Vascular cells essential in forming long-term memories

Neurons have largely been the focus of research on long-term memory. However, scientists are discovering that other cell types are crucial for memory formation and storage.

Published in Neuron, a new study led by neuroscientists at New York University and including scientists from Cold Spring Harbor Laboratory and the University of Cambridge, unveils the essential role of vascular system cells, called pericytes,in the formation of long-term memories of life events. These memories are lost in diseases such as Alzheimer’s disease. The research demonstrates that pericytes, which help upkeep the structural integrity of the capillaries, work with neurons to help ensure the formation of long-term memories.  Specifically, pericytes control the amount of blood flowing in the brain and play a key role in maintaining the barrier that stops pathogens and toxic substances from leaking out of the capillaries and into brain tissue.

“We now have a firmer understanding of the cellular mechanisms that allow memories to be both formed and stored,” said Cristina Alberini, a professor in New York University’s Center for Neural Science and the paper’s senior author. “It’s important because understanding the cooperation among different cell types will help us advance therapeutics aimed at addressing memory-related afflictions.”

“This work connects important dots between the newly discovered function of pericytes in memory and previous studies showing that pericytes are either lost or malfunction in several neurodegenerative diseases, including Alzheimer’s disease and other dementia,” explained author Benjamin Bessières, a postdoctoral researcher in NYU’s Center for Neural Science.

This discovery of the pericytes’ importance in long-term memory materialised because Alberini, Bessières, Kiran Pandey, and their colleagues studied the role of insulin-like growth factor 2 (IGF2). IGF2 is a protein that was known to increase after learning in brain regions, such as the hippocampus, and to play an essential role in the formation and storage of memories. 

They found that IGF2’s highest levels in the brain cells of the hippocampus derive from pericytes, rather than neurons, glial cells, or other vascular cells.  

IGF2’s presence in pericytes, then, raises the following question: How is this linked to memory? 

The scientists carried out a series of cognitive experiments using mice, comparing behaviours of those with pericytes that produced IGF2 and those that did not to isolate the significance of both pericytes and IGF2 in neurological processes. 

The mice were subjected to a series of memory tests like learning to identify objects placed in a new location. 

The results showed that production of IGF2 by pericytes in the hippocampus was enhanced by the learning event. More specifically, this increase in pericytic IGF2 happened in response to activity of neurons, revealing a coordinated, neuron-pericytic action. Also, IGF2 made by pericytes were shown to circle back to influence biological responses of neurons that are crucial for memory.

“IGF2 produced from pericytes and acting on neurons support the idea that a neurovascular unit regulates neuronal responses as well as functions of the blood barrier and may have repercussions on brain injury and inflammation,” explained Pandey, a postdoctoral researcher in NYU’s Center for Neural Science. 

“Cooperation between neurons and pericytes is necessary to assure that long-term memories are formed,” observed Alberini. “Our study provides a new view of the biology of memory—though more research is needed to further understand the roles of pericytes and the vascular system in memory and its diseases.”