In the dentate gyrus of the mammalian hippocampus, new neurons are generated throughout life (Gage 2000, Science 287:1433–38). The newly generated young neurons express functional glutamate receptors already during the first few days after cell division. Furthermore, the activation of NMDA (N-methyl D-aspartate) receptors was reported to modulate neuronal differentiation and survival (Deisseroth et al. 2004, Neuron 42:535–52; Tashiro et al. 2006, Nature 442:929–33). However, little is known about the functional properties of AMPA and NMDA receptors in the newly generated young granule cells.

We therefore analysed the functional properties of AMPA and NMDA receptors in nucleated membrane patches excised from mature and newly generated young granule cells in acute hippocampal brain slices of 20–23-day-old rats. Young and mature neurons were identified according to their different electrical input resistance (Schmidt-Hieber et al. 2004, Nature 429:184–187). Brief pulses of glutamate (5–100 ms, 1mM) were applied with the fast application technique using a Piezo-driven application device. Glutamate activated currents were recorded under voltage-clamp conditions (-80mV and +40mV) at a temperature of ~22°C. All neurons tested showed AMPAR- and NMDAR-mediated currents identified by the sensitivity to 20 mM CNQX and 50 mM D-AP5, respectively. However, the peak amplitude of AMPAR-mediated currents was substantially different with 527 39 pA (n=85) in young and 2208 174 pA (n=21) in mature cells, corresponding to a 3.1-fold difference in current density when normalized to patch area. By contrast the difference in NMDAR -mediated current amplitude was smaller (52 7 pA in young versus 93 12 pA in mature cells; n = 25 and 13, respectively), resulting in a decrease of the NMDAR- to AMPAR-conductance density ratio from 0.22 0.03 (n=25) to 0.09 0.01 (n=13) with development (p<0.001). In contrast to the large differences in density, the kinetic properties of the AMPARs were similar with a slightly slower desensitization time constant in the young neurons (10.30.3 ms in young versus 9.20.2 ms in mature cells; p < 0.12). Similarly, the deactivation time constant of NMDA receptors was not significantly different (25716 ms versus 26024 ms; p>0.95).

In conclusion, the expression levels of glutamate receptors strongly increase during the development of newly generated granule cells. By contrast, the functional properties of these receptors appear to be similar at different developmental stages. Supported by DFG Bi 624/2.