66 The Diencephalon

Functions of the Diencephalon

Distinct parts of diencephalon perform numerous vital functions, from regulating wakefulness to controlling the autonomic nervous system.

The diencephalon (“interbrain”) is the region of the vertebrate neural tube that gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube that later forms both the diencephalon and the telencephalon. In adults, the diencephalon appears at the upper end of the brain stem, situated between the cerebrum and the brain stem. It is made up of four distinct components: the thalamus, the subthalamus, the hypothalamus, and the epithalamus.

Other structures that are part of the diencephalon are:

• Anterior and posterior paraventricular nuclei
• Medial and lateral habenular nuclei
• Stria medullaris thalami
• Posterior commissure
• Pineal gland

Functions of Primary Diencephalon Structures

The thalamus is a kind of switchboard of information, believed to act as a relay between a variety of subcortical areas and the cerebral cortex. In particular, every sensory system (with the exception of the olfactory system) includes a thalamic nucleus that receives sensory signals and sends them to the associated primary cortical area. The thalamus also plays an important role in regulating states of sleep and wakefulness. Thalamic nuclei have strong reciprocal connections with the cerebral cortex, forming thalamo-cortico-thalamic circuits that are believed to be involved with consciousness. The thalamus plays a major role in regulating arousal, awareness level, and activity. Damage to the thalamus can lead to permanent coma.

The subthalamus connects to the globus pallidus, a basal nucleus of the telencephalon. It receives afferent connections from the substantia nigra and striatum and regulates skeletal muscle movements.

The hypothalamus performs numerous vital functions (e.g., regulation of certain metabolic processes), most of which relate directly or indirectly to the regulation of visceral activities by way of other brain regions and the autonomic nervous system. It synthesizes and secretes certain neurohormones, often called hypothalamic-releasing hormones, and these in turn stimulate or inhibit the secretion of pituitary hormones. The hypothalamus controls body temperature, hunger, thirst, fatigue, sleep, and circadian cycles.

The epithalamus functions as a connection between the limbic system and other parts of the brain. Some functions of its components include the secretion of melatonin by the pineal gland (involved in circadian rhythms) and regulation of motor pathways and emotions.

Thalamus

The thalamus is a small structure in the center of the brain that acts as a relay center for sensory and motor information.

The thalamus (derived from the Greek meaning “inner chamber”) is a midline symmetrical structure within the brain, situated between the cerebral cortex and midbrain. Its functions include relaying sensory and motor signals to the cerebral cortex and regulating consciousness, sleep, and alertness. The thalamus surrounds the third ventricle and is the main product of the embryonic diencephalon.

Overall Structure of the Thalamus

Each half of the thalamus is about the size and shape of a walnut: approximately 3 centimeters long, 2.5 centimeters across at the widest point, and about 2 centimeters high. Together, the two halves of the thalamus are a prominent bulb-shaped mass, about 5.7 cm in length, located obliquely (about 30°) and symmetrically on each side of the third ventricle.

The thalamus is part of a nuclear complex of composed of four parts: the hypothalamus, epithalamus, the ventral thalamus, and the dorsal thalamus. The thalamus has a system of myelinated fibers that separate the different thalamic subparts. These areas are defined by distinct clusters of neurons.

The thalamus derives its blood supply from four arteries including the polar artery ( posterior communicating artery), paramedian thalamic-subthalamic arteries, inferolateral (thalamogeniculate) arteries, and posterior (medial and lateral ) choroidal arteries. These are all derived from the vertebrobasilar arterial system except the polar artery. The thalamus is connected to the hippocampus via the mammillothalamic tract.

Primary Functions of the Thalamus

The thalamus has multiple functions, serving as a sort of switchboard of information. It is generally believed to act as a relay between a variety of subcortical areas and the cerebral cortex. In particular, every sensory system (with the exception of the olfactory system) has a thalamic nucleus that receives sensory signals and sends them to the associated primary cortical area. For the visual system, for example, inputs from the retina are sent to the lateral geniculate nucleus of the thalamus, which in turn projects to the primary visual cortex in the occipital lobe. The thalamus is believed to both process and relay sensory information. Each of the primary sensory relay areas receives strong back projections from the cerebral cortex. Similarly, the medial geniculate nucleus acts as a key auditory relay between the inferior colliculus of the midbrain and the primary auditory cortex. The ventral posterior nucleus is a key somatosensory relay, which sends touch and proprioceptive information to the primary somatosensory cortex.

