NBIO 401
Fall 2012
Limbic System
Class 26 – Monday, November 26, 2012
Robinson
Objectives:
-Be able to describe the major inputs and outputs, function, and the consequences of lesions
or electrical stimulation for each of the six components of the limbic system that we described
(i.e., hypothalamus, amygdala, hippocampus, cingulate cortex, nucleus accumbens, and
septal nuclei)
-Be able to describe the basic interconnections of the limbic system, and what fibers are in
the three main fiber tracks described in the lecture: 1) the stria terminalis, 2) the fornix, and 3)
the medial forebrain bundle.
-Be able to describe the location of these tracks in the brain.
-Be able to explain the three ways in which it hypothalamic activity can act to maintain
homeostasis.
-Be able to explain the different mechanisms through which the hypothalamus controls the
anterior and posterior pituitary gland.
-Know the two functions of cortical input to the limbic system that we discussed:
1) Recognizing potential threats to homeostasis or well being that the brain can, at least partially,
counteract with autonomic adjustments (e.g., seeing a car careening toward you eliciting
sympathetic activity to speed your escape). Such threats are abstract in the sense that they do
not directly challenge homeostasis as would dehydration or hypothermia. The cortex, with its
large processing power, is necessary to recognize these threats from visual and auditory stimuli
as opposed to internal conditions directly sensed by the hypothalamus.
2) Restraining or modifying behavior motivated by the limbic system. Phineas Gage (see p. 12)
makes this point well. Without the use of his frontal cortex he, among other deficits, acted more
directly on his urges and drives than was socially acceptable.
______________________________________________________________________________________________________________
In the previous lectures
we have described selected
sensory and motor systems that
are very capable and flexible,
i.e., you can do a very wide
variety of things with them. Of
the many behaviors available to
you, which do you actually
choose to exhibit in any
situation? This lecture and the
one on ascending modulatory
systems deal with the parts of
the brain that provide motivation
for appropriate behavior.
The limbic lobe is a term first used by Broca in 1878 for the ring of cortex visible on the
medial surface of each hemisphere. As Figure 1 shows, the limbic lobe is composed of the
cingulate cortex, medial temporal cortex, and the orbital cortex (the cortex near the bony
sockets, or orbits, holding the eyes) directly above the rostral end of the temporal cortex. The
olfactory bulbs stick out from this ring like the handle of a tennis racket. This ring cortex
marks the medial edge of cortex on the hemisphere, thus its name. Limbic is from the Latin
"limbus" for border.
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Anatomical connections and the behavioral consequences of lesions indicate that other
structures work with the cortex of the limbic lobe. Today, the cingulate cortex of the original
"limbic lobe" and the subcortical structures associated with it are called the limbic system.
The limbic system mediates the two components of emotional responses, 1) the
perceived feeling of the emotion and 2) the changes in your body that occur to prepare for
the appropriate behavior (e.g., moving blood to the muscles, dilating the pupils).
The limbic system includes the following six brain structures: 1) hypothalamus,
2) amygdala, 3) hippocampus, 4) cingulate cortex, 5) nucleus accumbens, and 6) septal
nuclei. Below we will describe the location, anatomical connections, and the function each of
these structures. The hypothalamus, amygdala, cingulate cortex, and hippocampus are all
composed of numerous subdivisions which have distinct connections and functions. For our
purposes here we will describe the inputs and functions of the whole structure, not its
individual parts.
1) HYPOTHALAMUS
Location - The hypothalamus is a relatively small region (weighing only about 4
grams in humans) lateral to and ventral to the walls of the third ventricle near the midline. As
shown in Figure 2, the hypothalamus is ventral to the anterior medial part of the thalamus and
dorsal and just caudal to the optic chiasm.
Connections, Input - The
hypothalamus receives input from
other limbic structures, the amygdala,
the hippocampus, and the septal
nuclei as well as from the brainstem
and spinal cord.
- The input from the amygdala
arrives via two pathways,
a) the stria terminalis (green
line labeled ST in Figure 2), a fiber
bundle that travels posterior and
medial from the amygdala inside the
temporal lobe, away from the
temporal pole by the hippocampus,
and arches over the thalamus and
under the corpus callosum. It then
turns ventrally in front of the
thalamus and travels down to the
hypothalamus.
b) the other pathway travels directly dorsal and medial from the amygdala directly to the
hypothalamus.
