The Limbic System

Cortical structures of the limbic lobe:

Sub-cortical structures of the limbic lobe:

  Subcortical nuclei of the limbic system include:
 Septal nuclei
 Nucleus accumbens
 Hypothalamic nuclei
 Mamillary body
 Amygdaloid complex and the adjacent substantia innominate
 Dorsal thalamus (particularly anterior and dorsomedial nuclei)
 Habenular nuclei
 Ventral tegmental area (VTA)
 Periaqueductal grey (PAG) – remember this is involved in the experience of pain
 Prefrontal cortex  targets the cingulate gyrus, and certain subcortical
structures such as the hypothalamus, dorsal thalamus, amygdaloid complex and
nuclei of the midbrain

Major efferent bundles of the limbic system:

 Fornix
 Primarily efferents of the hippocampus and subiculum
 Stria terminalis and Ventral amygdalofugal pathway
 Mainly efferents from the amygdaloid complex
 Mammillothalamic tract
 Efferents of the medial mamillary nucleus

Cytoarchitecture of the limbic cortex:

 Unlike the neocortex which typically is composed of a 6 layered cortex, the limbic
cortex (like the olfactory cortex) have fewer than six layers
 Classified as allocortex
 Three to five cellular layers  paleocortex (periallocortex)  parrahippocampal
gyrus (the entorhinal cortex), the uncus (piriform cortex) and the cortex overlying
termination of the lateral olfactory gyrus
 Structures with only three cellular layers  archicortex (allocortex)  dentate
gyrus and hippocampus

Papez Circuit:
 Circuit for the elaboration of emotion
 Proposed circuit involved:
 Emotion is mediated through the hypothalamus and is controlled and modulated
by fibres from the fornix
 Originating in the cingulate gyrus, the circuit projects to the hippocampus and
the entorhinal cortex through the cingulum
 The hippocampus then projects to the mamillary nuclei through the fornix by
coursing through the postcommissural fornix
 The medial mamillar nucleus in turn projects to the anterior nucleus of the
thalamus through the mammillothalamic tract
 The anterior nucleus of the thalamus then projects to the cortex of the cingulate
gyrus
Blood supply to the limbic system:
 Mainly through anterior and posterior cerebral arteries
 Also receives supply from choroidal artery and branches from the Circle of Willis
 Most of the cingulate gyrus and its isthmus is supplied by the pericallosal artery
which is a branch of the ACA
 Temporal branches of the PCA (P3) supply the parrahippocampal gyrus
 The uncus is primarily served by the uncal artery which are branches of the M1
segment of the MCA
 The anterior choroidal artery generally arises directly from the ICA and follows the
general trajectory of the optic tract
 It sends branches into the choroidal fissure of the temporal horn of the lateral
ventricle
 This vessel serves the choroid plexus of the temporal horn, the hippocampal
formation, parts of the amygdaloid complex and adjacent structures such as the
tail of the caudate nucleus, the stria terminalis and the sublenticular and
retrolenticular limbs of the internal capsule
 Vessels to the hypothalamic nuclei involves in the limbic system are primarily served
by branches from the circle of Willis
 Rostral areas are served by branches from the anterior communicating artery
and ACA
 Posterior areas are served by branches from posterior communicating artery and
proximal posterior cerebral artery
 The anterior nucleus of the thalamus ( an important synaptic station in the limbic
system) is supplied by thalamoperforating arteries – branches from the P1 segment
of the PCA

Hippocampal Formation:
 Subiculum, hippocampus and dentate gyrus
 Constitute the allocortex of Brodmann

Structure:
 Subiculum  transitional area between the allocortex (hippocampus) and the
periallocortex (entorhinal cortex) of the parahippocampal gyrus
 Can be subdivided into prosubiculum, subiculum proper, presubiculum and
parasubiculum
 Dentate gyrus and the hippocampus are made of three layers
 External layer: molecular layer – contains afferent axons and dendrites of cells
intrinsic to each structure
 Middle layer: granule cell layer – in the dentate gyrus, pyramidal cell layer – in
the hippocampus. Contains the efferent neurons of each structure
 Inner layer: polymorphic layer – contains axons of pyramidal and granule cells,
with few intrinsic neurons and many glial cells. It also contains the elaborate
basal dendrites of some larger pyramidal somata located in the pyramidal layer
known as double pyramidal cells (their dendrites extend into the external and
inner layer)
The hippocampus divisions:
 Based on cytoarchitectural criteria
 Designated as CA1-CA4 (CA = cornu ammonis, horn of Ammon)
 Area CA1 – parvocellular region which can be separated into two cell layers in
humans is found in the subiculum-hippocampal interface
 Area CA2 – is a mixed zone
 Area CA3 – magnocellular zone located within the hippocampus
 Area CA4 – located at the junction of the hippocampus and the dentate gyrus within
the hilus of the dentate gyrus

Afferent Fibres:
 Major input to the hippocampus is from entorhinal cortex through a diffuse
projection known as the perforant pathway
 These fibres terminate in the molecular layer of the dentate gyrus mostly, with
some termination in the subiculum and hippocampus
 Granule cells in the dentate gyrus, project into the molecular layer of CA3 in the
hippocampus
 CA3 neurons project to CA1 neurons of the hippocampus, which in turn give input to
the subiculum
 The subiculum also receives modest projection from the amygdaloid complex

