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The Neural Control of Feeding
Author Paul Kenyon

   
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Overview

This lecture focusses on the idea that some part(s) of the brain control feeding. As you read this material you may form the impression that things have not gone very well in this area over the years. To some extent this is true. A lot of the early research was influenced by theoretical models of motivation that were popular at the time. A considerable amount of effort was devoted to discovering areas of the brain that controlled motivation. You may consider that things were not helped by the early discovery of discrete nuclei in the brain which - when lesioned - had the dramatic effect of either increasing or decreasing body weight and food intake. These results were seized upon as being possible physiological substrates for the psychological states of hunger and satiety. In fact subsequent research has revealed that lesions can have more than one effect, and that the brain consists of circuits affecting behaviour(s). This lecture does not attempt to give an exhaustive coverage of the area. Instead we will look at two brain areas implicated in the control of eating, and see how ideas about their roles have changed over the last half century.

Do not panic, your computer screen is not on the blink! The picture of the Suomo at the top of the page is a negative to reflect the focus of this lecture on things that happen beneath the skin.


The Dual-Control Theory of Feeding

Dual-control theory was based on a homeostatic view of hunger and satiety.

  • A decline in glucose activated the lateral hypothalamus (LH)
  • Activity within the LH gave rise to hunger
  • Hunger motivated the search for and consumption of food
  • Food was broken down to release glucose
  • Glucose activated the ventromedial hypothalamus (VMH)
  • Activation of the VMH caused a feeling of satiety
  • Satiety inhibited further feeding

The diagrams below show the location of the LH and VMH, and a diagrammatic representation of the relationship between physiology, motivation and brain nuclei.
Point to ponder: Study the diagram and see if you can see why the system - as set out in the diagram - might not maintain homeostasis.

Cross section of rat brain showing approximate location of LH and VMH

 

Evidence for Control Centres for Feeding.

The idea that the VMH acts as the brain's satiety centre whereas the LH is a hunger centre, was put forward by Eliott Stellar in 1954 (Psychological Review, 61, 5-22) and it dominated thinking about feeding behaviour for the next 20 years. It was supported by the following set of experimental findings on the effects of removing, or electrically activating each area

Area of hypothalamus Effect of lesioning Effect of stimulating
Ventromedial hypothalamus Increases eating Decreases eating
Lateral hypothalamus Decreases eating Increases eating

Lesions to the VMH and LH produced the most straightforward and startling effects. This animation should help you visualize the location of the centres within the brain. As you examine the path taken by the lesioning electrodes consider how much 'collateral damage' is involved. How you would design an experiment to rule out the possibility that the effects of the lesion were in fact due to 'collateral damage' rather than destruction of a particular hypothalamic nuclei?

Lesion of ventromedial hypothalamus (VMH) Lesion of lateral hypothalamus (LH)  


Effect of VMH Lesions on Eating

Compared to controls VMH lesioned rats show:

  1. excessive eating ( hyperphagia )
  2. weight gain

The effects of the lesion are not permanent. After an initial increase, body weight stabilizes.

To reflect this VMH lesioned rats are said to be in either a

  • dynamic or
  • static phase of weight gain

It is clear that the simple dual point theory cannot explain the results.

VMH rats are able to reach satiety despite the absence of their satiety centre.

 

Effect of VMH Lesions on Hunger

The dual centre theory predicts that lesioning the VMH will increase:

  1. consummatory behaviour (eating)
  2. hunger (motivation to eat)

Although the consummatory behaviour of rats with VMH lesions is consistent with the theory, the motivational effects of VMH lesions are less clear-cut. This diagram shows the willingness of rats to press a lever to obtain food as the demands of the schedule are increased from a starting point where each bar press is rewarded with food (FR1), right up to a schedule where the rat must press 256 times to get one pellet (FR256). [Source: Teitelbaum, 1957]

The logic behind this experiment is "If you are hungry, you will be willing to work hard to get food". The results show that intact rats press the bar more as the schedule becomes more demanding. VMH lesioned rats in the dynamic phase press more frequently than normal rats when the less demanding schedules (FR1 through FR16) are in operation, but are less willing to work under the more demanding conditions imposed by FR64 and FR256 schedules of reinforcement. This laziness is even greater in VMH lesioned rats who are in the static phase.

