Medical Neurosciences
Professor of Neurosciences and Pediatrics
Key Concepts:
1. The diencephalon is positioned between the brainstem and cerebral hemispheres, serving as a
major relay center between the two.
2. The diencephalon consists of four parts: epithalamus (which includes pineal gland), thalamus,
metathalamus (which includes medial and lateral geniculate bodies that function as part of the
thalamus), and hypothalamus (which includes the mammillary bodies).
3. The anterior thalamic nuclei have reciprocal connections with the mammillary bodies and the
cingulate gyrus; it is considered part of the limbic system.
4. The lateral thalamic nuclei serve as relays for sensory and motor information; they project to
modality-specific regions of cerebral cortex with which they have reciprocal connections.
5. The medial thalamic nuclei have reciprocal connections with the prefrontal cortex and are
involved in behavior and memory.
6. The pulvinar and lateral posterior nuclei together coordinate with the lateral geniculate body to
function as relays for visual information.
7. The medial geniculate body is a relay center for auditory information.
8. Based upon their connections, thalamic nuclei are of three types: modality-specific relay nuclei,
nuclei projecting to association cortex, and diffusely projecting nuclei.
9. The hypothalamus is divided into medial and lateral regions by the fornix.
10. The fornix is a projection from the hippocampus to the mammillary bodies in the diencephalon,
forming part of the limbic system.
11. The hypothalamus contains several groups of nuclei that have important roles in sexual, eating
and other reward behavior, emotional behavior, as well as regulation of temperature, thirst, and
12. Neurons of the hypothalamus produce a variety of hormone releasing factors which project
directly or through the hypophyseal portal system indirectly to the pituitary gland.
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The diencephalon is positioned at the rostral end of the brainstem; it is surrounded on all sides by the
cerebral hemispheres. It is part of the “deep gray matter” of the brain. To understand its location and
extent, it is necessary to know how it develops from the neural tube. Both the diencephalum and
telencephalon develop from the prosencephalon. With development the two hemispheres of the
telencephalic vesicle expand, and they overgrow and surround the diencephalon.
The thalamus is the largest component of the diencephalon. Each hemisphere of the thalamus measures
3 cm in length, 2 cm in height and 1 cm in width, and contains approximately 10 million neurons.
The two hemispheres of the
thalamus are separated by the third
ventricle. In 70% of people, there
is a bridge of cells connecting the
left and right hemispheres; this is
called the massa intermedia (or
intermediate adhesion). Because of
flexures which appear in the
developing central nervous system,
the ventral surface of the thalamus
(and the diencephalon) is inferior,
not anterior. The lateral boundary
of the thalamus on each side is the
posterior limb of the internal
capsule1. Anterior to the thalamus
are the head of the caudate nucleus
and the genu of the internal capsule.
Posterior and inferior to the
thalamus is the midbrain.
The internal capsule contains the descending corticospinal and corticobulbar fibers that become the cerebral
peduncles at the level of the midbrain and the pyramids at the level of the medulla.
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The diencephalon consists of four regions:
o epithalamus
o thalamus
o subthalamus
o hypothalamus
During development the subthalamus is
separated from the other structures by fibers of
the internal capsule. Initially it is directly
below the thalamus, but in the adult it is
displaced laterally, forming the globus
pallidus and (not shown) the subthalamic
nucleus. Both the globus pallidus and subthalamic nucleus are part of the motor system.
The epithalamus consists of two important structures:
 habenular nuclei. These are two small bodies medial to the thalamic hemispheres near the
posterior region. They are part of an extensive network which integrates two primitive systems:
the olfactory system (smell) and the limbic system (emotions).
o The habenular nuclei receive input from the stria medullaris, which are fibers that run
the length of the thalamic hemispheres on their medial side.
o The habenular nuclei communicate with each other across the midline via the habenular
o These nuclei project to the interpeduncular nucleus of the midbrain.
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pineal gland. The pineal gland is located immediately posterior to the habenular commissure; it
is a single, midline structure projecting from the dorsal side of the brain just above the superior
colliculi of the midbrain.
o The pineal gland secretes melatonin, which is makes from serotonin, in a cycle that is
entrained by light and dark. It has a role in establishing circadian rhythms and in
facilitating sleep.
o This endocrine gland may also have a role in hormonal and gonadal control, as it secretes
thyrotropin-releasing hormone (TRH), leuteinizing hormone-releasing factor (LHRH),
and somatostatin-release inhibitory factor (SRIF).2
o During late teenage years the pineal gland calcifies. This makes it dense (or white) on
radiographic imaging studies of the head. As it is located in the midline almost in the
center of the head, it serves as a good marker of shifts in midline structures of the brain.
