14. Olfaction and the Limbic System
Revised August 8, 2007
The objectives of this chapter are to:
- Describe the structure of the olfactory system.
- Describe the organization of the limbic system and the input and output connections of the hippocampus, amygdala and septal nuclei.
Olfaction is not currently considered to be part of the limbic system but is discussed here for convenience.
Olfactory receptors and cranial nerve I: The olfactory receptors are neurons within the olfactory epithelium (#15100) located in the upper nasal cavity. Axons leave the olfactory receptors and synapse in the olfactory bulb. These axons are called the olfactory fila (#11847), which collectively make up cranial nerve I (olfactory nerve). They enter the anterior cranial fossa through the cribriform plate (#4477) of the ethmoid bone (#5186). The fila that make up the olfactory nerve are torn from their insertions into the olfactory bulb when the brain is removed from the skull.
Olfactory bulb and tract: Neurons in the olfactory bulb (#4965) called mitral cells are secondary sensory neurons of the olfactory system. Their axons leave the olfactory bulb and enter the olfactory tract (#4963). The olfactory tract is not a peripheral nerve. It is part of the central nervous system. The olfactory bulb and tract are parts of which major brain division? Anosmia (loss of smell) may result from traumatic shearing of the olfactory fila from the bulb, or from traumatic contusion, tumor or other lesion affecting the olfactory bulbs or tracts.
Lateral olfactory stria and olfactory cortex: Some fibers of the olfactory tract (fig 14a) turn laterally at the junction between the frontal cortex and anterior perforated substance to form the lateral olfactory stria (fig 14a, #6616), which projects to olfactory cortex. All gray matter areas that receive output from the olfactory bulb are called olfactory cortex, which is mainly on or near the dorsal surface of the uncus. The uncus (#6079)) is the rostral tip of the parahippocampal gyrus and the most medial part of the temporal lobe. Deep to the uncal cortex is the amygdala (#4860). In humans, the main areas of olfactory cortex are
- Piriform cortex: The most posterior part of the orbitofrontal cortex (fig 14a), lateral to the lateral olfactory stria, and extending to the adjacent sulcus dorsal to the uncus (#6624).
- Cortical Amygdala: The dorsal surface of the uncus. This is the superficial (“cortical”) part of the amygdala (#4860).
Both of these cortical areas are referred to as olfactory cortex (#4404).
Hypothalamus: Olfactory cortex projects to the hypothalamus. The hypothalamus (#6602) is thought to use olfactory information to affect feeding, reproductive activity, and autonomic reflexes triggered by olfactory signals ("the smell of fear"). How, then, do odors affect the output of the salivatory nuclei? Through what pathways can foul odors produce vomiting? Or, better, how can alluring odors affect autonomic neurons in the spinal cord involved in sexual function?
Orbital prefrontal cortex: Olfactory cortex and gustatory (taste) cortex project to orbital prefrontal cortex (the inferior surface of the frontal lobe), where information from both sensory modalities can be combined for the sensation of flavor.
II. The Limbic System
The limbic system consists of the limbic lobe and other cortical areas and nuclei that have connections with the limbic lobe. This group of structures is associated with learning, memory, emotion and motivation.
A. The Limbic Lobe
The limbic lobe (from limbus “border”) is the cerebral cortex that forms the inferior medial border of the cerebral hemisphere. Its main components are the cingulate gyrus, the parahippocampal gyrus, and the hippocampal formation (hippocampus).
1. The cingulate gyrus: The cortex adjacent to the corpus callosum is the cingulate gyrus (#4274, #4749). Deep to this cortex is a bundle of axons called the cingulum (#4898). The cingulate gyrus and cingulum curve around behind the splenium of the corpus callosum into the parahippocampal gyrus.
2. The parahippocampal gyrus: The parahippocampal gyrus is the most medial gyrus on the ventral surface of the temporal lobe (fig 14d). Its anterior half consists of a transitional cortex called entorhinal cortex (#4519), which is one of the four components of the hippocampal formation (hippocampus). Thus, the entorhinal cortex is part of both the parahippocampal gyrus and the hippocampal formation.
