Quisqualate receptors are specifically involved in cerebellar synaptic plasticity

Long-term modification of transmission efficacy at synapses is the cellular basis of memory and learning1–4. A special type of synaptic plasticity in the cerebellum was postulated theoretically5,6, and has since been verified4,7–9. Each cerebellar Purkinje cell (PC) receives two distinct excitatory inputs, one from parallel fibres (PFs) and the other from a climbing fibre (CF). When these two types of inputs are conjunctively activated, PF–PC transmission undergoes long-term depression (LTD)4,7–9. Accumulated evidence suggests that LTD plays a role in the motor learning processes of the cerebellum10–12. At the molecular level, LTD appears to be caused by desensitization of receptor molecules in PC dendrites towards the PF neurotransmitter4, presumably L-glutamate (Glu) (ref. 12). Glu receptors are heterogeneous and can be divided into several subtypes13–15. In this study, we compared the potency of several Glu agonists in inducing LTD and found a highly selective dependency of LTD on the quisqualate(QA)-selective subtype of Glu receptors.

[1]  D. Marr.  A theory of cerebellar cortex , 1969, The Journal of physiology.

[2]  J. Albus.  A Theory of Cerebellar Function , 1971 .

[3]  T. Bliss,et al.  Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path , 1973, The Journal of physiology.

[4]  P. Mcgeer,et al.  Kainic acid as a tool in neurobiology , 1978 .

[5]  R. Llinás,et al.  Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. , 1980, The Journal of physiology.

[6]  R. H. Evans,et al.  Excitatory amino acid transmitters. , 1981, Annual review of pharmacology and toxicology.

[7]  O. Oscarsson,et al.  Prolonged depolarization elicited in Purkinje cell dendrites by climbing fibre impulses in the cat. , 1981, The Journal of physiology.

[8]  A. Beaudet,et al.  Autoradiographic localization of specific kainic acid binding sites in pigeon and rat cerebellum , 1981, Brain Research.

[9]  Masao Ito,et al.  Long-lasting depression of parallel fiber-Purkinje cell transmission induced by conjunctive stimulation of parallel fibers and climbing fibers in the cerebellar cortex , 1982, Neuroscience Letters.

[10]  Masao Ito,et al.  Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells , 1982, The Journal of physiology.

[11]  E. Kandel,et al.  Molecular biology of learning: modulation of transmitter release. , 1982, Science.

[12]  M. Ito.  Cerebellar control of the vestibulo-ocular reflex--around the flocculus hypothesis. , 1982, Annual review of neuroscience.

[13]  F. Crépel,et al.  Voltage clamp analysis of the effect of excitatory amino acids and derivatives on Purkinje cell dendrites in rat cerebellar slices maintained in vitro , 1983, Brain Research.

[14]  H. Mclennan.  Receptors for the excitatory amino acids in the mammalian central nervous system , 1983, Progress in Neurobiology.

[15]  D. Alkon.  Calcium-mediated reduction of ionic currents: a biophysical memory trace. , 1984, Science.

[16]  G. Fagg,et al.  Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors , 1984, Brain Research Reviews.

[17]  E. Watanabe.  Neuronal events correlated with long-term adaptation of the horizontal vestibulo-ocular reflex in the primate flocculus , 1984, Brain Research.

[18]  Masao Ito.  The Cerebellum And Neural Control , 1984 .

[19]  K Okamoto,et al.  Pharmacological evidence for L‐aspartate as the neurotransmitter of cerebellar climbing fibres in the guinea‐pig. , 1985, The Journal of physiology.

[20]  J. Davies,et al.  Excitatory and inhibitory responses of purkinje cells, in the rat cerebellum in vivo, induced by excitatory amino acids , 1985, Neuroscience Letters.

[21]  A. Ishida,et al.  Quisqualate and L-glutamate inhibit retinal horizontal-cell responses to kainate. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Kano,et al.  Long-term depression of parallel fibre synapses following stimulation of climbing fibres , 1985, Brain Research.