Eyeblink Conditioning and Novel Object Recognition in the Rabbit: Behavioral Paradigms for Assaying Psychiatric Diseases

Craig Weiss, John F. Disterhoft

Analysis of data collected from behavioral paradigms has provided important information for understanding the etiology and progression of diseases that involve neural regions mediating abnormal behavior. The trace eyeblink conditioning (EBC) paradigm is particularly suited to examine cerebro-cerebellar interactions since the paradigm requires the cerebellum, forebrain, and awareness of the stimulus contingencies. Impairments in acquiring EBC have been noted in several neuropsychiatric conditions, including schizophrenia, Alzheimer's disease (AD), progressive supranuclear palsy, and post-traumatic stress disorder. Although several species have been used to examine EBC, the rabbit is unique in its tolerance for restraint, which facilitates imaging, its relatively large skull that facilitates chronic neuronal recordings, a genetic sequence for amyloid that is identical to humans which makes it a valuable model to study AD, and in contrast to rodents, it has a striatum that is differentiated into a caudate and a putamen that facilitates analysis of diseases involving the striatum. This review focuses on EBC during schizophrenia and AD since impairments in cerebro-cerebellar connections have been hypothesized to lead to a cognitive dysmetria. We also relate EBC to conditioned avoidance responses that are more often examined for effects of antipsychotic medications, and we propose that an analysis of novel object recognition (NOR) may add to our understanding of how the underlying neural circuitry has changed during disease states. We propose that the EBC and NOR paradigms will help to determine which therapeutics are effective for treating the cognitive aspects of schizophrenia and AD, and that neuroimaging may reveal biomarkers of the diseases and help to evaluate potential therapeutics. The rabbit, thus, provides an important translational system for studying neural mechanisms mediating maladaptive behaviors that underlie some psychiatric diseases, especially cognitive impairments associated with schizophrenia and AD, and object recognition provides a simple test of memory that can corroborate the results of EBC.