Abstract
The organisation of cells in the peripheral nervous system is crucial for its proper
function. Action potential generation, conduction and synaptic transmission to the
muscle fibres are dependent not only on cells directly implicated in these functions
(i.e. neurons and muscle fibers) but also on accessory cells with important
modulatory roles. These cells are also essential for adaptive responses by the
peripheral nervous system during development, injury and pathological conditions.
Schwann cells represent one of the principal cellular components regulating nerve
function. In peripheral nerves, myelin-forming Schwann cells specify distinct
domains in the axon, allowing fast and efficient propagation of the action potential.
At the neuromuscular junction, terminal Schwann cells are necessary for stability of
motor nerve terminals and motor endplates and they are involved in plastic responses
of the neuromuscular system to injury and in disease.
This thesis is a study of how the cellular organisation of the peripheral nerve and
neuromuscular junction determines their morphological and electrophysiological
characteristics as well as their functional role in plastic responses following
destabilizing stimuli. The mechanism by which Schwann cells regulate the length of
the myelinated segment over the axon is addressed and this parameter, i.e. the
internodal length, is shown experimentally for the first time as a key determinant of
nerve conduction velocity (Court et al., 2004). At the neuromuscular junction,
immunostaining with a panel of antibodies revealed a novel cell type, distinct from
Schwann cells and possibly related to fibroblasts. These cells lie outside the synaptic
basal lamina, but in adults they are highly restricted to the neuromuscular junction.
Studies of the development of the novel cells, and their reaction to nerve injury and
paralysis, suggest they play a crucial role in the maintenance and disposition of
motor nerve terminals and terminal Schwann cells. Finally, studies of periaxin null
mutant mice, which show a demyelinating neuropathy, yielded new insights into the
relationships between axons and Schwann cells at the neuromuscular junction.
Defects observed in morphology and electrophysiology of junctions in these mice
may contribute to their behavioural phenotype (i.e. trembling, weakness), suggesting
that disruption of nerve terminal-Schwann cell relationships may also contribute to
disability in demyelinating diseases.
