Loss of inner hair cell-auditory nerve fiber synapses is considered to be an important early stage of neural presbyacusis. Mass potentials, recorded at the cochlear round window, can be used to derive the neural index (NI), a sensitive measure for pharmacologically-induced synapse loss. Here, we investigate the applicability of the NI for measuring age-related auditory synapse loss in young-adult, middle-aged, and old Mongolian gerbils. Synapse loss, which was progressively evident in the 2 aged groups, correlated weakly with NI when measured at a fixed sound level of 60 dB SPL. However, the NI was confounded by decreases in single-unit firing rates at 60 dB SPL. NI at 30 dB above threshold, when firing rates were similar between age groups, did not correlate with synapse loss. Our results show that synapse loss is poorly reflected in the NI of aged gerbils, particularly if further peripheral pathologies are present. The NI may therefore not be a reliable clinical tool to assess synapse loss in aged humans with peripheral hearing loss.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.08.019 | DOI Listing |
The transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4) functions as an auxiliary factor of AMPA receptors (AMPARs) and plays a critical role in excitatory synapse plasticity as well as hippocampal-dependent learning and memory. Mice lacking SynDIG4 have reduced surface expression of GluA1 and GluA2 and are impaired in single tetanus-induced long-term potentiation and NMDA receptor (NMDAR)-dependent long-term depression. These findings suggest that SynDIG4 may play an important role in regulating AMPAR distribution through intracellular trafficking mechanisms; however, the precise roles by which SynDIG4 governs AMPAR distribution remain unclear.
View Article and Find Full Text PDFPhysiol Behav
January 2025
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:
C1q/TNF-related protein 14 (CTRP14), also known as C1q-like 1 (C1QL1), is a synaptic protein predominantly expressed in the brain. It plays a critical role in the formation and maintenance of the climbing fiber-Purkinje cell synapses, ensuring that only one single winning climbing fiber from the inferior olivary neuron synapses with the proximal dendrites of Purkinje cells during the early postnatal period. Loss of CTRP14/C1QL1 results in incomplete elimination of supernumerary climbing fibers, leading to multiple persistent climbing fibers synapsing with the Purkinje cells.
View Article and Find Full Text PDFJ Neurosci
January 2025
Nervous System Disorders and Therapy, GIGA Institute, University of Liège, 4000 Liège, Belgium
Synaptic vesicle glycoprotein 2A (SV2A) is a presynaptic protein targeted by the antiseizure drug levetiracetam. One or more of the three SV2 genes is expressed in all neurons and is essential to normal neurotransmission. Loss of SV2A results in a seizure phenotype in mice and mutations in humans are also linked to congential seizures.
View Article and Find Full Text PDFJ Neurosci
January 2025
Department of Neuroscience, The Ohio State University College of Medicine, Columbus, OH 43210
Pyramidal cells (PCs) in CA1 hippocampus can be classified by their radial position as deep or superficial and organize into subtype-specific circuits necessary for differential information processing. Specifically, superficial PCs receive fewer inhibitory synapses from parvalbumin (PV)-expressing interneurons than deep PCs, resulting in weaker feedforward inhibition of input from CA3 Schaffer collaterals. Using mice, we investigated mechanisms underlying CA1 PC differentiation and the development of this inhibitory circuit motif.
View Article and Find Full Text PDFJ Neurosci
January 2025
Institute of Neuroimmunology, Slovak Academy of Science, 84510 Bratislava, Slovakia.
Extracellular matrix (ECM) is a network of macromolecules which has two forms - perineuronal nets (PNNs) and a diffuse ECM (dECM) - both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how disrupted PNNs and dECM influence brain diffusibility.
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