
View Article and Find Full Text PDFHippocampus
January 2025
Department of Child and Adolescent Psychology, Neuroscience & Physiology, and Psychiatry and the Neuroscience Institute, New York University Grossman School of Medicine, New York University Langone Health, New York, New York, USA.
For many years, the hilus of the dentate gyrus (DG) was a mystery because anatomical data suggested a bewildering array of cells without clear organization. Moreover, some of the anatomical information led to more questions than answers. For example, it had been identified that one of the major cell types in the hilus, the mossy cell, innervates granule cells (GCs).
View Article and Find Full Text PDFElife
December 2024
Graduate School of Brain Science, Doshisha University, Kyoto, Japan.
Glutamate and GABA co-transmitting neurons exist in several brain regions; however, the mechanism by which these two neurotransmitters are co-released from the same synaptic terminals remains unclear. Here, we show that the supramammillary nucleus (SuM) to dentate granule cell synapses, which co-release glutamate and GABA, exhibit differences between glutamate and GABA release properties in paired-pulse ratio, Ca-sensitivity, presynaptic receptor modulation, and Ca channel-vesicle coupling configuration. Moreover, uniquantal synaptic responses show independent glutamatergic and GABAergic responses.
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