THE LEDOUX STRATEGY

for finding the brain circuits involved in emotional memory (inspired by Kandel and Mishkin)

By Joseph LeDoux

Step one:Create a memory: pair an electric shock with a loud noise, so that the noise is remembered as the beacon for imminent shock.

Step two: Identify the neural circuits that form and store the memory: make lesions in the brain by applying electrical current locally and testing if the animal can still learn to associate the tone and shock. Repeat as necessary until the major relay-stations in the brain necessary for fear memories are discovered. Fine tune the brain-circuit map using staining techniques that trace connections by tracking the trajectory of an axon from its cell body to its terminal ending.

Step three:Identify the cells in the circuit that contribute learning and memory: record neural activity in areas that, when damaged, disrupt learning and memory, identifying with much more precision the exact location where the memory is formed and stored.

Step four: Identify the molecules that are crucial to long term memory formation: Inject drugs that block synaptic plasticity—or learning—into the sites where the key cells are located. Use drugs that either block the induction of plasticity (i.e. NMDA antagonists) or that block the conversion of temporary memories into persistent or consolidated memories (i.e. blockers of protein synthesis).

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