There is a body of evidence which indicates that VMH lesioned rats are finicky eaters. Compared to normal rats they eat less when:

  • quinine is added to make food taste bitter
  • food is stale

These are not the behaviours you might expect if the VMH is a hunger centre whose destruction increases an animal's motivation for food!

These animal experiments appear to correspond to the observation that - compared to normal weight people - obese humans eat fewer peanuts if they have to shell them.

Effect of work on the eating behaviour of normal and obese humans

  Number who
Eat Don't eat
Normal subjects Nuts have Shells 10 10
Nuts have no shells 11 9
Obese subjects Nuts have Shells 1 19
Nuts have no shells 19 1

 

Effect of LH Lesions on Eating

The diagram below shows that initially, animals with lateral hypothalamic lesions exhibit severe loss of body weight due to their refusal to eat ( aphagia ) and drink ( adipsia ). But these effects are not permanent. Body weight does not decline inexorably. The table shows that rats go through 4 stages of recovery after LH lesions. Dual point theory cannot explain these results.

LH lesioned rats recover the ability to eat despite the absence of their feeding centre.

 

Set Point Theory

We have seen that the Dual-Centre hypothesis - which visualized the LH as a feeding centre and the VMH as a satiety centre - could not explain the long term effects of lesions to these areas. One solution to this problem was to suggest that these nuclei controlled body weight through a set-point mechanism .

According to this view:

  • LH lesions reduced the set point for body weight. Lesioned rats maintain body weight at a new lower level
  • VMH lesions increased the set point for body weight . Lesioned rats maintain body weight at a new higher level



One way of testing this idea was to starve rats so that they lost body weight before receiving LH lesions. According to set-point theory LH lesions should have little or no effect on these rats because starvation would reduce body weight so that it was already at the new set-point before the operation. The diagram below shows that preoperative starvation did have the effect predicted by set-point theory. LH lesions did not cause a further reduction in body weight.

Other experiments on rats made obese by VMH lesions revealed that if they were force fed (so that their body weight was increased ) and then allowed to feed ad lib, they would loose weight until they returned to the weight they reached during the static phase.

This result supports the hypothesis that VMH lesions increased the set point for body weight



LH Lesions Cause Sensory Neglect

Marshall et al (1971) found that LH lesions produce a range of sensory and motor impairments termed sensory neglect .

Rats with LH lesions

This experiment involved a very elegant design to ensure that the observed effects were not due to some non-specific effect such as illness.

It is clear from the diagram that there are two lateral hypothalamic nuclei; one on each side of the brain.

Marshall lesioned the LH on one side of the brain (called a unilateral lesion) and left the LH on the other side of the brain intact. He found that sensory neglect was only shown when one side of the body was stimulated. If the same stimulus was presented to the other side of the body, the rat reacted normally. This shows that the rat was able to respond. It was not suffereing from general malaise.

(Source: Marshall et al, Science, 174, 523-525, 1971)


Nigrostriatal Lesions Produce Aphagia and Adipsia  

One implication of Marshall et al's findings is that LH lesions may reduce arousal . You may recall Positive Incentive Theory (described in an earlier lecture), which suggests that eating is triggered by external stimuli such as the time of day, or the sight and smell of food. If LH lesions interfere with an animal's ability to process stimuli this could account for reduced food intake. Obviously this explanation casts doubt on the idea that the LH is specifically involved in food intake; all behaviour would be affected if sensation was disrupted. It is now thought that the sensory neglect produced by LH lesions is caused by the lesion destroying axons in the nigrostriatal tract that pass through the lateral hypothalamus and terminate in the caudate-putamen.

The animation shows the impact of LH lesions on the nigrostriatal pathway. 

