Facultad de Ciencias, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso, Chile.
Published: October 2022
AI Article Synopsis
Article Abstract
Synapse unsilencing is an essential mechanism for experience-dependent plasticity. Here, we showed that the application of the ligand Wnt-5a converts glutamatergic silent synapses into functional ones by increasing both α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) currents (I and I, respectively). These effects were mimicked by the hexapeptide Foxy-5 and inhibited by secreted frizzled-related protein sFRP-2. I potentiation was produced by increased synaptic potency, followed by an increase in the probability of release (Pr), even in the presence of 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX). At a longer time of Wnt-5a exposure, the Pr increments were higher in I than in I. In the presence of NMDAR inhibitors, Wnt-5a-induced conversion was fully inhibited in 69.0% of silent synapses, whereas in the remaining synapses were converted into functional one. Our study findings showed that the Wnt-5a-activated pathway triggers AMPAR insertion into mammalian glutamatergic synapses, unsilencing non-functional synapses and promoting the formation of nascent synapses during the early postnatal development of the brain circuits.
Unlabelled: The rich diversity of synapses facilitates the capacity of neural circuits to transmit, process and store information. Here, we used multiplex super-resolution proteometric imaging through array tomography to define features of single synapses in the adult mouse neocortex. We find that glutamatergic synapses cluster into subclasses that parallel the distinct biochemical and functional categories of receptor subunits: GluA1/4, GluA2/3 and GluN1/GluN2B.
Obesity and drugs of abuse share overlapping neural circuits and behaviors. Silent synapses are transient synapses that are important for remodeling brain circuits. They are prevalent during early development but largely disappear by adulthood.
Persistent, memorandum-specific neuronal spiking activity has long been hypothesized to underlie working memory. However, emerging evidence suggests a potential role for 'activity-silent' synaptic mechanisms. This issue remains controversial because evidence for either view has largely relied either on datasets that fail to capture single-trial population dynamics or on indirect measures of neuronal spiking.
Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (App/hMapt), monitoring brain connectivity by means of resting-state fMRI.
The precise organization of pre- and postsynaptic terminals is crucial for normal synaptic function in the brain. In addition to its canonical role as a neurotrophin-3 receptor tyrosine kinase, postsynaptic TrkC promotes excitatory synapse organization through interaction with presynaptic receptor-type tyrosine phosphatase PTPσ. To isolate the synaptic organizer function of TrkC from its role as a neurotrophin-3 receptor, we generated mice carrying TrkC point mutations that selectively abolish PTPσ binding.
