Yet, it plays a vital role in the organization of a number of auto-nomic functions and in the expression of related visceral behavioral processes. For example, endocrine function is controlled by the activity of different neurons of the hypothalamus. Likewise, temperature regulation is governed by the actions of different regions of the hypothala-mus. The control of water balance, drinking, feeding, and sexual behaviors are also governed by distinct neuronal mechanisms within the hypothalamus, as are the mechanisms regulating aggression, rage, and flight behaviors. This topic focuses on the anatomical and functional relationships of the hypothalamus with other regions of the brain and pituitary gland.
Hypothalamic Anatomy
Hypothalamic Nuclei
The relative positions of the major nuclei are outlined in Figure 24-1. The key regions include the supraoptic, paraventricular, ventromedial, suprachiasmatic, dorsome-dial, arcuate, and tuberal nuclei; the preoptic region; and the mammillary bodies. Additionally, there are four other regional areas, which are designated as the anterior, lateral, dorsal, and posterior hypothalamic areas.
Connections of the Hypothalamus
Afferent Connections
Significant modulation of hypothalamic processes is mediated by different groups of afferent fibers that originate primarily from the limbic system and reticular formation. The specific pathways over which such modulation occurs are described in the following sections.
Fornix.Briefly, the postcommissural fornix projects to the hypothalamus and anterior nucleus of the thalamus. This branch of the fornix arises from the subicular cortex of the hippocampal formation, and the hypothalamic component terminates largely in the medial hypothalamus and mammillary bodies (Figs. 24-1 and 24-2).
FIGURE 24-1 A schematic three-dimensional reconstruction of the loci of the nuclei of the hypothalamus.
FIGURE 24-2 Inputs from limbic structures. Projections from hippocampal formation through the fornix (shown in red), amygdala through the stria termi-nalis (shown in green), and septal area through the medial forebrain bundle (shown in blue) to the hypothalamus. Other inputs, such as those from the brainstem, are omitted from this diagram.
Stria Terminalis.In brief, this important pathway arises from the medial amygdala, and the periamygdalar cortex projects to the bed nucleus of the stria terminalis and much of the rostro-caudal extent of the medial hypothalamus (Fig. 24-2). Ventral Amygdalofugal Pathway. The ventral amygdalofugal pathway arises chiefly from the basolateral amygdala and parts of the adjoining pyriform cortex. Fibers of this bundle course medially from the amygdala into the lateral hypothalamus, where many terminate. Other axons of this bundle continue to pass in a caudal direction, where most synapse in the midbrain periaqueductal gray.
Medial Forebrain Bundle. The medial forebrain bundle is the principal pathway that traverses the rostro-caudal extent of the lateral hypothalamus. Many of the fibers constitute hypothalamic efferent projections to the brainstem. Other fibers represent ascending monoamin-ergic projections from the brainstem that supply much of the forebrain, including the cerebral cortex. Still other fibers arise from the septal area and diagonal band of Broca and project directly to the lateral and medial regions of hypothalamus, including the mammillary bodies (Fig. 24-2).
Thalamohypothalamic Fibers. The mediodorsal thalamic nucleus receives major inputs from the prefrontal cortex and adjoining portions of the anterior cingulate gyrus. Thalamohypothalamic fibers that issue from the mediodorsal nucleus project to posterior midline thalamic nuclei. From the posterior midline thalamus, a chain of neurons then pass rostrally through midline nuclei. Neurons that arise from the rostral aspect of the midline thala-mus (nucleus reuniens) project to the anterior lateral hypothalamus (Fig. 24-3). This circuitry provides an important anatomical substrate by which the prefrontal cortex and anterior cingulate gyrus can regulate functions associated with the lateral hypothalamus. Recent findings have provided evidence that the prefrontal cortex can influence hypothalamic functions via a monosynaptic projection to the hypothalamus.
Retinohypothalamic Fibers. An overwhelming number of retinal fibers terminate in the lateral geniculate nucleus, pre-tectal region, and superior colliculus. Nevertheless, it has been shown that some optic fibers (retinohypothalamic fibers) terminate in the region of the suprachiasmatic nucleus. Such inputs are important in regulating the sleep-wakefulness cycle and circadian rhythms that govern endocrine functions (see p. 439).
Mammillary Peduncle. The mamillary peduncle arises mainly from the ventral and dorsal tegmental nuclei of the mid-brain and presumably serves as a relay for ascending impulses to the hypothalamus from lower regions of the brainstem tegmentum. Ascending fibers from the dorsal tegmental nuclei terminate principally in the mammillary bodies, while those in the ventral tegmentum pass through the medial forebrain bundle to more rostral levels of the hypothalamus and limbic structures. Midbrain Periaqueductal Gray.
