Neuroanatomy An Illustrated Colour Text, 4 ed.

Chapter 16. Hypothalamus, limbic system and olfactory system


In order to survive, there must be continual adaptations to preserve the internal environment of the body (homeostasis). Interoceptor signals from the internal organs and body fluids initiate homeostatic responses; consequently, the internal physical and chemical environment remains balanced and stable. The hypothalamus is the structure responsible for this task.

Exteroceptive information from the outside world dictates behavioural responses, in order to achieve individual ‘homeostasis’ within the physical and social environment. Behaviour is relatively simple and stereotyped in lower animals and directed to satisfying the drives of thirst, hunger, sex and defence, in instinctive repertoires. The limbic system, which is strongly connected to the hypothalamus, is essential for this adaptive behaviour, which includes the ability to learn new responses based on previous experience (memory). The complex and non-stereotyped behaviour of humans is an attempt to preserve the individual within the physical landscape but also within a changing social environment (individual homeostasis). The association areas of the neocortex are capable of analysing exteroceptive information from the environment and other individuals, enabling adaptive personal and social responses. These phylogenetically more recent structures are partly connected to the limbic system.

As a result, the hypothalamus, limbic system and association neocortices act as interfaces in a hierarchical fashion between the internal structure of the individual and the environment. A reminder of this evolutionary ascent in humans is the olfactory system: vital for sensing the environment in lower animals, overwhelmed by visuospatial dominance in humans and intimately related to the limbic system.


The hypothalamus is able to integrate interoceptive signals from internal organs and fluid-filled cavities and make appropriate adjustments to the internal environment by virtue of its input and output systems.

The hypothalamic input is circulatory and neural in origin. The circulating blood provides physical (temperature, osmolality), chemical (blood glucose, acid–base state) and hormonal signals of the state of the body, its growth and development and its readiness for action (e.g. sex, suckling, defence etc). Neural signals come from two sources. First, the nucleus solitarius of the medulla projects to the hypothalamus and conveys information collected by the autonomic nervous system concerning the pressure within the smooth-muscled walls of organs (baroreceptors) and the chemical constituents of the fluid-filled cavities (chemoreceptors). Second, the state of neural arousal is communicated by two structures in the midbrain: the reticular formation via direct and indirect (via thalamus) routes, and the monoaminergic nuclei via the medial forebrain bundle.

The hypothalamus is capable of generating responses to these stimuli by circulatory and neural means. An intimate relationship with the pituitary gland and privileged access to its circulation (portal system) confers the role of ‘orchestrator of the endocrine system’ on the hypothalamus, as it directs hormonal synthesis and release. The neural output of the hypothalamus is two-fold. First, the autonomic nervous system projects to and controls internal organs, outside conscious control (and, hence, autonomous). Second, the hypothalamus is capable of initiating appropriate motor behavioural repertoires of an instinctive kind through its connections with the limbic system and limbic part of the corpus striatum (the nucleus accumbens). Its interconnections with the reticular formation also are capable of influencing the state of wakefulness and sleep.

The hypothalamus has the capability of influencing or overriding more complex adaptive behaviour because of its close links with two important structures: the limbic system and the association cortex of the frontal lobe (orbital part).

Topographical anatomy of the hypothalamus

The hypothalamus is the most ventral part of the diencephalon, lying beneath the thalamus and ventromedial to the subthalamus (Fig. 16.1). It forms the floor and the lower part of the lateral wall of the third ventricle, below the hypothalamic sulcus (see Fig. 12.2). On the base of the brain, parts of the hypothalamus can be seen occupying the small area circumscribed by the crura cerebri, optic chiasma and optic tracts (see Fig. 12.1). Between the rostral limits of the two crura cerebri, on either side of the midline, lie two distinct, rounded eminences, the mammillary bodies, which contain the mammillary nuclei. In the midline, immediately caudal to the optic chiasma, lies a small elevated area known as the tuber cinereum, from the apex of which extends the thin infundibulum (infundibular process), or pituitary stalk. This is attached to the pituitary gland (hypophysis), a pea-sized structure which lies within the sella turcica of the sphenoid bone. The pituitary gland consists of two major, cytologically distinct, parts: the posterior pituitary or neurohypophysis and the anterior pituitary or adenohypophysis (Figs 16.216.3). The posterior pituitary is a neuronal structure, being an expansion of the distal part of the infundibulum. The anterior pituitary is not neural in origin. The two parts are, however, closely linked by the pituitary (hypophyseal) portal system of vessels (Fig. 16.3), which are derived from the superior hypophyseal artery. Releasing factors, which are synthesised in the hypothalamus, pass to the adenohypophysis through these vessels to control the release of anterior pituitary hormones.


Figure 16.1 A sagittal section of the diencephalon. The diagram shows the medial aspect of the hypothalamus. The approximate location of some of the principal hypothalamic nuclei is shown.


