Wednesday, 13 January 2010

Memories that can last a lifetime

How does your brain store childhood memories for your entire life, even after the actual neurons present in your brain when you first experienced that memory have long since died and been replaced, many times over?

It's a fascinating question, and one which Horn et. al. (1998) attempt to answer using a computational model. Firstly, memories are not stored one-per-neuron: "Stored memories are not represented at specific neurons of the network, but their corresponding representations are distributed; many neurons participate in a given [memory], and a particular neuron participates in several different [memories] (Ruppin et. al., 1996).  Horn et. al. (1998) show that by adjusting the strengths of the synapses between neurons whenever a neuron dies in order to keep the activation of all of the remaining neurons the same, the overall network is capable of retaining the stored memories for quite a while.

Interestingly, this mechanism also counter-balances the 'pathological attractors' which tend to arise from the deletion or modification of synapses in this way during activity-dependent learning, and which represent symptoms of schizophrenia (Ruppin et. al., 1996).

This got me thinking: what if I could create a copy of this model to show memories being retained in this way during the course of normal neuronal death, but implement some existing medical hypotheses e.g. delayed NMDA receptor maturation (Greenstein and Ruppin, 1998) or excessive neuronal activity leading to excess glutamate production and neurodegeneration (Good Brain, Bad Brain module semester 2) to try to model a change in the normal neuronal death process which leads to a disorder such as Alzheimer's or schizophrenia (or both, if it can be shown that they are sufficiently closely-linked)? Horn et. al. (1998) also suggest that "recent findings [listed] indicate that signaling molecules involved in neuronal regulation are altered in Alzheimer's disease", adding further weight to this idea.

This would be taking a different angle to the research compared to the suggestion of simply trying to explain Rund (2009)'s findings that there may be a degenerative process in schizophrenia in the context of Alzheimer's disease (which is possibly looking like a very tenuous link to make).

So it looks like I could currently take three paths:
  1. Model possibly causes of Alzheimer's and/or schizophrenia, in the context of memory maintenance (Horn et. al., 1998).
  2. Model the shared elements of the progress of Alzheimer's and schizophrenia (i.e. synaptic runaway (Ruppin et. al., 1996; Greenstein and Ruppin, 1998; Hasselmo, 1994; Ruppin and Reggia, 1995; Horn et. al., 1996)).
  3. Model a degenerative process in schizophrenia (possibly drawing from Alzheimer's disease modelling), to corroborate Rund (2009)'s findings.

References
Greenstein-Messica, A. and Ruppin, E. (1998), "Synaptic runaway in associative networks and the pathogenesis of schizophrenia", in Neural Computation 10:451--465.

Hasselmo, M.E.  (1994), "Runaway synaptic modification in models of cortex: Implications for Alzheimer's disease", in Neural Networks 7:13--40.

Horn, D., Levy, N., Ruppin, E. (1996), "Neuronal-based synaptic compensation: a computational study in Alzheimer's disease", in Neural Computation 8:1227--1243.

Horn, D., Levy, N., Ruppin, E. (1998), "Memory maintenance via neuronal regulation", in Neural Computation 10:1--18.

Rund, B.R. (2009), "Is there a degenerativeprocess going on in the brain of people with schizophrenia?" in Frontiers in Neuroscience (3)36:1--6.

Ruppin, E. and Reggia J. (1995), "A neural model of memory impairment in diffuse cerebral atrophy", in British Journal of Psychiatry 166:19--28

Ruppin, E., Reggia, J., Horn, D. (1996), "Pathogenesis of schizophrenic delusions and hallucinations: a neural model", Schizophrenia Bulletin (22)1:105-123

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