Zebrafish brain atlases: a collective effort for a tiny vertebrate brain.

In the past two decades, digital brain atlases have emerged as essential tools for sharing and integrating complex neuroscience datasets. Concurrently, the larval zebrafish has become a prominent vertebrate model offering a strategic compromise for brain size, complexity, transparency, optogenetic access, and behavior. We provide a brief overview of digital atlases recently developed for the larval zebrafish brain, intersecting neuroanatomical information, gene expression patterns, and connectivity. These atlases are becoming pivotal by centralizing large datasets while supporting the generation of circuit hypotheses as functional measurements can be registered into an atlas' standard coordinate system to interrogate its structural database. As challenges persist in mapping neural circuits and incorporating functional measurements into zebrafish atlases, we emphasize the importance of collaborative efforts and standardized protocols to expand these resources to crack the complex codes of neuronal activity guiding behavior in this tiny vertebrate brain.

Neuronal activity remodels the F-actin based submembrane lattice in dendrites but not axons of hippocampal neurons.

The nanoscale organization of the F-actin cytoskeleton in neurons comprises membrane-associated periodical rings, bundles, and longitudinal fibers. The F-actin rings have been observed predominantly in axons but only sporadically in dendrites, where fluorescence nanoscopy reveals various patterns of F-actin arranged in mixed patches. These complex dendritic F-actin patterns pose a challenge for investigating quantitatively their regulatory mechanisms. We developed here a weakly supervised deep learning segmentation approach of fluorescence nanoscopy images of F-actin in cultured hippocampal neurons. This approach enabled the quantitative assessment of F-actin remodeling, revealing the disappearance of the rings during neuronal activity in dendrites, but not in axons. The dendritic F-actin cytoskeleton of activated neurons remodeled into longitudinal fibers. We show that this activity-dependent remodeling involves [Formula: see text] and NMDA receptor-dependent mechanisms. This highly dynamic restructuring of dendritic F-actin based submembrane lattice into longitudinal fibers may serve to support activity-dependent membrane remodeling, protein trafficking and neuronal plasticity.

Translocation of CaMKII to dendritic microtubules supports the plasticity of local synapses.

The processing of excitatory synaptic inputs involves compartmentalized dendritic Ca(2+) oscillations. The downstream signaling evoked by these local Ca(2+) transients and their impact on local synaptic development and remodeling are unknown. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an important decoder of Ca(2+) signals and mediator of synaptic plasticity. In addition to its known accumulation at spines, we observed with live imaging the dynamic recruitment of CaMKII to dendritic subdomains adjacent to activated synapses in cultured hippocampal neurons. This localized and transient enrichment of CaMKII to dendritic sites coincided spatially and temporally with dendritic Ca(2+) transients. We show that it involved an interaction with microtubular elements, required activation of the kinase, and led to localized dendritic CaMKII autophosphorylation. This process was accompanied by the adjacent remodeling of spines and synaptic AMPA receptor insertion. Replacement of endogenous CaMKII with a mutant that cannot translocate within dendrites lessened this activity-dependent synaptic plasticity. Thus, CaMKII could decode compartmental dendritic Ca(2+) transients to support remodeling of local synapses.

Interaction between αCaMKII and GluN2B controls ERK-dependent plasticity.

Understanding how brief synaptic events can lead to sustained changes in synaptic structure and strength is a necessary step in solving the rules governing learning and memory. Activation of ERK1/2 (extracellular signal regulated protein kinase 1/2) plays a key role in the control of functional and structural synaptic plasticity. One of the triggering events that activates ERK1/2 cascade is an NMDA receptor (NMDAR)-dependent rise in free intracellular Ca(2+) concentration. However the mechanism by which a short-lasting rise in Ca(2+) concentration is transduced into long-lasting ERK1/2-dependent plasticity remains unknown. Here we demonstrate that although synaptic activation in mouse cultured cortical neurons induces intracellular Ca(2+) elevation via both GluN2A and GluN2B-containing NMDARs, only GluN2B-containing NMDAR activation leads to a long-lasting ERK1/2 phosphorylation. We show that αCaMKII, but not ßCaMKII, is critically involved in this GluN2B-dependent activation of ERK1/2 signaling, through a direct interaction between GluN2B and αCaMKII. We then show that interfering with GluN2B/αCaMKII interaction prevents synaptic activity from inducing ERK-dependent increases in synaptic AMPA receptors and spine volume. Thus, in a developing circuit model, the brief activity of synaptic GluN2B-containing receptors and the interaction between GluN2B and αCaMKII have a role in long-term plasticity via the control of ERK1/2 signaling. Our findings suggest that the roles that these major molecular elements have in learning and memory may operate through a common pathway.