Figure 16.2 Supraoptic and paraventricular nuclei projecting to the posterior pituitary via the hypothalamohypophyseal tract.


Figure 16.3 Pituitary portal system linking anterior and posterior parts of the pituitary gland.

Hypothalamic nuclei

The hypothalamus consists of many nuclear divisions, only some of which will be described (Fig. 16.1). The region lying medial and ventral to the structures of the subthalamus is known as the lateral hypothalamus. It is traversed longitudinally by many fibres, including the medial forebrain bundle. The lateral hypothalamic area is important in the control of food and water intake and is, in part, equivalent to the physiologically defined feeding centre. Lateral hypothalamic lesions cause aphagia and adipsia.

The medial region of the hypothalamus contains various nuclei, only some of which have well-defined functions. Anteriorly lie the supraoptic, paraventricular and suprachiasmatic nuclei. The supraoptic and paraventricular nuclei both produce systemically acting hormones, which are released from the posterior pituitary into the general circulation. The supraoptic nucleus produces vasopressin (antidiuretic hormone), which increases water reabsorption by the kidney. The paraventricular nucleus synthesises oxytocin. In the female, activation of the paraventricular nucleus, and release of hormone, is induced by suckling. This stimulates milk production by the mammary gland and causes contraction of uterine muscle.

The axons of cells in the supraoptic and paraventricular nuclei pass to the neurohypophysis in the hypothalamohypophyseal tract (Fig. 16.2). The neuroendocrine products are transported in this tract to the neurohypophysis, where they are released into the capillary bed and, thus, reach the general circulation.

The supraoptic nucleus contains osmosensitive neurones that are activated by changes in the osmolality of circulating blood. An increase in osmolality causes release of vasopressin. This acts upon the kidney tubules to increase water reabsorption, thus maintaining water homeostasis.

The hypothalamus also synthesises releasing factors and release-inhibiting factors, which control the release of hormones by the adenohypophysis. The adenohypophysis produces adrenocorticotropic hormone (ACTH), luteinising hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), growth hormone and prolactin, which are released into the general circulation. The factors that control them are released from the terminals of hypothalamic neurones into the capillary bed of the pituitary portal system (Fig. 16.3). These vessels, which are intrinsic to the hypophyseal stalk, convey the released agents to the adenohypophysis, where they act upon the hormone-secreting cells. The synthesis of hypothalamic releasing factors is under feedback regulation by hormones produced by target organs.

imageTumours of the hypothalamus and pituitary gland

Tumours and other diseases of the hypothalamus and associated pituitary gland lead to under- or overproduction of circulating hormones. These, in turn, produce disorders of growth (dwarfismgigantismand acromegaly), sexual function (precocious pubertyhypogonadism), body water control (diabetes insipidus and pathological drinking), eating (obesity and bulimia) and adrenal cortical control (Cushing’s disease and adrenal insufficiency). Since the pituitary gland is closely adjacent to the optic chiasma, tumours of the gland (pituitary adenomas) may lead to bitemporal visual field loss.


image The hypothalamus is part of the diencephalon; it is connected to the pituitary gland via the infundibulum.

image The hypothalamus has autonomic, neuroendocrine and limbic functions and is involved in the coordination of homeostatic mechanisms.

image The hypothalamus produces hormones that are released from the posterior pituitary and also releasing factors that control the release of hormones from the anterior pituitary.

image The supraoptic and paraventricular nuclei of the hypothalamus produce vasopressin and oxytocin, respectively.

image Vasopressin and oxytocin are transported to the posterior pituitary in the hypothalamohypophyseal tract.

image The anterior pituitary produces: adrenocorticotropic hormone, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone, growth hormone and prolactin. Factors that control their secretion are released into the pituitary portal system of the pituitary stalk and carried to the anterior pituitary.

image The lateral hypothalamus and the ventromedial nucleus regulate eating and drinking.

The suprachiasmatic nucleus is concerned with the control of diurnal rhythms and the sleep/waking cycle. It receives some afferent fibres directly from the retina.

More caudally, dorsomedial and ventromedial nuclei lie deep to the lateral wall of the third ventricle. The ventromedial nucleus, like the lateral hypothalamus, is concerned with the control of food and fluid intake. The ventromedial nucleus is equated with the physiologically defined satiety centre and lesions of this region cause abnormally increased food intake. In the most caudal part of the hypothalamus lie the posterior nucleus and the medial mammillary nucleus, the latter being located within the mammillary body. The mammillary body is part of the limbic system, receiving afferents from the hippocampus and projecting to the anterior nuclei of the thalamus and the brain stem.

The hypothalamus is the brain centre for regulation of the autonomic nervous system. Generally, activation of the posterior hypothalamic domain is associated with sympathetic responses, whereas activation of the anterior hypothalamus is associated with parasympathetic activity.

