The guanine nucleotide exchange factor (GEF) Asef2 promotes dendritic spine formation via Rac activation and spinophilin-dependent targeting.

Dendritic spines are actin-rich protrusions that establish excitatory synaptic contacts with surrounding neurons. Reorganization of the actin cytoskeleton is critical for the development and plasticity of dendritic spines, which is the basis for learning and memory. Rho family GTPases are emerging as important modulators of spines and synapses, predominantly through their ability to regulate actin dynamics. Much less is known, however, about the function of guanine nucleotide exchange factors (GEFs), which activate these GTPases, in spine and synapse development. In this study we show that the Rho family GEF Asef2 is found at synaptic sites, where it promotes dendritic spine and synapse formation. Knockdown of endogenous Asef2 with shRNAs impairs spine and synapse formation, whereas exogenous expression of Asef2 causes an increase in spine and synapse density. This effect of Asef2 on spines and synapses is abrogated by expression of GEF activity-deficient Asef2 mutants or by knockdown of Rac, suggesting that Asef2-Rac signaling mediates spine development. Because Asef2 interacts with the F-actin-binding protein spinophilin, which localizes to spines, we investigated the role of spinophilin in Asef2-promoted spine formation. Spinophilin recruits Asef2 to spines, and knockdown of spinophilin hinders spine and synapse formation in Asef2-expressing neurons. Furthermore, inhibition of N-methyl-d-aspartate receptor (NMDA) activity blocks spinophilin-mediated localization of Asef2 to spines. These results collectively point to spinophilin-Asef2-Rac signaling as a novel mechanism for the development of dendritic spines and synapses.

Sex-specific impairment of spatial memory in rats following a reminder of predator stress.

It has been suggested that cognitive impairments exhibited by people with post-traumatic stress disorder (PTSD) result from intrusive, flashback memories transiently interfering with ongoing cognitive processing. Researchers have further speculated that females are more susceptible to developing PTSD because they form stronger traumatic memories than males, hence females may be more sensitive to the negative effects of intrusive memories on cognition. We have examined how the reminder of a naturalistic stress experience would affect rat spatial memory and if sex was a contributing factor to such effects. Male and female Sprague-Dawley rats were exposed, without contact, to an adult female cat for 30 min. Five weeks later, the rats were trained to locate a hidden platform in the radial-arm water maze and given a single long-term memory test trial 24 h later. Before long-term memory testing, the rats were given a 30-min reminder of the cat exposure experienced 5 weeks earlier. The results indicated that the stress reminder impaired spatial memory in the female rats only. Control manipulations revealed that this effect was not attributable to the original cat exposure adversely impacting learning that occurred 5 weeks later, or to merely exposing rats to a novel environment or predator-related cues immediately before testing. These findings provide evidence that the reminder of a naturalistic stressful experience can impair cognitive processing in rats; moreover, since female rats were more susceptible to the memory-impairing effects of the stress reminder, the findings could lend insight into the existing sex differences in susceptibility to PTSD.

Linking the genomic signatures of human beat synchronization and learned song in birds.

The development of rhythmicity is foundational to communicative and social behaviours in humans and many other species, and mechanisms of synchrony could be conserved across species. The goal of the current paper is to explore evolutionary hypotheses linking vocal learning and beat synchronization through genomic approaches, testing the prediction that genetic underpinnings of birdsong also contribute to the aetiology of human interactions with musical beat structure. We combined state-of-the-art-genomic datasets that account for underlying polygenicity of these traits: birdsong genome-wide transcriptomics linked to singing in zebra finches, and a human genome-wide association study of beat synchronization. Results of competitive gene set analysis revealed that the genetic architecture of human beat synchronization is significantly enriched for birdsong genes expressed in songbird Area X (a key nucleus for vocal learning, and homologous to human basal ganglia). These findings complement ethological and neural evidence of the relationship between vocal learning and beat synchronization, supporting a framework of some degree of common genomic substrates underlying rhythm-related behaviours in two clades, humans and songbirds (the largest evolutionary radiation of vocal learners). Future cross-species approaches investigating the genetic underpinnings of beat synchronization in a broad evolutionary context are discussed. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.

Species-level repertoire size predicts a correlation between individual song elaboration and reproductive success.

Birdsong has long been considered a sexually selected trait that relays honest information about male quality, and laboratory studies generally suggest that female songbirds prefer larger repertoires. However, analysis of field studies across species surprisingly revealed a weak correlation between song elaboration and reproductive success, and it remains unknown why only certain species show this correlation in nature. Taken together, these studies suggest that females in numerous species can detect and prefer larger repertoires in a laboratory setting, but larger individual repertoires correlate with reproductive success only in a subset of these species. This prompts the question: Do the species that show a stronger correlation between reproductive success and larger individual repertoires in nature have anything in common? In this study, we test whether between-species differences in two song-related variables-species average syllable repertoire size and adult song stability over time-can be used to predict the importance of individual song elaboration in reproductive success within a species. Our cross-species meta-analysis of field studies revealed that species with larger average syllable repertoire sizes exhibited a stronger correlation between individual elaboration and reproductive success than species with smaller syllable repertoires. Song stability versus plasticity in adulthood provided little predictive power on its own, suggesting that the putative correlation between repertoire size and age in open-ended learners does not explain the association between song elaboration and reproductive success.

Correlated evolution between repertoire size and song plasticity predicts that sexual selection on song promotes open-ended learning.

Some oscine songbird species modify their songs throughout their lives ('adult song plasticity' or 'open-ended learning'), while others crystallize their songs around sexual maturity. It remains unknown whether the strength of sexual selection on song characteristics, such as repertoire size, affects adult song plasticity, or whether adult song plasticity affects song evolution. Here, we compiled data about song plasticity, song characteristics, and mating system and then examined evolutionary interactions between these traits. Across 67 species, we found that lineages with adult song plasticity show directional evolution toward increased syllable and song repertoires, while several other song characteristics evolved faster, but in a non-directional manner. Song plasticity appears to drive bi-directional transitions between monogamous and polygynous social mating systems. Notably, our analysis of correlated evolution suggests that extreme syllable and song repertoire sizes drive the evolution of adult song plasticity or stability, providing novel evidence that sexual selection may indirectly influence open- versus closed-ended learning.

Super resolution microscopy is poised to reveal new insights into the formation and maturation of dendritic spines.

Dendritic spines and synapses are critical for neuronal communication, and they are perturbed in many neurological disorders; however, the study of these structures in living cells has been hindered by their small size. Super resolution microscopy, unlike conventional light microscopy, is diffraction unlimited and thus is well suited for imaging small structures, such as dendritic spines and synapses. Super resolution microscopy has already revealed important new information about spine and synapse morphology, actin remodeling, and nanodomain composition in both healthy cells and diseased states. In this review, we highlight the advancements in probes that make super resolution more amenable to live-cell imaging of spines and synapses. We also discuss recent data obtained by super resolution microscopy that has advanced our knowledge of dendritic spine and synapse structure, organization, and dynamics in both healthy and diseased contexts. Finally, we propose a series of critical questions for understanding spine and synapse formation and maturation that super resolution microscopy is poised to answer.