Function of the thalamus. The thalamus has a central role in the relay and modulation of sensory
information destined for the cerebral cortex. It also has a role in integrating motor function, facilitating
arousal and consciousness, modulating pain and emotions, and facilitating memory. It is appropriately
considered the “gateway” to the cortex. Specific functions include:
Motor integration. The thalamus receives input from the motor cortex, basal ganglia, and
cerebellum. Electrical stimulation of the ventral lateral nucleus of the thalamus serves as a
treatment for tremor caused by dysfunction of the
basal ganglia or cerebellum.
Sensory relay. Except for olfaction (smell), all
sensory information passes through the thalamus.
There are three different types of projections from the
thalamus to the cortex:
o relay nuclei to primary sensory cortex for a
specific sensory modality; each of these have
reciprocal innervation from specific regions of
cortex. The relay nuclei include:
 ventral posterior nuclei, for touch
and pressure sensation
 medial geniculate nuclei, for auditory
 lateral geniculate nuclei, for visual
nuclei to association areas of cerebral cortex.
These nuclei may integrate more than one
sensory modality before relaying information
to cerebral cortex.
An example is the
posterior group of nuclei, which project to
association cortex in the temporal, parietal, and occipital lobes.
Lesions that destroy the pineal gland lead to precocious puberty, while pineal tumors that secrete excessive
hormonal peptides delay the onset of puberty.
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Diffuse projection nuclei which
interact with other thalamic nuclei and
project widely throughout the cerebral
Arousal. The thalamus is considered part of
the reticular activating system, and it is
important in the maintenance of consciousness
and attention. It is not the only arousal system
in the brain, as some cholinergic, serotonergic,
and noradrenergic projections that bypass the
thalamus have been shone to activate cerebral
Modulation of pain. Fibers from the spinothalamic tracts (medial and lateral) and from the
trigeminothalamic tracts transmit nociceptive (pain) information to the ventral posterior nuclei
of the thalamus. The clinical response to pain also involves an affective, or emotional,
component which is transmitted via fibers which project to the dorsal medial nucleus and the
intralaminar nuclei.3
Memory and behavior. Impairment of memory (amnesia) may be caused by injury to several
different regions of the thalamus, including the anterior or dorsomedial nucleus, as well as the
intralaminar or midline nuclei. Disruption of the tract from the mammillary bodies to the
thalamus may also contribute to memory loss. Disruption of the tract from the medial thalamus
to the pre-frontal cortex may cause loss of emotionality and motivation, indifference to pain, and
impairment of judgment.
The thalamus can be understood by considering a classification based upon function, and it can be
understood by appreciating different types of output to the cerebral cortex. It is customary, however, to
study the thalamus from an anatomical perspective. Each hemisphere of the thalamus consists of nuclei
which are organized into specific groups. The groups are defined by the internal medullary lamina,
which consists of white matter tracts (myelinated axons) which traverse the thalamus. The groups are:
anterior group -- these nuclei have reciprocal connections with the mammillary bodies4, which
are considered part of the hypothalamus (below), and the cingulate gyrus of the cerebral cortex.
The anterior thalamic nuclei, as well as their connections, are considered part of the limbic
system, which regulates emotion.
medial group – the most developed of these nuclei is the dorsomedial nucleus (or mediodorsal
nucleus) (DM), which has reciprocal connections with the prefrontal cortex and receives
additional input from the temporal lobe, amygdala, substantia nigra, and adjacent thalamic
nuclei. These nuclei are part of a system which is concerned with decision making, judgment,
memory and behavior.
lateral group – this is the largest group of nuclei and will be discussed further below.
The specific intralaminar nuclei are called the centrolateral and parafascicular nuclei.
The mammillary bodies are located on the ventral aspect of the brain immediately above the midbrain.
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posterior group – these nuclei receive input from all sensory modalities; they project to
association areas of temporal, parietal, and occipital lobes. These nuclei do not receive feedback
from cortical regions to which they project, and they lack the spatial specificity of other thalamic
In addition, there is a miscellaneous group of nuclei which include:
midline nuclei, which are located in between the thalamic hemispheres in the massa intermedia.
These nuclei have a role in emotion, memory, and autonomic function.
intralaminar nuclei, which are dispersed amidst the “white matter” of the intermedullary lamina.
