Plasticity switch
CREB-mediated plasticity transcription
Also searched as CREB-mediated plasticity transcription.
A neuron that fires is not yet a neuron that has changed. CREB is the step in between: calcium arriving at the synapse switches it on, and it writes new BDNF. The finding that matters is that the same ion through the same receptor family does opposite things depending on where it enters. Calcium through synaptic receptors turns creb on as strongly as a calcium channel does. Calcium through extrasynaptic receptors — the ones reached by a glutamate flood rather than by a signal — triggers a dominant shut-off that blocks BDNF even while the synaptic signal is still arriving. Dominant is the word to hold on to. The damage does not merely fail to build; it overrides the building.
In depth
The transcription factor that turns electrical activity into lasting change — and the one an excitotoxic calcium flood shuts off.
What drives it
Quiets overexcitation reduces it.
Calcium entering through extrasynaptic NMDA receptors - reached by a glutamate flood rather than by synaptic release - activates a general and dominant CREB shut-off pathway that blocks induction of BDNF expression, while calcium through synaptic receptors switches CREB on as strongly as an L-type calcium channel does. The same ion, the same receptor family, opposite verdicts decided by location. doi 10.1038/nn835 · PMID 11953750 · PMC5339681
Neuronal overexcitation reduces it.
The excitotoxic glutamate flood reaches extrasynaptic receptors, and those receptors antagonise excitation-transcription coupling directly - inactivating ERK-MAPK signaling and shutting CREB down. The authors' own conclusion is that specific blockade of extrasynaptic receptors may prevent neuron loss. doi 10.1038/nn835 · PMID 11953750 · PMC5339681
What it drives
It increases Supports BDNF signaling.
Synaptic calcium entry induced CREB activity and BDNF gene expression together; when the CREB shut-off is triggered, BDNF induction is blocked. CREB is the step at which electrical activity becomes a transcribed neurotrophin. doi 10.1038/nn835 · PMID 11953750 · PMC5339681
It reduces Cell turnover.
Synaptic NMDA receptor activity is anti-apoptotic, while the extrasynaptic shut-off pathway drives loss of mitochondrial membrane potential and cell death. The shut-off also imports class IIa HDACs and the pro-apoptotic factor Foxo3A to the nucleus. doi 10.1038/nn835 · PMID 11953750 · PMC5339681
It increases Learning & memory.
10.1254/jphs.crj05005x — for an early-LTP to completely mature and reach its long-lasting form (long-LTP), therefore transforming a malleable short-term memory into an enduring one, subsequent waves of protein synthesis are required. doi 10.1254/jphs.crj05005x · PMC12898322
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.