Neural activity results in long term changes that underlie synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here, we identify a novel cadherin molecule Arcadlin (activity-regulated cadherin-like protein). arcadlin mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by N-methyl-D-aspartatedependent synaptic activity in long term potentiation. The extracellular domain of Arcadlin is most homologous to protocadherin-8; however, the cytoplasmic region is distinct from that of any cadherin family member. Arcadlin protein is expressed at the synapses and shows a homophilic binding activity in a Ca 2؉ -dependent manner. Furthermore, application of Arcadlin antibody reduces excitatory postsynaptic potential amplitude and blocks long term potentiation in hippocampal slices. Its close homology with cadherins, its rapid inducibility by neural activity, and its involvement in synaptic transmission suggest that Arcadlin may play an important role in activity-induced synaptic reorganization underlying long term memory.Glutamate receptor stimulation leads to a rapid Ca 2ϩ influx into neurons with associated protein phosphorylation events that underlie short term memory. In contrast, long term memory can be distinguished from short term memory in that it requires new mRNA and protein synthesis (1). To analyze components of the gene expression program underlying long term memory in the vertebrate brain, we and others have employed differential cloning techniques to identify mRNAs that are rapidly induced by excitatory activity. In addition to transcription factors, this approach has identified a number of immediate early genes that encode enzymes that may directly modify cellular function, including tissue-plasminogen activator, cyclooxygenase-2, a novel small molecular weight G-protein, and a cytoskeleton-associated protein (2-6). These proteins presumably interact with neuronal proteins and indirectly affect long term changes in connections and the efficacy thereof.LTP 1 provides a widely adopted mammalian model for activitydependent changes in synaptic efficacy. The mechanisms contributing to long term changes in synaptic transmission are still contentious. Among many possibilities, one of the hypotheses that has been proposed is that neural activity could lead to modifications in synaptic structure and eventually changes in synaptic connectivity. In support of this idea, numerous morphological studies have provided evidence that neural activity such as kindling or electrical stimulation induces modifications in dendritic arborization, spine densities, or synaptic morphology (7-10).Adhesion molecules are known to be involved in many aspects of cell-cell interactions, including cell migration, axonal growth, pathfinding, sprouting, and regeneration (11, 12). Recent reports have demonstrated that some adhesion molecules are expressed ...

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