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Garner AR, Rowland DC, Hwang SY, Baumgaertel K, Roth BL, Kentros C, Mayford M. Generation of a synthetic memory trace. Science . 2012 Mar 23 ; 335(6075):1513-6. PubMed Abstract

Comments on Paper and Primary News
Comment by:  John Neumaier
Submitted 26 March 2012 Posted 26 March 2012

The study by Mayford's group is the most elegant application of DREADD receptors so far. While it is not clear what the minimal ensemble of neurons that can represent the memory trace are, the fact that the distributed set of neurons can be selectively activated so unobtrusively (with CNO) is a real innovation.

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Comment by:  John Gray
Submitted 26 March 2012 Posted 26 March 2012

In this week’s issue of Science, Garner et al. take an ingenious leap forward in the use of the growing collection of tools for the remote activation of neurons. They utilize a genetic tool known as a DREADD receptor, a designer receptor exclusively activated by designer drug, pioneered in the laboratory of Bryan Roth (Alexander et al., 2009). DREADDs are G protein-coupled receptors that have been created to only be activated by clozapine-N-oxide (CNO), an analogue of clozapine that does not have a high-affinity binding site in the brain. Thus, when a DREADD, in this case, hM3Dq, is introduced into neurons in the brain, those cells can be activated by the administration of CNO. These exogenous receptors can be introduced into specific brain regions or cell types by viral injection or the use of transgenic mice. The conceptual advance that Garner et al. provide is the expression of hM3Dq only in neurons that were previously activated by experience. To accomplish this, they coupled the...  Read more

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Comment by:  Christoph Kellendonk
Submitted 30 March 2012 Posted 3 April 2012
  I recommend this paper

One major limitation in the study of cognition has been that cognitive processes such as learning and memory may be mediated by distributed networks in the brain that engage only a low percentage of neurons in a given brain structure (e.g., the hippocampus). In consequence, widely used tools such as brain imaging, in-vivo electrophysiology, and postmortem analysis do not have the necessary resolution and signal-to-noise ratio to study the functioning of these distributed networks.

Recently, Mark Mayford used an elegant transgenic mouse strategy to label cells that were activated by a learning experience. Using these mice, they were able to show that those cells are also reactivated during memory retrieval, suggesting that they form part of the "memory trace" encoding this learning experience. Now, in two equally elegant studies, Mayford's group and a group led by Susumu Tonegawa have studied what happens if you reactivate these neurons at later time points.

The data from the Tonegawa group suggest that the cells activated during learning not only get reactivated...  Read more

View all comments by Christoph Kellendonk
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