@article {69126, title = {Ketamine modulates a norepinephrine-astroglial circuit to persistently suppress futility-induced passivity.}, journal = {bioRxiv}, year = {2023}, month = {2023 Dec 29}, abstract = {

Mood-altering compounds hold promise for the treatment of many psychiatric disorders, such as depression, but connecting their molecular, circuit, and behavioral effects has been challenging. Here we find that, analogous to effects in rodent learned helplessness models, ketamine pre-exposure persistently suppresses futility-induced passivity in larval zebrafish. While antidepressants are thought to primarily act on neurons, brain-wide imaging in behaving zebrafish showed that ketamine elevates intracellular calcium in astroglia for many minutes, followed by persistent calcium downregulation post-washout. Calcium elevation depends on astroglial α1-adrenergic receptors and is required for suppression of passivity. Chemo-/optogenetic perturbations of noradrenergic neurons and astroglia demonstrate that the aftereffects of glial calcium elevation are sufficient to suppress passivity by inhibiting neuronal-astroglial integration of behavioral futility. Imaging in mouse cortex reveals that ketamine elevates astroglial calcium through conserved pathways, suggesting that ketamine exerts its behavioral effects by persistently modulating evolutionarily ancient neuromodulatory systems spanning neurons and astroglia.

}, doi = {10.1101/2022.12.29.522099}, url = {https://doi.org/10.1101/2022.12.29.522099}, author = {Marc Duque and Alex B. Chen and Eric Hsu and Sujatha Narayan and Altyn Rymbek and Shahinoor Begum and Gesine Saher and Adam E. Cohen and David E. Olson and David A. Prober and Dwight E. Bergles and Mark C. Fishman and Florian Engert and Misha B. Ahrens} } @article {68791, title = {Mapping memories: pulse-chase labeling reveals AMPA receptor dynamics during memory formation.}, journal = {bioRxiv}, year = {2023}, month = {2023 May 29}, abstract = {

A tool to map changes in synaptic strength during a defined time window could provide powerful insights into the mechanisms governing learning and memory. We developed a technique, Extracellular Protein Surface Labeling in Neurons (EPSILON), to map α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) insertion\ in vivo\ by pulse-chase labeling of surface AMPARs with membrane-impermeable dyes. This approach allows for single-synapse resolution maps of plasticity in genetically targeted neurons during memory formation. We investigated the relationship between synapse-level and cell-level memory encodings by mapping synaptic plasticity and cFos expression in hippocampal CA1 pyramidal cells upon contextual fear conditioning (CFC). We observed a strong correlation between synaptic plasticity and cFos expression, suggesting a synaptic mechanism for the association of cFos expression with memory engrams. The EPSILON technique is a useful tool for mapping synaptic plasticity and may be extended to investigate trafficking of other transmembrane proteins.

}, doi = {10.1101/2023.05.26.541296}, url = {https://doi.org/10.1101/2023.05.26.541296}, author = {Doyeon Kim and Pojeong Park and Xiuyuan Li and J. David Wong Campos and He Tian and Eric M. Moult and Jonathan B. Grimm and Luke Lavis and Adam E. Cohen} } @article {68792, title = {Voltage dynamics of dendritic integration and back-propagation in vivo}, journal = {bioRxiv}, year = {2023}, month = {2023 May 26}, abstract = {

Neurons integrate synaptic inputs within their dendrites and produce spiking outputs, which then propagate down the axon and back into the dendrites where they contribute to plasticity. Mapping the voltage dynamics in dendritic arbors of live animals is crucial for understanding neuronal computation and plasticity rules. Here we combine patterned channelrhodopsin activation with dual-plane structured illumination voltage imaging, for simultaneous perturbation and monitoring of dendritic and somatic voltage in Layer 2/3 pyramidal neurons in anesthetized and awake mice. We examined the integration of synaptic inputs and compared the dynamics of optogenetically evoked, spontaneous, and sensory-evoked back-propagating action potentials (bAPs). Our measurements revealed a broadly shared membrane voltage throughout the dendritic arbor, and few signatures of electrical compartmentalization among synaptic inputs. However, we observed spike rate acceleration-dependent propagation of bAPs into distal dendrites. We propose that this dendritic filtering of bAPs may play a critical role in activity-dependent plasticity.

}, doi = {10.1101/2023.05.25.542363}, url = {https://doi.org/10.1101/2023.05.25.542363}, author = {J. David Wong-Campos and Pojeong Park and Hunter Davis and Yitong Qi and He Tian and Daniel G. Itkis and Doyeon Kim and Sarah E. Plutkis and Luke Lavis and Adam E. Cohen} }