9.031 Neural Basis of Learning and Memory: Lecture 4
Classical conditioning in Drosophila: Cellular mechanisms
Flies demonstrate many forms of simple learning
Fruit flies can be conditioned to avoid odors which have been paired with electrical shock.
The procedure involved a T-maze (two-arm choice apparatus). Separate odors (3-octanol (OCT) or 4-methylcyclohexanol (MCH)) could be delivered to each arm.
Flies were drawn into a training tube containing one of the odors, and electrically shocked with brief voltage pulses (10V to 150V).
Flies were then placed at the intersection of the T-maze containing both odors. The fraction of flies avoiding the previously shock-paired odor was the indicator of learning.
Different memory time course dependent on the training schedule
So now that we have trained flies, what can we do with them?
Look at Drosophila mutants with abnormalities in the Gs coupled adenylyl cyclase - cAMP system.
rutabaga - mutation in the gene encoding Ca++/Calmodulin-dependent adenylate cyclase leading to lower cAMP levels. Moderate impairment of learning. Acquisition affected.
dunce - blocked cAMP phosphodiesterase which leads to high levels of cAMP. Moderate impairment of learning. Acquisition affected.
amnesiac - normal acquisition but deficient intermediate-term memory, affects a gene encoding a neuropeptide which acts through adenylate cyclase to increase cAMP. Suggests a role of neuropeptides in modulating or extending the effects of second messenger systems.
radish - normal long-term memory, disrupted anesthesia-resistant memory (intermediate term). Cellular mechanism is unknown.
dCREB2-b - blocks long-term memory, but acquisition and anesthesia-resistant memory (intermediate term) unaffected. Blockade of cAMP response element binding protein (CREB) transcription.
Memory stages can be dissected using pharmacological manipulations such as the protein synthesis inhibitor cycloheximide (CXM)
Consolidated memory has multiple components
Directions for molecular genetics
T.Tully and W.G.Quinn, "Classical conditioning and retention in normal and mutant Drosophila melanogaster", J.Comp.Physiol. A 157:263-277 (1985).
J.DeZazzo and T.Tully, "Dissection of memory formation:from behavioral pharmacology to molecular genetics", TINS 18:212-218 (1995).
M.B. Feany and W.G. Quinn, "A neuropeptide gene defined by the Drosphila memory mutant amnesiac", Science 268:869-873 (1995).