Cerebellum and eyeblink conditioning

Abstract

The cerebellum and brainstem constitute the essential neural circuit responsible for the acquisition and expression of the classically conditioned eyeblink response in numerous mammalian species, including humans. In this simple form of motor learning, a neutral conditioned stimulus (CS) overlaps and coterminates with a mildly aversive unconditioned stimulus (US), resulting, eventually, in the production of an eyeblink conditioned response (CR) to the CS alone. The forebrain is engaged when this basic delay procedure is made more difficult - for instance, if the CS and US are separated by a brief stimulus-free gap of time. In either case, it is generally accepted that the critical memory trace is formed and stored in the cerebellar interpositus nucleus (IP). The cerebellar cortex also plays a key role in normal acquisition by modulating the amplitude and/or timing characteristics of the eyeblink CR. Owing to the well-defined nature of the neural circuit, and the close correspondence between animal and human studies, eyeblink conditioning has been successfully used to investigate cerebellar dysfunction across a variety of human populations. Herein, research related to three representative disorders is discussed: fetal alcohol syndrome, attention-deficit hyperactivity disorder, and schizophrenia. The results advance understanding of these and similar clinical pathologies and the cerebellar deficits that may underlie them.