3. The hippocampal formation (hippocampus): The parahippocampal gyrus turns in upon itself along its medial margin and becomes the other three components of the hippocampal formation (hippocampus). Since this part of the hippocampal formation is rolled in upon itself, it cannot be seen from the surface of the brain. This rolled-in part of the hippocampus is an elongated structure located in the floor of the inferior horn of the lateral ventricle (#4885, #7939, monkey brain, and #5234).
Thus, there are four components of the hippocampal formation (fig 14f, fig 14e): the entorhinal cortex and the three components of the rolled-in part of the hippocampus – the dentate gyrus, Ammon’s horn (Cornu Ammonis, hippocampus proper) and the subiculum.
[The entorhinal axons synapse on the granule cells in the dentate gyrus (#4682). The granule cell axons synapse on the pyramidal cells of Ammon's horn (fig 14f), which synapse on the pyramidal cells of the subiculum.]
Recent explicit memory: The hippocampus is necessary for storing recent memories of facts and events – explicit (declarative) memory. It receives information from many cortical areas. For example, processed information from all sensory cortices projects to the inferior temporal cortex, which in turn sends axons to the entorhinal cortex. Through these connections, the hippocampus is informed about sensory processing in all cortical areas. This is undoubtedly important in forming memories.
Amnestic syndrome: Bilateral hippocampal damage causes the amnestic syndrome, a profound loss of recent explicit memory and inability to form new memories (anterograde amnesia), but with preserved immediate (working) memory, preserved remote memory for long-known information, such as where you grew up, and preserved implicit (nondeclarative) memory for motor skills and habits.
Alzheimer’s disease is the most common dementia. Its pathologic changes are most severe in the hippocampal formation, and its most prominent symptom is loss of recent explicit memory.
B. The Circuit of Papez
A circle of connections from the hippocampus to the mammillary body, to anterior thalamus, to cingulate cortex, and back to the hippocampus through the cingulum and parahippocampal gyrus is known as the Papez circuit (fig 14g). Historically, it was the anatomic basis of the concept of the limbic system. Currently, it is not associated with any specific function, but it illustrates many of the connections of the limbic system.
Axons of cells in the hippocampal formation (mainly the subiculum, but also Ammon’s horn) collect on the surface of the hippocampus in the floor of the temporal horn to form a layer of white matter called the alveus (#4679). These axons gather into a bundle known as the fimbria (#4681). Posteriorly, as this bundle leaves the hippocampal formation, it is called the fornix (#5239).
The fornix is the major projection from the hippocampus. The fornix goes forward under the splenium and body of the corpus callosum and above the third ventricle (#5390, #8404, #6260). This portion of the course of the fornix is seen on the medial surface of the hemisphere (fig 14d). The fornix (#8499) bends to form the anterior margin of the foramen of Monro and courses posterior to the anterior commissure. It then dives into the hypothalamus and divides the hypothalamus into medial and lateral zones (#11864). It terminates in the mammillary body (#8506, #8311).
The mammillary body projects to the anterior nucleus of the thalamus through the mammillothalamic tract (#6640). The anterior nucleus (#8314) sends thalamocortical axons via the internal capsule to the cingulate gyrus (#4749). Axons from the cingulate gyrus form the cingulum (#4898, #4751), which goes to the parahippocampal gyrus and the entorhinal cortex, completing the circuit back to hippocampal formation.
Click for the Pathway Quiz: Papez Circuit .
C. Other Cortical Areas and Nuclei
The main other cortical area of the limbic system is the orbitomedial prefrontal cortex, which is composed of
- The orbital prefrontal cortex, on the inferior surface of the frontal lobe
- The medial prefrontal cortex, which is roughly equivalent to the anterior cingulate gyrus
The main nuclei of the limbic system are
- The basolateral amygdala
- The septal nuclei
- The nucleus accumbens (ventral striatum) and the ventral pallidum
- The hypothalamus, especially the mammillary bodies
- The anterior nucleus of the thalamus and the dorsomedial (mediodorsal) nucleus of the thalamus
Some of these structures were described with the Papez circuit above. Here, we will describe the amygdala and the septal nuclei, with references to some other limbic system structures.