FIGURE 24-3 Inputs from cerebral cortex. Diagrams illustrate the pathways by which the prefrontal cortex (green) and anterior cingu-late gyrus (red) supply the hypothalamus by virtue of relays in the mediodorsal and midline thalamic nuclear groups (blue).
The midbrain periaqueductal gray (PAG) matter is functionally related to the medial hypothalamus. Consequently, it shares reciprocal connections with parts of the medial hypothalamus. The dorsal part of the midbrain PAG contains both ascending and descending projections. Its ascending projections reach the posterior half of the medial hypothalamus and, thus, serve as a feedback mechanism with respect to several of the functions of the medial hypothalamus, which are mediated via their descending projections to the midbrain PAG.
Monoaminergic Pathways.These inputs from the brainstem tegmentum, together with the inputs from limbic structures, provide significant modulation of hypothalamic processes.
Efferent Projections
Projections from the Mammillary Bodies. The mammillary bodies give rise to at least two groups of fiber projections. One ascends to the thalamus, and the other descends to the brainstem (Fig. 24-4). The ascending pathway is called the mammillothalamic tract. It projects to the anterior thalamic nucleus and comprises a component of the Papez circuit, which is a circular series of pathways linking the cingulate gyrus to the hippocampal formation to the mammillary bodies to the anterior thalamic nucleus, with a return flow back to the cingulate gyrus.
A second pathway arising from the mammillary bodies is called the mammillotegmental tract, which projects to the midbrain tegmentum (Fig. 24-4). Other fibers forming a multisynaptic chain descend in the mammillary peduncle from the mammillary bodies to the reticular formation. Projections from the midbrain tegmentum to autonomic nuclei of the lower brainstem and spinal cord might provide an anatomical substrate for hypothalamic control of autonomic functions. However, as described below, other descending pathways from the hypothalamus are equally (if not more) tenable.
Projections from the Medial Hypothalamus. Fibers originating from the medial hypothalamus have both ascending and descending projections. The ascending projections reach the medial nucleus of the amygdala (Fig. 24-5). This projection could be viewed as a feedback pathway to the amygdala associated with a major descending projection from the medial amygdala to the medial hypothalamus that regulates emotional behavior and related hypothalamic processes.
FIGURE 24-4 Efferent projections of the mam-millary bodies to the anterior thalamic nucleus via the mammillothalamic tract and to the mid-brain tegmentum via the mammillotegmental tract.
FIGURE 24-5 Major efferent projections of the hypothalamus. Not shown in this illustration are connections from the hypothalamus to the pituitary gland.
Descending fibers project principally to the dorsal half of the midbrain PAG. This pathway enables emotional (i.e., aggression, rage, and flight) and autonomic (i.e., marked changes in heart rate and blood pressure) responses integrated within the medial hypothalamus to be transmitted downstream to the midbrain PAG. For this reason, the midbrain PAG can be viewed functionally as a caudal extension of the medial hypothalamus. Moreover, the midbrain PAG then transmits this information to the lower sympathetic, parasympathetic (i.e., pontine tegmentum, solitary nucleus, ventrolateral medulla, dorsal motor nucleus of cranial nerve [CN] X, and intermediolateral cell column of the spinal cord), and somatic motor regions of the lower brainstem and spinal cord; from here, ultimate expression of these responses is achieved. Projections from the Medial Forebrain Bundle (Lateral Hypothala-mus). Cells situated at all levels of the lateral hypothala-mus give rise to axons that pass both rostrally and caudally within the medial forebrain bundle. Ascending fibers within the medial forebrain bundle supply the septal area, preoptic region, and nuclei of the diagonal band of Broca. In addition, some fibers of the far rostral lateral hypothala-mus have been shown to have long axons that project as far as the hippocampal formation, prefrontal cortex, and other parts of the frontal and parietal lobes (Fig. 24-5). Such a pathway could provide the cerebral cortex with direct information concerning the internal milieu of the organism as well as synchronize cortical activity with hypothalamic functions. Other fibers ascending in the medial forebrain bundle enter the stria medullaris and pass caudally to the habenular complex, where they terminate in the lateral habenular nucleus.
Descending fibers of the lateral hypothalamus pass through the medial forebrain bundle to ventral regions of the midbrain PAG and other regions of the midbrain and pontine tegmentum. This pathway could also serve as an anatomical substrate by which the lateral regions of the hypothalamus could regulate autonomic and somatomotor components of emotional responses normally associated with this region.