-The input from the hippocampus arrives via the fornix (dark blue line labeled “from
hippocampus in Figure 2), a fiber bundle that travels posterior and medial from the
hippocampus, buried inside the medial part of the temporal lobe and arches over the
thalamus above the stria terminalis and under the corpus callosum. The fornix turns ventrally
in front of the thalamus and travels down to the mammilary bodies.
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-Input from the septal nuclei arrives via the medial forebrain bundle, a fiber bundle running
in the medial and ventral part of the brain from the septal nuclei, through the lateral
hypothalamus and into the rostral medulla. (As apparent in Figure 2, the septal nuclei are
located just off the midline on the roof of the lateral ventricle under the corpus callosum.
They are dorsal and rostral to the
hypothalamus.)
Figure 3 shows the general location of
the medial forebrain bundle in a parasagittal
section of a rat brain. The medial forebrain
bundle carries fibers traveling in both
directions and is structured like a frayed
rope with fibers entering and leaving it at all
levels. Some fibers in the medial forebrain
bundle travel only short distances, some
travel a long way. Fibers leave the septal
nuclei and travel ventral and caudal to enter
the hypothalamus.
There is also a small input from the
brainstem and spinal cord, reaching the
hypothalamus via the medial forebrain
bundle.
Output We can divide the output of
the hypothalamus into four categories:
a) output that goes back
to the amygdala (via the stria
terminalis), hippocampus (via
the fornix), and septal nuclei
(via the medial forebrain
bundle) traveling in the
reverse direction along same
pathways via which input
from these structures
reached the hypothalamus
b) output to autonomic
centers in the brainstem and
spinal cord traveling to the
brainstem via the medial
forebrain bundle (light blue in
Figure 4)
c) output, both neural
and humoral (relating to
bodily fluids), to the pituitary
gland (two red arrows in the
bottom center of Figure 4)
d) output via the medial forebrain bundle to the anterior part of the thalamus which, in
turn, projects to the prefrontal, orbital, and cingulate regions of the cerebral cortex (dark blue
arrow in the center of Figure 4).
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Function - The hypothalamus has two basic functions, maintaining homeostasis and
preparing the body for emotional responses. It may also play a role in relaying signals
about the state of the body relevant to emotional response to other limbic structures.
HOMEOSTASIS The hypothalamus maintains critical features of the environment inside
the body, such as temperature, salinity, and glucose concentration, within narrow healthy
limits. It receives information about the state of the body via input from the brainstem and
spinal cord and from neurons inside the hypothalamus. These neurons sense temperature,
blood salinity, blood glucose concentration, and temperature among other values. When one
of these values deviates from a narrow zone the hypothalamus elicits responses to move it
back into the acceptable range. It does so via three mechanisms:
a) The hypothalamus mediates changes in the body with the autonomic nervous
system. Seen very crudely, anterior hypothalamic regions elicit parasympathetic activity and
posterior hypothalamic regions elicit sympathetic activity.
For example, if blood salinity raises
above its normal value, then the neurons in
the hypothalamus that are sensitive to blood
salinity will increase their firing rate. Figure
5 shows an example of a hypothalamic
neuron that increases its firing rate when
blood salinity rises above its ideal level and
decreases when it falls below that level.
The response of hypothalamic
neurons to increased salinity reduces water
loss from the body by causing a decrease in
parasympathetic drive to reduce sweating
and saliva production.
b) The hypothalamus modulates the output of the pituitary gland. The hypothalamus
controls the posterior pituitary with neural signals. It controls the anterior pituitary with
humoral signals.
1. posterior pituitary – As illustrated in Figure 6A, neurons in the hypothalamus send
their axons down to the posterior lobe of the pituitary (also called the neurohypophysis). The
terminals of these axons release these
peptides into a capillary bed in the posterior
pituitary via which these substances enter
the blood. For example, when blood salinity
raises above its acceptable value the
hypothalamus, in addition to its autonomic
actions, also releases antidiuretic
hormone(ADH) into the blood to reduce the
amount of water that the kidneys pull out of
the blood to reduce water loss.