The fornix:
 While majorly an efferent pathway from the hippocampus, it also conveys
cholinergic septohippocampal projections to the hippocampal formation and
entorhinal cortex
Efferent fibres:
 Hippocampal formation efferents originate primarily from the subiculum and to
some extent from the pyramidal cell layer of the hippocampus
 In both cases, these axons enter the alveus, coalesce to form the fimbria of the
hippocampus and continue as the fornix
 These fibres are glutamatergic and traverse the entire extent of the fornix – some
cross the midline in the hippocampal decussation anterior to the splenium of the
corpus callosum
 At the level of the anterior commissure, the fornix divides into postcommissural and
precommissural parts
 Subiculum fibres mainly give fibres to the postcommissural fornix which
terminate in the medial mamillary nucleus
 The precommissural fornix is composed of fibres arising from the hippocampus
and are diffusely organised distributing to the septal nuclei and medial areas of
the frontal cortex, preoptic and anterior hypothalamic nuclei as well as the
nucleus accumbens

Complete Circuit of Papez:

 Subiculum  medial mamillary nucleus (via the postcommissural fibres of the fornix)
 Medial mamillary nucleus  anterior nucleus of the thalamus (via the
mammillothalamic tract)
 Anterior nucleus of the thalamus  cingulate gyrus (via thalamocortical fibres)
 Cingulate cortex  entorhinal cortex, subiculum and hippocampus (via the
cingulum)
 Other areas of the cortex are includes largely through connections of the cingulate
gyrus which connects to most of the other areas of the brain

Limbic System and Memory:

 Consolidates long-term memories from immediate and short-term memories
 This means in patients with hippocampal formation lesions, they are unable to
form long term memories from short term memories

Hippocampal Formation Injury:

 Bilateral damage can occur after: myocardial infarction (sometimes), near-drowning,
severe hypoglycaemia due to a stroke
 The part of the hippocampal formation most vulnerable to anoxia is CA1
 Affected patients retain short-term memory but have difficult learning new
concepts because the short term memory cannot be retained as long-term
memory

Alzheimer Disease:
 The subiculum and entorhinal cortices are among the first sites in which
neurofibrillary tangles and neuritic plaques begin to appear
 This may be the cause for difficulties in declarative memory in AD
Thiamine Deficiency:
 May cause defects in memory
 Thiamine = vitamin B1, and is seen typically in the context of chronic alcoholism,
cancer cachexia or prolonged malnutrition which causes a characteristic
degeneration pattern in the brain
 The mamillary bodies are typically involved with incursion to the dorsomedial
nucleus of the thalamus and columns of the fornix. There is also a loss of neurons in
the hippocampal formation
 This is known as Korsakoff psychosis – patients show a defect in short-term memory
and consequently long term memory for events occurring after the onset of the
disease
 Signs and symptoms include confabulation (creating a synthetic memory)
 Thiamine deficiency may also manifest more acutely as a triad of eye movement
abnormalities, ataxia and confusion  Wernicke encephalopathy (which is
reversible)
 Korsakoff psychosis is irreversible

Long Term Potentiation and Memory:

 LTP is the supposed mechanism for formation of long-term memories from short-
term ones
 LTP:
 High temporal stimulation of a neuron leads to fast release of glutamate
 This activates NMDA receptors on the post synaptic neuron which triggers an
intracellular cascade which increases the amount of calcium in the post synaptic
cell
 Calcium activates proteins and kinases, which leads to the formation of nitric
oxide which can diffuse back into the presynaptic cell and permanently increase
the release of glutamate
 Overall this increases the likelihood of future stimulation
Amygdaloid Complex

Structure:
 Almond shaped group of cells in the rostromedial part of the temporal lobe
 Internal to the uncus
 Immediately rostral to the hippocampal formation and anterior to the end of the
temporal horn of the lateral ventricle
 Amygdaloid complex nuclei include:
 Larger basolateral group
o Extensive interconnections with cortical structures
 Smaller corticomedial group (including the central nucleus)
o More closely related to olfaction, and receives olfactory input,
hypothalamic input from the ventromedial, lateral, dorsomedial and
dorsal nuclei of the thalamus
o These nuclei are also believed to be involved in visceral function

Afferent Fibres:
 Basolateral cell groups receive input from the dorsal thalamus, the prefrontal cortex,
the cingulate and parahippocampal gyri, the temporal lobe and insular cortex, and
the subiculum
 Supply a wide range of somatosensory, visual and visceral information to the
amygdaloid complex
Efferent Fibres:
 Two major efferent pathways:
 Stria terminalis
 Ventral amygdalofugal pathway

Stria Terminalis  Mostly lies in the groove between the caudate nucleus
and the dorsal thalamus where it is accompanied by the
superior thalamostriate (terminal) vein
 Associated along it’s length with discontinuous
aggregations of cells called the bed nucleus of the stria
terminalis
 This tract is involved in distributing to various nuclei of
the hypothalamus such as: the preoptic nuclei,
ventromedial nucleus, anterior nucleus and lateral
hypothalamic area
 It also distributes to the nucleus accumbens, the septal
nuclei and the rostral areas of the caudate nucleus and
putamen
Ventral  Major efferent fibre bundle of the amygdaloid complex
amygdalofugal  Arise from the basolateral group and the central nucleus
pathway of the corticomedial cell group and follow two general
trajectories
 Axons arising primarily from the basolateral cells pass
medially through the substantia innominate to eventually
synapse in the hypothalamus and septal nuclei
 The substantia innominate gives rise to a diffuse
cholinergic projection to the cerebral cortex (may play a
role in exciting the cortex in response to behaviourally
significant stimuli)
 Basolateral group cells also project to frontal, prefrontal,
cingulate, insular and inferior temporal cortices
 Other fibres, majorly from the central nucleus of the
corticomedial group turn caudally and descend to the
brainstem and terminate in visceral nuclei (DMX), raphe
nuclei (magnus, obscurus, pallidus) and other areas like
the locus ceruleus, parabrachial nuclei and
periaqueductal gray