Colmers W F, Lukowiak K, Pittman Q J
Neuroscience Research Group, University of Calgary, Alberta, Canada.
J Neurosci. 1988 Oct;8(10):3827-37. doi: 10.1523/JNEUROSCI.08-10-03827.1988.
Neuropeptide Y (NPY), the most abundant peptide in mammalian CNS, has been shown to inhibit excitatory neurotransmission presynaptically at the stratum radiatum-CA1 synapse in the in vitro rat hippocampal slice. We examined the site and mechanism of this inhibition in a series of in vitro intra- and extracellular recordings in areas CA1 and CA3, the source of much of the excitatory synaptic input to the CA1 neurons. NPY's inhibitory action at the stratum radiatum-CA1 synapse was unaffected by high concentrations of the antagonists bicuculline, theophylline, or atropine, suggesting that it does not act by stimulating the release of the known presynaptic inhibitory transmitters GABA, adenosine, or ACh, respectively. Bath application of 10(-6) NPY, a concentration that strongly inhibited the stratum radiatum-CA1 synapse had no effect on CA3 neuron resting potential, input resistance or action potential amplitude, threshold, or duration. NPY also does not alter the amplitude or duration of the prolonged CA3 action potentials evoked in the presence of TTX, tetraethyl-ammonium, and elevated external Ca2+ or those evoked in the presence of TTX and Ba2+ ions. NPY therefore does not alter the passive or active properties of the somata of the presynaptic CA3 neurons. Neither the afferent fiber volley of the Schaffer collaterals in stratum radiatum of area CA1 nor the excitability of the CA3 terminals in CA1 was affected by NPY application. However, application of the transient K+ current blocker, 4-aminopyridine (4-AP) at concentrations of 10 and 50 microM, completely abolished the action of 10(-6) M NPY on the stratum radiatum-CA1 excitatory synaptic potentials. This action of 4-AP could be reversed by reducing extracellular Ca2+ concentrations from a control level of 1.5 to 0.7 mM (in 10 microM 4-AP) and to 0.5 mM (in 50 microM 4-AP). The evidence suggests that NPY inhibits excitatory synaptic transmission at the Schaffer collateral-CA1 synapse by acting directly at the terminal to reduce a Ca2+ influx.
神经肽Y（NPY）是哺乳动物中枢神经系统中含量最为丰富的肽，已证实在体外大鼠海马切片中，它能在放射层-CA1突触处对兴奋性神经传递进行突触前抑制。我们在CA1区和CA3区进行了一系列体外细胞内和细胞外记录，以研究这种抑制作用的位点和机制，CA3区是向CA1神经元提供大部分兴奋性突触输入的来源。NPY在放射层-CA1突触处的抑制作用不受高浓度拮抗剂荷包牡丹碱、茶碱或阿托品的影响，这表明它并非分别通过刺激已知的突触前抑制性递质γ-氨基丁酸（GABA）、腺苷或乙酰胆碱（ACh）的释放来发挥作用。浴槽中加入10⁻⁶ NPY（此浓度能强烈抑制放射层-CA1突触）对CA3神经元的静息电位、输入电阻、动作电位幅度、阈值或持续时间均无影响。NPY也不会改变在存在河豚毒素（TTX）、四乙铵以及细胞外钙离子浓度升高的情况下诱发的延长的CA3动作电位的幅度或持续时间，或者在存在TTX和钡离子的情况下诱发的CA3动作电位的幅度或持续时间。因此，NPY不会改变突触前CA3神经元胞体的被动或主动特性。施加NPY既不影响CA1区放射层中谢弗侧支的传入纤维群峰电位，也不影响CA1区中CA3终末的兴奋性。然而，施加浓度为10和50微摩尔的瞬时钾离子电流阻断剂4-氨基吡啶（4-AP），能完全消除10⁻⁶ 摩尔NPY对放射层-CA1兴奋性突触电位的作用。通过将细胞外钙离子浓度从对照水平的1.5毫摩尔降低至0.7毫摩尔（在10微摩尔4-AP存在时）以及降至0.5毫摩尔（在50微摩尔4-AP存在时），4-AP的这种作用可以被逆转。有证据表明，NPY通过直接作用于终末以减少钙离子内流，从而抑制谢弗侧支-CA1突触处的兴奋性突触传递。
