The ability to feel and express emotion is a unique feature that has been observed in a significant number of animals. Humans in particular experience and express an eclectic plethora of emotions that help to shape an individual’s behavior. The region of the brain believed to be responsible for these activities formed a physical border between the hypothalamus and the cerebrum. Therefore, it was called the limbic system; arising from the Latin word limbus, meaning edge.
The limbic system – also known as the circle of Papez (or Papez’s Circuit) is considered to be the epicentre of emotional and behavioral expression. A quick way to remember the functions of the limbic system is to think about five “F’s”:
- Feeding (satiety & hunger)
- Forgetting (memory)
- Fighting (emotional response)
- Family (sexual reproduction and maternal instincts)
- Fornicating (sexual arousal)
It is able to complete these activities through intricate connections to other systems of the brain. Traditionally, it has been divided into two groups: a cortical and a subcortical component. The former comprises of the neocortex, orbital frontal cortex, hippocampus, insular cortex and the cingulate, subcallosal and parahippocampal gyri. The latter, on the other hand, includes the amygdala, olfactory bulb, septal nuclei, hypothalamus and the anterior and dorsomedial nuclei of the thalamus. The cortical region is referred to as the limbic lobe (discussed below). The subcortical region works in conjunction with the limbic lobe. This article will discuss the gross anatomy of the limbic system and associated pathways.
The limbic lobe refers to a specific group of anatomical structures found in the region of the cortex on the medial aspect of cerebral hemisphere forming a rim around the corpus callosum. It also includes cingulate and parahippocampal gyri. These structures also have interdependent functional similarities associated with the formation of memories and the expression of a variety of emotions. These structures are:
- The subcallosal gyrus is a relatively small gyrus that is found anterior to the lamina terminalis (anterior wall of the hypothalamus) and the anterior commissure. Also, it is inferior to the rostrum (first part) of the corpus callosum and posterosuperior to the orbitofrontal cortex of the cerebrum. The area also corresponds with sections of Brodmann areas 24 and 32, and area 25. It is believed to be involved in depression.
- The cingulate gyrus is best appreciated while visualizing the medial aspect of either hemisphere of the cerebrum. It is a “C” shaped structure that is divided into a prelimbic and an infralimbic cortex, an anterior cingulate and a retrosplenial cortex. The cingulate cortex commences ventral to the rostrum of the corpus callosum, curves rostrally then follows the genu of the corpus callosum to progress posteriorly to blend with the precuneus of the parietal lobe. The cingulate gyrus is separated from the corpus callosum by the callosal sulcus (inferiorly) and from the medial frontal gyrus and paracentral lobule by the cingulate sulcus superiorly. The cingulate sulcus is continuous with the marginal sulcus, which separates the paracentral lobule from the precuneus. It is believed that the cingulate gyrus is strongly associated with the perception of neuropathic pain and nociception.
- The parahippocampal gyrus is more readily appreciated on the inferior surface of the temporal lobe of the cerebrum. It is located medial to the rhinal sulcus (an anterior continuation of the collateral sulcus) and the lateral occipitotemporal gyrus, lateral to the uncus, geniculate bodies and pulvinar of the thalamus, and anterior to the medial occipitotemporal gyrus. The area corresponds with several Brodmann areas such as the entorhinal cortex (area 27, 28), and areas 35, 36, 48 and 49. The parahippocampal gyrus provides a path of communication between the hippocampus and all cortical association areas through which afferent impulses enter the hippocampus.
- The inferior surface of the frontal lobe rests on the roof of the orbit in the anterior cranial fossa. This region of the cerebrum is therefore known as the orbitofrontal cortex. The olfactory bulb and tract can be found running along the olfactory sulcus. The olfactory sulcus separates the straight gyrus of the orbitofrontal cortex from the medial orbital gyrus. The orbitofrontal cortex perceives smell, which can also be involved in the formation of memories.
