Optical controlling reveals time-dependent roles for adult-born dentate granule cells

Abstract

Accumulating evidence suggests that global depletion of adult hippocampal neurogenesis influences its function and the timing of the depletion impacts the deficits. However, behavioral roles of adult-born neurons during their establishment of projections to CA3 pyramidal neurons remain largely unknown. Here we combined retroviral and optogenetic approaches to birth-date and reversibly control a group of adult-born neurons in adult mice. We show that adult-born neurons form functional synapses on CA3 pyramidal neurons as early as 2 weeks after birth, and that this projection to the CA3 area becomes stable by 4 weeks in age. Newborn neurons at this age exhibit enhanced plasticity compared to other stages. Notably, we found that reversibly silencing this cohort of ~4 week-old cells after training, but not cells of other ages, substantially disrupted retrieval of hippocampal memory. Our results identify a restricted time window for adult-born neurons exhibiting an essential role in hippocampal memory retrieval.

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

“…Instead, FXGs are present only after axons become synaptically-integrated into circuits. Further, by manipulating adult neurogenesis, we determined that FXGs persist for months after the period of robust plasticity in newly born adult neurons (30)(31)(32). Therefore, we propose that FXGs regulate local translation in the mature axonal arbour, likely in the context of adult plasticity.…”

“…In the dentate gyrus newly born granule cells are generated throughout life and exhibit a period of heightened plasticity as they integrate into the mature circuitry (30)(31)(32). Adult neurogenesis is more robust in rats than mice (33).…”

Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal Cord Injury

“…To investigate whether a spinal cord distant lesion impacts hippocampal neurogenesis that is believed to contribute to memory formation and depression, [32][33][34] mice received BrdU injections between Weeks 13 and 16 post-injury, and brain sections were double-labeled with antibodies specific for BrdU and newlygenerated immature neurons (DCX) or mature neurons (NeuN). BrdU positive cells, as well as cells co-labeled with DCX and NeuN, were quantified in the hippocampal DG sub-regions (including GL, SGZ, and hilus) at 16 weeks after SCI (Fig.…”

“…[32][33][34] Remote impaired neurogenesis has been shown after peripheral neuropathy and spinal cord lesions. 18,[35][36][37] However, the relationship between injury severity and the development of hippocampal neurogenesis following SCI is less clear.…”

Forced neuronal interactions cause poor communication

“…Indeed, new neurons display increased plastic properties 1 and the role of new neurons in the formation of memory traces was confirmed by optogenetic silencing in mice undergoing a Morris water maze test, which resulted in impaired hippocampal memory retrieval. 2 Similarly, inhibiting post-natal neurogenesis reduces the behavioral effects of antidepressant treatments. 3 It is thought that the functional role of neurons born post-natally critically depends on the mechanisms by which they integrate into the mature hippocampal network, which are still poorly-known.…”