Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus

Abstract

Activity-dependent synaptic plasticity and neurogenesis are two forms of brain plasticity that can participate in functional remodeling of neural networks during the formation of memories. We examined whether long-term potentiation (LTP) of excitatory synaptic transmission, a well characterized form of synaptic plasticity believed to play a critical role in memory formation, can regulate the rate of neurogenesis in the adult rat dentate gyrus in vivo. We first show that induction of LTP at medial perforant path-granule cell synapses stimulates the proliferation of progenitor cells in the dentate gyrus with a consequential long-term persistence of a larger population of surviving newborn cells. Using protocols to examine the effect of LTP on survival, we next show that LTP induction promotes survival of 1-to 2-week-old dentate granule cells. In no case did LTP appear to affect neuronal differentiation. Finally, we show that LTP induces expression of the plasticity-related transcription factor Zif268 in a substantial fraction of 2-week-old but not 1-week-old neurons, suggesting the prosurvival effect of LTP can be observed in the absence of LTP-mediated Zif268 induction in newborn cells. Our results indicate that electrically induced LTP in the dentate gyrus in vivo provides a cellular/molecular environment that favors both proliferation and survival of adult-generated neurons.

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

“…58 Long-term potentiation can induce proliferation of progenitor cells in the dentate gyrus. 59,60 In light of the proposed function here for MIF in adult neurogenesis, these two events may be linked. However, again a note of caution should be added to remind that other factors (developmental, others) might also account for the learning deficits observed in our MIF À/À mice.…”

The role of the N-methyl-d-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells

“…A number of studies have shown that the induction of LTP can activate proliferation in the SGZ in the adult hippocampus. In acutely-implanted anaesthetised rats, LTP induced at perforant path-DG synapses significantly enhanced the proliferation and cell cycle completion of NSPCs (as identified by BrdU incorporation 24 h after HFS) in the SGZ of the DG [9]. The induction of LTP was not found to affect the proliferation of progenitor cells expressing immature neuron markers or the rate of differentiation (as the number of cells double-labelled with BrdU and Prox-1 was similar between the LTP and pseudotetanus groups); however, LTP did significantly enhance the one-month survival of cells that were proliferating 4 d after the HFS [9].…”

“…Early on, extrinsic cues from the environment, such as learning [5], physical activity [6], and enriched environments [7,8], were found to potently enhance hippocampal neurogenesis. It was not long before a link was made to synaptic plasticity [9], which is also enhanced by physical exercise [10], and is widely accepted as the synaptic mechanism underlying hippocampal learning and memory [11]. Synaptic plasticity and adult hippocampal neurogenesis are intimately linked, as long-term potentiation (LTP), an activity-dependent change in synaptic efficacy, can influence the activation and proliferation of NSPCs in the DG (e.g., [12]), as well as the survival of newborn neurons (e.g., [13]).…”

“…Early on, extrinsic cues from the environment, such as learning [5], physical activity [6], and enriched environments [7,8], were found to potently enhance hippocampal neurogenesis. It was not long before a link was made to synaptic plasticity [9], which is also enhanced by physical exercise [10], and is widely accepted as the synaptic mechanism underlying hippocampal learning and memory [11].…”

Forced neuronal interactions cause poor communication

“…8 This competition mechanism may underlie the elimination of a great proportion of postnatal-born neurons during the course of their maturation 9 and the mitigation of this elimination process by neuronal activity. 10 A question arising from these observations is whether improving the synaptic integration of new neurons may result in their increased survival and, eventually, enhance hippocampal function, a hypothesis we tested in a recent study. 11 To this aim, we used a retroviral approach to overexpress synaptic adhesion molecules in a cohort of birth-dated post-natal-born neurons.…”