Abstract
Introduction In the early 1980's we observed that neuropeptides can alter the affinity and density of the monoamine agonist and antagonist binding sites in different regions of the CNS, in a receptor subtype specific way [1,2]. This indicated the presence of neuropeptide-monoamine receptor-receptor interactions in the plasma membrane. The molecular mechanisms for
Highlights
In the early 1980's we observed that neuropeptides can alter the affinity and density of the monoamine agonist and antagonist binding sites in different regions of the Central Nervous System (CNS), in a receptor subtype specific way [1,2]
The allosteric receptor–receptor interactions in heteroreceptor complexes appear to represent a new principle in biology making possible integration of signals already at the level of the plasma membrane
According to our hypothesis long-lived heteroreceptor complexes with stabilized and conserved allosteric receptor-receptor interactions in the postsynaptic membrane can be an essential part of the molecular structure for long-term memory in the neuronal networks
Summary
In the early 1980's we observed that neuropeptides can alter the affinity and density of the monoamine agonist and antagonist binding sites in different regions of the CNS, in a receptor subtype specific way [1,2]. One molecular basis for learning and memory may be brought about by reorganization of the available higher order heteroreceptor complexes structurally and/or by resetting the multiple allosteric receptor–receptor interactions in these complexes as well as by the formation of novel heteroreceptor complexes via e.g., alterations in the pattern of synaptic and volume transmission signals [4,111,112,113] Such multiple molecular changes in the heteromers and their receptor-receptor interactions may be the molecular basis for learning and short-term memory, involving multiple changes in the receptor-protein architecture of the heteroreceptor complexes of the postsynaptic membrane as illustrated by the change of barcode (Figure 1). This pattern is learned by the transient reorganization of the postsynaptic receptor complexes into inter alia higher order heteroreceptor complexes including ion channels,GPCR interacting proteins and homomer-ion channel complexes This receptor reorganization leads to a novel bar code which can represent a short term memory of the new pattern of transmitter release to be learned which can involve extrasynaptic receptor complexes. It can involve the release of soluble factors like purines and trophic factors and extracellular vesicles like
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