“Decisive” brain pathway for working memory

A study of the University of Barcelona (UB) has identified a molecular pathway in the brain that is “decisive” for the correct functioning of the working memoryan essential cognitive function to carry out day-to-day activities and temporarily retain information.

The conclusions, published in the magazine ‘Cell Reports‘, they reveal the “determining” role of the Munc13-1 protein in healthy brain function and its clinical relevance in neurodevelopmental disorders, the UB reports in a statement this Monday.

Working memory allows us to understand information, learn and manage responses with the ability to control, abilities that are often affected in some neurodegenerative diseases.

Bursts to strengthen synapses

Neurons do not communicate at a constant rate, but in many circuits there are brief bursts of activity that temporarily strengthen synapses, allowing more efficient transmission of information.

Two of these transient processes are short-term facilitation and post-tetanic potentiation (PPT), both “particularly prominent” at mossy fiber synapses, which are thought to contribute to working memory.

MUNC13-1

The team focused on the study of the Munc13-1 protein, a “key” factor that prepares synaptic vesicles to release neurotransmitters, a step known as vesicular interlocking, and demonstrated that it must be regulated by calcium through two complementary pathways (calcium-phospholipid and calcium-calmodulin signaling).

The results in mice reveal that when Munc13-1 could not adequately detect calcium signals, synapses lost much of their ability to temporarily strengthen during repeated activity.

According to the UB professor and author of the study, Francisco José López-Múricathe study presents “experimental evidence for the idea that working memory may depend not only on sustained neuronal activation but also on transient changes in synaptic transmission.”

With the discovery of a concrete molecular mechanism that links short-term synaptic strengthening with short-term working memory performance, the work “expands our understanding of how the brain stores and rapidly updates information.”