Serotonin Induces Structural Plasticity of Both Extrinsic Modulating and Intrinsic Mediating Circuits In Vitro in Aplysia Californica

Abstract

Summary: Long-term sensitization of the gill withdrawal reflex in Aplysia requires heterosynaptic, modulatory input that is mediated in part by the growth of new synaptic connections between sensory neurons and their follower cells (intrinsic mediating circuit). Whether modulatory interneurons (the extrinsic modulatory circuit) also display learning-related structural synaptic plasticity remains unknown. To test this idea, we added a bona fide serotonergic modulatory neuron, the metacerebral cell (MCC), to sensory-motor neuron co-cultures and examined the modulating presynaptic varicosities of MCCs before and after repeated pulses of serotonin (5-HT) that induced long-term facilitation (LTF). We observed robust growth of new serotonergic varicosities that were positive for serotonin and capable of synaptic recycling. Our findings demonstrate that, in addition to structural changes in the intrinsic mediating circuit, there are also significant learning-related structural changes in the extrinsic modulating circuit, and these changes might provide a cellular mechanism for savings and for spread of memory. : Upreti et al. show that, in Aplysia californica, modulatory neurons can undergo robust structural and functional changes after long-term facilitation, suggesting that learning-induced changes must include remodeling and structural alterations of the extrinsic modulating circuit. Keywords: structural plasticity, neuromodulation, modulatory neurotransmitter, serotonin, synaptic plasticity, Aplysia californica