Good clinical teaching is concerned with providing role models for good practice, making good practice visible and explaining it to trainees. This is the very basis of clinicians as professionals, the seventh role, and should be the foundation for the further development of clinicians as excellent clinical teachers.

The effect on neonatal brain plasticity of two neurotrophins, brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), was studied using the rat olivocerebellar projection as a model. Unilateral transection of climbing fibres (CFs) in the rat before postnatal day 7 induces reinnervation of the deafferented hemicerebellum, but this does not occur if the transection is performed after postnatal day 10. Eleven-day-old day rats underwent unilateral CF transection followed by neurotrophin injection into the denervated cerebellar cortex 24 h later. The exogenous neurotrophins induced CF reinnervation of the denervated hemicerebellum. However BDNF was more efficacious than NT-3. Thus two neurotrophins can extend the window of neonatal brain plasticity, therefore suggesting potential therapeutic use after brain trauma.

The total number of axons in the cervical and abdominal vagus nerves of the ferret was counted. The ratio of myelinated to non-myelinated, and afferent to efferent axons was determined. The fibre diameter spectrum of myelinated axons was measured. The total number of axons in the ferret cervical vagus is similar to other mammals (approximately 28,000); the majority of axons are afferent (approx. 24,000) and also the majority of axons are nonmyelinated (approx. 27,000). The dorsal abdominal trunk is about twice the size of the ventral trunk although both trunks have the same number of efferent axons. The abdominal vagal trunks are over 90% afferent.

1. During normal development of the vertebrate central nervous system, a considerable number of neurons die. The factors controlling which neurons die and which survive are not fully understood. 2. Target populations are known to maintain their innervating neurons. However, the role of afferents in maintaining their targets is still under review. 3. In the developing nervous system, deafferentation of a neuron population is difficult to achieve because plasticity (structural re-organization) can cause re-innervation of the area. Re-innervation alters, rather than removes, the afferent supply. 4. Afferent input is important for neuronal survival during development because deafferentation increases neuronal death by 20-30% and increasing input diminishes neuronal death. 5. Deafferented neurons die at the normal time for cell death for any given population. This occurs after the arrival of afferent axons but before the completion of connectivity and the onset of function. 6. Neuronal survival is maintained by any input, such as reinnervation by inappropriate fibres, but for optimal survival, morphological maturation and the acquisition of normal physiology, the correct input is required. 7. Afferents maintain their target neurons via a combination of electrical activity and delivery of trophic agents, which adjust intracellular calcium, thereby facilitating protein synthesis, mitochondrial function and suppressing apoptosis. 8. Evidence from animal and in vitro experiments indicates that afferents play an extremely important role in the survival of developing neurons in the immature vertebrate nervous system.

The climbing fiber input to the cerebellum is crucial for its normal function but those factors which control the development of this precisely organized pathway are not fully elucidated. The neurotrophins are a family of peptides, which have many roles during development of the nervous system, including the cerebellum. Since the cerebellum and inferior olive express neurotrophins and their receptors, we propose that neurotrophins are involved in the regulation of climbing fiber development. Here we review the temporo-spatial expression of neurotrophins and their receptors at key ages during climbing fiber development and then examine evidence linking neurotrophins to climbing fiber development, including some of the intracellular pathways involved. During prenatal development the expression of neurotrophins in the hindbrain coupled with their function in neurogenesis and migration, is consistent with a role of NT3 in inferior olivary genesis. Subsequently, cerebellar expression of two neurotrophins, NT3 and NT4, is concurrent with olivary receptor expression and the time of olivary axonal outgrowth and this continues postnatally during early climbing fiber synaptogenesis on Purkinje cells. The expression-pattern of neurotrophins changes with age, with falling NGF, NT3 and NT4 but increasing granule cell BDNF. Importantly, olivary expression of neurotrophin receptors, and therefore climbing fiber responsiveness to neurotrophins, falls specifically during maturation of the climbing fiber-Purkinje cell synapse. The function of BDNF is less certain, but experimental studies indicate that it has a role in climbing fiber innervation of Purkinje cells, particularly synaptogenesis and synaptic plasticity. Its importance is highlighted by the overlap of BDNF signalling with several cellular pathways, which regulate climbing fiber maturation. From the data presented, we propose not only that neurotrophins are involved in climbing fiber development, but also that several act in a specific temporal order.