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ResearchBlogging.orgA quote from Nobel Laureate Eric Kandel in the December 11 issue of Science reminded me of a short article by David Glanzman covering a remarkable paper on pan-neuronal (aka 'intrinsic') plasticity and its involvement in learning and memory. Here is the quote:
Q: Synaptic plasticity is a central concept in your work on memory. You've been working with Aplysia since 1962. What else do you think we can learn from these lowly snails?

With almost all kinds of synaptic changes, there is a parallel change in the excitability of nerve cells. For example, in Aplysia, a number of neurons fire spontaneously, in bursts. If you [stimulate] a bursting cell [synaptically], you can change its bursting activity for long periods of time [which implies plasticity not only in the synapse but the neuron itself]. This just blew me away. [But] I've never come back to it.
I received this quote from my postdoc advisor John Byrne. He traced Eric Kandel's mention back to an old finding in Aplysia published in 1977. By now, of course, intrinsic plasticity is a well-documented phenomenon, but its complexity has so far hampered research into the relationship of synapse-specific plasticity and neuron-wide, intrinsic plasticity. Moreover, some forms of intrinsic plasticity appear to be somewhat input-specific, for instance, if the affect only certain branches of the neuron, containing many synapses. Now, Jack Byrne and my then fellow postdoc in his lab Riccardo Mozzachiodi have published a very timely review on our current understanding of intrinsic plasticity with regards to synaptic plasticity, entitled "More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory".The review covers many examples from both vertebrate and invertebrate model systems and is a great primer into the 'other' learning mechanism. The review does of course not yet include the paper on the involvement of Na/K pumps in intrinsic plasticity as this paper came out just now, a few weeks after Mozzachiodi and Byrne was published. This new paper shows that not only ion-channels contribute to intrinsic plasticity, but even such seemingly 'boring' molecules as Na/K-ATPases.


I became interested in intrinsic plasticity since evidence started to come in that operant conditioning was relying on intrinsic plasticity in Aplysia. Now that also in Drosophila it appears that a completely different set of genes is required for modifying behavioral circuits during operant conditioning (or self-learning, as we have recently defined it), while the well-known synaptic plasticity genes are not required. Maybe this differential genetic requirement reflects the mechanisms also differentially affecting synaptic vs. intrinsic plasticity? Could it be that intrinsic plasticity allows to modify the firing properties of a central neuron in a behaviorally relevant network and thereby affecting the entire network, rather than just some small-scale property in it? If this were the case, it would make a lot of sense to regulate such far-reaching network alterations and only allow them after sufficient training - which is exactly what we just found in Drosophila. Thus, there is quite some circumstantial evidence suggesting that synaptic and intrinsic plasticity may also be behaviorally differentiable. However, no clear direct experimental evidence is available, yet.


Interestingly, a PubMed search for "Intrinsic plasticity" OR "intrinsic excitability" yields only 274 articles (with only a handful of papers before 2000), while a search for "synaptic plasticity" yields 8564. Anybody out there looking for a cutting-edge research field?


Pulver, S., & Griffith, L. (2009). Spike integration and cellular memory in a rhythmic network from Na+/K+ pump current dynamics Nature Neuroscience, 13 (1), 53-59 DOI: 10.1038/nn.2444
Mozzachiodi, R., & Byrne, J. (2009). More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory Trends in Neurosciences DOI: 10.1016/j.tins.2009.10.001
Posted on Sunday 27 December 2009 - 17:15:04 comment: 0
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