A hippocampal mossy fiber synapse, which is implicated in learning and memory, has a complex structure in which mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions (PAJs) and wrap around a multiply-branched spine, forming synaptic junctions. Here, we electron microscopically analyzed the ultrastructure of this synapse in afadin-deficient mice. Transmission electron microscopy analysis revealed that typical PAJs with prominent symmetrical plasma membrane darkening undercoated with the thick filamentous cytoskeleton were observed in the control synapse, whereas in the afadin-deficient synapse, atypical PAJs with the symmetrical plasma membrane darkening, which was much less in thickness and darkness than those of the control typical PAJs, were observed. Immunoelectron microscopy analysis revealed that nectin-1, nectin-3, and N-cadherin were localized at the control typical PAJs, whereas nectin-1 and nectin-3 were localized at the afadin-deficient atypical PAJs to extents lower than those in the control synapse and N-cadherin was localized at their nonjunctional flanking regions. These results indicate that the atypical PAJs are formed by nectin-1 and nectin-3 independently of afadin and N-cadherin and that the typical PAJs are formed by afadin and N-cadherin cooperatively with nectin-1 and nectin-3. Serial block face-scanning electron microscopy analysis revealed that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities, and the density of synaptic vesicles docked to active zones were decreased in the afadin-deficient synapse. These results indicate that afadin plays multiple roles in the complex ultrastructural morphogenesis of hippocampal mossy fiber synapses.
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http://dx.doi.org/10.1002/cne.24238 | DOI Listing |
Alzheimers Dement
December 2024
University of Missouri, Columbia, MO, USA.
Background: This study was to elucidate the impact of blast-induced neurotrauma (BINT) on phosphoproteome networks and cognition in a genetically heterogeneous population of mice (rTg4510) with the human tau P301L mutation linked to Alzheimer's disease-related dementia (ADRD) including frontotemporal dementia.
Method: Mild traumatic brain injury was induced in rTg4510 mice exposed to a single low-density blast (LIB) at an upright position. After assessment of cognitive function by the automated-Home Cage Monitoring (aHCM) system, frontal cortex tissue was collected at 40 days post-injury.
Alzheimers Dement
December 2024
Interdisciplinary Institute for Neuroscience (UMR 5297), University of Bordeaux, Bordeaux, Gironde, France.
Background: PhospholipaseC γ2 (PLCG2) is known to have direct link with genetic risk factors for Alzheimer's like dementia (AD). PLCG2 has been previously demonstrated to have association with Aß uptake through microglia. And mostly expressed in dentate gyrus (DG) network of hippocampus.
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 PDFAlzheimers Dement
December 2024
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.
Introduction: We investigated whether the cerebellum develops neuropathology that correlates with well-accepted Alzheimer's disease (AD) neuropathological markers and cognitive status.
Methods: We studied cerebellar cytoarchitecture in a cohort (N = 30) of brain donors. In a larger cohort (N = 605), we queried whether the weight of the contents of the posterior fossa (PF), which contains primarily cerebellum, correlated with dementia status.
Cerebellum
December 2024
School of Life Sciences, Arizona State University, Tempe, AZ, 85287, USA.
The vestibular processing regions of the cerebellum integrate vestibular information with other sensory modalities and motor signals to regulate balance, gaze stability, and spatial orientation. A class of excitatory glutamatergic interneurons known as unipolar brush cells (UBCs) are highly concentrated within the granule cell layer of these regions. UBCs receive vestibular signals directly from primary vestibular afferents and indirectly from mossy fibers.
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