Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

Abstract

Neurogenesis in the hippocampus is characterized by the birth of thousand of cells that generate neurons throughout life. The fate of these adult newborn neurons depends on life experiences. In particular, spatial learning promotes the survival and death of new neurons. Whether learning influences the development of the dendritic tree of the surviving neurons (a key parameter for synaptic integration and signal processing) is unknown. Here we show that learning accelerates the maturation of their dendritic trees and their integration into the hippocampal network. We demonstrate that these learning effects on dendritic arbors are homeostatically regulated, persist for several months, and are specific to neurons born during adulthood. Finally, we show that this dendritic shaping depends on the cognitive demand and relies on the activation of NMDA receptors. In the search for the structural changes underlying long-term memory, these findings lead to the conclusion that shaping neo-networks is important in forming spatial memories.adult neurogenesis | memory | spatial learning | hippocampus | dendrite I n the search for the mechanisms underlying long-term memory formation, structural changes have been proposed to play a major role (1). Adult neurogenesis, a novel form of structural plasticity, occurs in the dentate gyrus (DG), a key structure in processing spatial relational memory (2). Adult neurogenesis in the DG is a complex, multistep process that starts with the proliferation of neural precursors residing in the dentate subgranular layer (2). At least 50% of the daughter cells die within a few days after their birth. The adult-born cells that survive this initial period of cell death differentiate mainly into granule neurons. These new mature neurons are synaptically integrated into the dentate network, where they receive functional inputs (3) and form functional synapses with their target cells (4).Adult-born neurons contribute to the formation of memories, particularly spatial memory as measured in the water maze (5, 6). Reciprocally, spatial learning has been shown to influence adult neurogenesis (7). We have shown that during spatial learning and similar to the selective stabilization process observed during brain development, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons (8). This homeostatic regulation of the numbers of newly born neurons is important for spatial memory, because its alteration leads to memory deficits (8, 9).One of the requirements for the new neurons to process information is the development of extensive dendritic arbors capable of receiving and integrating complex spatiotemporal patterns of synaptic inputs (4). Whether learning influences such a dendritic development is unknown. To address this issue, we used doublecortin (Dcx) and retroviral labeling to examine to what extent spatial learning in the water maze affects the dendritic morphology of adult-born neurons. Furthermore, we investigated whether the ...

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

“…Blockade of N-methyl-D-aspartate (NMDA) receptors does not disrupt learning-induced changes in cell numbers (Tronel et al 2010). These results are consistent with the role of NMDA during the developmental period (Rajan and Cline 1998;Sin et al 2002;Niell et al 2004;Prithviraj and Inglis 2008).…”

“…Interestingly, there is no critical time window for experience-induced dendritic plasticity of adult-born neurons as spatial learning sculpts the dendritic arbor of adult-born neurons even when they are several months old (Lemaire et al 2012). The effects of learning are specific for neurons born during adulthood as neurons born during development remained unchanged after learning (Tronel et al 2010;Lemaire et al 2012). …”

“…However, this does not exclude the possibility that neuromodulators may act differently on developmental and adult-born neurons. When focusing on their structural plasticity, adult-born, but not developmentally generated, neurons are able to reshape in response to learning (Tronel et al 2010;Lemaire et al 2012), suggesting that these dissimilarities confer them different functions. Some studies, indeed, highlighted a specific behavioral signature for neurons born in development ( pups or juvenile) versus adulthood (Wei et al 2011;Nakashiba et al 2012;Tronel et al 2014).…”

“…To address this issue, one can examine the dendritic arbor and spine density as measures of the available postsynaptic space that indirectly reflects the presence of inputs (Tronel et al 2010). Two neuronal populations were examined: (1) the population comprising new neurons generated 1 wk before the start of the training and whose survival was promoted by learning, and (2) the youngest population comprising newly born neurons generated 3 d before training or during the early phase of training that were spared by the apoptotic wave.…”

Conditional reduction of adult neurogenesis impairs bidirectional hippocampal synaptic plasticity

“…It has been proposed that these unique characteristics may make new neurons within this critical period more sensitive to life experience. In particular, it has been shown that learning or experiencing an enriched environment determines the survival, dendritic development, and population response of the new neurons (22)(23)(24)(25)(26). This exceptional plasticity of the young neurons may be particularly useful for information processing (27,28).…”