van Rossum, Mark

Morris, Richard

Billings, Guy

2010-10-06T10:07:27Z

2010-10-06T10:07:27Z

2009

Numerous experiments have demonstrated that the activity of neurons can alter the strength of excitatory synapses. This synaptic plasticity is bidirectional and synapses can be strengthened (potentiation) or weakened (depression). Synaptic plasticity offers a mechanism that links the ongoing activity of the brain with persistent physical changes to its structure. For this reason it is widely believed that synaptic plasticity mediates learning and memory. The hypothesis that synapses store memories by modifying their strengths raises an important issue. There should be a balance between the necessity that synapses change frequently, allowing new memories to be stored with high fidelity, and the necessity that synapses retain previously stored information. This is the plasticity stability dilemma. In this thesis the plasticity stability dilemma is studied in the context of the two dominant paradigms of activity dependent synaptic plasticity: Spike timing dependent plasticity (STDP) and long term potentiation and depression (LTP/D). Models of biological synapses are analysed and processes that might ameliorate the plasticity stability dilemma are identified. Two popular existing models of STDP are compared. Through this comparison it is demonstrated that the synaptic weight dynamics of STDP has a large impact upon the retention time of correlation between the weights of a single neuron and a memory. In networks it is shown that lateral inhibition stabilises the synaptic weights and receptive fields. To analyse LTP a novel model of LTP/D is proposed. The model centres on the distinction between early LTP/D, when synaptic modifications are persistent on a short timescale, and late LTP/D when synaptic modifications are persistent on a long timescale. In the context of the hippocampus it is proposed that early LTP/D allows the rapid and continuous storage of short lasting memory traces over a long lasting trace established with late LTP/D. It is shown that this might confer a longer memory retention time than in a system with only one phase of LTP/D. Experimental predictions about the dynamics of amnesia based upon this model are proposed. Synaptic tagging is a phenomenon whereby early LTP can be converted into late LTP, by subsequent induction of late LTP in a separate but nearby input. Synaptic tagging is incorporated into the LTP/D framework. Using this model it is demonstrated that synaptic tagging could lead to the conversion of a short lasting memory trace into a longer lasting trace. It is proposed that this allows the rescue of memory traces that were initially destined for complete decay. When combined with early and late LTP/D iii synaptic tagging might allow the management of hippocampal memory traces, such that not all memories must be stored on the longest, most stable late phase timescale. This lessens the plasticity stability dilemma in the hippocampus, where it has been hypothesised that memory traces must be frequently and vividly formed, but that not all traces demand eventual consolidation at the systems level.

http://hdl.handle.net/1842/3853

en

The University of Edinburgh

synaptic plasticity

learning

memory

Spike timing dependent plasticity

Memory stability and synaptic plasticity

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy