Adult-born neurons add flexibility to hippocampal memories

Abstract

Although most neurons are generated embryonically, neurogenesis is maintained at low rates in specific brain areas throughout adulthood, including the dentate gyrus of the mammalian hippocampus. Episodic-like memories encoded in the hippocampus require the dentate gyrus to decorrelate similar experiences by generating distinct neuronal representations from overlapping inputs (pattern separation). Adult-born neurons integrating into the dentate gyrus circuit compete with resident mature cells for neuronal inputs and outputs, and recruit inhibitory circuits to limit hippocampal activity. They display transient hyperexcitability and hyperplasticity during maturation, making them more likely to be recruited by any given experience. Behavioral evidence suggests that adult-born neurons support pattern separation in the rodent dentate gyrus during encoding, and they have been proposed to provide a temporal stamp to memories encoded in close succession. The constant addition of neurons gradually degrades old connections, promoting generalization and ultimately forgetting of remote memories in the hippocampus. This makes space for new memories, preventing saturation and interference. Overall, a small population of adult-born neurons appears to make a unique contribution to hippocampal information encoding and removal. Although several inconsistencies regarding the functional relevance of neurogenesis remain, in this review we argue that immature neurons confer a unique form of transience on the dentate gyrus that complements synaptic plasticity to help animals flexibly adapt to changing environments.

Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner

“…In contrast to sSLR memory, which has been closely tied to adult hippocampal neurogenesis, MWM long-term spatial memory involves hippocampal cellular processes without necessarily depending on adult hippocampal neurogenesis unless the task is altered to require increased pattern separation, cognitive flexibility, or difficulty. 118 , 119 , 122 , 124 , 129 , 189 , 190 Dendritic spine formation is one such cellular process that occurs in the hippocampus. Although the ANLS has been implicated in learning-induced increases in hippocampal 28 and cortical 35 dendritic spine density, these studies were conducted using males only.…”

Memantine increases the dendritic complexity of hippocampal young neurons in the juvenile brain after cranial irradiation

“…They become fully mature within 4-6 weeks after birth ( 1 , 8 ). In rodents, newborn granule neurons have been shown to contribute to certain cognitive tasks such as pattern separation and maintenance of memory functions ( 1 , 9 , 10 ). In humans, persistence of postnatal hippocampal neurogenesis remains debated, however, there is a consensus that DCX-expressing young neurons are detectable during the first decade of childhood, and whether these cells are newborn neurons or late developing neurons is still an active area of research ( 11 – 13 ).…”

Editorial: “Unravelling neural stem cell biology: players and strategies”

“…Exercise, diet, environmental enrichment and activities affecting cognition and learning exert a strong influence on neurogenesis ( Ma et al, 2017 ; Gronska-Peski et al, 2021 ; Folsz et al, 2023 ; Melgar-Locatelli et al, 2023 ). Mazzitelli-Fuentes et al describe for the first time that in adult teleosteans learning induces neurogenesis, adding insight to the relationship between these two processes across species, and showing that learning-induced neurogenesis is relevant in zebrafish specifically in two pallial regions: the caudal lateral pallium and the rostral medial pallium, involving NSCs proliferation and activity-dependent survival.…”