Neuroanatomy

Limbic System I: The Hippocampus/Amygdala

Competencies:

  • Discuss what is meant by the concept of the extended limbic system.
  • Describe the Pappez circuit.
  • Describe the internal connections of the hippocampal formation.
  • Explain how these connections of the hippocampal formation contribute to cognitive processing and how disruption of these connections lead to the clinical manifestations seen in degenerative diseases such as Alzheimer's disease.
  • Explain how the anatomy of the amygdala provides a model for the integration of visceral and gustatory sensory information and the behavioral (e.g. affect, goal oriented) responses to those stimuli.

To master the material presented in this lecure:

Read ...

Purves text, Chapter 29, pp 599-603, 703-710
Haines, pp 276-279,206-209..

Look at the Review Questions below ...

Listen to the lecture and focus on the folowing points ...

  • The limbic system as originally defined by Paul Broca, consisted of those cortical and subcortical structures that were situated around the edge and ventricles (limbus = "lip") of the telencephalon.
  • The modern concept of the limbic system has broadened this view to encompass an "extended" reticulo-limbic system comprised of several converging and diverging circuits involved in the promotion and maintenance of arousal, attention, mood and affect, learning and memory, and the regulation of specific goal driven behaviors.

The Hippocampus

  • The hippocampus and dentate gyrus represent the morphologically distinctive three-layered archicortex.  Along with the subiculum and entorhinal cortex (paleocortex), the hippocampus is the critically important site for the formation of declarative memories and the processing and integration of these memories in order to transport them from short-term to long-term storage.
  • The hippocampus is positioned as a critical fulcrum in a neural circuit originally described by James Papez as a "circuit of emotion" and may actually be more appropriately characterized as a "circuit of learning".   Starting in the hypothalamus, components of this circuit include:
    • the mammillary nucleus
    • the mammillo-thalamic tract
    • the anterior nucleus of the thalamus
    • the anterior limb of the internal capsule
    • the cingulate bundle and cortex
    • the entorhinal cortex
    • the perforant/alvear paths
    • the hippocampus
    • the fornix
  • Equally, if not more important for cognitve function and the processing of declarative memories are the direct projections that travers the ansa lenticularis from the medial prefrontal cortex and anterior temporal lobe (olfactory system, amygdala).
  • The final output projections from the hippocampus (primarily subiculum; projections from CA1-3 project to contralateral hippocampus and to basal forebrain) gather in the alveus and form a bundle along the ventricular edge of the hippocampus called the fimbria.  At the caudal end of the hippocampus, the fimbria curves upward and becomes the fornix.  The fornix curves around following the lateral ventricle and descends behind the anterior commissure to terminate in the mammillary nucleus.
  • A precommissural component of the fornix terminates in the basal forebrain.  The precommissural fornix also contains axons of neurons from the major monoamine systems that project to the hippocampus.  The most prominent of these projections arises from the basal forebrain cholinergic system (medial septal nucleus, nucleus of the diagonal band of Broca).  These neurons are critically involved in the modulation of cortical activity necessary for the formation of long-term memory.
  • Temporal lobe epilepsies are often driven by seizures initiated in the hippocampus.  As noted early on by Somner, distinctive patterns of damage, affecting primarily the CA1 subfield pyramidal neurons, are seen.  Similarly, in Alzheimer's disease, neuronal loss is selective, affecting pyramidal cells of the CA1 and subiculum as well as the entorhinal cortex.  Neurons of the dentate gyrus and CA3 are relatively unaffected.

The Amygdala

  • The amygdaloid nuclei can be divided into three functional groupings: the phylogenetically older cortico-medial group, the phylogenetically younger baso-lateral group, and the extended central group which is functionally and anatomically associated with the nuclei of the basal forebrain.
    • The cortical group is an extension of the olfactory cortex and accessory olfactory system.  Through its connections with the preoptic, anterior and ventromedial hypothalamus, the corticomedial amygdala is primarily involved in the regulation of appetitvie and consummatory behaviors (e.g. reproduction, feeding, drinking, etc.)
    • The baso-lateral group is an extension of the insular, cingulate, and prefrontal cortex. Through its connections with the cingulate and prefrontal cortex plays important role in learning and memory (particulary emotional memories), motivation and planning.
    • The central and medial group of nuclei are an extension of the caudate nucleus; the central nucleus primarily extending from the ventral striatum, the medial nuclei an extension of the tail of the caudate. Both groups are involved involved in both the processing and integration of viscerosensory information from the brainstem ands filtering information from cortical inputs.
  • There are the two major pathways into and out of the amygdala: the stria terminalis, which projects from the amygdala and terminates in the telencephalic basal forebrain (pre-commissural component) and the anterior hypothalamus (post-commissural component); and the ventral amygdaloid pathway which wraps around the ansa lenticularis and joins the medial forebrain bundle. The primary thalamic relay is the dorsal medial thalamus.
  • Given the relationships between the cortex (lateral amygdala) and the caudate (medial, central amygada), the flow of information is identical to the "direct loop" associated with motor system function. The anterior hypothalamus becomes the key motor center for goal-oriented behavior elicited by sensory information processed by this amygdaloid "loop".
  • The medial forebrain bundle (MFB) is a major (but difficult to identify) pathway that runs in the lateral hypothalamus.  The traffic is bidirectional:  axonal bundles which originate in the prefrontal cortex, amygdala and hypothalamus with projections to brainstem control centers converge in the MFB.   Likewise, reciprocol projections carrying viscerosensory information from the brainstem to hypothalamic and telencephalic integration centers similarly converge in the bundle.
  • Four important and neurochemically distinct brainstem systems exert diffuse but critical modulatory influences on limbic function:
    • Dopamine neurons of the ventral tegmental area that project to the nucleus accumbens and prefrontal cortex are critically important in the regulation of goal-driven behaviors and are involved in the both the pleasurable and addictive effect of most drugs of abuse.  This system is thought to be the substrate for the pharmacological effect of psychotropic agents used to treat schizophrenia.
    • Locus coeruleus neurons of the dorsal pons use noradrenaline as their primary neurotransmitter.  These neurons have wide-spread projections throughout the neuroaxis and are important for the maintenance of arousal and attention, mood and affect, learning and memory.
    • Serotonergic neurons of the dorsal raphe and raphe medianus have unique wide-spread projections to the diencephalon and telencephalon similar to locus coeruleus neurons.  They are also important for the maintenance of arousal and attention, mood and affect, learning and memory.  Atypical antidepressant agents like fluoxetine (Prozac) as well as drugs such as fenfluramine uniquely target the ascending serotonergic system.
    • The cholinergic neurons of the basal forebrain (medial septum, bed nucleus of the diagonal band of Broca and nucleus basalis of Meynert) work in concert with the noradrenergic and serotonergic brainstem projections to modulate and enhance hippocampal and cortical function and have significant effects on learning and memory.  This system, which is severly affected in Alzheimer's disease, is the common target of so-called memory enhancing drugs.

 

Consider the Following Questions ...

  • Your patient can look up a telephone number and read it to you, but cannot memorize the number long enough to dial. What areas of the brain are likely to be involved?
  • The serotonergic, noradrenergic and cholinergic innervation of the hippocampus comes from which nuclei?
  • A limbic circuit including mammillary bodies, anterior thalamic nucleus and anterior cingulate gyrus would be completed by what tracts and additional structures?

Copyright © 1997- 2014 [University of Illinois at Chicago, College of Medicine, Department of Anatomy and Cell Biology].  Last revised: December 31, 2013.