Neurocircuitry Of A Novel Gastrointestinal-circulatory Reflex
Funder
National Health and Medical Research Council
Funding Amount
$515,625.00
Summary
The gastrointestinal tract receives about one third of the blood pumped around the body by the heart. This implies that the gut circulation plays a major role in blood pressure control. Gut blood flow changes according to the demands imposed by altered behavioural activity. Engagement in physical exercise results in increased blood flow to the working muscles of the limbs and diversion away from the gut. Alternatively, food consumption promotes an increase in blood flow to the gut to aid digesti ....The gastrointestinal tract receives about one third of the blood pumped around the body by the heart. This implies that the gut circulation plays a major role in blood pressure control. Gut blood flow changes according to the demands imposed by altered behavioural activity. Engagement in physical exercise results in increased blood flow to the working muscles of the limbs and diversion away from the gut. Alternatively, food consumption promotes an increase in blood flow to the gut to aid digestion. While this is a normal bodily process, there are also adverse implications of the re-distribution of blood flow: in the elderly compensation for these changes is often impaired and can result in low blood pressure and fainting. In addition, the incidence of angina-related heart pain is greater after food consumption and this may be associated with re-distribution of blood flow to the gut. Cholecystokinin (CCK), a hormone which is released from special cells that line the intestine, plays a role in the control of blood flow to the gut. We have developed the hypothesis that CCK acts on nerves which send a signal to the brain which, in turn, acting through other nerves, produces an increase in the flow of blood to the gut. This project is designed to study the nerve pathways in the brain which control this novel mechanism. We will record the activity of specific brain cells and nerves which are involved in the control of the blood supply to the gut. We will also examine which chemicals the brain cells and nerves use for communication with each other and so build up a model of the brain areas which are involved in gut blood flow control. This project will shed new light on the mechanisms of gut blood flow control and identify the associated brain pathways. The information will be of importance in the treatment of diseases of the circulation and food consumption-related cardiovascular changes in the elderly and obese as well as in sufferers of angina.Read moreRead less
Standardisation Of Prepulse Inhibition Of The Startle Reflex For Pharmacological And Interspecies Comparisons
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
People and other animals startle when they here a sudden loud sound. How much one startles depends in part on how loud the sound is. The relationship between the loudness of the sound and the size of the startle resembles a ski slope. Each individual has a ski slope that differs from others; the beginning of the ski slope (threshold) occurs at a different loudness, the slope is a different steepness, and the height of the ski slope where the plateau occurs is different. There are genetic differe ....People and other animals startle when they here a sudden loud sound. How much one startles depends in part on how loud the sound is. The relationship between the loudness of the sound and the size of the startle resembles a ski slope. Each individual has a ski slope that differs from others; the beginning of the ski slope (threshold) occurs at a different loudness, the slope is a different steepness, and the height of the ski slope where the plateau occurs is different. There are genetic differences in ski slopes as well. The size of the startle reflex can also be reduced by preceding the startling sound with a quiet stimulus a few tens of milliseconds before the startling stimulus. This is known as prepulse inhibition of the startle reflex or PPI for short. There is much interest in PPI, because it differs in people with certain mental illnesses, such as schizophrenia or post-traumatic stress disorder, and certain neurological illnesses, such as Huntington's chorea. It is also affected by drugs, including stimulants, stress hormones, and cannabis. In almost all the hundreds of experiments on PPI the effect of the prepulse on the response to a startling stimulus is measured at only one startling stimulus loudness. This loudness can be at very different parts of the ski slope for different people or other animals: it may be in the steep slope for one person, well into the plateau for another, or even at the bottom of the ski slope below the threshold in others. The effect of PPI is very different depending on what part of the ski slope the loudness represents. A lack of consistent effects in the literature on PPI by drugs and genetics is explained by this difference. Experiments are planned that will investigate the effect of drugs that are similar to those that treat schizophrenia, stress hormones and cannabis on the effect of prepulses on the whole ski slope. This procedure will provide the consistency in results so far absent.Read moreRead less