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7:30-10:00 Limbic System

MWF Physiology
Anatomy Bldg. Emmylou Jane B. Valencia, M.D.

OUTLINE Components of the Limbic Lobe

I. Limbic System
II. Hippocampal Formation
III. Memory
IV. Amygdala / Amygdaloid Complex
V. Cingulate Gyrus
VI. Overview of the Limbic System

LIMBIC SYSTEM

Limbic Lobe

 Synthetic lobe whose parts are derived from the different lobes of
the brain (frontal, parietal and temporal)
 Formed of:
o Archicortex (hippocampal formation and dentate gyrus)
o Paleocortex (rostral parahippocampal gyrus and uncus)
o Juxtacortex or Mesocortex (cingulate gyrus)
 Limbic lobe PLUS all the subcortical and cortical structures
 Limbic Lobe related to it:
o A number of structures/gray matter on the medial and basal o Amygdala
surfaces of the hemisphere that form a LIMBUS (border or a o Hypothalamus (particularly the mammillary bodies)
ring) around the brainstem o Thalamus (particularly the anterior and medial thalamic
o First coined by Pierre Paul Broca (French anatomist, nuclei)
anthropologist, surgeon) in 1878 o Brainstem reticular formation
o Thomas Willis in 1664: cerebri limbus o Epithalamus
o Anterior pole of the temporal lobe, in the ventral portion of o Neocortical areas in the basal frontotemporal region
the frontal lobe, and in the cingulate gyrus lying deep in the o Olfactory cortex
longitudinal fissure in the midsurface of each cerebral o Ventral parts of the striatum
hemisphere
o This conglomerate of neural structures, which constitute the
old part of the brain and are highly interconnected, seems to
play a role in the following processes:
 Emotional behavior
 Memory
 Integration of homeostatic responses such as those
related to preservation of the species, securing food,
and the fight – or – flight response
 Sexual behavior
 Motivation

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 Superior Dissection of the Hippocampus and Fornix Papez Circuit

 Closed circuit of connections starting and ending in the

 Limbic System: Pathways/Tract hippocampus
o Alveus  It was suggested that the structures connected by this circuit play
o Fimbria a role in emotional reactions
o Fornix  The circuit consisted of outflow of impulses from the
o Mammillothalamic tract of Vicq d’ Azyr hippocampus via the fornix to the mamillary bodies of the
hypothalamus
Hippocampus and Fornix  From there, via the mammillothalamic tract, to the anterior
thalamic nucleus
 And then, via the thalamocortical fiber system, to the cingulate
gyrus, from which impulses returned to the hippocampus via the
entorhinal area

Neural Circuit for Emotion

Functions of the Limbic Lobe

 Emotion
 Behavior
 Drive
o Aggression
o Libido
 Memory
 Five F’s:
o Feeding
o Fighting  Proposed by James Papez and extended by Paul MacLean
o Family  Association areas function for interpretation
o Forgetting
o Fornication

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 HIPPOCAMPAL FORMATION

 Three Regions:
o Hippocampus
o Dentate Gyrus
 Toothed or beaded surface
 Occupies the interval between the hippocampus and
the subiculum part of the parahippocampus
o Subiculum/Parahippocampal Gyrus
 Direct continuation of the hippocampus Three Major Layers of the Hippocampus

Fields of the Hippocampus

Schematic Diagram of the Components of the Hippocampal
Formation

 CA1:
o Largest hippocampal field located in the superior division
o Sommer’s sector
o Vulnerable sector
Terminology o Highly sensitive to anoxia and ischemia
o Trigger zone for temporal lobe epilepsy
 Late 1500s, Arantius: Hippocampus (resemblance to a sea o Located near the subiculum
horse)  CA2 and CA3:
 1600s: Pes Hippocampus o In the inferior division
 1800s: Ammon’s horn or Cornu Ammonis (resemblance to o Resistant sectors
ancient Egyptian deity Ammon or to a ram’s horn)  CA4
 C – shaped structure in coronal sections, bulging into the inferior o Bratz sector
horn of the lateral ventricle o Transition zone between the hippocampus
 The hippocampus is closely associated with the adjacent dentate o Medium vulnerability
gyrus and together, they form an S – shaped structure o Located near the dentate gyrus
 These fields are involved in hypoxia and memory

