Reduction of the threshold for long-term potentiation by prior theta-frequency synaptic activity

Activation of the lateral perforant path input to the dentate gyrus with theta-patterned conditioning trains produced LTP of synaptic efficacy that changed in magnitude as an inverted U-shaped function of the number of trains. The LTP induction function was not fixed, however, and could be shifted to the left by administering 5 Hz "priming" stimulation to the lateral path 10 min prior to the conditioning trains. The priming effect was input specific and selective to a narrow window of stimulus frequencies. The shift to the left of the LTP induction function by priming stimulation was blocked by the muscarinic receptor antagonist atropine sulphate. Nimodipine, an antagonist of L-type voltage-sensitive calcium channels, did not mimic the priming effect but instead produced a general facilitation of LTP induction. These data demonstrate that the degree to which LTP is induced in the lateral path is a non-linear function of afferent activity, and that this function, including LTP threshold, can be shifted to the left by prior synaptic activity at hippocampal theta-rhythm frequencies.