Effects Of Low Frequency Stimulation Of Dorsal Norepinephrine Bundle On Learning-dependent Long-term Potentiation In Mossy Fiber-CA3 Synapses And Behavioral Learning In Rats

In this paper the methods of chronically implanting microelectrodes, combined electrophysiology with behavioral learning in vivo, were used to study the effects of low frequency stimulation (LFS) of the dorsal norepinephrine bundle (DNEB) on the learning-dependent long-term potentiation (Ld-LTP) at the hippocampal mossy fiber synapses onto CA3 pyramidal neurons. Paired-pulse technique at the intervals of 75-ms, 150-ms and 300-ms was used as the test stimulation. The results showed as follows:1. At MF-CA3 synapses, different stimulus intensity or interpulse interval resulted in different reactions to paired-pulse, including PPD (paired-pulse depression, the response to the second pulse is smaller than that to the first one) and PPF (paired-pulse facilitation, the response to the second pulse is larger than that to the first one). When the stimulus intensity is a half of the value that induced the largest response of synapses, the paired-pulse stimulation of 75-ms interval produced a stable PPD while the stimulation of 150-ms or 300-ms produced a stable PPF.2. At MF-CA3 synapses, paired-pulse stimulation in control group did not produce the added efficacy over seven days.3. LFS (1Hz or 5Hz, 1 min, 2/3 intensity of test pulse) of DNEB depressed the amplitude of the first PS at the MF-CA3 synapses and it returned to the baseline within 2 hours.4. The treatment on DNEB of 1Hz (60 pulses, 1 min, 2/3 intensity of test pulse)delivered 5 min after daily trainings exhibited a complete reversal of Ld-LTP and also inhibited the normal behavioral learning of animals.5. The treatment on DNEB of 5Hz (300 pulses, 1 min, 2/3 intensity of test pulse) delivered 5 min after daily trainings exhibited a complete reversal of Ld-LTP but had no effect on the normal behavioral learning of animals.6. At MF-CA3 synapses, both the facilitation ration of PPF and the depression ration of PPD decreased to some degree during the expression of Ld-LTP. The result suggested that the expression of Ld-LTP at the MF-CA3 synapses may be presynaptic.7. Whether the DP was induced by the treatment on DNEB of 1Hz or 5Hz delivered 5 min after daily trainings, both PPD and PPF changed during the learning behavior, which suggested that presynaptic mechanisms may be involves in the DP of learning-dependent long-term potentiation. The DP induced by 1Hz shored a more influence on the PPE (paired-pulse efficacy) during the behavior learning than that induced by 5Hz, which suggested that 1Hz-DP had a stronger relation with presynaptic mechanisms while 5Hz-DP had a less with it.In conclusion, the results of our experiment showed that 1Hz or 5Hz stimulation of DNEB could completely reverse the Ld-LTP at MF-CA3 synapses. The behavioral learning of animal could be blocked with the stimulation of 1Hz while the stimulation of 5 Hz did not show any effect on it. It indicated that the NE afferent to hippocampus participated in the reversal of Ld-LTP and even the mechanisms of the memory loss ("forgetting"). It also suggested that not only the IHz-DP or the 5Hz-DP has different relation with the presynaptic mechanisms but also has different effects on the behavioral learning. These results were discussed in the paper.