2. anterior pituitary – As shown in
Figure 6B, neurons in the hypothalamus
send their axons to terminate in a capillary
bed inside the hypothalamus. The terminals
of these axons send releasing factors into the capillary bed and the blood containing these
factors then travels down the stalk of the pituitary (called the infundibulum) into the anterior
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pituitary (also called the adenohypophysis). Cells in the anterior pituitary sensitive to a
particular factor will release a hormone into the blood if it receives that factor from the
hypothalamus. The hormones released from the anterior pituitary gland control the endocrine
system and are not directly related to maintaining internal homeostasis.
c) The hypothalamus elicits motivation for behavior to restore the errant variable to its
accepted value. For example, when blood salinity raises above its acceptable value the
hypothalamus elicits drinking by making us thirsty. Creating the appropriate motivation is
usually the most effective solution to the problem of an internal value moving out of its normal
range. Drinking water is much more effective in reducing salinity than reducing urine
production. The hypothalamus elicits motivational states via its ascending projections to the
thalamus.
Experimental manipulation of particular parts of the hypothalamus can badly impair the
regulation of these motivational states. For example, bilateral lesions of the lateral
hypothalamus result in overeating and extreme weight gain. Electrical stimulation of different
hypothalamic regions can elicit eating or drinking or stop eating or drinking in progress. It can
also elicit increases or decreases in body temperature.
PREPARING THE BODY FOR EMOTIONAL RESPONSES In addition to changing the body to
maintain homeostasis the hypothalamus elicits autonomic changes to prepare the body for
emotional responses. For example, if you see a car careening toward you the stimulus is
abstract in the sense that, by itself, it causes no change in your temperature or other internal
conditions. Yet your cerebral cortex evaluates the significance of the stimulus and, via your
hypothalamus, causes strong sympathetic activation that releases adrenaline, increases
blood flow to your skeletal muscles, and the dilates your pupils. Descending influences
originating in the cerebral cortex and traveling through limbic structures reach the
hypothalamus to cause appropriate changes based on external stimuli.
Relaying signals about the state of the body to other limbic structures Signals
about emotional responses also travel from the hypothalamus to other limbic structures.
The James - Lange theory of emotions proposes that we feel an emotion only after our
body has reacted to some situation. We are, in effect, observing and responding to the
condition of our body.
Many observations have led to skepticism about this theory in its entirety. For example
feelings can arise faster than, and outlast, the physiological changes that accompany them.
Nonetheless, it is also clear that feedback about the state of our body plays a role in
emotional feelings. For example, patients with severed spinal cords experience a reduction
in the intensity of their emotions.
The hypothalamus is in a position anatomically to relay emotion-related information
from the brainstem and spinal cord to other parts of the limbic system.
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2) AMYGDALA
Location – As
illustrated in Figure 7, the
amygdala (Latin for almond
because of its shape) is a
round nucleus roughly the
size of a large olive
embedded in the
dorsomedial part of the
temporal lobe about 3/4 of
the way toward the temporal
pole.
Connections, Input
As the left side of Figure 8
illustrates, the amygdala
receives input from orbital,
cingulate, entorhinal, and
temporal cortex. It also
receives input from
subcortical structures, the
hypothalamus, hippocampus,
brainstem, septal nuclei, and thalamus.
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Connections - Output – The right half of Figure 8 shows that the amygdala projects to
orbital, cingulate, temporal, and entorhinal cortex. It also projects to subcortical structures,
the hypothalamus (both directly and via the stria terminalis), the hippocampus, the septal
nuclei and the thalamus.
Function In general the amygdala represents an interconnection between the cortex
and the hypothalamus.
The amygdala’s connections to the cortex probably mediate the feeling of emotions.
Electrical stimulation of the amygdala in humans can elicit a variety of emotions but most
commonly fear. In animals such stimulation most commonly elicits rage, defensive postures
and behavior, and fleeing.
Bilateral lesions of the amygdala result in decrease in aggression and generally docile
animals. They are unable to retrieve or learn associations between stimuli (e.g., an
aggressive enemy) and emotional response (fear, flee now!).
The amygdala’s connections to the hypothalamus represent higher level control of the
hypothalamus. Stimulation of the amygdala can elicit the same drive-related behaviors
elicited by stimulating the hypothalamus directly, e.g., eating or drinking, but the effect is
more natural in that it has slower onset and offset.