The almond-shaped amygdala (amygdaloid body) is located anterosuperior to the temporal (inferior) horn of the lateral ventricle, inferior to the lentiform nucleus (putamen and globus pallidus interna and externa) and deep to the uncus. The apex of the tail of the caudate nucleus fuses and the amygdala merge in the roof of the temporal horn of the lateral ventricle. The amygdala can be subdivided into a large ventrolateral component and a smaller dorsomedial division. The ventrolateral group has central and basolateral nuclei that link the corticomedial nuclei of the dorsomedial division to the entorhinal cortex. The corticomedial nuclei receive sensory input from the olfactory bulb. From the posterior aspect of the amygdala, the stria terminalis emerges and pursues a concave pathway. It extends posteriorly along the ventral surfaces of the basal ganglia and thalamus. Subsequently, the stria terminalis travels superiorly in a posterior relation to the thalamus. Finally, it travels anteriorly along the dorsal or ventricular surface of the thalamus, between the thalamus and the caudate nucleus and rostral to the thalamostriate veins. These fibers allow communication between the amygdala and regions of the hypothalamus to regulate the fear and anxiety responses.
The uncus is the home of the amygdala. It is located on the inferior surface of the cerebrum, posteromedial to the temporal lobe, lateral to the posterior perforated substance and mammillary bodies, anterior to the lateral geniculate body and anterolateral to the mesencephalic midbrain. In gross specimen, the uncus appears to be an anteromedial extension of the parahippocampal gyrus. There are three major components of the uncus. Posteriorly there is an intralimbic gyrus; anteriorly there is the uncinate gyrus and the tail of the dentate gyrus between them. The uncus is also related to two other gyri that are superficially related to the amygdala known as the gyrus semilunaris and the gyrus ambiens. The former is located medially and continuous with the lateral olfactory stria; while the latter is located laterally and is continuous with the lateral olfactory gyrus (thin grey matter covering of the lateral olfactory stria).
The hippocampal formation is an umbrella term used in reference to a specific cluster of structures. These structures are the hippocampus, dentate gyrus, subicular complex, and entorhinal cortex. The hippocampus is a bundle of grey matter, residing in the floor of the temporal horn of the lateral ventricle; that resembles a ram’s horn. Subsequently it has also been called cornu ammonis (after the ancient Egyptian deity, Ammon). Anteriorly, the cornu ammonis is wider than the posterior extension and is indented to resemble a paw. This region of the hippocampus is called the pes hippocampus.
As the hippocampus courses posteriorly, its ventricular surface forms a convexity before travelling superomedially to merge with the crus of the fornix. The dentate gyrus is a serrated grey matter structure that is found medial to the hippocampus and lateral to the parahippocampal gyrus as it travels along the floor of the temporal horn of the lateral ventricle. It extends anteriorly into the uncus and continues superomedially with the fimbria of the hippocampus (see below) and becomes the indusium griseum (a thin grey matter structure that covers the dorsal surface of the corpus callosum).
In a coronal section, the cornu ammonis (CA) is subdivided into three regions, CA1 (adjacent to the subiculum), CA3 (proximal to the dentate gyrus and CA2 (between CA1 and CA3). The subicular complex is a region of the hippocampus (best appreciated in coronal section) that is made up of (from superficial to deep) a parasubiculum, presubiculum, and a subiculum. This complex contains pyramidal neurons that project to the entorhinal cortex and other parts of the hippocampal formation. Histologically, the subiculum, which is adjacent to CA1, contains the apical dendrites of subicular pyramidal cells and polymorphic cell layers. The distinguishing factor between the presubiculum and the subiculum is the significantly packed area of pyramidal cells.
Finally, the entorhinal cortex (Brodmann 28) is made up of the anterior pole of the parahippocampal gyrus and the uncus and is preceded by the gyrus semilunaris. This cortex extends rostrocaudally from the anterior amygdala to parts of the hippocampal formation. It is a direct recipient of afferents stimulation from the olfactory bulb. The entorhinal cortex is histologically divided into six layers based on their cellularity.
