Murphy G G, Glanzman D L
Interdepartmental Graduate Program in Neuroscience, School of Medicine, University of California, Los Angeles 90095, USA.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9931-6. doi: 10.1073/pnas.93.18.9931.
Classical conditioning of Aplysia's siphon-withdrawal reflex is thought to be due to a presynaptic mechanism-activity-dependent presynaptic facilitation of sensorimotor connections. Recent experiments with sensorimotor synapses in dissociated cell culture, however, provide an alternative cellular mechanism for classical conditioning-Hebbian long-term potentiation (LTP) of sensorimotor connections. Induction of Hebbian LTP of these connections is mediated by activation of N-methyl-D-aspartate-related receptors and requires the postsynaptic elevation of intracellular Ca2+. To determine whether the enhancement of sensorimotor synapses during classical conditioning in Aplysia-like LTP of sensorimotor synapses in culture-also depends upon the elevation of postsynaptic Ca2+, we carried out experiments involving the cellular analog of classical conditioning of siphon withdrawal. We examined changes in the strength of monosynaptic siphon sensorimotor connections in the abdominal ganglion of Aplysia following paired presentations of sensory neuron activation and tail nerve shock. This training regimen resulted in significant enhancement of the monosynaptic sensorimotor excitatory postsynaptic potential, as compared with the sensorimotor excitatory postsynaptic potential in preparations that received only test stimulation. Infusing the motor neuron with 1,2-bis(2-aminophenoxy)ethane-N,N-N',N'-tetraacetic acid, a specific chelator of intracellular Ca2+, prior to paired stimulation training blocked this synaptic enhancement. Our results implicate a postsynaptic, possibly Hebbian, mechanism in classical conditioning in Aplysia.
海兔虹吸管收缩反射的经典条件作用被认为是由于一种突触前机制——感觉运动连接的活动依赖性突触前易化。然而，最近在解离细胞培养中的感觉运动突触实验为经典条件作用提供了另一种细胞机制——感觉运动连接的赫布型长时程增强（LTP）。这些连接的赫布型LTP的诱导是由N-甲基-D-天冬氨酸相关受体的激活介导的，并且需要细胞内Ca2+的突触后升高。为了确定海兔经典条件作用过程中感觉运动突触的增强——类似于培养中感觉运动突触的LTP——是否也依赖于突触后Ca2+的升高，我们进行了涉及虹吸管收缩经典条件作用细胞模拟的实验。我们检查了在感觉神经元激活和尾神经电击配对呈现后，海兔腹神经节中单突触虹吸管感觉运动连接强度的变化。与仅接受测试刺激的标本中的感觉运动兴奋性突触后电位相比，这种训练方案导致单突触感觉运动兴奋性突触后电位显著增强。在配对刺激训练之前，向运动神经元注入1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸，一种细胞内Ca2+的特异性螯合剂，阻断了这种突触增强。我们的结果表明海兔经典条件作用中存在一种突触后机制，可能是赫布型机制。
