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 were suggested to express functional glutamate receptors from very early stages on already during the first few days after cell division. Furthermore, the activation NMDA (N-methyl-D-aspartate) - receptors was reported to modulate neuronal differentiation and survival. However, not much is known about the functional properties of AMPA and NMDA receptors in the newly generated young neurons.

Therefore, we 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 juvenile rats. Young and mature granule cells were identified according to their electrical input resistance, which was shown to be > 1 GOhm and < 400 MOhm for young and mature cells, respectively (Schmidt-Hieber et al. 2004, Stocca et al. 2008). Brief pulses of glutamate (5-100 ms) were applied with the fast application technique using a piezo-driven application device. All neurons tested showed AMPA- and NMDA-receptor mediated currents identified by the sensitivity to CNQX and D-AP5, respectively. However, the peak amplitude of AMPA-R mediated currents was substantially different with an average amplitude of ~500 pA and ~2000 pA in young and mature cells, respectively. The difference in NMDA-R mediated current density was smaller, resulting in a decrease of the NMDA to AMPA ratio with development. Fiber tract stimulation of the medial perforant path in the presence of gabazine could evoke EPSPs and APs in most young GCs tested. In conclusion, the expression density of glutamate receptors is low in young neurons and strongly increases during the development of newly generated granule cells. However, functional glutamatergic synapses can effectively discharge newly generated granule cells already very early in development.

Supported by DFG Bi 624/2.