A proposal regarding the biology of memory: participation of intracrine peptide networks

Although progress has recently been made in defining its neurobiological underpinnings, memory remains an incompletely understood process. Here it is proposed that intracrine peptide action plays a role in memory and therefore in consciousness. Intracrine function is the intracellular action of a peptide either in its cell of synthesis or in target cells following internalization. Intracrine functionality has been associated with growth factors, transcription factors, and enzymes. Some intracrines have been shown to modify their own synthesis, the synthesis of components of their signaling cascades, and/or the synthesis of other intracrines, making it likely that these factors participate in peptinergic regulatory loops/networks. Moreover, some intracrines can affect cellular ion flows over short time periods, while stimulating protein synthesis and growth over longer periods. Intracrines have been reported in the brain (for example, angiotensin, brain derived neurotrophic factor, reelin, and fibroblast growth factor 2) and it is here suggested that intracrine expression/action occurs commonly in the nervous system and, in particular, in the cerebral cortex. This intracrine action leads to the formation of long-lived intra- and intercellular intracrine feed back loops. The intracrine networks thus formed participate in producing both short and long term synaptic potentiation; the former effect is primarily related to intracrine effects on ion flows, the latter to intracrine directed protein synthesis. In addition, intracrine networks provide a previously unappreciated dynamic substrate for the integration of information and ultimately for the formation of the associations that underlay consciousness.