Eyeblink Conditioning in Animal Models and Humans

The knowledge base on behavioral parameters and neural substrates involved in eyeblink classical conditioning is extensive and continues to expand. The close parallels in behavior and neurobiology in mammalian species including humans make eyeblink conditioning an ideal paradigm for translational studies. Applications presented in this chapter include eyeblink conditioning’s utility in the investigation of severe neurological conditions at the beginning and end of the life span: fetal alcohol syndrome (FAS) and Alzheimer’s disease (AD). Recent studies in children with FAS demonstrate that delay eyeblink conditioning has a high sensitivity for diagnosis of prenatal exposure to alcohol. Contributing to the understanding of the neural mechanisms in the cerebellum damaged by prenatal alcohol exposure is a developmental rat model tested with eyeblink classical conditioning. Disruption of the hippocampal cholinergic system is associated with impaired delay eyeblink conditioning in normal rabbits. This result led to the hypothesis that the hippocampal cholinergic disruption observed early in AD might cause delay eyeblink conditioning to be impaired. This hypothesis was confirmed, and delay eyeblink conditioning has been demonstrated to have high sensitivity for AD. The hypercholesterolemic rabbit model of AD shows many neuropathologies of human AD and is impaired in delay eyeblink conditioning. Both the rat FAS and the rabbit AD models have demonstrated utility in the elucidation of disease mechanisms and the identification of treatments.