Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, PC36
Early motor development, activity-dependent plasticity, dystonia & deep brain stimulation (DBS).
1. Evelina ChildrenG
Dystonia is thought to arise from excessive cerebral plasticity & reduced inhibition. Dystonia seems activity-dependent. Dominant genes predispose to dystonias & Brain Derived Nerve Growth Factor (BDNF) single nucleotide polymorphisms may determine manifest cariers. Rapid repetitive pre-synaptic stimulation produces release of BDNF from electrically active neurones & enlargement of dendritic spines leading to Long Term Potentiation (LTP). LTP is enhanced in immature compared to adult brain. By contrast, inactivity, immobility, slowly repetitive pre-synaptic stimulation may lead to reduction in AMPA receptors in post-synaptic membranes stimulating type I metabotropic glutamate receptors that activate phosphoinosotide turnover in dendritic spines leading to Long Term Depression (LTD) & reduced BDNF production. Primary dystonias utilize fundamental mechanisms for neuronal sensori-motor organization, though the balance between LTP & LDP may underpin many other functions including memory. Repetitive transcranial magnetic or direct current stimulation may reduce cortical plasticity & increase inhibition, altering LTP-LTD neuronal balance in focal dystonias, offering benefits lasting weeks. Deep brain stimulation (DBS) may continuously maintain a functional neuronal LTP-LDP balance over many years. Potent environmental inputs may initiate a subtle re-organization of the sensori-motor plasticity essential for normal human function & development. Dystonic disordered motor control resembles that of developing babies & infants adapted by a long underwater evolutionary process. In water, slow movements are economical but rapid movements inhibited by viscous drag: the occasional flick is possible to dart away but cannot be sustained. Water exerts a constant pressure on all surfaces of the body. Gravity is partly counter-balanced by buoyancy. In air, buoyancy & viscous drag are lost, gravity bears down. The movements of the newborn are slow & ponderous, but within months become frankly fast, rhythmic or fragmented, though undirected. In infancy (1-12 months) bizarre limb postures & attitudes flow in a constant rehearsal of future purposeful movements. These infantile motor patterns appear dystonic, exhibiting abundant plasticity & little inhibition. Early excessive movements offer the immature motor system opportunities to explore the physical environment. By contrast the immobile embryo, newborn or infant has a bleak neurodevelopmental prognosis without exploratory motor behaviours to gain rewards for their actions. Certain forms of cerebral palsy may represent excessive cerebral plasticity.
Where applicable, experiments conform with Society ethical requirements