The hypothalamus is diencephalic region in the third ventricle situated caudal to the hypothalamic sulcus and the thalamus. It is involved in sexual arousal, emotional response, endocrine regulation, sexual development, thermoregulation, regulation of satiety and hunger, and is also involved in osmoregulation. It not only feeds information into the limbic system, but it serves as its final output. The hippocampohypothalamic fibers connect the hippocampus with the mammillary bodies via the fornix.
This pathway serves as the major output of the limbic system. There are also amygdalohypothalamic fibers that journey from the amygdaloid complex, travels caudal to the lentiform nucleus via the stria terminalis and enters the hypothalamus. There are several nuclei that make up the hypothalamus (see article on The Hypothalamus). The preoptic, dorsomedial, lateral, and ventromedial nuclei are examples of hypothalamic nuclei that are closely related to the limbic system. The preoptic nucleus regulates the secretion of gonadotropin releasing hormone (GnRH), which is important for sexual development. The lateral nucleus modulates the feeding impulse (lesions associated with this nucleus has been associated with anorexia nervosa), while the dorsomedial and ventromedial nuclei are involved in the regulation of satiety, fear and sexual activity. Destruction of these regions in lab rats has resulted in obesity.
Other Components of the Limbic System
The alveus is a thin veil of white matter covering the hippocampus, deep to the ependymal layer. The nerve fibers traveling through the alveus from the cornu ammonis unite on the medial surface to for the fimbria of the hippocampus. The fimbria continues their journey superomedially and become the fimbria of the fornix as the hippocampus terminates and the fornix begins at ventral to the splenium of the corpus callosum. It should be noted at this point where the crura of the fornix ascend posterior to the thalamus, they communicate with each other via the commissure of the fornix. The decussating fibers permit communication between the hippocampi of each side.
The Habenular nucleus lies deep to the Habenular commissure that resides in the suprapineal space (above the pineal gland and recess). This nucleus communicates with the rest of the limbic system via the stria medullaris thalami (along the midline of the roof of the third ventricle). In addition to connecting the Habenular nucleus to the hypothalamus, it also connects it to nuclei of the septum (septal area). The septum communicates superiorly with the septum pellucidum (separates the left and right lateral ventricles). It also contains dorsal, medial, caudal and ventral groups of nuclei inferior to the septum pellucidum. The lateral septal nucleus (recipient of most afferent stimuli) is found in the central group, while the dorsal septal nucleus resides in the dorsal group. The nucleus of the diagonal band of Broca and the medial septal nucleus reside in the medial group and the triangular septal and fimbrial nuclei reside in the caudal group. The septum also communicates with the limbic system via the precommisural fornix (anterior fibers of the fornix).
The mammillary bodies are a pair of rounded structures found inferior to the floor of the third ventricle. They are posterior to the pituitary gland and the tuber cinereum (floor of the hypothalamus) and anterior to the posterior perforated substance and interpeduncular fossa. The mammillary bodies communicate with the limbic system via the postcommisural fornix (posterior fibers of the fornix) and by way of the mammillothalamic tract.
Circle of Papez
In 1937, James Papez made a proposition that there had to be reciprocating interactions between the cerebral cortex and the hypothalamus in order for emotional behavior to be consciously perceived. This proposal laid the framework for what is termed the circle of Papez. This circuit involves communication between the entorhinal area, cingulate gyrus, mammillary nucleus, hippocampal formation and anterior thalamic nucleus. The perforant and alvear tracts provide a pathway between the entorhinal cortex and the hippocampal formation. By way of the fornix and fimbria, the hippocampal formation can then transmit information to the mammillary bodies. Subsequently, the mammillary bodies communicate with the anterior thalamic nucleus through the mammillothalamic tract. The internal capsule then takes information from the thalamus to the cingulate gyrus, which then returns impulses to the entorhinal area via the cingulum. The afferent and efferent information travelling to and from the limbic system originate in cortical, reticular and diencephalic regions of the brain.