Neuronal memory allocation

Memory allocation was first discovered in the lateral amygdala by Sheena Josselyn and colleagues in Alcino J. Silva's laboratory.

[3] The transcription factor cAMP response element-binding protein (CREB) is a well-studied mechanism of neuronal memory allocation.

[4][5][8] CREB modulates cellular processes that lead to neuronal allocation, particularly with regards to dendritic spine density and morphology.

[3] Indeed, Sano and colleagues in the Silva lab showed that CREB also regulates neuronal memory allocation in the amygdala.

For example, the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) pathways appear to participate in neuronal allocation.

[3] When activated by the second messengers such as cAMP and calcium ions, enzymes such as PKA and MAP kinase can translocate to the nucleus and phosphorylate CREB to initiate transcription of target genes.

[11][12] PKA inhibitors can block the development of long-lasting LTP, and this is accompanied by a reduction in the transcription of genes modulated by the CREB protein.

Several studies provide evidence that neurons receiving “priming activity” (such as neurotransmitters, paracrine signals, or hormones) minutes to days prior will show a lower threshold for induction of long term potentiation (LTP).

[17] Signaling mechanisms implicated in these metaplastic effects include autophosphorylation of αCaMKII,[18] changes in NMDA receptor subunit composition,[19] and activation of voltage-dependent calcium channels.

[30][31] Similarly, on the recruited neurons displaying increased excitability, specific synapses need to be selected for in order to store the information in the form of synaptic plasticity.

Cellular excitability has been proposed as one of the mechanisms responsible for heterosynaptic metaplasticity, the modulation of subsequent plasticity at different synapses.

It has been proposed that understanding the implications of the molecular, cellular and systemic mechanisms of these processes may elucidate how they are coordinated and integrated during memory formation.

[3] For example, identifying the plasticity-related proteins (PRPs) involved in synaptic tagging and capture as well as the upstream and downstream molecules of CREB can help reveal potential interactions.

Multiple intracellular signaling pathways activate CREB , promoting transcription and translation of target proteins that support long-term neuronal plasticity and allocation.
A strong stimulus may produce both a tag on the synapse being stimulated and a genomic signaling cascade leading to the formation of plasticity products. The tag will then serve to capture these plasticity products. A weak signal on a nearby synapse may produce a tag but not a genomic signal. This tag can also serve to, capture plasticity products and strengthen the weakly-stimulated synapse. [ 17 ]