Rapid regrowth of hippocampal mossy fibres and preceding maturation of NMDA receptor-mediated neurotransmission.

Early in postnatal development, glutamatergic synapses contain primarily NMDA receptors and progressively acquire AMPA receptor function. To determine whether this transformation occurs in a process of regenerative synaptogenesis following axotomy, we investigated the recovery of AMPA and NMDA receptor-mediated neurotransmission after the transection of mossy fibres (MF) in organotypic hippocampal cultures. An NMDA component could already be elicited 1 day after the lesion and reached a saturated level after 3 days. Thereafter, an AMPA component appeared and slowly matured after 10 days. The preceding establishment of NMDA receptor function implies that immature MF synapses are functionally silent at least for the first several days of recovery. The appearance of AMPA receptor-mediated neurotransmission was unchanged in the presence of an NMDA-receptor antagonist or tetrodotoxin, which suggests that the AMPA receptor maturation is virtually independent of neuronal activity. Thus, the conversion of silent to functional synapses is not unique to synaptic plasticity or developmental processes but also occurs in recovery after brain damage, but its mechanism is likely to differ from NMDA receptor-dependent recruitment of AMPA receptors in synaptic plasticity.