The Role of Ependymin in Neuronal Plasticity and LTP

Abstract

Ependymin is a brain extracellular glycoprotein that has been implicated in the formation of long-term synaptic changes after learning and neuronal regeneration. It was first identified as a brain protein that became more highly labeled after goldfish learned a new pattern of swimming behavior (Shashoua, 1976, 1977a, 1979). This type of change did not occur in a variety of experiments that controlled for the effects of stress, motor activity and physical strength of the animals (Shashoua, 1977b). Injections of anti-ependymin sera into the 4th ventricle of gold-fish brain at 8–24 hr after initiation of training blocked long-term (LTM) but not short-term memory (Shashoua and Moore, 1978). A blockade of LTM was also obtained for another training procedure in which goldfish learned to avoid a shock by escaping into another compartment in a shuttle box following the onset of a light in an avoidance conditioning experiment (Piront and Schmidt, 1988). More recent studies indicate that ependymin is also involved in classical (Pavlovian) conditioning (Shashoua and Hesse, 1989a). Goldfish were trained in a soundproof light-tight chamber (see Fig. 1) to associate the onset of light as the conditioning stimulus (CS) with the delivery of a shock as the US using the CS-US parameters established by Bitterman (1964). Measurements of the concentration of ependymin in goldfish brain extracts enriched with ECF proteins (Shashoua, 1981) using an ELISA procedure demonstrated that goldfish receiving the CS-US stimuli in a “paired” presentation showed changes whereas the controls receiving the same number of stimuli “unpaired” showed no changes (see Table I) in comparison to unstimulated animals. For the “paired stimulus” group there was an initial decrease at 3.5 hr after the start of the training followed by an increase at 52 hr, a time span that corresponds to the transcription and translation of messenger RNA in goldfish brain (Shashoua, 1970). This type of result was similar to that obtained for goldfish trained to swim with a float (R. Schmidt, 1986). Thus in two separate experiments it is found that ependymin is used up by the CNS as a consequence of the training procedure. The response of the brain is to synthesize and secrete more of the protein into the brain extracellular space. Moreover the quantity of ependymin that is depleted from ECF in a 70-mg goldfish brain is substantial, being about 71.tg for the acquisition of the classical conditioning experiment.