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The Journal of Neuroscience, March 21, 2007, 27(12):3064-3068; doi:10.1523/JNEUROSCI.2581-06.2007

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Brief Communications
Differential Classical Conditioning of the Gill-Withdrawal Reflex in Aplysia Recruits Both NMDA Receptor-Dependent Enhancement and NMDA Receptor-Dependent Depression of the Reflex

Shekib A. Jami,¹ William G. Wright,^1,2 and David L. Glanzman^1,3

¹Department of Physiological Science, University of California, Los Angeles (UCLA), Los Angeles, California 90095-1606, ²Biological Sciences, Chapman University, Orange, California 92866, and ³Department of Neurobiology and the Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1761

Correspondence should be addressed to Dr. David L. Glanzman, Gonda (Goldschmied) Neuroscience and Genetics Research Center, University of California, Los Angeles, 695 Young Drive South, Box 951761, Los Angeles, CA 90095-1761. Email: dglanzman{at}physci.ucla.edu

Differential classical conditioning of the gill-withdrawal response (GWR) in Aplysia can be elicited by training in which a conditioned stimulus (CS) delivered to one side of the siphon (the CS+) is paired with a noxious unconditioned stimulus (US; tail shock), while a second conditioned stimulus (the CS–), delivered to a different siphon site, is unpaired with the US. NMDA receptor (NMDAR) activation has been shown previously to be critical for nondifferential classical conditioning in Aplysia. Here, we used a semi-intact preparation to test whether differential classical conditioning of the GWR also depends on activation of NMDARs. Differential training produced conditioned enhancement of the reflexive response to the CS+ and a reduction in the response to the CS–. Comparison of the results after differential training with those after training in which only the two CSs were presented (CS-alone experiments) indicated that the decrement in the response to CS– after differential training was not caused by habituation. Surprisingly, differential training in the NMDAR antagonist APV (DL-2-amino-5-phosphonovalerate) blocked not only the conditioned enhancement of the GWR, but also the conditioning-induced depression of the GWR. We suggest that differential conditioning involves an NMDAR-dependent, competitive interaction between the separate neural pathways activated by the CS+ and CS–.

Key words: Aplysia; LTP; APV; synaptic competition; synaptic homeostasis; conditioned inhibition

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Received June 20, 2006; revised Jan. 25, 2007; accepted Jan. 26, 2007.

Correspondence should be addressed to Dr. David L. Glanzman, Gonda (Goldschmied) Neuroscience and Genetics Research Center, University of California, Los Angeles, 695 Young Drive South, Box 951761, Los Angeles, CA 90095-1761. Email: dglanzman{at}physci.ucla.edu

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