Selective glutamate receptor antagonists can induce or prevent axonal sprouting in rat hippocampal slice cultures

After the transection of the Schaffer collateral pathway in hippocampal sli ce cultures, reactive sprouting is induced in the CA3 area, and eventually synaptic transmission between areas CA1 and CA3 is restored. Using this mod el, we have studied the role of ionotropic glutamate receptors in the initi ation of axonal sprouting and the regeneration of functional synapses. We s how that neither reactive sprouting nor functional recovery of synaptic tra nsmission occur in the presence of the non-N-methyl-D-aspartate (NMDA) rece ptor antagonist 6-nitro-7-sulfamoylbenzoquinoxaline-2,3-dione (CNQX). In co ntrast, the NMDA receptor antagonists methyl-10,11-dihydro-5-H-dibenzocyclo hepten-5,10-imine (MK-801) or 3-(RS)-2-carboxypiperazine-4-yl)-propyl-1-pho sphonic acid (CPP) did not interfere with these processes. Moreover, we obs erved that the application of NMDA receptor antagonists induced massive axo nal sprouting and an increase in the frequency of miniature excitatory post synaptic currents in unlesioned cultures. Our results thus indicate that NM DA and non-NMDA receptors exert a differential effect on reactive sprouting and the recovery of synaptic transmission after injury in the hippocampus. Activation of non-NMDA receptors appears necessary for these processes to occur, whereas activation of NMDA receptors suppresses growth-associated pr otein -43 expression and axonal outgrowth.