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Distinct roles for the ryanodine and IP3 receptor intracellular calcium release channels in memory formation using a single-trial discrimination avoidance task for young chicks

thesis
posted on 09.02.2017, 05:16 authored by Baker, Kathryn Denise
Calcium signalling has a vital function in memory processing, with well-established roles for channels controlling calcium influx from the extracellular environment. In contrast, there is limited evidence examining the involvement of channels controlling calcium release from intracellular stores, including ryanodine receptors (RyRs) and inositol (1,4,5)-trisphosphate (IP3) receptors (IP3Rs). Previous investigations using a single-trial discrimination avoidance task in young chicks revealed the inhibition of RyRs resulted in a persistent retention loss observed by 40 min post-training, during the intermediate stage of memory formation in this model. Extending upon this finding, the aim in this thesis was to investigate the roles of IP3Rs and RyRs in memory formation using the single-trial discrimination avoidance task developed for young chicks. Chicks were trained using both a strongly and weakly reinforced variant of this task which resulted in a persistent or labile memory trace, respectively. The findings were interpreted within the framework of the Gibbs and Ng three stage memory model derived from this task. The temporally precise task and detail inherent in the model enabled the investigation of molecules likely to activate, or be activated following, RyRs and IP3Rs. Using strongly reinforced training, the inhibition of IP3Rs, metabotropic glutamate receptor subtype 1 (mGluR1) and small-conductance calcium-activated (SK) channels each yielded retention loss by 90 min post-training, 30 min into the protein synthesis-dependent long-term memory (LTM) stage. These findings suggest that IP3Rs are required during LTM formation and may be activated following mGluR1. In addition, IP3Rs may provide a calcium source to activate SK channels, potentially impacting on dendritic excitability and synaptic plasticity. Using weakly reinforced training, the administration of a RyR agonist promoted the consolidation of the LTM stage, demonstrating that RyRs are involved in triggering LTM consolidation. Further investigations examined whether RyR-dependent calcium release was dependent upon nitric oxide (NO) and noradrenergic mechanisms, also temporally implicated in the same stage of memory formation. Findings using strongly reinforced training indicated the capacity of NO, RyR-dependent calcium release and noradrenaline (NA) to modulate memory. Retention loss induced by a RyR antagonist was prevented by a NO donor or NA. A RyR agonist also prevented retention loss induced by either NO synthase or β1+2-adrenoceptor inhibition. However, differential findings were observed using weakly reinforced training, as retention loss facilitated by a RyR agonist was prevented by a β1+2-adrenoceptor antagonist, but not a NO synthase inhibitor. In addition, a RyR antagonist compromised LTM consolidation promoted by a NO donor, but not NA. These findings indicate that NO promotes memory formation through mechanisms dependent upon RyRs. RyRs appear to facilitate memory formation through noradrenergic activation of β2-adrenoceptors. These findings demonstrate important roles for intracellular calcium release channels in memory processing. The requirement of RyRs and IP3Rs in different stages of memory provides compelling evidence for distinct roles for these channels in memory formation. This thesis addresses a novel area in the neurobiology of memory literature and represents an important step in understanding memory consolidation. Increased knowledge of the function of intracellular calcium stores in memory processing may have important implications for the understanding of disorders with memory impairments which involve altered calcium signalling.

History

Principal supervisor

Dr Thomas M. Edwards

Year of Award

2011

Department, School or Centre

Psychology and Psychiatry

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences