Use this URL to cite or link to this record in EThOS:
Title: Cellular identity of cerebellar memory
Author: Fukunaga, I.
ISNI:       0000 0004 2731 5539
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2009
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
The cerebellum is essential for some forms of motor learning and storage of motor memories. The simple organization of the cerebellum provides special opportunities to analyse mechanisms underlying learning and memory in a real neural network. A dominant hypothesis of cerebellar function is one based on suggestions by Marr and Albus, where Purkinje cell responses to parallel fibre inputs are modified under climbing fibre control. A candidate cellular mechanism is a long-term depression of parallel fibre-Purkinje cell synapses (pf-PC LTD) seen, in vitro, after conjunctive activation of parallel and climbing fibres. The associative and persistent nature of pf- PC LTD suggests that it may underlie behavioural forms of cerebellum-dependent learning. Activation of the metabotropic glutamate receptor type 1 (mGlu 1 receptor) is critical for the induction of pf-PC LTD. If pf-PC LTD underlies learning, then blocking this receptor should lead to impairment of cerebellum-dependent learning. The studies described here test the role of the mGlu 1 receptor in one form of cerebellum-dependent associative learning. Chapters 2 and 3 describe slice electrophysiological experiments that assess the mGlu1 antagonists CPCCOEt, YM-298198 and JNJ16259685. CPCCOEt was found to have a non-specific action, while YM-298198 and JNJ16259685 were found to be very potent and highly specific. Chapter 4 describes the effects of cerebellar infusions of JNJ16259685 on classical conditioning of the rabbit nictitating membrane response and reveals that conditioning was not impaired. The result suggests there could be dissociation between pf-PC LTD and cerebellar learning. It is known that pf-PC LTD in vitro may not be a single phenomenon since it can be induced with a range of protocols that can differ significantly from the normal physiology. Thus, there may be a form of pf-PC LTD in vivo that is relatively independent of mGlu 1 receptor function. Alternatively, behavioural learning may depend upon plasticities involving other neuronal types in the cerebellar cortex.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available