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Heterosynaptic plasticity in pyramidal neurons of the hippocampus

Haslehurst, P; (2014) Heterosynaptic plasticity in pyramidal neurons of the hippocampus. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Homeostatic synaptic plasticity (HSP) is an adjustment of synaptic strength which compensates for chronically altered activity levels in a neuron’s inputs. It is proposed that HSP allows the neuron to retain its ability to discriminate between different inputs in a changing environment. HSP has been demonstrated at several levels: the network, the individual neuron, and the synapse. Synapse-specific HSP involves a paradox: if intense transmission strengthens a synapse, HSP will act in a compensatory direction to weaken the same synapse, effectively erasing the memory trace laid down by the initial stimulus. As a solution to this paradox, it has been proposed that the synapse’s homeostatic “tariff” is actually shared with its neighbouring synapses, thus maintaining the strength of the synapse relative to its neighbours. My project aimed to test this hypothesis directly by strengthening a single synapse with a glutamate uncaging “tetanus”, and then estimating changes in the strength of neighbouring synapses by acquiring high-magnification confocal images of the corresponding spines and measuring their head diameters at various time points. The results reported in this thesis confirm the hypothesis – a fraction of spines within 20 to 30 μm of the strengthened spine undergo substantial shrinkage. This heterosynaptic effect is long- lasting (it is still evident 60 minutes after uncaging), and large spines are more likely to shrink than small ones. This thesis also reports followup experiments in which possible mechanisms were explored. Rapid confocal scanning of calcium indicator dye was used to detect possible calcium signals flowing from the uncaging target along the dendrite into neighbouring spines. However, KN62 was found to abolish the heterosynaptic shrinkage effect, indicating that CaMK2 activation is required, which suggests that calcium may not be the signal for heterosynaptic shrinkage.

Type: Thesis (Doctoral)
Title: Heterosynaptic plasticity in pyramidal neurons of the hippocampus
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1428059
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