Marinesco Stéphane, Wickremasinghe Nimalee, Kolkman Kristine E, Carew Thomas J
Department of Neurobiology and Behavior, CNLM, University of California, Irvine, CA 92697-4550, USA.
J Neurophysiol. 2004 Oct;92(4):2487-96. doi: 10.1152/jn.00210.2004. Epub 2004 May 12.
Serotonin (5-HT) plays an important role in sensitization of defensive reflexes in Aplysia and is also involved in several aspects of arousal, such as the control of locomotion and of cardiovascular tone. In the preceding paper, we showed that tail-nerve shock, a noxious stimulus that readily induces sensitization, increases the firing rate of a large number of serotonergic neurons throughout the CNS. However, the functional consequences of such an increase in serotonergic tone are still poorly understood. In this study, we examined this question by using the 5-HT precursor 5-hydroxytryptophan (5-HTP) to specifically increase 5-HT release in the CNS. Increased tonic 5-HT release after 5-HTP treatment was manifested by facilitation of sensorimotor (SN-MN) synapses, increased firing rate of serotonergic neurons in the pedal and abdominal ganglia, and enhanced 5-HT release evoked by tail-nerve shock. When 5-HTP was administered to freely moving animals, it produced a strong arousal response characterized by increased locomotion and heart rate, which was reminiscent of the defensive arousal reaction triggered by noxious stimulation such as tail-shock. In contrast, 5-HTP actually inhibited the tail-induced siphon-withdrawal reflex. It is possible that 5-HT-induced facilitation of SN-MN synapses was counteracted by inhibition of polysynaptic reflex pathways between SNs and MNs, resulting in transient behavioral inhibition of the reflex, which could favor escape locomotion and/or respiration shortly after an aversive stimulus. We conclude that a major function associated with the activation of the Aplysia serotonergic system evoked by noxious stimuli is the triggering of a defensive arousal response. It is known that tail-shock-induced serotonergic activation contributes to memory encoding at least in part by facilitating SN-MN synapses. However, this effect in isolation might not be sufficient for the behavioral expression of sensitization.
血清素(5-羟色胺,5-HT)在海兔防御反射的敏感化过程中发挥着重要作用,并且还参与了觉醒的多个方面,例如对运动和心血管张力的控制。在之前的论文中,我们表明,尾部神经电击作为一种容易诱发敏感化的有害刺激,会提高整个中枢神经系统中大量血清素能神经元的放电频率。然而,血清素能张力增加的功能后果仍知之甚少。在本研究中,我们通过使用5-HT前体5-羟色氨酸(5-HTP)来特异性增加中枢神经系统中的5-HT释放,从而研究了这个问题。5-HTP处理后持续性5-HT释放的增加表现为感觉运动(SN-MN)突触的易化、足神经节和腹神经节中血清素能神经元放电频率的增加,以及尾部神经电击诱发的5-HT释放增强。当将5-HTP给予自由活动的动物时,它会产生强烈的觉醒反应,其特征为运动增加和心率加快,这让人联想到由有害刺激(如尾部电击)引发的防御性觉醒反应。相比之下,5-HTP实际上抑制了尾部诱发的虹吸管收缩反射。有可能5-HT诱导的SN-MN突触易化被SN与MN之间多突触反射通路的抑制所抵消,从而导致反射的短暂行为抑制,这可能有利于在厌恶刺激后不久进行逃避运动和/或呼吸。我们得出结论,由有害刺激诱发的海兔血清素能系统激活所关联的一个主要功能是触发防御性觉醒反应。已知尾部电击诱导的血清素能激活至少部分地通过促进SN-MN突触来促进记忆编码。然而,孤立的这种效应可能不足以实现敏感化的行为表达。