Non-associative learning and serotonin induce similar Bi-directional changes in excitability of a neuron critical for learning in the medicinal leech

In studies of the cellular basis of learning, much attention has focused on plasticity in synaptic transmission in terms of transmitter release and th e number or responsiveness of neurotransmitter receptors. However, changes in postsynaptic excitability independent of receptors may also play an impo rtant role. Changes in excitability of a single interneuron in the leech, t he S-cell, were measured during non-associative learning of the whole-body shortening reflex. This interneuron was chosen because it is known to be ne cessary for sensitization and full dishabituation of the shortening respons e. During sensitization, S-cell excitability increased, and this enhancemen t corresponded to facilitation of the shortening reflex and increased S-cel l activity during the elicited response. During habituation training, there was a decrement in both the shortening reflex and the elicited S-cell acti vity, along with decreased S-cell excitability. Conversely, dishabituation facilitated both the shortening response and S-cell activity during shorten ing, with an accompanying increase in S-cell excitability. Bath application of 1-10 muM serotonin (5HT), a modulatory neurotransmitter that is critica l for sensitization, for full dishabituation, and for associative learning, increased S-cell excitability. S-cell excitability also increased after st imulation of the serotonergic Retzius cells. However, focal application of serotonin onto the S-cell soma hyperpolarized the interneuron, and bath app lication of a lower dose of serotonin (0.1 muM) decreased excitability. The observed changes in postsynaptic excitability appear to contribute to non- associative learning, and modulatory neurotransmitters, such as serotonin, evidently help regulate excitability. Such changes in S-cell excitability m ay also be relevant for more complex, associative forms of learning.