Summary: New neurons born in the adult hippocampus are crucial for structural synaptic remodeling and for consolidating memories during REM sleep, according to a recent study in mice.
Source: Cell Press
Adult neurogenesis — the production of new neurons in the hippocampus of a mature brain — is well established in mice, but how these adult-born neurons become functionally integrated into existing circuits has been unclear. A study published June 4 in the journal Neuron reveals that neurons generated during adulthood play a key role in consolidating memories during rapid eye movement (REM) sleep.
Previous research linked adult-born neurons (ABNs) to memory formation and synaptic plasticity, making them compelling candidates for involvement in sleep-dependent memory consolidation. During sleep, hippocampal networks often replay activity patterns similar to those experienced during learning, but the specific role of ABNs in this process had remained unknown.
Lead author Masanori Sakaguchi, associate professor at the International Institute for Integrative Sleep Medicine at the University of Tsukuba, Japan, and colleagues show that ABNs are necessary for synaptic structural remodeling and for stabilizing memories during REM sleep in mice.
“This study is the first to demonstrate ABN activity and function during sleep in animals,” Sakaguchi explains. “Our results help reveal how adult-born neurons connect to established mechanisms of memory consolidation that operate during sleep.”
The team observed ABN activity using advanced calcium imaging techniques that allowed continuous visualization of neuronal activity over several hours in naturally sleeping mice. Because individual REM episodes in mice typically last under a minute, the researchers used optogenetics — genetically modifying neurons so they can be activated or silenced with light — to precisely manipulate ABN activity during these brief REM bouts.
Surprisingly, the researchers found that most young ABNs are largely inactive during sleep. However, a small subset of ABNs became active during contextual fear learning (when mice received a mild foot shock) and these same neurons were selectively reactivated during subsequent REM sleep episodes. This reactivation occurred against a background of generally reduced ABN activity during REM.
Crucially, when the investigators silenced this sparse ABN activity during REM sleep, the mice showed impaired memory consolidation. Both optogenetic suppression and artificial elevation of ABN activity during REM produced memory deficits, indicating that precise, coordinated ABN firing patterns are required for normal consolidation. The study also found that interfering with ABN activity disrupted structural remodeling of dendritic spines on these neurons, linking ABN activation during REM sleep to the synaptic changes that underlie lasting memory.
These findings raise several important questions for future research: Does ABN reactivation during REM reflect a form of memory replay? What circuit mechanisms coordinate ABN activity across REM episodes? And how do ABNs influence downstream neurons to stabilize memories? Answering these questions will clarify how newly generated neurons become integrated into existing hippocampal networks and how they contribute to long-term memory storage.
“We believe these mechanisms are essential for new neurons to join established circuitry and carry out memory-related functions,” Sakaguchi says. He adds that a deeper understanding of ABN contributions during sleep could inform new therapies aimed at restoring or regenerating damaged brain tissue.
Funding: This research was supported by grants from the World Premier International Research Center Initiative, Takeda Science Foundation, Shimadzu Science Foundation, Kanae Foundation, Research Foundation for Opto-Science and Technology, Ichiro Kanehara Foundation, Kato Memorial Bioscience Foundation, Japan Foundation for Applied Enzymology, Senshin Medical Research Foundation, Life Science Foundation of Japan, Uehara Memorial Foundation, Brain Science Foundation, Kowa Life Science Foundation, the Inamori Research Grants Program, and GSK Japan.
About this neurogenesis research article
Source:
Cell Press
Media contacts:
Carly Britton – Cell Press
Original research (open access):
“Sparse activity of hippocampal adult-born neurons during REM sleep is necessary for memory consolidation.” Neuron. DOI: 10.1016/j.neuron.2020.05.008
Abstract
Sparse activity of hippocampal adult-born neurons during REM sleep is necessary for memory consolidation
This study investigates whether young adult-born neurons in the dentate gyrus contribute to memory consolidation during sleep. Using calcium imaging in freely moving mice, the authors show that contextual fear learning recruits a selective population of young ABNs that are reactivated during subsequent REM sleep, even as overall ABN activity is reduced. Optogenetic silencing of this sparse REM-associated ABN activity altered spine remodeling on ABN dendrites and impaired memory consolidation, providing a causal link between ABN activation during REM sleep and memory stabilization.
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