Nakanishi K, Saito H, Abe K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Eur J Neurosci. 2001 Feb;13(4):793-800. doi: 10.1046/j.1460-9568.2001.01446.x.
The supramammillary nucleus (SUM) of the hypothalamus sends neural projections to the hippocampus and is supposed to be involved in learning and memory. To test the possibility that SUM afferents modulate hippocampal functions, we investigated the effect of electrical stimulation of the SUM on the induction of long-term potentiation (LTP) at medial perforant path (PP)--granule cell synapses in the dentate gyrus (DG) of anaesthetized rats. High-frequency stimulation of the SUM (100 pulses at 100 Hz) alone did not change PP--DG field potentials. However, when the SUM stimulation was applied simultaneously with weak tetanic stimulation of the PP (20 pulses at 20 Hz) which alone did not induce any potentiation, it produced a long-lasting potentiation of the population spike, without an accompanying increase in the population excitatory postsynaptic potential (EPSP). The EPSP-spike (E-S) potentiation induced by pairing SUM and PP stimulation was abolished by lesions of the fimbria--fornix, a major pathway of SUM afferents. SUM stimulation applied 1 s before or after PP stimulation failed to produce E-S potentiation, and SUM stimulation augmented PP--DG field potentials during tetanic stimulation. Furthermore, the E-S potentiation was abolished by blocking GABAergic neurotransmission with picrotoxin. These results suggest that coactivation of SUM and PP inputs produces a long-lasting increase of granule cell excitability by modulating GABAergic inhibition. SUM afferents may contribute to associative memory processing by modulating hippocampal excitability.
下丘脑乳头体上核（SUM）向海马体发送神经投射，并且被认为参与学习和记忆。为了测试SUM传入神经调节海马体功能的可能性，我们研究了电刺激SUM对麻醉大鼠齿状回（DG）内侧穿通通路（PP）-颗粒细胞突触处长期增强（LTP）诱导的影响。单独高频刺激SUM（100Hz，100个脉冲）并不会改变PP-DG场电位。然而，当SUM刺激与单独不能诱导任何增强的PP弱强直刺激（20Hz，20个脉冲）同时施加时，它会产生群体峰电位的持久增强，而群体兴奋性突触后电位（EPSP）没有随之增加。通过切断SUM传入神经的主要通路穹窿海马伞，可消除由SUM和PP刺激配对诱导的EPSP-峰电位（E-S）增强。在PP刺激之前或之后1秒施加SUM刺激未能产生E-S增强，并且SUM刺激在强直刺激期间增强了PP-DG场电位。此外，用印防己毒素阻断GABA能神经传递可消除E-S增强。这些结果表明，SUM和PP输入的共同激活通过调节GABA能抑制作用，使颗粒细胞兴奋性产生持久增加。SUM传入神经可能通过调节海马体兴奋性，对联想记忆处理有贡献。