These nuclei have numerous afferent and efferent connections, essential for their role in internal
regulation of cortical activity.
reticular nuclei, which are neurons that constitute a thin jacket which encase each hemisphere of
the thalamus. These nuclei represent a continuation of the reticular formation into the
diencephalon. They contain inhibitory, GABAergic neurons which project only within the
thalamus, giving them a role in internal regulation of thalamic activity.
Finally, the metathalamus includes two nuclei which appear as protuberances on the posterior region of
the posterior hemispheres:
medial geniculate body, which is a relay center for auditory information. These nuclei receive
input via the lateral lemniscus and inferior colliculus, and feedback from the auditory cortex.
The medial geniculate likely has a role in recognition of sound patterns, spatial localization of
sound, and auditory memory.
lateral geniculate body, which is a relay center for visual information. These nuclei receive
input from both retinas via the optic tract, and feedback from the visual cortex in the occipital
lobes. The primary outputs from the lateral geniculate are the optic radiation of the internal
capsule to the primary visual cortex. There is additional output to the pulvinar and to the
secondary visual cortex.
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Lateral group of nuclei. This is the largest group of nuclei in the thalamus. If the medial and lateral
geniculate nuclei are included (based upon anatomy rather than embryology), the lateral group contains
all of the modality-specific sensory and motor relay neurons. The group is divided into two sections:
Dorsal nuclei
o lateral dorsal (LD) – although anatomically part of the lateral group, this nucleus is
functionally part of the anterior group, forming part of the limbic system. It receives
input from the hippocampus via the fornix and it projects to the cingulate gyrus.
o lateral posterior (LP) and pulvinar – these nuclei function together and have reciprocal
connections with the lateral geniculate body. Both communicate with association areas
of temporal, parietal and occipital lobes. The pulvinar is a relay for visual information; it
plays a role in selective visual attention. The pulvinar is also a relay center for pain, as
surgical lesions of this nucleus have effectively relieved intractable pain.
Ventral nuclei
o ventral anterior (VA) – this nucleus receives inhibitory input from globus pallidus and
substantia nigra, and it receives excitatory input from premotor and prefrontal cerebral
cortex. It is a relay between basal ganglia and cerebral cortex involved in planning and
executing movement. The medial part of VA nucleus is concerned with voluntary eye
and head movements, while the lateral part is concerned with body and limb movements.
ventral lateral (VL) - this nucleus is also involved with motor control It receives input
from deep cerebellar nuclei (dentate) via the superior cerebellar peduncle and red
nucleus. It has reciprocal connections with primary motor cortex. There are reciprocal
projections to parietal association areas, which are involved with processing spatial
information for targeted movements. The VA nucleus, which receives input primarily
from basal ganglia and VL nucleus, which receives input primarily from the cerebellum,
constitute the “motor thalamus” involved with movement planning and control.
ventral posterior – this nucleus receives sensory input, including taste, from the
contralateral side of the face and body. The ventral posterior medial (VPM) region
receives input from the trigeminal lemniscus and taste fibers, and the ventral posterior
lateral (VPL) region receives input from the medial lemniscus and spinothalamic tract.
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Sensory Relay
Touch, position
Spinal cord
Cranial nerves
Inferior colliculus
Ventral posterior
Lateral geniculate
Medial geniculate
Parietal sensory cortex (medial)
Parietal sensory cortex (lateral)
Primary visual cortex
Primary auditory cortex
Motor Relay
Movement planning
Movement control
Basal ganglia
Ventral anterior
Ventral lateral
Supplementary motor cortex, cingulate
Premotor & primary motor cortex
Lateral dorsal
Cingulate cortex
Cingulate cortex
Prefrontal cortex, cingulate, n. basalis
Limbic Rela y
Learning, emotion, memory
Mammillary bodies
Relay to Association Cortex
Emotion, cognition, learning,
Sensory integration, perception,
eye movement control, language
Basal ganglia, amygdala,
hypothalamus, n. accumbens,
olfactory system
Superior colliculus; parietal,
temporal, occipital lobes
Medial lemniscus, spinothalamic
Temporal-parietal association cortex
Parietal, temporal, occipital cortex
Diffuse Projections to Cortex
Regulation of thalamic activity
Regulation of cortical activity
Thalamus, cortex
Brainstem, spinal cord, basal
Slow pain, forebrain excitability
Most important nuclei
Modality specific
Multimodal associative
Nonspecific & reticular
Cerebral cortex, basal ganglia
Cortex including cingulate, amygdala
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SUBTHALAMUS – This will be further discussed as part of the presentation on basal ganglia
The hypothalamus is ventral and inferior to the thalamus. It too is divided by the third ventricle, which
forms a “W” shape when viewed sagitally. Anterior to the hypothalamus is the lamina terminalis. Below
the first protrusion of the “W” is the optic chiasm. Below the second is the tuber cinerium, which is a
narrowing of the hypothalamus to a small neck. As it proceeds inferiorly, the tuber cinerium merges with
the median eminence, which then becomes the infundibular stalk, which is continuous with the
hypophysis, or posterior lobe of the pituitary gland. Posterior to the “W” are the mammillary bodies.
