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Picking apart how neurons learn

odified mice lacking different proteins required for establishing LTD.

Mice lacking the PICK1 protein are unable to establish LTD or remove AMPA receptors from cell surfaces. When PICK1 is added artificially back into these neurons, AMPA receptors are removed and LTD is restored, showing that PICK1 is necessary for LTD.

Mice lacking the part of the AMPA receptor thought to physically interact with PICK1 also do not establish LTD. This result confirms that PICK1 must physically touch the AMPA receptor for LTD to occur.

The second critical step in establishing LTD involves a chemical change to the AMPA receptor, called phosphorylation. Mice lacking a small part of the AMPA receptor - the part where phosphorylation is thought to occur - do not undergo LTD. This result confirms that phosphorylation is an essential step toward LTD.

With these three different mouse populations in hand, the research team is poised to further dissect the molecular mechanisms behind learning. "The next step is to determine whether LTD is crucial for motor learning, the so-called holy grail in the field," says one of the study's co-first authors, Jordan Steinberg, an M.D., Ph.D. candidate at Hopkins.


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Source:Johns Hopkins Medical Institutions


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