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Free keywords:
AMPA receptors; NMDA receptor; iGluR; Connectome; LTP; ID; ASD; Psychiatric and neurodevelopmental disorders; SCZ
Abstract:
On this planet, the mammalian brain is probably the most complex cellular network. In this system, glutamate is the dominant neurotransmitter, and it mediates the fast communication between the units of the network. Glutamate’s main sites of fast action are the ionotropic glutamate receptors (iGluRs). The iGluRs are a group of receptors that are related in their amino acid sequences and belong to the superfamily of ion channels containing a P-loop as an ion pore. These P-loop channels consist of several subunits. In the case of iGluRs, this subunit assembly is tetrameric. Most iGluRs are associated with auxiliary proteins. The auxiliary proteins can be involved in surface delivery and trafficking of the iGluR, but they can also modulate iGluR channel properties.
The iGluR family consists of four subgroups: AMPA, NMDA, kainate, and orphan receptors, distinguished by their pharmacological profile. The AMPA receptors are directly responsible for the fast signal transmission at synapses, which represents the communication points between the individual neurons. In contrast, the NMDA receptors do not directly participate in fast synaptic transmission; instead, they are the most fundamental modulators of the strength of the synaptic AMPA receptor currents during development and in the mature brain. Together with the AMPA receptors, NMDA receptors keep synapses flexible and thus permit a continuous incorporation or removal of new information into and from the network; in other words, they are necessary for the formation and the extinction of memory. This simple picture of iGluR-mediated neurotransmission is, however, likely to be substantially modified in the future, in view of the great complexity of the iGluR system and its involvement in neurological and neuropsychiatric disorders.