Limbic system

The limbic system earns its title from its position on the medial rim of the brain (le grand lobe limbique). It consists of a number of structures with complex and often looped connections that all ultimately project into the hypothalamus (Fig. 16.4). The powerful input to the limbic system from the neocortical association areas links complex ‘goal-directed’ behaviour to more primitive, instinctive behaviour and internal homeostasis in a cascade of neural connections (Figs 16.516.6). In a simplified way, we may conceive of information from the outside world collected in modality-specific ways (e.g. vision, hearing and touch) and refined in the parieto-occipital association areas (perceptuospatial function). This information is then conveyed to the frontal association areas involved in planned behaviour (regulation) and also to the inferior temporal association areas, where information can reach supramodal status and meaning (semantic processing). Entry of information into the limbic system is either directly to the amygdala, or indirectly to the hippocampal formation, via the entorhinal area. The amygdala appears to provide an affective connotation to experience and especially that relevant to social stimuli. Perhaps affect is an evolutionary development from more primitive ‘feelings’, derived from the sensory autonomic input from bodily organs into the hypothalamus. The informational flow into the hippocampal formation permits a link to previous experience since the hippocampal formation is essential to remembering and learning (memory).


Figure 16.4 The principal parts of the limbic system and their relationship with the hypothalamus.


Figure 16.5 The link between associative areas of neocortex, the limbic system and the hypothalamus.


Figure 16.6 The interconnections between associative neocortical regions and the component parts of the limbic system.

The limbic system is able to influence motor responses appropriate to its informational analyses, through projections to the nucleus accumbens, which forms part of the basal ganglia.


The amygdala lies near the temporal pole, between the inferior horn of the lateral ventricle and the lentiform complex (Fig. 16.7, see also Fig. 13.8). It receives afferents from the inferior temporal association cortex, the septum and the olfactory tract. In addition it receives catecholamine- and serotonin-containing projections from the brain stem in the medial forebrain bundle. The principal efferent projection from the amygdala is the stria terminalis, which runs in the wall of the lateral ventricle, following the curvature of the caudate nucleus, to terminate ultimately in the hypothalamus. The ventral amygdalofugal path also projects to the hypothalamus.


Figure 16.7 Coronal section of the brain showing the location of the amygdala and anterior commissure and their relationships with the basal ganglia. Mulligan’s stain (see Fig. 1.5).


The septum, or septal region, lies beneath the rostral part of the corpus callosum (Fig. 16.7). It interconnects with the amygdala and projects to the hypothalamus via the medial forebrain bundle. The septum also connects to the monoaminergic nuclei in the brain stem. It does so via fibres that project to the habenular nuclei of the diencephalon and constitute the stria medullaris thalami. The habenular nuclei in turn project, via the fasciculus retroflexus, to the interpeduncular nuclei, which project to the brain stem as well as the hypothalamus. In this way, two major pathways link the septum, the hypothalamus and the monoaminergic nuclei of the brain stem.

Hippocampal formation

The hippocampal formation consists of the hippocampus itself, the dentate gyrus and parts of the parahippocampal gyrus. The hippocampus is formed by an infolding of the inferomedial part of the temporal lobe into the lateral ventricle, along the line of the choroid fissure (Fig. 16.8, see also Figs 13.8–13.12Fig. 13.8Fig. 13.9Fig. 13.10Fig. 13.11Fig. 13.12). The dentate gyrus lies between the parahippocampal gyrus and the hippocampus.


Figure 16.8 Transverse section through the hippocampus and inferior horn of the lateral ventricle.

The hippocampal formation receives afferents principally from the inferior temporal cortex via the entorhinal area of the temporal lobe. It also receives fibres from the contralateral entorhinal area and hippocampus via the fornix system and hippocampal commissure. The principal efferent pathway from the hippocampus is the fornix (Figs 16.9-16.11, see also Figs 12.2, 13.2, 13.7–13.12Fig. 12.2Fig. 13.2Fig. 13.7Fig. 13.8Fig. 13.9Fig. 13.10Fig. 13.11Fig. 13.12). The fornix is a prominent C-shaped fascicle of fibres that links the hippocampus with the mammillary body of the hypothalamus. Efferent fibres converge on the ventricular surface of the hippocampus as the fimbria. This passes posteriorly and superiorly to become continuous with the crus of the fornix, which then curves forward beneath the splenium of the corpus callosum (Fig. 16.12). The two crura unite in the midline, beneath the corpus callosum, to form the body of the fornix (Fig. 16.10); some fibres cross to the opposite side through the small hippocampal commissure. As it passes forwards beneath the corpus callosum, the body of the fornix divides into two columns. These curve downwards, forming the anterior border of the interventricular foramen, and enter the hypothalamus, where the majority of fibres terminate in the mammillary body. The mammillary body, in turn, projects to the anterior nuclear group of the thalamus via the mammillothalamic tract and to the brain stem via the mammillotegmental tract. The anterior nuclei of the thalamus have major connections with the cingulate gyrus.


