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1. Synaptic Odyssey

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   Harris, Kristen M. (January 2020, The journal of neuroscience)
2. Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency

   https://doi.org/10.7554/eLife.31755  

   Haas, Kalina T; Compans, Benjamin; Letellier, Mathieu; Bartol, Thomas M; Grillo-Bosch, Dolors; Sejnowski, Terrence J; Sainlos, Matthieu; Choquet, Daniel; Thoumine, Olivier; Hosy, Eric (July 2018, eLife)

   The nanoscale organization of neurotransmitter receptors regarding pre-synaptic release sites is a fundamental determinant of the synaptic transmission amplitude and reliability. How modifications in the pre- and post-synaptic machinery alignments affects synaptic currents, has only been addressed with computer modelling. Using single molecule super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a truncated form of NLG1 disrupted this correlation without affecting the intrinsic AMPAR organization, shifting the pre-synaptic release machinery away from AMPAR nanodomains. Electrophysiology in dissociated and organotypic hippocampal rodent cultures shows these treatments significantly decrease AMPAR-mediated miniature and EPSC amplitudes. Computer modelling predicts that ~100 nm lateral shift between AMPAR nanoclusters and glutamate release sites induces a significant reduction in AMPAR-mediated currents. Thus, our results suggest the synapses necessity to release glutamate precisely in front of AMPAR nanodomains, to maintain a high synaptic responses efficiency. 

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3. Connectomics: Relating synaptic connectivity to physiology

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4. Mitochondrial ROS signaling during synaptic potentiation

   https://doi.org/10.1016/j.bpj.2021.11.223  

   Stavrovskaya, Irina; Mitaishvilli, Erna; Morin, Bethany Kristi; Walls, Aria; Terry, Grace; Peixoto, Pablo M. (February 2022, Biophysical journal)

   Exacerbated emission of reactive oxygen species (ROS) from presynaptic mito- chondria is a well-studied hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis. Outside the context of pathology, the potential physiological role of mitochondrial ROS in presynaptic function and plasticity remains largely understudied. Here, we investigated this potential role by combining optogenetic techniques, electrophysiological recordings, confocal microscopy, and a well-established protocol for induction and mea- surement of synaptic potentiation in drosophila neuromuscular preparations. We observed an expected increase in spontaneous miniature excitatory junction potentials (mEJP), accompanied by a temporary increase in ROS emission seen by confocal imaging of presynaptic motor neuron mitochondria expressing roGFP2-Orp1. Furthermore, we were able to replicate this increase in mEJP frequency after optogenetic induction of ROS emission from pre-synaptic mito- chondria expressing mito-killer red. These preliminary but exiting results may indicate a potential role of mitochondrial ROS signaling in synaptic potentia- tion. Further studies will inquire about this role, as well as the potential signaling targets of mitochondrial ROS in the presynaptic structure of drosophila neuromuscular junctions. 

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5. Activity-Dependent Internalization of Glun2B-Containing NMDARs Is Required for Synaptic Incorporation of Glun2A and Synaptic Plasticity

   https://doi.org/10.1523/JNEUROSCI.0823-24.2024  

   Storey, Granville P; Riquelme, Raul; Barria, Andres (January 2025, The Journal of Neuroscience)

   NMDA-type glutamate receptors are heterotetrameric complexes composed of two GluN1 and two GluN2 subunits. The precise composition of the GluN2 subunits determines the channel's biophysical properties and influences its interaction with postsynaptic scaffolding proteins and signaling molecules involved in synaptic physiology and plasticity. The precise regulation of NMDAR subunit composition at synapses is crucial for proper synaptogenesis, neuronal circuit development, and synaptic plasticity, a cellular model of memory formation. In the forebrain during early development, NMDARs contain solely the GluN2B subunit, which is necessary for proper synaptogenesis and synaptic plasticity. In rodents, GluN2A subunit expression begins in the second postnatal week, replacing GluN2B-containing NMDARs at synapses in an activity- or sensory experience-dependent process. This switch in NMDAR subunit composition at synapses alters channel properties and reduces synaptic plasticity. The molecular mechanism regulating the switch remains unclear. We have investigated the role of activity-dependent internalization of GluN2B-containing receptors in shaping synaptic NMDAR subunit composition. Using molecular, pharmacological, and electrophysiological approaches in cultured organotypic hippocampal slices from rats of both sexes, we show that the process of incorporating GluN2A-containing NMDAR receptors requires activity-dependent internalization of GluN2B-containing NMDARs. Interestingly, blockade of GluN2A synaptic incorporation was associated with impaired potentiation of AMPA-mediated synaptic transmission, suggesting a potential coupling between the trafficking of AMPARs into synapses and that of GluN2A-containing NMDARs. These insights contribute to our understanding of the molecular mechanisms underlying synaptic trafficking of glutamate receptors and synaptic plasticity. They may also have implications for therapeutic strategies targeting NMDAR function in neurological disorders. 

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