Long-lasting forms of postsynaptic plasticity commonly involve protein synthesis-dependent structural changes of dendritic spines. However, the relationship between protein synthesis and presynaptic structural plasticity remains unclear. Here, we investigated structural changes in cannabinoid-receptor 1 (CB1)-mediated long-term depression of inhibitory transmission (iLTD), a form of presynaptic plasticity that involves a protein synthesis-dependent long-lasting reduction in GABA release. We found that CB1-iLTD in acute rat hippocampal slices was associated with protein synthesis-dependent presynaptic structural changes. Using proteomics, we determined that CB1 activation in hippocampal neurons resulted in increased ribosomal proteins and initiation factors, but decreased levels of proteins involved in regulation of the actin cytoskeleton, such as ARPC2 and WASF1/WAVE1, and presynaptic release. Moreover, while CB1-iLTD increased ubiquitin/proteasome activity, ubiquitination but not proteasomal degradation was critical for structural and functional presynaptic CB1-iLTD. Thus, CB1-iLTD relies on both protein synthesis and ubiquitination to elicit structural changes that underlie long-term reduction of GABA release.
All data generated in this study are included in the manuscript and supporting files. Source data files are provided for Figure 2.The mass spectrometry proteomics data have been deposited to the ProteomeX change with identifier Consortium via the PRIDE  partner repository with the dataset identifier PXD020008 and 10.6019/PXD020008.
UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites.UbiSite, https://doi.org/10.1038/s41594-018-0084-y.
UniProt: the universal protein knowledgebaseUniprot, Nucleic Acids Res 46: 2699 (2018).
- Hannah R Monday
- Pablo E Castillo
- Pablo E Castillo
- Pablo E Castillo
- Bryen A Jordan
- Mathieu Bourdenx
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Experimental procedures adhered to NIH and Albert Einstein College of Medicine Institutional Animal Care and Use Committee guidelines as approved by protocol #00001047.
- Gary L Westbrook, Oregon Health and Science University, United States
© 2020, Monday et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Ultrasonic vocalizations (USVs) fulfill an important role in communication and navigation in many species. Because of their social and affective significance, rodent USVs are increasingly used as a behavioral measure in neurodevelopmental and neurolinguistic research. Reliably attributing USVs to their emitter during close interactions has emerged as a difficult, key challenge. If addressed, all subsequent analyses gain substantial confidence. We present a hybrid ultrasonic tracking system, Hybrid Vocalization Localizer (HyVL), that synergistically integrates a high-resolution acoustic camera with high-quality ultrasonic microphones. HyVL is the first to achieve millimeter precision (~3.4–4.8 mm, 91% assigned) in localizing USVs, ~3× better than other systems, approaching the physical limits (mouse snout ~10 mm). We analyze mouse courtship interactions and demonstrate that males and females vocalize in starkly different relative spatial positions, and that the fraction of female vocalizations has likely been overestimated previously due to imprecise localization. Further, we find that when two male mice interact with one female, one of the males takes a dominant role in the interaction both in terms of the vocalization rate and the location relative to the female. HyVL substantially improves the precision with which social communication between rodents can be studied. It is also affordable, open-source, easy to set up, can be integrated with existing setups, and reduces the required number of experiments and animals.
How does the human brain combine information across the eyes? It has been known for many years that cortical normalization mechanisms implement ‘ocularity invariance’: equalizing neural responses to spatial patterns presented either monocularly or binocularly. Here, we used a novel combination of electrophysiology, psychophysics, pupillometry, and computational modeling to ask whether this invariance also holds for flickering luminance stimuli with no spatial contrast. We find dramatic violations of ocularity invariance for these stimuli, both in the cortex and also in the subcortical pathways that govern pupil diameter. Specifically, we find substantial binocular facilitation in both pathways with the effect being strongest in the cortex. Near-linear binocular additivity (instead of ocularity invariance) was also found using a perceptual luminance matching task. Ocularity invariance is, therefore, not a ubiquitous feature of visual processing, and the brain appears to repurpose a generic normalization algorithm for different visual functions by adjusting the amount of interocular suppression.