Maintaining a dynamic neuronal synapse pool is critical to brain development. The extracellular matrix (ECM) regulates synaptic plasticity via mechanisms that are still being defined and are studied predominantly in adulthood. Using live imaging of excitatory synapses in zebrafish hindbrain we observed a bimodal distribution of short-lived (dynamic) and longer-lived (stable) synapses. Disruption of ECM via digestion or brevican deletion destabilized dynamic but not stable synapses and led to decreased synapse density. Conversely, loss of matrix metalloproteinase 14 (MMP14) led to accumulation of brevican and increased the stable synapse pool, resulting in increased synapse density. Microglial MMP14 was essential to these effects in both fish and human iPSC-derived cultures. Both MMP14 and brevican were required for experience-dependent synapse plasticity in a motor learning assay. These data, complemented by mathematical modeling, define an essential role of ECM remodeling in maintaining a dynamic subset of synapses during brain development.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888425PMC
http://dx.doi.org/10.1101/2025.02.27.640672DOI Listing

Publication Analysis

Top Keywords

brain development
12
extracellular matrix
8
synapse plasticity
8
maintaining dynamic
8
synapse pool
8
stable synapses
8
synapse density
8
synapse
6
matrix proteolysis
4
proteolysis maintains
4

Similar Publications

Background: Butyrate may inhibit SARS-CoV-2 replication and affect the development of COVID-19. However, there have been no systematic comprehensive analyses of the role of butyrate metabolism-related genes (BMRGs) in COVID-19.

Methods: We performed differential expression analysis of BMRGs in the brain, liver and pancreas of COVID-19 patients and controls in GSE157852 and GSE151803.

View Article and Find Full Text PDF

The release of synaptic vesicles (SVs) at the synaptic junction is a complex process involving various specialized proteins that work in unison. Among these, Bassoon has emerged as a significant protein, particularly noted for its association with various neurological and aging-related diseases. Due to its structural and functional roles, Bassoon has become a focus of recent research, especially in understanding its implications in neurodegenerative and psychiatric disorders.

View Article and Find Full Text PDF

The relationship between brain and visceral asymmetry: Evidence from situs inversus in humans.

Handb Clin Neurol

March 2025

Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium. Electronic address:

This review examines the relationship between visceral and brain asymmetry and explores whether their alignment observed in some vertebrate species also exists in humans. While the development of visceral and brain asymmetry may have occurred for different reasons, it is possible that the basic mechanisms for left-right differentiation of the visceral system were duplicated in the brain. We describe the main phenotypical anomalies and the general mechanism of left-right differentiation in vertebrates, followed by a systematic review of available human studies on behavioral and brain asymmetry in individuals with reversed visceral organization.

View Article and Find Full Text PDF

This chapter reviews notions about the lateralization of numbers and calculation in the brain, including its developmental pattern. Such notions have changed dramatically in recent decades. What was once considered a function almost exclusively located in the left hemisphere has been found to be sustained by complex brain networks encompassing both hemispheres.

View Article and Find Full Text PDF

Hemispheric asymmetries in face recognition in health and dysfunction.

Handb Clin Neurol

March 2025

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. Electronic address:

A defining characteristic of the human brain is that, notwithstanding the clear anatomic similarities, the two cerebral hemispheres have several different functional superiorities. The focus of this chapter is on the hemispheric asymmetry associated with the function of face identity processing, a finely tuned and expert behavior for almost all humans that is acquired incidentally from birth and continues to be refined through early adulthood. The first section lays out the well-accepted doctrine that face perception is a product of the right hemisphere, a finding based on longstanding behavioral data from healthy adult human observers.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!