Glanzman D L
Department of Physiological Science, University of California, Los Angeles 90024-1568.
J Neurobiol. 1994 Jun;25(6):666-93. doi: 10.1002/neu.480250608.
The monosynaptic component of the neuronal circuit that mediates the withdrawal reflex of Aplysia californica can be reconstituted in dissociated cell culture. Study of these in vitro monosynaptic connections has yielded insights into the basic cellular mechanisms of synaptogenesis and long-term synaptic plasticity. One such insight has been that the development of the presynaptic sensory neurons is strongly regulated by the postsynaptic motor neuron. Sensory neurons which have been cocultured with a target motor neuron have more elaborate structures--characterized by neurites with more branches and varicosities--than do sensory neurons grown alone in culture or sensory neurons that have been cocultured with an inappropriate target cell. Another way in which the motor neuron regulates the development of sensory neurons is apparent when sensorimotor cocultures with two presynaptic cells are examined. In such cocultures the outgrowth from the different presynaptic cells is obviously segregated on the processes of the postsynaptic cell. By contrast, when two sensory neurons are placed into cell culture without a motor neuron, their processes readily grow together. In addition to regulating the in vitro development of sensory neurons, the motor neuron also regulates learning-related changes in the structure of sensory neurons. Application of the endogenous facilitatory transmitter serotonin (5-HT) causes long-term facilitation of in vitro sensorimotor synapses due in part to growth of new presynaptic varicosities. But 5-HT applied to sensory neurons alone in culture does not produce structural changes in these cells. More recently it has been found that sensorimotor synapses in cell culture can exhibit long-term potentiation (LTP). Like LTP of some hippocampal synapses, LTP of in vitro Aplysia synapses is regulated by the voltage of the postsynaptic cell. Pairing high-frequency stimulation of sensory neurons with strong hyperpolarization of the motor neuron blocks the induction of LTP. Moreover, LTP of sensorimotor synapses can be induced in Hebbian fashion by pairing weak presynaptic stimulation with strong postsynaptic depolarization. These findings implicate a Hebbian mechanism in classical conditioning in Aplysia. They also indicate that Hebbian LTP is a phylogenetically ancient form of synaptic plasticity.
介导加州海兔退缩反射的神经回路的单突触成分可以在离体细胞培养中重建。对这些体外单突触连接的研究已经深入了解了突触形成和长期突触可塑性的基本细胞机制。其中一个深刻见解是，突触前感觉神经元的发育受到突触后运动神经元的强烈调节。与靶运动神经元共培养的感觉神经元比单独培养的感觉神经元或与不适当靶细胞共培养的感觉神经元具有更复杂的结构——其特征是神经突有更多分支和膨体。当检查具有两个突触前细胞的感觉运动共培养物时，运动神经元调节感觉神经元发育的另一种方式就很明显了。在这种共培养物中，来自不同突触前细胞的生长明显在突触后细胞的突起上分离。相比之下，当将两个感觉神经元置于没有运动神经元的细胞培养中时，它们的突起很容易生长在一起。除了调节感觉神经元的体外发育外，运动神经元还调节感觉神经元结构中与学习相关的变化。内源性易化递质5-羟色胺（5-HT）的应用会导致体外感觉运动突触的长期易化，部分原因是新的突触前膨体的生长。但是单独应用于培养中的感觉神经元的5-HT不会在这些细胞中产生结构变化。最近发现，细胞培养中的感觉运动突触可以表现出长期增强（LTP）。与一些海马突触的LTP一样，体外海兔突触的LTP受突触后细胞电压的调节。将感觉神经元的高频刺激与运动神经元的强超极化配对会阻断LTP的诱导。此外，感觉运动突触的LTP可以通过将弱突触前刺激与强突触后去极化配对以赫布方式诱导。这些发现暗示了海兔经典条件反射中的赫布机制。它们还表明，赫布LTP是一种系统发育上古老的突触可塑性形式。