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 Neuronal Population in the Hippocampus  Travels through (perforates) the adjacent subicular
area enroute to the hippocampus and the dentate
gyrus
o Alvear Path
 Smaller input
 Arrives in the hippocampus at the ventricular surface,
where the alveus is formed

 Principal Neurons
o Only neurons with axons which contribute to the outflow tract
from the hippocampus
o More densely packed in the superior region than the inferior
region
Efferent Pathway
o Axons of pyramidal cells are directed toward the ventricular
surface, where they gather to form the alveus and fimbria
and finally join the fornix as the outflow tract from the
hippocampus
o Recurrent axon collaterals terminate within stratum oriens or
reach the molecular layer
o Influence facilitation
 Intrinsic Neurons
o Axons remain within the hippocampus
o Polymorphic neurons
o Inhibitory (GABAnergic) to the pyramidal cell activity

Afferent Pathways

 The output from the hippocampal formation consists of axons of

 Figure above shows reciprocally, hippocampal output originating
in CA1 and the subiculum is relayed back to the entorhinal cortex
 The bulk of extrinsic input to the hippocampal formation comes
from the entorhinal area (Brodmann's area 28) of the
parahippocampal gyrus and, to a lesser extent, the septal area
 Other inputs include those from the contralateral hippocampus,
hypothalamus, amygdala, thalamus, locus ceruleus, raphe nuclei,
and ventral tegmental area of Tsai
 Two Routes:
o Perforant Path
 Main input
pyramidal neurons in the hippocampus and subiculum
o Axons of granule neurons in the dentate gyrus have no
extrinsic connections but terminate locally as mossy fibers on
hippocampal pyramidal neurons
o Both the hippocampus and the subiculum project on the
entorhinal cortex
 Subiculum – originating fibers constitute the major component
of the fornix
o Distributed, via its postcommissural division, to the
mammillary bodies of the hypothalamus and the anterior
nucleus of the thalamus
 Hippocampal – originating fibers in the fornix constitute its
smaller precommissural division
o Distributed to the septal nuclei, the medial area of the frontal
cortex, the anterior and preoptic hypothalamic nuclei, and the
ventral striatum

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 Fornix
 Fiber bundle that reciprocally connects the hippocampal
formation with a number of subcortical areas including the
thalamus and septal regions
 Thalamus functions not only for motor and sensory, but also for
memory and emotion
o Small infarct to the thalamus, the patient has difficulty in
remembering
Entorhinal – Hippocampal – Entorhinal Circuitry
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Functions of Hippocampal Formation
 Modulation of:
o Aggressive behavior
o Autonomic and endocrine functions
o Certain forms of learning and memory
 Intoxicated patients or patients with infarct to the
temporal lobe affecting the hippocampus, memory is
affected, patient tends to be aggressive
 Endocrine Functions:
o Significant inputs of the HF to the hypothalamus 
modulates endocrine functions associated with
hypothalamus
o Supporting evidence:
 Estradiol concentrating neurons are densely packed in
the ventral regions of the hippocampal formation
 Corticosterone as well
 Stimulation of the HF inhibits ovulation (rat studies)
 Lesions in the hippocampus or the fornix disrupt the
diurnal rhythm for ACTH release
 Aggression and Rage
o Experimental studies in animals
 Activation of the part of the hippocampal formation
closest to the amygdala facilitates predatory attack
behavior
 Activation of the HF near the septal formation
suppresses the aggression
 Lesion to this area causes seizures or aggressiveness
o In humans, published reports linking lesions, tumors, and
epileptogenic activity of the hippocampal formation with
aggressive reactions (varied; hostility and explosive acts of
physical violence
 Learning and Memory
o Case of H.M. (Henry Molaison)
 Temporal lobe epilepsy  underwent removal of the
both medial temporal lobe  after the surgery, lost the
capacity for consolidating short term memory to long
term memory
 May be seen also in patients after a heart attack,
developed amnestic syndrome similar to HM
MEMORY
 Explicit “Knowing that”
o Conscious retrieval of information
o Supports the learning and retention of facts and the
conscious recollection of prior events
o Episodic (Unique)
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  Short Term Memory / Working Memory: memory of AMYGDALA/AMYGDALOID COMPLEX
limited amount of information (e.g. 7 – digit phone
number; decays in seconds if not refreshed  Amygdala
continuously) o “Almonds”
 Long Term / Remote Memory: memory that can be o Located at the tip of the temporal lobe beneath the cortex of
retrieved after delays the uncus and rostral to the hippocampus and inferior horn of
 Semantic (Generic): memory of culturally and the lateral ventricle
educationally acquired encyclopedic knowledge (e.g.
math, historical information, etc.)
 Implicit “Knowing how”
o Supports learning and retention of skills
o Memory of experience-affected behaviors that are performed
unconsciously
o PROCEDURAL MEMORY
 Repeated performance of motor act
 E.g. biking: enhances and automates future skill of the
same act; resistant to forgetting
 Priming: short lived enhancement of perceptually
based performance following recent exposure to
visually similar object