1. The amygdala: The amygdala is a nuclear complex that is rostral to the hippocampus (#4709, monkey). It is more typically seen in a coronal section, (fig 14h). Notice on #4709 that the amygdala is located at the rostral superior tip of the temporal horn. Therefore, in contrast to the hippocampal formation, which can be seen on any coronal slice that includes the temporal horn, the amygdala will only be seen on a coronal slice that goes through the very anterior tip of the temporal horn or just in front of it (fig 14h).
The three main nuclear groups of the amygdala are the cortical amygdala (“cortical” nuclei), the basolateral amygdala (basolateral nuclei), and the centromedial extended amygdala (central nucleus, medial nucleus and other nuclei):
a. The cortical amygdala has been considered above in relation to the olfactory system. Notice on fig 14h that the amygdala extends medially to the dorsal surface of the uncus. This superficial part of the amygdala is the cortical amygdala, an area of olfactory cortex as described above.
b. The basolateral amygdala: The basolateral amygdala (#6262) is considered part of the limbic system. It receives information from all sensory modalities. It assigns emotional significance (especially fear) to sensory information, and it produces fear-related "fright, fight and flight" autonomic responses via pathways to the hypothalamus and brainstem (see below). In contrast, human amygdala activity is decreased – consistent with decreased monitoring of environmental stimuli – during romantic love, sexual stimulation and orgasm.
The basolateral amygdala is involved in enhancing our memories of emotionally significant experiences, either pleasant or unpleasant. In this regard, it has receptors for adrenergic and corticosteroid adrenal stress hormones, and connections to regions such as the hippocampal formation, the nucleus accumbens (ventral striatum), dorsomedial nucleus (#6457) of the thalamus, and the orbitomedial prefrontal cortex.
c. The centromedial extended amygdala receives input from the cortical amygdala and the basolateral amygdala and projects to the hypothalamus and brainstem autonomic nuclei. Two pathways connect the amygdala and the hypothalamus: the ventral amygdalofugal pathway (#6644) and the stria terminalis.
[The stria terminalis leaves the posterior amygdala to accompany the tail of the caudate nucleus in the roof of the temporal horn. It has a semicircular course, immediately medial to the C-shaped caudate nucleus. In the body of the lateral ventricle, this tract lies in the groove between the caudate nucleus and the thalamus, next to the thalamostriate vein (vena terminalis) (fig 14b) and can be seen in coronal sections through the thalamus (#5956). In humans, axons of the stria terminalis mainly descend behind the anterior commissure to reach the preoptic area and the hypothalamus (fig 14c).]
Amygdala clinical correlations: fear
- The human amygdala is involved in recognizing fear-related stimuli such as fear in facial expressions, voice, or body posture. Lesions of the amygdala in humans cause impaired recognition of the facial expression of emotional states, especially fear.
- The aura of fear that may accompany complex partial seizures (temporal lobe epilepsy) is most likely due to involvement of the amygdala. Another type of aura that may occur is olfactory hallucinations (e.g., foul odors), probably due to involvement of the cortical amygdala or the adjacent piriform cortex.
- In human brains, the basolateral amygdala has the highest concentration of benzodiazepine receptors and thus is probably the critical site for the anxiety-relieving action of benzodiazepines (e.g., Valium®).
- The amygdala is central to theories of pathophysiology of some anxiety disorders, particularly posttraumatic stress disorder and social phobia (social anxiety disorder).
2. The septal nuclei: The septum pellucidum (#4800) is a thin sheet located between the right and left lateral ventricles. Rostrally, near the anterior commissure, the sheet is considerably thicker and houses the septal nuclei (#6600). These nuclei receive afferents from the hypothalamus and hippocampus. The hippocampal input is through the fornix (#6652), which courses through the septal nuclei (#6653). The septal nuclei project to the hypothalamus.
[Information on the role of the septal nuclei in humans is limited. Hypersexuality has been reported following septal damage in humans. Temporary hyperemotionality and increased rage reactions have also been reported.]
- Limbic Parts
- Limbic Zoom
- Amygdala and relation to the ventricles
- Septal Nucleus and Basal Nucleus region
- Accumbens Nucleus
- Complex Partial Seizure (Ottawa)
- Limbic Parts
- Limbic Zoom
- Septal Nucleus
- Hippocampus and Septal Nuclei
- Innominata region of basal nucleus, septal nuclei and accumbens