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Eyeblink classical conditioning is a relatively simple form of associative learning that has become an invaluable tool in our understanding of the neural mechanisms of learning. When studying rabbits in this paradigm, we observed a dramatic modification of learning rate by conducting training during episodes of either hippocampal theta or hippocampal non-theta activity as determined by on-line slow-wave spectral analysis. Specifically, if animals were given trials only when a computer analysis verified a predominance of slow-wave oscillations at theta frequencies (3-8 Hz), they learned in half as many trials as animals trained during non-theta hippocampal activity (58 vs. 115). This finding provides important evidence from awake, behaving animals that supports recent advances in our knowledge of (i) brain sites and neurobiological mechanisms of learning and memory, specifically hippocampus and theta oscillations, (ii) the biological plausibility of current models of hippocampal function that posit important roles for oscillatory potentials, and (iii) the design of interfaces between biological and cybernetic (electronic) systems that can optimize cognitive processes and performance.

Hippocampal theta activity has been established as a key predictor of acquisition rate in rabbit (Orcytolagus cuniculus) classical conditioning. The current study used an online brain--computer interface to administer conditioning trials only in the explicit presence or absence of spontaneous theta activity in the hippocampus-dependent task of trace conditioning. The findings indicate that animals given theta-contingent training learned significantly faster than those given nontheta-contingent training. In parallel with the behavioral results, the theta-triggered group, and not the nontheta-triggered group, exhibited profound increases in hippocampal conditioned unit responses early in training. The results not only suggest that theta-contingent training has a dramatic facilitory effect on trace conditioning but also implicate theta activity in enhancing the plasticity of hippocampal neurons.

The adducin family of proteins interacts with the actin cytoskeleton and the plasma membrane in a calcium-and cAMP-dependent manner. Thus, adducins may be involved in changes in cytoskeletal organization resulting from synaptic stimulation. ␤-Adducin knockout mice were examined in physiological and behavioral paradigms related to synaptic plasticity to elucidate the role the adducin family plays in processes underlying learning and memory. In situ hybridization for ␣-and ␤-adducin demonstrates that these mRNAs are found throughout the brain, with high levels of expression in the hippocampus. Schaffer collateral-CA1 tetanic long-term potentiation decayed rapidly in acute hippocampal slices from ␤-adducin knock-out mice, although baseline spine morphology and postsynaptic density were normal. Interestingly, the input-output relationship was significantly increased in hippocampal slices from ␤-adducin knock-out mice. Furthermore, ␤-adducin knock-out mice were impaired in performance of fear conditioning and the water maze paradigm. The current results indicate that ␤-adducin may play an important role in the cellular mechanisms underlying activitydependent synaptic plasticity associated with learning and memory.

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