The animation shows how lesions - aimed at the LH - would damage axons of the nigrostriatal system at the point where they pass through the lateral hypothalamus. You may remember that we studied this system in a previous lecture. The nigrostriatal tract utilizes dopamine ( DA ) as its transmitter. Parkinson's disease is associated with a massive reduction in dopamine in the caudate nucleus.


One implication of Marshall et al's findings is that LH lesions may reduce arousal . You may recall Positive Incentive Theory (described in an earlier lecture), which suggests that eating is triggered by external stimuli such as the time of day, or the sight and smell of food. If LH lesions interfere with an animal's ability to process stimuli this could account for reduced food intake. Obviously this explanation casts doubt on the idea that the LH is specifically involved in food intake; all behaviour would be affected if sensation was disrupted. It is now thought that the sensory neglect produced by LH lesions is caused by the lesion destroying axons in the nigrostriatal tract that pass through the lateral hypothalamus and terminate in the caudate-putamen.

The animation shows how lesions - aimed at the LH - would damage axons of the nigrostriatal system at the point where they pass through the lateral hypothalamus. You may remember that we studied this system in a previous lecture. The nigrostriatal tract utilizes dopamine ( DA ) as its transmitter. Parkinson's disease is associated with a massive reduction in dopamine in the caudate nucleus.

Ungerstedt (Acta Physiol. Scand. 82, (Suppl. 367, 69-93, 1971) carried out a series of elegant experiments that show that the sensory neglect following LH lesions is probably the result of collateral damage to the nigrostriatal DA system.

Ungerstedt injected the neurotoxin (chemical nerve poison) 6-hydroxydopamine [6-OHDA] into the cell bodies of the nigrostriatal tract which are found in the substantia nigra . The animated diagram illustrates the important point that the substantia nigra lies caudal to the LH, so any effect of the chemical lesion cannot be attributed to LH damage. A separate group of rats were given conventional (electrical ) lesions in the LH.

Results : Both types of lesion (LH and substantia nigra) produced the "lateral hypothalamic syndrome" i.e. initial apahagia and adipsia followed by a gradual but complete recovery of food and water intake.


Chemical Lesions of the LH

We have seen that electrical lesions of the LH have failed to provide clear cut answers to the role of the LH in feeding. Chemical lesions on the other hand did provide a resolution of the issue of sensory neglect. Recently research has employed chemical lesions to destroy cells in the LH whilst sparing axons of the nearby nigrostriatal tract. Kainic acid and ibotenic acid lesions of cells in the LH produce a long-lasting decrease in food intake and body weight, but they do not produce sensory neglect (Winn et al, Neuroscience, 12, 225-240, 1984).

However it is widely acknowledge that it is a gross oversimplification to call the LH a 'feeding centre' because:


Role of the LH & VMH - What do contemporary textbooks say?

The search for a role for the LH in hunger continues. It may play a role in controlling insulin release. According to this idea, excitation in the LH stimulates the release of insulin from the pancreas. Lesioning the LH is followed by a reduction in insulin release. Insulin allows glucose to be broken down to provide a source of energy. The body compensates for the lack of glucose-derived energy by breaking down stored body-fat to provide fuel. As a result of fat-breakdown, body weight declines. But the blood is full of excess energy-rich free fatty acids and the animal fails to eat because its body is telling the brain areas controlling feeding that there is no need to take in more energy (Schneider & Tarshis, Elements of Physiological Psychology, McGraw Hill, 1995, p 386-7, 1995).

Pinel ( Biopsychology , Allyn & Bacon,p260-261, 2000) has provided a complementary explanation for the role of the VMH in feeding. He suggests that animals with VMH lesions " overeat because they become obese ". He argues that VMH lesions increase blood insulin levels. This triggers lipogenesis (the conversion of glucose into fat). Because any food the animal eats is rapidly converted into fat, they suffer an energy deficiency. Consequently they eat in a vain attempt to overcome the lack of glucose circulating in their bloodstream.

Copyright Dr. C.A.P. Kenyon 1994-2006