What Behavioral Changes Happened Over Time To The Rats Who Had Their Lateral Hypothalamus Destroyed?

Overview

This lecture focusses on the idea that some role(s) of the brain control feeding. As yous read this fabric yous may class the impression that things accept non gone very well in this area over the years. To some extent this is truthful. A lot of the early research was influenced past theoretical models of motivation that were popular at the fourth dimension. A considerable amount of effort was devoted to discovering areas of the brain that controlled motivation. You may consider that things were non helped by the early on discovery of discrete nuclei in the encephalon which - when lesioned - had the dramatic effect of either increasing or decreasing body weight and food intake. These results were seized upon equally being possible physiological substrates for the psychological states of hunger and satiety. In fact subsequent research has revealed that lesions tin can have more than 1 result, 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 volition look at two brain areas implicated in the control of eating, and see how ideas about their roles have changed over the terminal half century.

Do non panic, your calculator screen is not on the blink! The picture of the Suomo at the pinnacle of the folio 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)
Action inside the LH gave ascent to hunger
Hunger motivated the search for and consumption of nutrient
Nutrient was cleaved down to release glucose
Glucose activated the ventromedial hypothalamus (VMH)
Activation of the VMH caused a feeling of satiety
Satiety inhibited farther 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.

Signal to ponder: Study the diagram and see if you tin can encounter why the system - as gear up out in the diagram - might not maintain homeostasis.

Cross department of rat encephalon showing gauge location of LH and VMH

Evidence for Control Centres for Feeding.

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

Area of hypothalamus	Event 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 nearly straightforward and startling furnishings. This animation should help yous visualize the location of the centres inside the brain. Every bit you lot examine the path taken by the lesioning electrodes consider how much 'collateral harm' is involved. How you lot would pattern 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 bear witness:

excessive eating ( hyperphagia )
weight gain

The furnishings of the lesion are non permanent. After an initial increase, body weight stabilizes.

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

dynamic or
static stage 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 absenteeism of their satiety heart.

Effect of VMH Lesions on Hunger

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

consummatory behaviour (eating)
hunger (motivation to consume)

Although the consummatory behaviour of rats with VMH lesions is consistent with the theory, the motivational effects of VMH lesions are less lucent. 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 nutrient (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 y'all are hungry, you will be willing to piece of work hard to become food". The results show that intact rats printing the bar more as the schedule becomes more enervating. VMH lesioned rats in the dynamic phase press more frequently than normal rats when the less enervating schedules (FR1 through FR16) are in functioning, but are less willing to work under the more demanding atmospheric condition imposed by FR64 and FR256 schedules of reinforcement. This laziness is even greater in VMH lesioned rats who are in the static stage.

There is a body of show which indicates that VMH lesioned rats are choosy 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 look if the VMH is a hunger middle whose destruction increases an fauna's motivation for nutrient!

These animal experiments appear to correspond to the observation that - compared to normal weight people - obese humans swallow 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 consume
Normal subjects	Nuts have Shells	10	x
Normal subjects	Basics have no shells	xi	9
Obese subjects	Nuts take Shells	one	19
Obese subjects	Nuts have no shells	19	1

Effect of LH Lesions on Eating

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

LH lesioned rats recover the power to eat despite the absenteeism of their feeding eye.

Fix Point Theory

We accept seen that the Dual-Middle hypothesis - which visualized the LH as a feeding heart and the VMH as a satiety eye - could non explain the long term effects of lesions to these areas. I solution to this problem was to propose that these nuclei controlled torso weight through a set-point machinery .

Co-ordinate to this view:

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

One way of testing this thought was to starve rats so that they lost body weight before receiving LH lesions. According to set up-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 non cause a further reduction in body weight.

Other experiments on rats made obese by VMH lesions revealed that if they were force fed (and then that their body weight was increased ) and then allowed to feed advertizing 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 ready point for body weight

LH Lesions Crusade Sensory Fail

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

Rats with LH lesions

Practice non respond to touch, auditory, or visual stimuli
Remain immobile unless disturbed
Do not right themselves when placed on their side

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

It is articulate 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 constitute that sensory neglect was only shown when 1 side of the trunk was stimulated. If the aforementioned stimulus was presented to the other side of the trunk, 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'due south findings is that LH lesions may reduce arousal . You may remember 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 nutrient intake. Evidently this explanation casts doubt on the idea that the LH is specifically involved in nutrient intake; all behaviour would be affected if awareness was disrupted. It is at present thought that the sensory neglect produced by LH lesions is caused by the lesion destroying axons in the nigrostriatal tract that laissez passer through the lateral hypothalamus and terminate in the caudate-putamen.

The animation shows the touch 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 nosotros studied this system in a previous lecture. The nigrostriatal tract utilizes dopamine ( DA ) as its transmitter. Parkinson'southward affliction is associated with a massive reduction in dopamine in the caudate nucleus.

1 implication of Marshall et al'southward findings is that LH lesions may reduce arousal . You lot may recall Positive Incentive Theory (described in an earlier lecture), which suggests that eating is triggered by external stimuli such as the fourth dimension of twenty-four hours, or the sight and smell of food. If LH lesions interfere with an animate being's ability to process stimuli this could account for reduced nutrient intake. Plain 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 past LH lesions is acquired 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 harm axons of the nigrostriatal organisation at the point where they pass through the lateral hypothalamus. You lot may remember that we studied this organisation in a previous lecture. The nigrostriatal tract utilizes dopamine ( DA ) equally 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 serial of elegant experiments that show that the sensory neglect following LH lesions is probably the result of collateral damage to the nigrostriatal DA organisation.

Ungerstedt injected the neurotoxin (chemical nervus poisonous substance) 6-hydroxydopamine [6-OHDA] into the cell bodies of the nigrostriatal tract which are found in the substantia nigra . The animated diagram illustrates the of import point that the substantia nigra lies caudal to the LH, so any effect of the chemical lesion cannot be attributed to LH damage. A split up 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.east. 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 take failed to provide clear cut answers to the role of the LH in feeding. Chemical lesions on the other paw did provide a resolution of the event of sensory neglect. Recently enquiry 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 subtract in food intake and body weight, simply they do not produce sensory neglect (Winn et al, Neuroscience, 12, 225-240, 1984).

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

Animals recover from LH lesions
LH lesions disrupt aggression, sexual behaviour, and reinforcement
Nigrostriatal lesions produce aphagia and adipsia

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

The search for a office for the LH in hunger continues. It may play a part in decision-making insulin release. According to this idea, excitation in the LH stimulates the release of insulin from the pancreas. Lesioning the LH is followed past a reduction in insulin release. Insulin allows glucose to be cleaved downward 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. Every bit a result of fat-breakup, body weight declines. Simply the blood is full of excess energy-rich free fatty acids and the animate being fails to consume because its body is telling the brain areas controlling feeding that there is no demand to have in more free energy (Schneider & Tarshis, Elements of Physiological Psychology, McGraw Loma, 1995, p 386-7, 1995).

Pinel ( Biopsychology , Allyn & Salary,p260-261, 2000) has provided a complementary explanation for the role of the VMH in feeding. He suggests that animals with VMH lesions " overeat considering they go 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.