Below are sagittal (left) and inferior (right) views of the hypothalamic region.
When considering a mid-sagittal view of the hypothalamus, it is only possible to see the ventricle that
divides the hypothalamus. Hypothalamic nuclei are located on either side. Each portion of the
hypothalamus has a medial region and a lateral region.
The two are separated by the fornix, which begins in the
hypothalamus, arcs posteriorly, superiorly and then
anteriorly over the thalamus, and curves ventrally to
sweep through the hypothalamus and terminate in the
mammillary bodies. The fornix is not part of the
hypothalamus; it is part of the limbic system.5 The
lateral hypothalamus contains longitudinal tracts of the
median forebrain bundle and scattered neurons of the
lateral hypothalamic nuclei.
The body of the fornix should not be confused with the stria medularis of the thalamus, which is below the fornix.
Similarly, the commissure of the fornix should not be confused with the habenular commissure.
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Nuclei of the medial hypothalamus. In this region there are four groups of nuclei. From rostral to
caudal they are:
 preoptic region – nuclei in this region are located below the anterior commissure6 and adjacent
to the lamina terminalis. Neurons in the medial preoptic nuclei produce gonadotropic releasing
hormone which travels to the anterior pituitary via the tuberoinfundibular tract. This nucleus is
associated with sexual arousal, reproduction, and appetite. It is twice as large in young males
compared to young females.7
suprachiasmatic region – located above the optic chiasm, this region contains four groups of
o supraoptic nuclei
o paraventricular nuclei – both supraoptic and paraventricular nuclei send axons to the
neurohypophysis (posterior pituitary), producing and transporting vasopressin,
antidiuretic hormone (ADH),8 and oxytocin9 for storage prior to release at axon
o anterior hypothalamic nuclei – these nuclei regulate thirst, and control the desire to
drink. Lesions in this area may result in patients refusing to drink despite severe
o suprachiasmatic nuclei – these nuclei regulate body temperature and control circadian
rhythms of all types, including those than influence wakefulness and sleep. They receive
input from specialized retinal ganglion cells and they project to other regions of the
tuberal region – two groups of nuclei are separated by the fornix
o ventromedial hypothalamic nucleus10 -- this nucleus serves as the satiety center,
determining when an individual is “full” and needs to eat no more. If the ventromedial
nucleus is destroyed, the individual experiences voracious appetite, and develops obesity
The anterior commissure connects the temporal lobes of both hemispheres. Anterior fibers share olfactory
information and posterior fibers share audiovisual information.
The neuroscientist Simon LeVay found the size of pre-optic nuclei in the brains of gay men to be smaller than
those of heterosexual men. His work was controversial, partly because the brains he studied were mostly from men
who had died of AIDS, creating confusion about whether the findings were related to disease or to sexual
preference. Similar findings have been replicated in sheep, among which up to 10% of rams may express
exclusively homosexual preferences.
Production of ADH (also called vasopressin) is regulated by the osmolarity of the blood that bathes the supraoptic
nucleus. This is a region that lacks the blood-brain barrier in order to facilitate this communication between body
and brain. Lesions of this nucleus or its projections to the posterior pituitary result in diabetes insipidus, a
condition (unrelated to regulation of blood sugar) that is characterized by excessive excretion of urine and inability
to concentrate urine. ADH secretion in healthy individuals is diminished by alcohol intake, which explains
increased urination under these circumstances.
Oxytocin causes contraction of the smooth muscle of the uterus. A commercial preparation (Pitocin) is
administered to induce labor. Oxytocin also promotes the “let down” of milk from mammary glands during
lactation by new mothers.
There is also a dorsomedial hypothalamic nucleus, which is not well developed in humans. In rats stimulation
of this nucleus produces unusually aggressive behavior, or “sham rage,” which is present only as long as the
stimulus is present.
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and aggression.
