Are noradrenergic neurons of the peri-acqueductal gray (PAG) excitatory or inhibitory?

University of Bristol Undergraduate Dissertation Project

Neuronal firing from the PAG induces anti-nociception at the spinal cord. There are few direct connections from the PAG to the spinal cord, therefore other descending fibres must be involved in the transmission of nociceptive information. There is evidence that pontine noradrenergic neurons in the A5, locus coeruleus (LC) and A7 mediate the connection. However, the neurotransmitter phenotype of this connection has never been determined. 

My project attempted to determine the neurotransmitter phenotype of this pathway by using immunohistochemistry. The ventrolateral (VL) PAG of rats was injectedwith a fluorescent anterograde virus. Triple immunohistochemistry was performed with green fluorescent protein to reveal the PAG projections labelled with the virus, dopamine beta-hydroxylase (DBH) to reveal the location of noradrenergic neurons, and excitatory or inhibitory vesicular transporters to determine the neurotransmitter phenotype.

The experiment showed that the VL PAG innervates noradrenergic cell groups differently; the A5 receives more innervations than the A7 or the LC. This suggests that the A5 may play a larger role in anti-nociception than previously anticipated. This study also showed that pontine noradrenergic cell groups receive as much excitation as inhibition from the VL PAG, therefore other modulatory mechanisms must be involved in the induction of anti-nociception.

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