Classical conditioning

Int Rev Neurobiol. 1997;41:341-66. doi: 10.1016/s0074-7742(08)60359-1.


Evidence has amassed from research in humans indicating that the cerebellar circuitry serving as the substrate for eyeblink classical conditioning is similar to that in nonhuman primates. In patients with bilateral cerebellar lesions or neurodegenerative cerebellar disease, few conditioned eyeblink responses are produced with either the ipsilesional or the contralesional eye. Cerebellar patients with lateralized lesions, like rabbits with experimentally produced unilateral cerebellar lesions, produce relatively normal conditioned responses (CRs) with the contralesional eye and few or no CRs with the ipsilesional eye. Age-related deficits in eyeblink classical conditioning appear in humans and rabbits in middle age. In normal aging in many species, including humans, there is Purkinje cell loss in cerebellar cortex. In rabbits, the Purkinje cell number correlates highly with the rate of learning, regardless of age. Positron emission tomography imaging of normal young adults during eyeblink conditioning reveals changes in activity in the cerebellum. Timed interval tapping, a task that assesses cerebellar function, also predicts performance on eyeblink conditioning. In dual-task conditions involving simultaneous performance of eyeblink conditioning and timed interval tapping, eyeblink conditioning is impaired. Investigations of patients with lesions or neurodegenerative disease not involving the cerebellum demonstrate that acquisition of CRs is possible, although prolonged in the case of hippocampal cholinergic disruption. Evidence to date suggests that the human analogue of the rabbit interpositus nucleus, the globose nucleus, is essential for the production of the conditioned eyeblink response and that cerebellar cortical Purkinje cells play a role in normal acquisition.

Publication types

  • Review

MeSH terms

  • Aging / pathology
  • Animals
  • Cell Count
  • Cerebellar Diseases / diagnostic imaging
  • Cerebellar Diseases / pathology
  • Cerebellar Diseases / psychology*
  • Cerebellum / diagnostic imaging
  • Cerebellum / physiology*
  • Conditioning, Eyelid / physiology*
  • Humans
  • Neurodegenerative Diseases / psychology
  • Purkinje Cells / pathology
  • Rabbits
  • Tomography, Emission-Computed