@article {69841, title = {DELTA: a method for brain-wide measurement of synaptic protein turnover reveals localized plasticity during learning.}, journal = {Nat Neurosci}, year = {2025}, month = {2025 Mar 31}, abstract = {

Synaptic plasticity alters neuronal connections in response to experience, which is thought to underlie learning and memory. However, the loci of learning-related synaptic plasticity, and the degree to which plasticity is localized or distributed, remain largely unknown. Here we describe a new method, DELTA, for mapping brain-wide changes in synaptic protein turnover with single-synapse resolution, based on Janelia Fluor dyes and HaloTag knock-in mice. During associative learning, the turnover of the ionotropic glutamate receptor subunit GluA2, an indicator of synaptic plasticity, was enhanced in several brain regions, most markedly hippocampal area CA1. More broadly distributed increases in the turnover of synaptic proteins were observed in response to environmental enrichment. In CA1, GluA2 stability was regulated in an input-specific manner, with more turnover in layers containing input from CA3 compared to entorhinal cortex. DELTA will facilitate exploration of the molecular and circuit basis of learning and memory and other forms of plasticity at scales ranging from single synapses to the entire brain.

}, issn = {1546-1726}, doi = {10.1038/s41593-025-01923-4}, url = {https://doi.org/10.1038/s41593-025-01923-4}, author = {Mohar, Boaz and Michel, Gabriela and Wang, Yi-Zhi and Hernandez, Veronica and Grimm, Jonathan B and Park, Jin-Yong and Patel, Ronak and Clarke, Morgan and Brown, Timothy A and Bergmann, Cornelius and Gebis, Kamil K and Wilen, Anika P and Liu, Bian and Johnson, Richard and Graves, Austin and Tchumatchenko, Tatjana and Savas, Jeffrey N and Fornasiero, Eugenio F and Huganir, Richard L and Tillberg, Paul W and Lavis, Luke D and Svoboda, Karel and Spruston, Nelson} } @article {69301, title = {Motor neurons generate pose-targeted movements via proprioceptive sculpting.}, journal = {Nature}, year = {2024}, month = {2024 Mar 20}, abstract = {

Motor neurons are the final common pathway through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster. Counterintuitively, we find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron. A feedback model predicts that this convergent behaviour results from motor neuron drive interacting with proprioceptive feedback. We identify and genetically suppress a single class of proprioceptive neuron that changes the motor neuron-induced convergence as predicted by the feedback model. These data suggest a framework for how the brain controls movements: instead of directly generating movement in a given direction by activating a fixed set of motor neurons, the brain controls movements by adding bias to a continuing proprioceptive-motor loop.

}, issn = {1476-4687}, doi = {10.1038/s41586-024-07222-5}, author = {Gorko, Benjamin and Siwanowicz, Igor and Close, Kari and Christoforou, Christina and Hibbard, Karen L and Kabra, Mayank and Lee, Allen and Park, Jin-Yong and Li, Si Ying and Chen, Alex B and Namiki, Shigehiro and Chen, Chenghao and Tuthill, John C and Bock, Davi D and Rouault, Herv{\'e} and Branson, Kristin and Ihrke, Gudrun and Huston, Stephen J} } @article {68566, title = {Synaptic gradients transform object location to action.}, journal = {Nature}, volume = {613}, year = {2023}, month = {2023 Jan 04}, pages = {534-42}, abstract = {

To survive, animals must convert sensory information into appropriate behaviours. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs) into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly{\textquoteright}s directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

}, issn = {1476-4687}, doi = {10.1038/s41586-022-05562-8}, author = {Dombrovski, Mark and Peek, Martin Y and Park, Jin-Yong and Vaccari, Andrea and Sumathipala, Marissa and Morrow, Carmen and Breads, Patrick and Zhao, Arthur and Kurmangaliyev, Yerbol Z and Sanfilippo, Piero and Rehan, Aadil and Polsky, Jason and Alghailani, Shada and Tenshaw, Emily and Namiki, Shigehiro and Zipursky, S Lawrence and Card, Gwyneth M} } @article {5335, title = {Synergistic actions of metabotropic acetylcholine and glutamate receptors on the excitability of hippocampal CA1 pyramidal neurons.}, journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience}, volume = {32}, year = {2012}, month = {2012 May 2}, pages = {6081-91}, abstract = {

A variety of neurotransmitters are responsible for regulating neural activity during different behavioral states. Unique responses to combinations of neurotransmitters provide a powerful mechanism by which neural networks could be differentially activated during a broad range of behaviors. Here, we show, using whole-cell recordings in rat hippocampal slices, that group I metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors (mAChRs) synergistically increase the excitability of hippocampal CA1 pyramidal neurons by converting the post-burst afterhyperpolarization to an afterdepolarization via a rapidly reversible upregulation of Ca(v)2.3 R-type calcium channels. Coactivation of mAChRs and mGluRs also induced a long-lasting enhancement of the responses mediated by each receptor type. These results suggest that cooperative signaling via mAChRs and group I mGluRs could provide a mechanism by which cognitive processes may be modulated by conjoint activation of two separate neurotransmitter systems.

}, keywords = {Action Potentials, Animals, Calcium Channels, Cation Transport Proteins, Inbred C57BL, Knockout, Male, Metabotropic Glutamate, Mice, Muscarinic, Pyramidal Cells, R-Type, Rats, Receptors, Wistar}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.6519-11.2012}, author = {Park, Jin-Yong and Spruston, Nelson} } @article {6780, title = {A post-burst after depolarization is mediated by group i metabotropic glutamate receptor-dependent upregulation of Ca(v)2.3 R-type calcium channels in CA1 pyramidal neurons.}, journal = {PLoS Biology}, volume = {8}, year = {2010}, month = {2010}, pages = {e1000534}, abstract = {

Activation of group I metabotropic glutamate receptors (subtypes mGluR1 and mGluR5) regulates neural activity in a variety of ways. In CA1 pyramidal neurons, activation of group I mGluRs eliminates the post-burst afterhyperpolarization (AHP) and produces an afterdepolarization (ADP) in its place. Here we show that upregulation of Ca(v)2.3 R-type calcium channels is responsible for a component of the ADP lasting several hundred milliseconds. This medium-duration ADP is rapidly and reversibly induced by activation of mGluR5 and requires activation of phospholipase C (PLC) and release of calcium from internal stores. Effects of mGluR activation on subthreshold membrane potential changes are negligible but are large following action potential firing. Furthermore, the medium ADP exhibits a biphasic activity dependence consisting of short-term facilitation and longer-term inhibition. These findings suggest that mGluRs may dramatically alter the firing of CA1 pyramidal neurons via a complex, activity-dependent modulation of Ca(v)2.3 R-type channels that are activated during spiking at physiologically relevant rates and patterns.

}, keywords = {Action Potentials, Animals, Calcium Channels, Cation Transport Proteins, Female, Inbred C57BL, Ion Channel Gating, Male, Metabotropic Glutamate, Methoxyhydroxyphenylglycol, Mice, Neurons, Patch-Clamp Techniques, Pyramidal Cells, R-Type, Rats, Receptors, Up-Regulation, Wistar, Xenopus}, issn = {1545-7885}, doi = {10.1371/journal.pbio.1000534}, author = {Park, Jin-Yong and Remy, Stefan and Varela, Juan and Cooper, Donald C and Chung, Sungkwon and Kang, Ho-Won and Lee, Jung-Ha and Spruston, Nelson} }