Brain gangliosides and memory formation

Abstract

It is generally accepted that the process of molecular facilitation of neuronal circuits by means of stabilization of synaptic contacts represents the structural basis for memory formation. At the distinct zone of synaptic contact the following basic events occur: alterations of the electrical field strength at the outer surface of synaptic membranes, conformational changes of membrane-bound functional proteins (ion channels, ion pumps, receptors) and activation of second messenger cascade. Finally a trophic feed-back between synaptic terminals and their cell bodies through retro- and anterograde neuronal transport exists, which guarantees a stabilization of the newly formed synaptic connection. As a controlled Ca(2+)-exchange between the extracellular space (mM Ca(2+)-concentration) and the synaptoplasm (microM Ca2+) is essential for all these events, the present research concentrates on Ca(2+)-mediated primary messenger systems at the outer leaflet of synaptic membranes and on Ca(2+)-mediated modulatory mechanisms. These enable an always efficient electroresponsiveness although the environmental temperature might have changed. In this regard gangliosides being amphiphilic sialic acid containing glycosphingolipids, which are highly accumulated in complex composition in synaptic membranes play an important role. According to specific physico-chemical properties, they are assumed to fulfill the task of neuromodulators in connection with calcium, and thus contribute to the transmission and storage of information. The outcome of a series of experiments derived from neurology, ecophysiology, behavioral sciences, electron microscopy, biochemistry and physical chemistry give strong circumstantial evidence for this concept.