The thalamus also plays an important role in regulating states of sleep and wakefulness. Thalamic nuclei have strong reciprocal connections with the cerebral cortex, forming thalamo-cortico-thalamic circuits that are believed to be involved with consciousness. The thalamus plays a major role in regulating arousal, awareness level, and activity. Damage to the thalamus can lead to permanent coma. Fatal familial insomnia is a hereditary prion disease characterized by degeneration of the thalamus and leading to a gradual progression to a state of total insomnia that is eventually fatal.

Hypothalamus

The hypothalamus serves as a gateway between the nervous system and endocrine system.

The hypothalamus (derived from the Greek for “under chamber”) is a portion of the brain that contains a number of small, distinct nuclei with various functions and less anatomically distinct areas. The hypothalamus is located below the thalamus just above the brain stem. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is roughly the size of an almond.

General Functions

One of the most important functions of the hypothalamus is linking the nervous system to the endocrine system via the pituitary gland (hypophysis).

The hypothalamus contains thyrotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, corticotropin-releasing hormone, somatostatin, and dopamine, as well as vasopressin and oxytocin. These hormones are released into the bloodstream and target other organ systems, most notably the pituitary. The hypothalamus affects the endocrine system and governs emotional behavior such as anger and sexual activity. Most of the hypothalamic hormones generated are distributed to the pituitary via the hypophyseal portal system. The hypothalamus maintains homeostasis, including the regulation of blood pressure, heart rate, and temperature.

The hypothalamus coordinates hormonal and behavioral circadian rhythms, complex patterns of neuroendocrine outputs, complex homeostatic mechanisms, and important behaviors. It must therefore respond to many different signals, some of which are generated externally and some internally. The hypothalamus is thus richly connected with many parts of the central nervous system, including the brainstem, reticular formation and autonomic zones, and the limbic forebrain (particularly the amygdala, septum, diagonal band of Broca, olfactory bulbs, and cerebral cortex).

The hypothalamus can sample the blood composition at the subfornical organ and the organum vasculosum of the lamina terminalis. This is important for the uptake of circulating hormones and to determine concentration of substances in the blood.

Temperature Regulation

The hypothalamus functions as a type of thermostat for the body. It sets a desired body temperature and stimulates either heat production and retention to raise the blood temperature to a higher level, or sweating and vasodilation to cool the blood to a lower temperature. All fevers result from a raised setting in the hypothalamus; elevated body temperatures due to any other cause are classified as hyperthermia. Rarely, direct damage to the hypothalamus such as from a stroke causes a fever; this is sometimes called a hypothalamic fever. However, such damage more commonly causes abnormally low body temperatures.

Appetite

The extreme lateral part of the ventromedial nucleus of the hypothalamus is responsible for control of food intake. Stimulation of this area causes increased food intake. Bilateral lesion in this area causes complete cessation of food intake. Medial parts of the nucleus have a controlling effect on the lateral part. Bilateral lesion of the medial part of the ventromedial nucleus causes hyperphagia and obesity. Further lesion of the lateral part of the ventromedial nucleus in the same animal produces complete cessation of food intake.

Fear Processing

The medial zone of hypothalamus is part of a circuitry that controls motivated behaviors, such as defensive behaviors and social defeat. Analyses of Fos-labeling showed that a series of nuclei in the behavioral control column is important in regulating the expression of innate and conditioned defensive behaviors. Nuclei in the medial zone are also mobilized during an encounter with an aggressor. The defeated animal has an increase in Fos levels in sexually dimorphic structures.

