SYNAPTIC PLASTICITY: PHYSIOLOGY AND NEUROLOGICAL DISEASE - Synaptic Plasticity: New Research - page 1

Chapter 1
S YNAPTIC P LASTICITY : P HYSIOLOGY AND
N EUROLOGICAL D ISEASE
Stephen D. Skaper *
Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and
Development Limited, New Frontiers Science Park.Third Avenue,CM19 5AW, Harlow,
Essex, United Kingdom
A BSTRACT
Neuroplasticity is both a substrate of learning and memory and a mediator of
responses to neuronal cell attrition and injury (compensatory plasticity). It is a continuous
process in reaction to neuronal activity and neuronal injury, death, and genesis, which
involves modulation of structural and functional processes of axons, dendrites, and
synapses. The varied structural elements that embody plasticity include long-term
potentiation (a cellular correlate of learning and memory), synaptic efficacy, synaptic
remodelling, synaptogenesis, neurite extension including axonal sprouting and dendritic
remodelling, and neurogenesis and recruitment. Degenerative diseases of the human brain
have long been viewed as among the most enigmatic and intractable problems in
biomedicine. As research on human neurodegeneration has moved from descriptive
phenomenology to mechanistic analysis, it has become increasing apparent that the
morphological lesions long used by neuropathologists to confirm a clinical diagnosis
after death might provide an experimentally tractable handle to understand causative
pathways. For example, Alzheimer's disease (AD) is an aging-dependent
neurodegenerative disorder that is characterised by neuropathologically by the deposition
of insoluble amyloid β-peptide (Aβ) in extracellular plaques and aggregated tau protein,
which is found largely in the intracellular neurofibrillary tangles. There is growing
evidence that mild cognitive impairment in early AD may be due to synaptic dysfunction
caused by the accumulation of non-fibrillar, oligomeric Aβ, long before widespread
synaptic loss and neurodegeneration occur. Soluble Aβ oligomers can adversely affect
synaptic structure and plasticity at extremely low concentrations, although the molecular
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