Most of the molecular mechanisms contributing to long-term memory have been found to consolidate information within a brief time window after learning, but not to maintain information during memory storage. However, with the discovery that synaptic long-term potentiation is maintained by the persistently active protein kinase, protein kinase Mζ (PKMζ), a possible mechanism of memory storage has been identified. Recent research shows how PKMζ might perpetuate information both at synapses and during long-term memory.
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This research was supported by the US National Institutes of Health (NIH) (grants R01 MH53576 and MH57068). The article is dedicated to the memory of the late James H. Schwartz, a pioneer in the study of persistent kinases and memory25.
The author declares no competing financial interests.
- Cellular memory consolidation
The molecular mechanisms that convert memories into an enduring form. The process typically lasts for a few hours after learning and is associated with new protein synthesis. It is distinct from systems memory consolidation, which involves shifts in the neuronal circuitry that subserves a memory and can take weeks or longer.
- Long-term memory storage
The physiological mechanism in the brain that perpetuates enduring memories. The storage phase of long-term memory begins from a few hours to a day after learning and can last a lifetime.
- Long-term potentiation
A persistent enhancement of excitatory synaptic transmission lasting hours to days, triggered by strong, typically high-frequency, afferent stimulation of the synapse. It is widely studied as a putative physiological basis of long-term memory.
- PDZ domain
A common protein structural motif that interacts with specific carboxy-terminal sequences of other proteins. The intracellular distribution and trafficking of many proteins are regulated by their binding to PDZ domain-containing proteins.
- Postsynaptic density
A cytoskeletal specialization of the synapse identified by electron microscopy as an electron-dense region at the membrane of the postsynaptic neuron. It concentrates and organizes neurotransmitter receptors, receptor-binding proteins and postsynaptic signalling molecules.
- Synaptic tagging
A hypothesis to explain the potentiation during late-LTP (long-term potentiation) of activated synapses by proteins newly synthesized in the neuronal cell body or dendrite. Afferent stimulation sets up a 'tag' specifically at activated synapses that captures the newly synthesized plasticity-related proteins.
- Trace eye-blink conditioning
A form of classical conditioning in which the conditioned stimulus (CS; typically an auditory or visual stimulus) precedes the unconditioned stimulus (US; an eye-blink-eliciting stimulus such as a puff of air to the cornea) by a stimulus-free period (trace interval). Trace eye-blink conditioning requires both an intact cerebellum and hippocampus.
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