Bilateral amygdala lesions can cause the same deficits as those of the hypothalamus
but less severe.
3) HIPPOCAMPUS
Location As you can see in Figure 9, the hippocampus is an approximately tubeshaped structure roughly the size of your little finger. It is inside the temporal lobe and curves
posterior, dorsal, and medial moving from the amygdala away from the temporal pole.
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Connections - Input – Figure 10 shows the inputs to the hippocampus. Chief among these
is the entorhinal cortex. The entorhinal cortex is that on the ventromedial surface of the
temporal lobe. It receives input from other cortical areas, cingulate, orbital, and prefrontal.
The hippocampus also receives direct input from the amygdala and hypothalamus (via the
fornix).
Connections - Output - The hippocampus projects to the anterior thalamus which, in
turn projects to prefrontal, orbital, and cingulate cortex. It also projects to other limbic
structures, the amygdala and the hypothalamus (via the fornix). (FIGURES 12 & 15)
Function - The hippocampus mediates the formation of new declarative memories. A
declarative memory is one of a fact that we can express or declare clearly. (This is as
opposed to motor learning like that done by the cerebellum, or emotional learning like that
done by the amygdala).
Bilateral lesions of the hippocampus damage a patient’s ability to form new memories
after the lesion. Memories formed before the lesion are fine. For example, a patient with
bilateral hippocampus lesions will always feel as if she is meeting her neurologist for the first
time even after hundreds of meetings.
This deficit is specific. Patients with bilateral hippocampus lesions will improve their
ability to do a jigsaw puzzle as they do it over and over though they never remember seeing it
before.
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4) CINGULATE CORTEX
Location - The cingulate cortex is on the medial surface of the cerebral hemisphere
above the corpus callosum (e.g., Figures 1, 8, & 10).
Connections - Input Cingulate cortex receives input from VP thalamus (remember, the
one that relays somatosensory information to the cerebral cortex) carrying pain information,
and from the anterior thalamus. It also receives input from the amygdala.
Connections - Output Cingulate cortex projects to entorhinal cortex and amygdala.
Function - Cingulate cortex helps mediate the emotional response to pain and to more
abstract stimuli.
5) NUCLEUS ACCUMBENS
Location - The nucleus accumbens (or nucleus accumbens septi) is often referred to
as the emotional component of the basal ganglia, and it is found where the head of the
caudate meets the anterior portion of the putamen (Figure 11A) just lateral to the septum
pellucidum. The nucleus accumbens (septi) comes from the Latin phrase meaning “the
nucleus leaning against the septum”
Connections – Inputs – The nucleus accumbens receives input from the amygdala.
Connections – Outputs – Axons of neurons in the nucleus accumbens terminate
within the basal ganglia, indicating that the nucleus accumbens represents a link between the
limbic system and the basal ganglia.
Function - The nucleus accumbens plays an important role in modulating motivation
and reinforcement. Particularly, this area appears to be the site of action for many addictive
drugs such as cocaine and amphetamines. Cocaine and amphetamines increase dopamine
levels in the nucleus accumbens and administration of dopamine antagonists to this nucleus
can nullify the pleasurable aspects of drug use.
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6) SEPTAL NUCLEI
Location - As you can see in Figure 11B, the septal nuclei are located near the midline
on the floor of the lateral ventricle just above the anterior commissure. They are on the
medial wall of the cerebral hemisphere just beneath the base of the septum pellucidum.
They form the floor of the medial portion of the lateral ventricles and are found just anterior to
the hypothalamus. They are dorsal and rostral to the hypothalamus.
Connections – Inputs – The septal nuclei receive a large input from the hippocampus
via the fornix, and a smaller projection from the amygdala and the medial part of the midbrain
(mesencephalic) reticular formation.
Connections – Outputs – The axons of neurons in the septal nuclei travel via the
fornix back to the hippocampus, via the stria terminalis to the hypothalamus, and via the
medial forebrain bundle to the amygdala.
Function - The septal nuclei seem related to the experience of pleasure. Excitation of this
area in humans results in extreme feelings of pleasure and joy. Animals will lever press
repeatedly to obtain electrical stimulation of this area, to the point of forgoing food and sleep.
