Newly generated neurons incorporated into neural circuits in the dentate gyrus of the adult brain have been postulated to play a role in learning and memory. Noting that not all newly generated neurons survive and that their survival depends on experience, Tashiro et al. used a retrovirus-mediated single-cell gene knockout technique to eliminate N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic input from individual identifiable neurons and see whether their survival depended on incoming synaptic activity. Retroviral vectors expressing Cre recombinase fused to green fluorescent protein (GFP) were injected into the dentate gyrus of floxed NR1 mice, so that newly generated neurons in which the NR1 subunit of the NMDAR was disrupted (NR1KO neurons) were also labeled with GFP. Although NR1KO neurons resembled new wild-type neurons morphologically, and electron microscopy revealed synapses onto their dendritic spines, they failed to generate NMDAR-mediated currents and were resistant to the toxic effects of high concentrations of NMDA. A decrease in the density of both NR1KO and wild-type new neurons occurred in the weeks after viral injection; this decrease was greater for the NR1KO neurons, a difference that resulted from increased neuronal death 2 to 3 weeks after their "birth." Injection of an NMDAR antagonist during this critical period led to an increase in NR1KO neuron survival, suggesting that survival was competitively regulated. Thus, the authors conclude that the survival of new neurons (and their incorporation into neural circuits) depends on synaptic input, providing a potential mechanism for them to contribute to learning and memory.
A. Tashiro, V. M. Sandler, N. Toni, C. Zhao, F. H. Gage, NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442, 929-933 (2006). [PubMed]