Physiological roles of plasticity of inhibitory synaptic transmission

1. 最近的研究表明，突触后神经元的活性可以通过突触后神经元释放的内源性大麻素逆行作用于突触前末端来影响突触前功能。在这项研究中，我们试图阐明内源性大麻素介导的突触传递的逆行调节的生理作用。我们对培养的新生大鼠海马神经元进行了成对的全细胞记录，并记录了诱发兴奋性和抑制性突触后电流。我们的研究结果总结如下。(1)内源性大麻素可以通过去极化或激活I组代谢谷氨酸受体（mGluR）从突触后神经元释放（Ohno-Shosaku et al., Eur J Neurosci 15, 2002）。(2)内源性大麻素的释放也可通过毒碱乙酰胆碱受体的M_1和M_3亚型的激活（准备中）来诱导。(3)突触后去极化和I组mGluRs或M_1/M_3受体的激活协同作用（oho - shosaku et al., Eur J Neurosci, in press）。(4)释放的内源性大麻素逆行作用于突触前大麻素CB1受体，抑制突触前末端的递质释放。(5)抑制性突触的突触前末端大麻素敏感性高（约50%），兴奋性突触的大麻素敏感性低，其余抑制性突触几乎不存在大麻素敏感性（Ohno-Shosaku et al., J Neurosci 22, 2002）。这些结果表明内源性大麻素介导目标特异性逆行信号，通过突触后神经元活动影响某些类型的突触前末端的递质释放。

1. Recent studies have revealed that the activity of postsynaptic neurons can influence presynaptic functions via endocannabinoids that are released from postsynaptic neurons and act retrogradely on presynaptic terminals. In this study, we attempted to clarify physiological roles of endocannabinoid-mediated retrograde modulation of synaptic transmissions.2. We made paired whole-cell recordings from cultured hippocampal neurons prepared from newborn rats, and recorded evoked excitatory and inhibitory postsynaptic currents. Our results are summarized as follows. (1) Endocannabinoids can be released from postsynaptic neurons by depolarization or by activation of group I metabotropic glutamate receptors (mGluR) (Ohno-Shosaku et al., Eur J Neurosci 15, 2002). (2) Endocannabinoid release is also induced by activation of the M_1 and M_3 subtypes of muscarinic acetylcholine receptors (in preparation), (3) Postsynaptic depolarization and activation of group I mGluRs or M_1/M_3 receptors work in a cooperative manner to release endocannabinoids (Ohno-Shosaku et al., Eur J Neurosci, in press). (4) The released endocannabinoids act retrogradely onto presynaptic cannabinoid CB1 receptors and suppress the transmitter release from presynaptic terminals. (5) The cannabinoid-sensitivity of presynaptic terminals is high in a subpopulation (about 50 %) of inhibitory synapses, low in excitatory synapses, and almost absent in the rest of inhibitory synapses (Ohno-Shosaku et al., J Neurosci 22, 2002).3. These results suggest that endocannabinoids mediate target-specific retrograde signals, by which the postsynaptic neuronal activity influences the transmitter release from certain types of presynaptic terminals.