Figure 16.9 The interconnection of limbic structures that constitute the Papez circuit.


Figure 16.10 Dissection of the medial aspect of the diencephalon to show the relationships of the fornix, mammillary body and mammillothalamic tract.


Figure 16.11 The Papez circuit projected onto the medial aspect of the cerebral hemisphere.


Figure 16.12 The hippocampus–fimbria–fornix system. The brain is viewed from above. The cerebral cortex and white matter, including the corpus callosum, have been removed to reveal the lateral ventricle and its contents. (A) Choroid plexus of lateral ventricle intact; (B) Choroid plexus removed.

Cingulate gyrus

The cingulate gyrus and the parahippocampal gyrus are in continuity with one another around the splenium of the corpus callosum (Fig. 13.16). The cingulate gyrus projects to the parahippocampal gyrus via the fibres of the cingulum (Ch. 13). The principal structures of the limbic system are thus linked by a series of connections, which constitute the Papez circuit (Figs 16.916.10).

Limbic system

image The amygdala is located near to the temporal pole. It receives projections from the olfactory system and the temporal cortex, and has reciprocal connections with the septum.

image The hippocampal formation is made up of the hippocampus, dentate gyrus and parahippocampal gyrus of the temporal lobe. It receives fibres from the entorhinal cortex and projects via the fornix to the mammillary body of the hypothalamus.

image The principal components of the limbic system are interconnected in the Papez circuit.

imageLimbic lobe disorders

Alcohol abuse, in a setting of dietary deficiency of thiamine, leads to capillary haemorrhages in the upper brain stem and limbic structures. The patient falls into confusion and coma (Wernicke’s encephalopathy). Partial recovery may occur, with failure to remember previous experience (retrograde amnesia) or to learn new facts (anterograde amnesia). This is known as Korsakoff’s psychosis. A similar amnesic syndrome occurs when bilateral, surgical temporal lobectomy incorporates the hippocampal formations.

Temporal lobe or complex partial seizures arising close to the amygdala and hippocampi can lead to complex experiences of smell, mood and memory. The states of disordered thinking, hallucinations and strange or violent behaviour can mimic schizophrenia. Surgical ablation of the amygdala has eliminated uncontrollable rage reactions in some psychotic patients.

Olfactory system

Olfactory receptors are specialised, ciliated nerve cells that lie in the olfactory epithelium of the nasal cavity. Their axons assemble into numerous small fascicles (the true olfactory nerves) that enter the cranial cavity through the foramina of the cribriform plate of the ethmoid bone (see Fig. 5.1) and then attach to the olfactory bulb on the inferior surface of the frontal lobe (Fig. 16.13, see also Fig. 10.1). Preliminary processing of olfactory information occurs within the olfactory bulb, which contains interneurones and large mitral cells; axons from the latter leave the bulb in the olfactory tract.


Figure 16.13 Ventral surface of the brain. The illustration shows the olfactory bulb and tract, the lateral olfactory stria and the primary olfactory area of the cerebral cortex (uncus).

The olfactory tract passes backwards on the basal surface of the frontal lobe and, just before reaching the level of the optic chiasma, most olfactory tract fibres are deflected laterally, in the lateral olfactory stria (Fig. 16.13). These fibres pass into the depths of the lateral fissure, which they cross to reach the temporal lobe. They terminate mainly in the primary olfactory cortex of the uncus (Fig. 16.13, see also Fig. 13.2), on the inferomedial aspect of the temporal lobe, and in the subjacent amygdala. Adjacent to the uncus, the anterior part of the parahippocampal gyrus, or entorhinal area, constitutes the olfactory association cortex. The primary and association cortices are also collectively referred to as the pyriform cortex and are responsible for the appreciation of olfactory stimuli. The olfactory projection is unique among the sensory systems in that it consists of a sequence of only two neurones between the sensory receptors and cerebral cortex and does not project via the thalamus.

Olfactory system

image Olfactory nerve fibres terminate in the olfactory bulb.

image Second-order fibres run in the olfactory tract and terminate in the primary olfactory cortex of the uncus in the temporal lobe.

image Adjacent to this, the anterior part of the parahippocampal gyrus, or entorhinal cortex, constitutes the olfactory association cortex.


Anosmia follows damage to the olfactory nerves. There is loss not only of the sense of smell but also of the flavour of foods. However, elementary aspects of taste, e.g. sweet, salt, bitter and sour, are preserved. Anosmia frequently follows head trauma and can occur when tumours of the meninges (meningiomas) invade the olfactory nerves.