Moreover, electrical recording from this area registers increased activity during sexual
orgasm. However, the septal nuclei do not appear to be solely involved in feelings of
pleasure. They also represent important cholinergic inputs (further discussed in Lecture 30)
to the hippocampus and may play a role in modulating memory function. Interestingly, in
certain animals, damage to this area results in a permanent condition known as ‘sham rage’animals become incredibly angry/violent.
In addition to knowing about the six components of the limbic system that we have
reviewed above you may be interested in two other topics related to the limbic system, Papez
Circuit and the emotional function of the prefrontal cortex as demonstrated by damage to it.
We discuss each of these topics on the following two pages.
Finally, on page 13 there is a schematic of the connections between different limbic
structures. There is a lot of information in this schematic and you are responsible for only
those facts listed above. The most important facts are the connections of each of the three
major fiber bundles and the connections of the hypothalamus to the pituitary gland.
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Figure 12
PAPEZ CIRCUIT
In the 1930s an American psychologist, James Papez, proposed that an interconnected
group of structures in the brain controlled the experience and expression of emotions. These
structures form a circuit that is called Papez Circuit (illustrated in Figure 12). We can begin
tracing this circuit at the cingulate cortex. It projects to the entorhinal cortex which projects, in
turn, to the hippocampus. The hippocampus projects, via the fornix, to the mammilary bodies
of the hypothalamus and other parts of the hypothalamus (not shown in Figure 16). The
hypothalamus projects to the anterior nucleus of the thalamus which projects to the cingulate
cortex, completing the circuit.
Papez believed that areas of the neocortex outside the circuit helped modulate emotion
because damage to the cortex can disturb emotions (e.g., Phineas Gage). Papez also
proposed that activity in other neocortical areas caused by signals from the cingulate cortex
added nuance or "emotional coloring" to the experience of emotion.
Evidence indicates that some of the structures in Papez circuit mediate emotion. For
example, tumors in the cingulate cortex are often associated with excess fear and irritability.
Damage to the anterior thalamus can cause spontaneous crying or laughing. Papez thought
that the hippocampus was involved in emotion because rabies infections cause both clear
abnormalities in hippocampal neurons and hyper-emotional responses like exaggerated fear
and aggressiveness. We now know that the hippocampus primarily mediates declarative
memory. The amygdala, not part of Papez circuit, is probably more linked to emotional
responses than is the hippocampus.
From a modern perspective we can see Papez circuit as an early, and reasonably
accurate, attempt to identify the brain regions involved in emotion. We have much more data
than Papez did and, because of this, have a more specific idea about what each limbic
structure does.
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Frontal Cortex and Emotion
A dramatic, if crude,
demonstration that prefrontal
influences emotion occurred
when, in 1848, an 25 year old
construction foreman, Phineas
Gage, working on a railroad in
New Hampshire was the victim of
an industrial accident. He was
tamping explosive powder into a
hole bored into a large rock in
preparation for blowing part of the
rock away to clear the path for a
railroad. He looked away and his
tamping bar struck the rock and
made a spark that ignited the
explosive. The explosion drove
Gage’s tamping rod, which was
over a meter long and about 2
inches in diameter, upward into
his left cheek and out the top of
his skull, destroying a large part
Figure 13
of his frontal cortex bilaterally.
Figure 13 shows the position of the tamping rod in Gage’s skull.
Gage survived this horrible injury and the major infection that followed it but his
personality was permanently changed. Once calm, productive, and organized he became
capricious, unable to plan toward goals, profane, easily distracted, impatient of advice or
restraint, and generally unrestrained in trying to satisfy his drives, eating and drinking to
excess and seeking sex constantly and with little finesse.
Many of these same characteristics are exhibited by people receiving frontal
lobotomies. Surgery consisted of severing many of
the fiber connections between the frontal lobes and the
rest of the brain using a stiff, narrow probe inserted
into the brain trough a hole in the bone above the eye
as shown in Figure 13. These surgeries were
performed on people with a variety of complaints,
including depression and anxiety.
While their IQ did not suffer greatly, patients
receiving frontal lobotomies commonly exhibit blunting
of emotions and loss of the emotional component of
thoughts. They, like Phineas Gage, often developed
"inappropriate behavior", or, as it was characterized at
the time, an apparent “lowering of moral standards”.
Also like Gage, these patients were easily distracted
and had considerable difficulty planning and working
toward goals.
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-Class 26, page 13-