Tuesday, February 12, 2008

Neuronal CPEB Stabilizes Synapse-Specific LTF

Si, K. et al. (December 26, 2003). A neuronal isoform of CPEB Regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia. Cell, Vol. 115, 893-904.

Synaptic plasticity has been offered as one answer to questions regarding the neurobiological mechanisms of memory. The gist of plasticity is that the synapses are effectively "strengthened", forming a stronger connection between neighboring neurons. Plasticity has at least two forms: one a short-term form lasting minutes, and the other a long-term form lasting days or weeks. How does each work? And how are specific, individual synapses strengthened when most cellular mechanisms (e.g. gene expression) are thought to act cell-wide?

Short-term changes are characterized by covalent modifications of preexisting proteins and the strengthening of preexisting connections. However, specific mechanisms for this are not offered by the authors. This paper takes aim instead at long-term plasticity, characterized by creation and projection of of new synaptic connections and growth of new synaptic terminals, requiring both structural changes in the shape, size, and morphology of the synapse as well as regulatory controls that determine where and when to grow.

The article shows that neural stimulation can: (1) send a signal from the synapse to the nucleus that kicks off the gene expression process necessary for long-term facilitation, and (2) "mark" the specific activated synapse so that translation can occur (proper materials can be synthesized) at the specifically marked synapse. CPEB, which resembles a prion (a protein that can switch between two functionally distinct morphological states), seems to act as the needed "marker". ApCPEB appears necessary for the long-term stabilization of facilitation, but not for short-term facilitation. Its ability to polyadenylate (elongate) the mRNA that reaches the marked synapse stabilizes this mRNA molecule, allowing it to resist catalyzation longer thereby increasing its output of building-block proteins. Interestingly, this process can be kicked off by as little as one, single stimulation event.

For a more holistic review of memory mechanisms, see Molecular Mechanisms for Storage.

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