Modulation of an NCAM-Related Adhesion Molecule with Long-Term Synaptic Plasticity in Aplysia

Abstract

A form of learning in the marine mollusk Aplysia, long-term sensitization of the gill- and siphon-withdrawal reflex, results in the formation of new synaptic connections between the presynaptic siphon sensory neurons and their target cells. These structural changes can be mimicked, when the cells are maintained in culture, by application of serotonin, an endogenous facilitating neurotransmitter in Aplysia. A group of cell surface proteins, designated Aplysia cell adhesion molecules (apCAM's) was down-regulated in the sensory neurons in response to serotonin. The deduced amino acid sequence obtained from complementary DNA clones indicated that the apCAM's are a family of proteins that seem to arise from a single gene. The apCAM's are members of the immunoglobulin class of cell adhesion molecules and resemble two neural cell adhesion molecules, NCAM and fasciclin II. In addition to regulating newly synthesized apCAM, serotonin also altered the amount of preexisting apCAM on the cell surface of the presynaptic sensory neurons. By contrast, the apCAM on the surface of the postsynaptic motor neuron was not modulated by serotonin. This rapid, transmitter-mediated down-regulation of a cell adhesion molecule in the sensory neurons may be one of the early molecular changes in long-term synaptic facilitation.

Regulation of axonal growth in the vertebrate nervous system by interactions between glycoproteins belonging to two subgroups of the immunoglobulin superfamily.

“…This would generate preference among the possible contacts of an extending growth cone with axons leading in different directions and so exert a guiding function. Specification of selective axon behavior by interaction of Ig/FNIII-like proteins at the cell surface acting in concert with regulatory influences on the synthesis or activity of such molecules by cell-intrinsic or environmental mechanisms (Karagogeos et al, 1991;De la Rosa, 1990;Jones et al, 1992;Mayford et al, 1992) might be a powerful and dynamic means of regulating the growth and the guidance of axons in the developing vertebrate nervous systems.…”

Embryonic neural cell adhesion molecule (N-CAM) is elevated in the denervated rat dentate gyrus

“…They probably play an important part in establishing, stabilizing, and modifying mature synapses. Putative adhesion molecules have been suggested to be involved in long-term potentiation and have recently been shown to change during learning in Aplysia (Bailey et al, 1992;Mayford et al, 1992). Increased amounts of polysialylated N-CAM have been reported in the hippocampus during the acquisition and consolidation phases of a passive avoidance response in the adult rat, though studies to localize subcellular distribution have not been carried out (Doyle et al, 1992).…”

Memory through metamorphosis in normal and mutant Drosophila

“…Much less is known, however, about how these early biochemical changes give rise to longer-lasting neuronal changes. One persistent view is that LTM ultimately is encoded as a change in the number or pattern of synaptic connections (Greenough and Bailey, 1988;Montarolo et al, 1986;Bailey et al, 1992;Mayford et al, 1992). Potentially, a genetic dissection of LTM formation in Drosophila could expedite our understanding of the process-primarily because genes involved in the behavior can be identified without any a priori knowledge of the underlying biochemistry or anatomy.…”