SYNAPTIC TRANSMISSION AND HIPPOCAMPAL LONG-TERM POTENTIATION IN OLFACTORY CYCLIC NUCLEOTIDE-GATED CHANNEL-TYPE-1 NULL MOUSE

Field potential recording was used to investigate properties of synapt ic transmission and long-term potentiation (LTP) at Schaffer collatera l-CA1 synapses in both hippocampal slices of mutant mice in which the alpha-subunit of the olfactory cyclic nucleotide-gated channel (alpha 3/OCNC)1 was rendered null and also in slices prepared from their wild -type (Wt) littermates. Several measures of basal synaptic transmissio n were unaltered in the OCNC1 knockout (KO),including maximum field ex citatory postsynaptic potential ( fEPSP) slope, maximum fEPSP and fibe r volley amplitude, and the function relating fiber volley amplitude t o fEPSP slope and paired-pulse facilitation. When a high-frequency sti mulation protocol was used to induce LTP, similar responses were seen in both groups [KO: 1 min, 299 +/- 50% (mean +/- SE), 60 min, 123 +/- 10%; Wt: 1 min, 287 +/- 63%; 60 min, 132 +/- 19%). However, on theta-b urst stimulation, the initial amplitude of LTP was smaller (1 min afte r induction, 147 +/- 16% of baseline) and the response decayed faster in the OCNC1 KO (60 min, 127 +/- 18%) than in Wt(1 min, 200 +/- 14%; 6 0 min, 169 +/- 19%). Analysis of waveforms evoked by LTP-inducing teta nic stimuli revealed a similar difference between groups. The developm ent of potentiation throughout the tetanic stimulus was similar in OCN C1 KO and Wt mice when high-frequency stimulation was used, but OCNC1 KO mice showed a significant decrease when compared with Wt mice recei ving theta-burst stimulation. These results suggest that activation of cyclic nucleotide-gated channels may contribute to the induction of L TP by weaker, more physiological stimuli, possibly via Ca2+ influx.