Critical maturational period of new neurons in adult dentate gyrus for their involvement in memory formation

Abstract

Adult dentate gyrus produces new neurons continuously throughout life. Multiple lines of evidence have pointed to the possibility that young neurons during a certain maturational stage mediate an important role in memory processing. In this review, we highlight the existing evidence of a 'critical period' for new neurons in their involvement in memory formation, describe the unique properties of young neurons as potential mechanisms underlying the critical period, and discuss the implications of the critical period for the function of adult neurogenesis.

Lithium rescues synaptic plasticity and memory in Down syndrome mice

“…This finding is consistent with recent data demonstrating that increasing the number of DCX + newborn neurons through the genetic inhibition of apoptosis potentiates neurogenesis-dependent LTP in the DG without affecting the performance of WT mice in CFC or NOR tests (12). The lack of behavioral benefits in WT mice upon neurogenesis induction could reflect the existence of physiological regulatory mechanisms balancing the excess production of newly generated cells in WT mice (53). This concept is supported by evidence that the number of NeuN + newborn neurons is not increased upon the enhancement of neurogenesis (12).…”

“…In WT mice, despite enhanced NPC proliferation (59% over basal), lithium treatment did not enhance the total number of surviving BrdU + cells or newly generated neurons (BrdU + NeuN + ), resulting in a significant reduction in the survival rates of these cells. This suggests the existence of physiological regulatory mechanisms that balance the excess production of newly generated cells in WT mice as previously proposed (53). This view is supported by the observation that the number of apoptotic cells was significantly increased in the DG of WT mice after lithium treatment (Supplemental Figure 8), and the number of BrdU + NeuN + newborn neurons was similar in both lithium-treated WT and Ts65Dn mice ( Figure 6E).…”

Zif268 / egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning

“…In this basal condition, a small proportion of young WT newborn DGCs expressed Zif268, which increased significantly over time (F 5,34 = 10.97, P < 0.001). Consistent with previous reports (4,6), the proportion of Zif268 + /BrdU + cells before 21 dpi was lower than in mature preexisting neurons (Zif268 + in NeuN + mature neurons: 1.9 ± 0.2%), but became significantly higher in 43-d-old newborn DGCs (Zif268 + in BrdU + cells: 1.1 ± 0.3%; 0.8 ± 0.3%; 3.0 ± 0.9%; 6.9 ± 2.1%; 2.5 ± 0.6%; 25 ± 2.8%, at 7, 14, 21, 28, 34, and 43 dpi P = 0.007, respectively).…”

“…We used the spatial Morris water-maze task with a massed protocol that results in long-lasting spatial memory and increased incorporation of new neurons in the adult DG (22). Guided by evidence indicating that new neurons within 1-3 wk after birth have a unique role in hippocampal-dependent memory formation (6), and by the differential requirement for zif268 observed above in populations of newborn DGCs of different ages (Fig. 1C), we submitted WT and zif268-KO mice to spatial learning 9 or 18 d after BrdU injections and analyzed memory performance and survival rate 25 d after acquisition ( Fig.…”

“…After birth, the majority of newborn dentate granule cells (DGCs) follow a 2-mo race of development to become fully mature and integrate into existing circuits (2-4), a condition for their contribution to hippocampal functions, in particular to hippocampal-dependent learning and memory and spatial pattern discrimination (5). The cells' involvement as part of neuronal networks supporting learning and memory is believed to be timelocked to a critical stage of maturation (6). From the second week after birth, axons of newborn DGCs elongate (3) and contact hilar and CA3 pyramidal cells (7), then dendrites extend in the molecular layer and spines start to appear (2, 3).…”