 The ventromedial nucleus also projects to the basal forebrain, particularly to the
basal nucleus of Meynert11
o arcuate (infundibular) nucleus – located just above the infundibular stalk, this nucleus
contains dopamine, which regulates secretion of prolactin and growth hormone via the
hypophyseal portal system in the adenohypophysis (anterior pituitary).
 The arcuate nucleus also produces the neurotransmitter β endorphin, a
peptide which has a key role in control of pain12
 mammillary region -- this area contains two groups of nuclei:
o mammillary nuclei – these are clearly seen on the inferior surface of the diencephalon as
the mammillary bodies. When the ventral aspect of the brain is viewed, the mammillary
bodies appear in the interpeduncular fossa between the cerebral peduncles. Each
mammillary body contains a medial and lateral nucleus. The medial nucleus is the
destination of the fornix and therefore part of the limbic system which connects the
hippocampus in the temporal lobe with the diencephalon. The medial nucleus is also the
origin of the mammilothalamic tract.
o posterior hypothalamic nuclei – these nuclei project to the brainstem.
Nuclei of the lateral hypothalamus.
o lateral hypothalamic nuclei -- located lateral to the fornix and the mamillothalamic tract
these nuclei serve as the hunger center, determining when an individual needs to eat.
They partner with the ventromedial nuclei in regulating food intake. Neurons of the
lateral hypothalamic nuclei produce hypocretin (also called orexin), and they project
very widely throughout the brain. Loss of orexinergic neurons is associated with
narcolepsy, and orexin neurons in the lateral hypothalamus are also associated with
reward processes.
The majority of cholinergic neurons in the brain arise from the basal nucleus of Meynert. They project
throughout the brain and have a role in integrating subcortical functions. Drugs which block acetylcholine (like
scopolamine, used in patches to treat sea-sickness) can cause confusion and memory disorders.
β endorphin is produced from the precursor propiomelanocortin (POMC), which also gives rise to other peptide
hormones, including ACTH (adrenocorticotropic hormone) and α- and γ-MSH (melanocyte-stimulating hormone).
Release of β endorphin is the reason that pain after a sudden injury dulls quickly. It stimulates μ-opioid receptors,
as do chemicals extracted from opium, such as morphine and codeine.
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Hypothalamic connections. The hypothalamus has both local connections and regional connections. To
conduct its endocrine function, it communicates with the pituitary via two pathways:
hypothalamo-hypophyseal tract – this tract begins in the supraoptic and paraventricular nuclei
of the hypothalamus and projects to the neurohypophysis, the posterior lobe of the pituitary
gland. Axons from the supraoptic nuclei transport vasopressin (ADH) and axons from the
paraventricular nuclei transport oxytocin.
tubero-infundibular tract -- this tract begins in the arcuate nucleus and projects to capillaries
in the median eminence and infundibular stem. Axons in this tract transport hypothalamic
releasing factors to the anterior lobe of the pituitary gland via the hypophyseal portal system.
As noted above, the hypothalamus also has rich connections regionally. Afferent connections come from
retina, hippocampus (via the fornix), amygdala, globus pallidus, cerebellum, and prefrontal cortex.
Efferent connections project to anterior thalamus, autonomic cranial nerve nuclei, amygdala,
hippocampus, cerebellum, and prefrontal cortex.
Functions of the hypothalamus. As might be expected for extensive afferent and efferent networks, the
hypothalamus has a wide variety of functions. Most have been briefly referenced above. By way of
summary, these include:
 Hormonal regulation of the anterior pituitary
 Autonomic regulation of brainstem and spinal autonomic centers
 Temperature regulation
 Control of emotional behavior (ranging from fear to aggression)
 Sexual arousal and behavior
 Eating behavior (and weight gain) and other reward-related processes
 Regulation of thirst and drinking
 Regulation of wakefulness and sleep (and other circadian rhythms)
 Memory
The diencephalon is not supplied by a single artery. Parts of it receive blood from the posterior cerebral
arteries, the posterior communicating arteries, the tip of the basilar artery (before it bifurcates into
the posterior cerebral arteries), and the internal carotid artery. This chart is for reference only:
Posterior cerebral
Posterior communicating
Internal carotid
Anterior choroidal
medial thalamus
posterolateral thalamus
anterolateral thalamus
lateral thalamus
Anterior cerebral
Anterior communicating
Posterior cerebral
Posterior communicating
preoptic & supraoptic n,
anterolateral hypothalamus
tuber & mammillary n,
posterolateral hypothalamus