The hidden fitness of the male zebra finch courtship song.

Vocal learning in songbirds is thought to have evolved through sexual selection, with female preference driving males to develop large and varied song repertoires1-3. However, many songbird species learn only a single song in their lifetime4. How sexual selection drives the evolution of single-song repertoires is not known. Here, by applying dimensionality-reduction techniques to the singing behaviour of zebra finches (Taeniopygia guttata), we show that syllable spread in low-dimensional feature space explains how single songs function as honest indicators of fitness. We find that this Gestalt measure of behaviour captures the spectrotemporal distinctiveness of song syllables in zebra finches; that females strongly prefer songs that occupy more latent space; and that matching path lengths in low-dimensional space is difficult for young males. Our findings clarify how simple vocal repertoires may have evolved in songbirds and indicate divergent strategies for how sexual selection can shape vocal learning.

Altered steady state and activity-dependent de novo protein expression in fragile X syndrome.

Whether fragile X mental retardation protein (FMRP) target mRNAs and neuronal activity contributing to elevated basal neuronal protein synthesis in fragile X syndrome (FXS) is unclear. Our proteomic experiments reveal that the de novo translational profile in FXS model mice is altered at steady state and in response to metabotropic glutamate receptor (mGluR) stimulation, but the proteins expressed differ under these conditions. Several altered proteins, including Hexokinase 1 and Ras, also are expressed in the blood of FXS model mice and pharmacological treatments previously reported to ameliorate phenotypes modify their abundance in blood. In addition, plasma levels of Hexokinase 1 and Ras differ between FXS patients and healthy volunteers. Our data suggest that brain-based de novo proteomics in FXS model mice can be used to find altered expression of proteins in blood that could serve as disease-state biomarkers in individuals with FXS.

BONLAC: A combinatorial proteomic technique to measure stimulus-induced translational profiles in brain slices.

Stimulus-triggered protein synthesis is critical for brain health and function. However, due to technical hurdles, de novo neuronal translation is predominantly studied in cultured cells, whereas electrophysiological and circuit analyses often are performed in brain slices. The different properties of these two experimental systems create an information gap about stimulus-induced alterations in the expression of new proteins in mature circuits. To address this, we adapted two existing techniques, BONCAT and SILAC, to a combined proteomic technique, BONLAC, for use in acute adult hippocampal slices. Using BDNF-induced protein synthesis as a proof of concept, we found alterations in expression of proteins involved in neurotransmission, trafficking, and cation binding that differed from those found in a similar screen in cultured neurons. Our results indicate important differences between cultured neurons and slices, and suggest that BONLAC could be used to dissect proteomic changes underlying synaptic events in adult circuits. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.