Anderson Lab ~ Current Projects

1. Evidence for pre-determination and selective projection of sympathetic neurons

It is possible that different types of sympathetic neurons are specified prior to them contacting their target. The correct pattern of adult innervation is then achieved by neurons of the appropriate phenotype navigating to the correct target tissues. We are currently looking for evidence that different classes of sympathetic neurons can be distinguished in the rat and mouse before the neurons extend an axon to their target. The differences may lie in the expression of different transcription factors or neurotrophic factor receptors which can be detected by immunohistochemistry or in transgenic animals with a reporter gene.

Mouse sympathetic chain stained for tyrosine hydroxylase (green) and GFRalpha1 (red). Image © CR Anderson

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2. Control of sympathetic neuron phenotype by target tissues

We have already shown that the distinctive chemical phenotype of sympathetic neurons innervating the pineal gland depends on signal derived from pineal gland cells. Target derived signals are also important in other parts of the autonomic nervous system. We have developed transplantation techniques so that target tissues can be exchanged in neonatal rat pups to expose sympathetic neurons to a variety of signals. These studies illustrate the range of phenotypic characters that can be controlled by the target tissue.

Section through stellate ganglion in a neonatal mouse showing neurons immunoreactive for c-ret (green) and tyrosine hydroxylase (red). The blue cells are neurons retrogradely-labelled from the paw pad. Image © K Munro

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3. Neurocardiology: organisation of the cardiac nervous system

The cardiac nervous system consists of intrinsic cardiac ganglia formed by parasympathetic postganglionic neurons, which are innervated by vagal preganglionic terminals, and the terminals of extrinsic sensory and sympathetic postganglionic neurons. We are using immunohistochemical and retrograde tracing methods to identify different subtypes of neuron within each of these systems. Once identified, we then attempt to relate each type of neuron to a specific function, by looking at the precise target tissue that the terminals are associated with.

Cardiac sympathetic neurons are concentrated on the inferior edge (right side) of the rat stellate ganglion. They are immunoreactive for both NPY (green) and calbindin (red) and so appear orange in the above image. Image © CR Anderson

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4. Neurocardiology: role of the intrinsic cardiac nervous system in control of the heart

In this project we are interested in whether the intrinsic components of the cardiac nervous system of the rat and guinea pig can bring about changes in cardiac performance in the absence of any input from extrinsic nerves. The approach is to record cardiac parameters in an anaesthetised animal and neurally isolate the heart by cutting the vagi and blocking sympathetic cardiac transmission with propranolol. We then look to see the result of challenging the cardiovascular system and whether blocking the effects of intrinsic cardiac neurons with atropine alters the response.

Neurons in the rat nucleus ambiguous labelled after a pericardial injection of cholera toxin subunit B (green) and counterstained for immunoreactivity to CGRP (red). Image © I Grkovic