Neuronal plasticity in relation to long -term memory for sensitization in Aplysia

One of the fundamental problems in neuroscience is to understand the biological mechanisms of learning and memory, at the anatomical, biophysical, cellular and molecular levels. To that end, simple model systems, like the marine mollusc Aplysia, have been exceptionally useful, primarily because of the tractability of their nervous system. The tail-elicited siphon withdrawal reflex of Aplysia displays short- and long-term sensitization, a form of learning that involves the augmentation of a response elicited by a weak stimulus following training with a strong stimulus. Long-term memory for sensitization has been associated with changes in the properties of sensory neurons, including synaptic plasticity. Whereas short-term sensitization partly relies on broadening of sensory neuron spikes and facilitation of transmitter release, the contribution of spike broadening in long-term sensitization has not been previously examined. Long-term sensitization, induced by four days of training, is partly mediated by increases in the number of synaptic contacts between sensory neurons and motor neurons. However, it is not known whether long-term sensitization is also accompanied by increases in the amount of transmitter release. Here, we first adopt a computational approach to examine how the properties of synaptic transmission would be expected to change, if transmitter release were upregulated. We find that, under conditions of enhanced transmitter release, short-term homosynaptic depression would be augmented due to desensitization of postsynaptic receptors. Subsequently, we present experimental data suggesting that short-term homosynaptic depression of sensorimotor synapses is, indeed, partly dependent on receptor desensitization, and would, therefore, be sensitive to changes in amount of transmitter release. Further experimental data indicate that the dynamics of synaptic depression are not affected by long-term sensitization training, suggesting that there is no increase in transmitter release. Interestingly, rather than broadening the sensory neuron spikes, long-term sensitization leads to spike narrowing, which may serve to improve the fidelity of sensory neuron responses to peripheral stimuli. Finally, we present data for a latent effect of long-term sensitization training: priming of animals for further learning