Anatomic Correlates of Memory

 Episodic Memory
o Mesial temporal cortex (hippocampus, entorhinal cortex
and parahippocampal gyrus) are critical for this type of
memory
o Dealing with epileptic patients, you must go back to the  Functions:
history o KEY to emotional experiences
o Unable to acquire new explicit memory (anterograde o What stimuli are responded to
amnesia) o How overt responses these stimuli organize
o No new information is retained beyond the span of 40-60 sec o Internal responses of the body’s organs
o Other brain structures implicated in episodic memory:  Damage to the amygdala:
 Hippocampus-mammillary body-anterior and medial o Loses the ability to recognize affective meaning of facial
thalamic nuclei via the fornix and mammillothalamic expression especially threatening faces
tract o Fail to recognize the affective content of speech
 Cortico-cortical connections from the anterior and o CENTRAL ROLE IN EMOTION REGULATION,
posterior neocortices to the entorhinal cortex ESPECIALLY IN RELATION TO VIOLENT BEHAVIOR
 Basal forebrain cholinergic nuclei
 Short Term Memory (Working) Amygdalar Nuclei
o 2 separate neural systems that handle verbal and non –
verbal information  2 Main Groups
o Patients with left hemisphere dominance for language o Corticomedial – central group
 Left Prefrontal Cortex subserves the working memory o Basolateral group
for the verbal material
 Right Prefrontal Cortex subserves working memory
for nonverbal material
 Semantic Memory
o Temporal, parietal and occipital lobes
o Right hemisphere damage is more important than left
hemisphere damage
o Malignant infarct causes memory problem  can lead to
coma or herniation
 Procedural (Skill Learning) Memory
o Function of subcortical circuits particularly in the basal
ganglia and cerebellum
o Fine and gross motor skills
 Priming
o Not certain