Sexual Dimorphism

Several hypothalamic nuclei are sexually dimorphic, with clear differences in both structure and function between males and females. Some differences are apparent even in gross neuroanatomy, most notably is the sexually dimorphic nucleus within the preoptic area. However, most are subtle changes in the connectivity and chemical sensitivity of particular sets of neurons. In neonatal life, gonadal steroids influence the development of the neuroendocrine hypothalamus. For instance, they determine the ability of females to exhibit a normal reproductive cycle and of males and females to display appropriate reproductive behaviors in adult life.

In 2004 and 2006, two studies by Berglund, Lindström, and Savic used Positron Emission Tomography (PET) to observe how the hypothalamus responds to smelling common odors, the scent of testosterone found in male sweat, and the scent of estrogen found in female urine. These studies showed that the hypothalamus of heterosexual men and homosexual women both respond to estrogen. Also, the hypothalamus of homosexual men and heterosexual women both respond to testosterone. In all four groups, common odors were processed similarly involving only the olfactory brain.

Epithalamus and Pineal Gland

The epithalamus connects the limbic system to other parts of the brain.

The epithalamus is a dorsal posterior segment of the diencephalon (as shown in the figure below).

It includes the habenula and their interconnecting fibers (the habenular commissure), the stria medullaris, and the pineal gland. The habenular commissure is a band of nerve fibers situated in front of the pineal gland that connects the habenular nuclei on both sides of the diencephalon. The stria medullaris, also known as stria medullaris thalami, is a fiber bundle containing afferent fibers from the septal nuclei, lateral preoptic hypothalamic region, and anterior thalamic nuclei to the habenula.

Pineal Gland

The pineal gland (also called the pineal body, epiphysis cerebri, epiphysis, conarium, or the “third eye”) is the only unpaired midline brain structure. It is about the size of a grain of rice (5–8 mm) in humans. The pineal gland lies between the laterally positioned thalamic bodies and behind the habenular commissure. It is located behind the third ventricle and is bathed in cerebrospinal fluid supplied through a small pineal recess of the third ventricle.

Epithalamic Function

The epithalamus acts as a connection between the limbic system and other parts of the brain. Some functions of its components include the secretion of melatonin by the pineal gland (involved in circadian rhythms) and regulation of motor pathways and emotions. It is wired with the limbic system and basal ganglia.

Circumventricular Organs

Circumventricular organs are situated adjacent to the brain ventricles and sense concentrations of various compounds in the blood.

Circumventricular organs (CVOs) are positioned at distinct sites around the margin of the ventricular system of the brain. They are among the few sites in the brain that have an incomplete blood-brain barrier. As a result, neurons located in circumventricular organs can directly sense the concentrations of various compounds, particularly peptide hormones, in the bloodstream without the need for specialized transport systems that move those compounds across the blood-brain barrier. A useful mnemonic device for remembering this aspect of their function, though not the source of the name, is that they allow factors to circumvent’ the blood-brain barrier. These organs secrete or are sites of action of a variety of different hormones, neurotransmitters, and cytokines. They are sometimes classified by whether they are secretory or sensory.

CVOs allow for linkage between the central nervous system (CNS) and peripheral blood flow, and are an integral part of neuroendocrine function.

Sensory Circumventricular Organs

The sensory organs are able to sense plasma molecules and pass that information into other regions of the brain. Therefore, they provide direct information to the autonomic nervous system from the systemic circulation. These organs include:

• Area postrema: Site of the chemoreceptor trigger zone for vomiting, sends major and minor efferents to sections of the brain involved in the autonomic control of cardiovascular and respiratory activities.
• Subfornical organ: Active in osmoregulation, cardiovascular regulation, and energy homeostasis.
• Vascular organ of lamina terminalis: Responsible for the homeostatic conservation of osmolarity.

Secretory Circumventricular Organs

The secretory organs are responsible for secreting hormones and glycoproteins into the peripheral vascular system using feedback from both the brain environment and external stimuli. These include:

• Subcommissural organ (SCO): Secretion of the glycoprotein SCO-spondin.
• Posterior pituitary: Stores and releases oxytocin and vasopressin, also known as antidiuretic hormone, produced in the hypothalamus.
• Pineal gland: The main function is the secretion of melatonin.
• Median eminence: Allows for the transport of neurohormones between the CSF and the peripheral blood supply.