Environmental challenges vary from stressful to life-threatening and animals must respond to them for survival. Typical defensive responses range from fear, which involves an increase in heart rate and blood pressure, to escape where muscles are prepared to help the animal run away from the threat. Humans produce similar responses to these challenging situations. The nervous system organizes the responses. When animals are faced with a threat nerves send messages to alert the brain, which in turn sends messages to the tissues and organs which need to respond. Nerve cells transfer information using chemicals called neurotransmitters and the researcher will look at how specific neurotransmitters interact at nerve junctions in the brain to produce the right defensive responses. To do this the researcher will use electrophysiological and neuropharmacological approaches. This study is important to help us understand nerve signal processing and could provide us with a mechanism that can be applied to many functions of the brain. This project will also provide training opportunities in physiology for undergraduate and graduate students, and presentations will be made at the elementary school level to encourage interest in science.
For survival, animals depend on the ability to produce defense responses to overcome environmental challenges. In response to an imposed threat or stressor, sympathetic nerve activity increases to raise blood pressure and heart rate and to divert blood flow to the muscles needed for escape. Coordination of the entire pattern of complex behavioral and autonomic events requires central processing at key sites in the nervous system. Nerve cells, or neurons, in a brain region called the dorsal periaqueductal grey (dPAG) contribute to the organization of the nervous and cardiovascular responses. Neurons communicate at junctions, or synapses, by releasing chemicals called neurotransmitters that act at receptors on subsequent neurons to produce the required effects in the nervous system. The traditional idea of simple excitatory or inhibitory neurotransmission is outdated and it is clear that transmission at synapses is complex. This study examined a mechanism of nerve signal processing which allows the brain to change sympathetic nerve activity, blood pressure and heart rate to respond to stressful or threatening situations. Results from this project show that under normal conditions, neurons in the dPAG are inhibited by the neurotransmitter gamma amino-butyric acid (GABA) and excited by the neurotransmitter glutamate. The level of activity in the neurons mediating defense responses depends on the balance of the amount of GABA and glutamate released. Situations in which the release of these neurotransmitters is changed, alters the balance and results in either an increase or decrease in the activity of the neurons and consequently an increase or decrease in sympathetic nerve activity. Endocannabinoids (ECBs) are inhibitory neuromodulators that can alter the release of GABA or glutamate. We have shown that ECBs decrease the release of GABA from dPAG neurons. Taking away the inhibitory influence of GABA leads to an increase in sympathetic nerve activity, and consequently an increase in blood pressure and heart rate. Our data suggests that threatening stimuli that trigger the defense pathway can lead to release of ECBs in the dPAG. Released ECBs in turn inhibit ongoing GABA release, leading to disinhibition of subsequent sympathetic neurons to increase blood pressure and heart rate. This integration of neurotransmission is important to enable an animal to produce physiological changes essential for survival and is a basic component of behavioral neuroscience Studies for this project have shown how altered neurotransmission at synapses can modify activity of the nervous system to produce an appropriate behavioral response. This mechanism of synaptic signal processing is likely to occur in a range of neural processes and has the potential to impact diverse disciplines including memory, emotions and behavior. Information from these studies could also be incorporated into mathematical or physiological approaches to signal processing, identifying areas of adaptability in the nervous system. This project also had broader impacts by providing unique opportunities to advance discovery in systems physiology and educating students from elementary to post-graduate levels, contributing to the teaching of neuroscience at all levels of education. Outreach to young people in the community was undertaken to encourage science as a career option and encouraging potential career professionals in cross-disciplinary fields.
