CHARACTERIZATION OF ANTIBODIES SPECIFIC FOR CHICK BRAIN NEURAL CELL-ADHESION MOLECULES WHICH CAUSE AMNESIA FOR A PASSIVE-AVOIDANCE TASK

Antisera were prepared against six postsynaptic density glycoprotein f ractions (150-180, 62-80, 50, 41, 33, and 28 kDa) that show enhanced f ucosylation during memory formation after training day-old chicks in a one-trial passive avoidance task. Each antiserum was tested for its p ossible effect on memory retention. Bilateral intracranial injections of two of the antisera, R-1 and R-6, or their IgGs (IgG-1 and IgG-6), resulted in amnesia for the passive avoidance task when chicks were te sted 24 h later. IgG-1 and IgG-6 antibodies were amnestic only when in jected 5.5 h after training, and had no effect when injections were ma de 30 min before training, thus resembling an effect previously observ ed with polyclonal or monoclonal anti-N-CAM antibodies. IgG-1 and IgG- 6 antibodies were found to be specific for protein epitopes of glycopr oteins that contain a high amount of N-linked mannose and fucose, and a very low amount of polysialic acid and O-linked galactose. Absorptio n of IgG-6 antibodies with neural cell adhesion molecule (N-CAM) isola ted from synaptic plasma membranes derived from day-old chick brain re sulted in loss of amnestic effect. As we have previously shown that lo ng-term memory for the passive avoidance task requires two waves of gl ycoprotein synthesis, the first occurring immediately after training a nd the second 5-8 h later, the present results suggest strongly that i soforms of N-CAM molecules with a low level of sialic acid are involve d specifically in the establishment of an enduring memory for the expe rience of the passive avoidance task in chicks, possibly by stabilisin g changes in synaptic connectivity that encode the memory.