Ionotropic glutamate receptor activated by N-methyl- d-aspartate: a key molecule of conscious life

We want to propose that basic stereotyped integrative functions are the result of sequentially built neuronal circuits in the primitive regions of the brain in whose build-up a particular subunit composition iGluR-NMDA would play a central role. iGluR-NMDA is a multiregulated heteromeric glutamate receptor-ion channel found in plasma membranes of neurons and other cells. iGluR-NMDA may be composed of up to five subunits, depending on the type of cell involved and its location. There are three major types of subunits and there are variations within each type allowing for up to 13 possible subunits, at least in the rat, which differ from each other in aminoacid sequence and thus, in tertiary structure. The actual iGluR-NMDA heteropolymer involved in a given function may thus have a great number of subunit composition possibilities which would be the result of the particular genes expressed in a given type of cell. The iGluR-NMDA is an ion channel that opens in response to glutamate in a highly regulated fashion in which different molecules and ions present in the interstitial fluid determine whether or not the channel opens upon glutamate binding. The original function of iGluR-NMDA may have been that of allowing calcium influx to cells. As the brain receives external stimuli through the senses, new circuits will be formed stepwise in the neocortex in which a particular subunit composition iGluR-NMDA will be involved. Differentiation between external stimuli generated circuits and those governing internal functions will allow distinction between self and non-self, thus generating conscious awareness. The role of the particular subunit composition iGluR-NMDA proposed would be that of providing a means of calcium influx to the synapses to be formed and, if the same stimulus is forthcoming, allowing permanent synapses formation through the membrane incorporation of calcium dependent adhesion molecules such as cadherins and cytoskeleton reorganization promoted by nectins.