Cell-adhesion molecules, glucocorticoids and long-term-memory formation

The transition from short- to long-term memory requires lasting modulations of synaptic connectivity. In a variety of species and learning tasks, enhanced synthesis of glycoprotein cell-adhesion molecules (CAMs), such as neural CAM (NCAM) and LI, 5–8 h post-training is a necessary step in this process. If the training event is weak, this phase of glycoprotein synthesis does not occur and memory is not retained. Antibodies or fragments that bind to the extracellular domains of NCAM or LI at this time produce amnesia for the task. Centrally administered corticosterone enhances retention of weak learning, and steroid-receptor antagonists are amnestic. The effects of corticosterone are mediated through synthesis of ‘second-wave’ glycoproteins. As ‘nootropic’ drugs such as piracetam only enhance long-term retention and are ineffective in adrenalectomized animals, the interaction between glucocorticoids and glycoproteins might provide a site for pharmacological intervention in alleviating the losses of memory that occur in neurodegenerative disorders.