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 Basolateral Nuclei
 Largest division
 Thought to attach the emotional significance to a stimulus
 RECEIVES information about the particular characteristic of a
stimulus from higher-order sensory cortical areas in the temporal
and insular cortical areas and from association cortex
 Major EFFERENT connections are directed back to the cerebral
cortex, either directly or indirectly
 CORTICAL AREAS receiving direct projection are:
o Limbic association cortex
o Cingulate gyrus
o Temporal pole
o Medial orbitofrontal cortex
o Prefrontal cortex
o Projects directly to hippocampus
 thought to be important in learning the emotional
significance of complex stimulus
 INDIRECTLY connect to the cortex
 Via VENTRAL AMYGDALOFUGAL PATHWAY  medial dorsal
nucleus (thalamic relay for association areas in the frontal lobe)
 Projection to the cholinergic forebrain neurons located in the
basal nucleus
 Project to the central amygdala nuclei: important in mediating
responses to emotional stimuli
Centromedial Nuclei
 Central Nuclei
o Mediate emotional responses
o Regulate autonomic nervous system
o RECEIVE viscerosensory input from the brainstem nuclei,
in particular, the solitary nucleus and the parabrachial
nucleus
o KEY PATH for fear conditioning, which helps to shape
responses to emotional stimuli
o Substance abuse and dependence
 Medial Nuclei
o RECEIVE information from the olfactory bulb
o In animals, play a role in behaviors triggered by olfactory
stimuli especially sexual responses
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2 Main Output Pathways from the Amygdala
 STRIA TERMINALIS
o Arises predominantly from the corticomedial group
o Supplies the septal nuclei
o Anterior, preoptic, and ventromedial nuclei of the
hypothalamus
 VENTRAL AMYGDALOFUGAL
o Originates from the basolateral and central amygdalar nuclei
o Projects to thalamus (DM nucleus)
o Prefrontal, entorhinal area, cingulate
o Nucleus basalis, septal area, hypothalamus
Kluver-Bucy Syndrome
 Anterior parts of both temporal lobes are destroyed
 Changes of behaviour in the animal:
o Not afraid of anything (very aggressive)
o Extreme curiosity about everything
o Forgets rapidly
o Tendency to place everything in its mouth & sometimes even
tries to eat solid objects
o Strong sex drive: copulates with immature animals, animals
of the wrong sex, or even animals of different species
CINGULATE GYRUS
 Lies directly above the corpus callosum
 Anteriorly, it continues around the genu of the corpus callosum
and blends into the subcallosal gyrus of the medial orbitofrontal
cortex
 Posteriorly, the gyrus wraps around the splenium where it
connects with the parahippocampal gyrus
2 Major Subdivisions
 Anterior Cingulate Cortex (ACC)
o Executive function
o Part of network that includes OMPFC (orbitomedial prefrontal
cortex), amygdala, and insula
o Emotion, autonomic, and motor control
 Posterior Cingulate Cortex (PCC)
o Receptive function
o Part of network that includes hippocampal formation and
posterior parietal association areas
o Visuospatial and memory functions
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 Ablation of Anterior Temporal Cortex

 Kluver – Bucy Syndrome: consummatory behaviour

Ablation of Posterior Orbital Frontal Cortex

 Insomnia associated with intense motor restlessness

 Unable to sit still & moves about continuously

Ablation of Anterior Cingulate Gyrus & Subcollosal Gyrus

 Releases the rage centers of the septum and hypothalamus from

prefrontal inhibitory influence
 More vicious & much more subject to fits of rage than normally

Functions of the Limbic System

 Homeostatic mechanism for the preservation of the individual and

preservation of species
 Emotional behavior
OVERVIEW OF THE LIMBIC SYSTEM  Memory
 Matching up sensory input with the autonomic – endocrine drives
 Highly complex system that is interconnected by a multiplicity of and putting it into the context of situation
pathways and reciprocal circuits (e.g. hypothalamus)  Motivation
 Main components of the limbic system are densely  Remember that different functions of the limbic system are NOT
interconnected and are connected with neural systems that distributed equally among its components
subserve somatosensory, somatomotor and autonomic and  Hippocampus: memory
endocrine functions  Amygdala: emotion and sexuality
 Thus, they are in unique position to integrate exteroceptive and  Anterior Cingulate Gyrus: motivation
interoceptive information and are essential for maintenance of  Orbitofrontal Cortex: behavior
emotional stability, learning ability and memory function

Limbic Loop

 Afferent Limb
o Consists of the collaterals to the limbic system from the
pathway connecting neocortical association cortices with the
prefrontal association cortex
o Autonomic and endocrine are reciprocally connected with the
same limbic system centers that receive cortical collaterals
 Efferent Limb
o Consists of projections from the limbic centers to prefrontal
association cortex
 Prefrontal Cortex
o Plays a role in guiding behavior and is indirectly involved in
the initiation of movement
o The input from the limbic centers into the PFC subserves the
effect emotion on the motor function

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