A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain - PubMed (original) (raw)

A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain

Shaoyu Ge et al. Neuron. 2007.

Abstract

Active adult neurogenesis occurs in discrete brain regions of all mammals and is widely regarded as a neuronal replacement mechanism. Whether adult-born neurons make unique contributions to brain functions is largely unknown. Here we systematically characterized synaptic plasticity of retrovirally labeled adult-born dentate granule cells at different stages during their neuronal maturation. We identified a critical period between 1 and 1.5 months of the cell age when adult-born neurons exhibit enhanced long-term potentiation with increased potentiation amplitude and decreased induction threshold. Furthermore, such enhanced plasticity in adult-born neurons depends on developmentally regulated synaptic expression of NR2B-containing NMDA receptors. Our study demonstrates that adult-born neurons exhibit the same classic critical period plasticity as neurons in the developing nervous system. The transient nature of such enhanced plasticity may provide a fundamental mechanism allowing adult-born neurons within the critical period to serve as major mediators of experience-induced plasticity while maintaining stability of the mature circuitry.

PubMed Disclaimer

Figures

Figure 1.

Adult-born neurons exhibit enhanced synaptic plasticity within a critical period. (A) LTP recorded from newborn DGCs at 1 mpi in the adult brain. Shown in the top row is an example of LTP of EPSPs recorded under the whole-cell current-clamp. Representative EPSPs averaged from 5 consecutive stimuli were taken before and after LTP induction by a physiological relevant TBS (arrow) at the time points (1 and 2) indicated in the graph. Shown at the bottom is the summary of LTP recorded from newborn DGCs at 1 mpi in the presence or absence of APV (50 µM). Normalized EPSP amplitudes are shown. Values represent mean ± SEM. (B, C) LTP recorded from mature DGCs and from newborn DGCs at 4 mpi. Same as in (A), except that GFP− mature DGCs (B) or newborn GFP+ DGCs at 4 mpi (C) were recorded. (D, E) A critical period with enhanced synaptic plasticity for adult-born neurons. Shown in (D) are percentages of DGCs at different stages of neuronal maturation that exhibited significant LTP. Shown in (E) is the summary of the mean enhancement of EPSPs (at 45–55 min during recording) from newborn GFP+ DGCs at different stages and from GFP− mature DGCs. Values represent mean ± SEM (*: p < 0.01; t-test). The value of LTP for individual cell examined under each condition is shown in Figure S3 in the Supplementary Data.

Figure 2.

Developmental regulation of synaptic expression of NR2B-containing NMDARs in adult-born neurons during their maturation. (A) Blockade of NR2B-containing NMDAR-mediated EPSCs by ifenprodil. Shown are normalized NMDAR-mediated EPSCs from newborn DGCs at 1 mpi recorded under the whole-cell voltage-clamp (Vm = −65 mV) before and after bath application of ifenprodil (3 µM) as indicated. Glycine (10 µM), bicuculline (10 µM) and NBQX (100 µM) were present throughout the recording. Values represent mean ± SEM (n = 6). Insert shows sample EPSC traces recorded at different time points. Scale bars: 100 ms and 20 pA. (B) Contribution of NR2B-containing NMDARs to the total NMDAR-mediated EPSCs in newborn and mature DGCs in the adult brain. Top panel shows pharmacologically isolated NMDAR-mediated EPSCs from a newborn GFP+ DGC at 1 mpi, 2 mpi, and from a mature DGC recorded (1) before, (2) 15–20 min after bath application of ifenprodil (3 µM), and (3) followed by APV (50 µM). ottom panel shows the summary of inhibition of NMDAR-mediated EPSC by ifenprodil in newly generated DGCs at different maturation stages and in mature DGCs. Values represent mean ± SEM. The total number of cells examined under each condition is indicated in parentheses (*: p < 0.01; t-test).

Figure 3.

Differential requirement of NR2B-signaling for LTP of mature and newborn DGCs in the adult brain. (A) Summary of LTP of EPSPs in GFP+ newborn DGCs at 1 mpi, 2 mpi and in mature DGCs, with or without the addition of ifenprodil (3 µM). EPSPs averaged from 5 consecutive stimuli were taken before and after LTP induction by TBS (arrow) at the time points (1 and 2) indicated in the graphs. Same groups of cells for 1 mpi were used as in Fig. 1A. (B) Summary of the modulation of the mean enhancement of EPSPs (at 45–55 min during recording) by ifenprodil (3 µM) or Ro25-6981 (0.5 µM). Values represent mean ± SEM. The total number of cells examined at each condition is indicated in parentheses (*: p < 0.01; t-test).

Figure 4.

Differential modulation of enhanced synaptic plasticity of adult-born neurons by ifenprodil and APV. (A to C) LTP of EPSPs in GFP+ newborn DGCs at 1 mpi in the presence of different amount inhibition of NMDAR-mediated EPSCs by ifenprodil or APV. EPSPs averaged from 5 consecutive stimuli were taken before and after LTP induction by TBS (arrow) at the time points (1 and 2) indicated in the graphs. (D) Summary of modulation of the mean enhancement of EPSPs (at 45–55 min during recording) by ifenprodil or APV. Values represent mean ± SEM. The total number of cells examined at each condition is indicated in parentheses (*: p < 0.01; t-test).

References

1. Abrous DN, Koehl M, Le Moal M. Adult neurogenesis: from precursors to network and physiology. Physiol Rev. 2005;85:523–569. - PubMed
1. Aimone JB, Wiles J, Gage FH. Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci. 2006;9:723–727. - PubMed
1. Barria A, Malinow R. NMDA Receptor Subunit Composition Controls Synaptic Plasticity by Regulating Binding to CaMKII. Neuron. 2005;48:289–301. - PubMed
1. Barth AL, Malenka RC. NMDAR EPSC kinetics do not regulate the critical period for LTP at thalamocortical synapses. Nat Neurosci. 2001;4:235–236. - PubMed
1. Cameron HA, McEwen BS, Gould E. Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci. 1995;15:4687–4692. - PMC - PubMed

A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain - PubMed (original) (raw)