The Limbic System[1]

8/14/2019 The Limbic System[1]

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The Limbic System

Juan Enrique Toro Perez

UWO Fellow Neurology Residents

Neurosciences Review

Tutor: Jorge Burneo


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Objectives Revisin historica

Introduccion al sistema lmbico

Funciones mas importantes de los componenetes del

sistema lmbico:

Anatomy Neurons & nuclei

Neuroconnections

Neurotramsmitters

Functions

Correlacin clnica

Quiz


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The limbic system is a network of diverse cortical & subcortical

structures located mainly medially & ventrally & involved in the

preservation of self & species.

Limbus - boarder as it boarders the corpus callosum

In most mammals except primates & cetaceans, it is the largest area of

the brain.


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Paul Broca (1878) - 'Grand lobe limbique'

James Papez (1930)limbic system important in emotion Paul Bucy & Heinrich Kluver (1930)Kluver-Bucy syndrome in

rhesus monkey with temporal lobe removal: placid behaviour,

visual agnosia, oral tendancies, hypersexuality. Later work showed

that removal of the amygdala alone in humans could cause these

features.

James Papez (1937)Papez circuitcircuit involving many limbic

structures.

Donald Hebb (1940s)Hebb rule: When an axon of a cell A

excite(s) cell B & repeatedly or persistently takes part in firing it,

some growth process or metabolic change takes place in one or

both cells so that As efficiency as one of the cells firing B is

increased.

Paul MacLean (1950)limbic structures were responsible for

visceral function & called these structures the Limbic System to

explain how emotional affect influences autonomic responses.


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Patient H.M. - Henry Gustavo Molaison(Feb 26, 1926 - Dec 2, 2008; Hartford, Connecticut)

In 1953 at the age of 27 years HM had bilateral

medial temporal lobe resection for his medically

refractory epilepsy. Resection included hippocampal

formations and parahippocampal gyri.

Result:

Seizures improved

Repetition intact

Recall impaired

Anterograde amnesia & retrograde amnesia for severalyears preceding his surgery

Able to learn new tasks not requiring conscious recall

Personality & general intelligence were preserved


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James Olds & Peter Milner (1954)rats implanted with brain

electrodes would repeatedly stimulate specific regions on their

own. They could go on for extended periods without sleeping oreating.


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Overview of the LimbicSystem


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Components of the Limbic System

Limbic Cortex Parahippocampal gyrus Cingulate gyrus

Medial orbitofrontalcortex

Temporal pole

Anterior insula Hippocampal Formation

Dentate gyrus

Hippocampus

Subiculum

Amyglala Complex Olfactory Cortex

Diencephalon Hypothalamus Thalamus

Anterior nucleus

Mediodorsal nucleus

Internal medullary lamina

Habenula

Basal Ganglia Ventral striatum

Nucleus accumbens

Ventral caudate &putamen

Ventral pallidum Basal Forebrain

Septal Nuclei

Brainstem


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Limbic Cortexmedial view


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Limbic Cortexinferior view


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Limbic Cortexlateral view


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Cortical Structure


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Neurotransmitters

Influencia modulatoria en estructuras lmbicas:

Dopamine: Brainstem ventral tegmental nuclei

Through medial forebrain bundle & connect with cingulate gyrus, hippocampus, amygdala

Serotonin: Brainstem dorsal & median raphe nuclei

Project diffusely & synapse on limbic structures Noradrenergic system

Brainstem nuclei

Projects diffusely & synapse on limbic structures

Cholinergic system: Arise from medial septal nuclei, nucleus of diagonal band & nucleus basalis of Meynert

Projects diffusely & connects with limbic system

Activate muscarinic receptors

Modulate neuronal excitability & synaptic plasticity.

GABA: Septal nuclei of hippocampal formation


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Components& Functions

Key Structure Function Mnemonic

Hypothalamus

Homeostasis

Autonomic

Neuroendocrine

H

Olfactory cortex Olfaction O

Hippocampal formation Memory M

AmygdalaEmotions

Drives E


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Neuroconnections


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Limbic Cortex

Hippocampal Formation

Amyglala Complex

Olfactory Cortex

Diencephalon

Hypothalamus (Homeostasis) Thalamus

Anterior nucleus

Mediodorsal nucleus


Habenula

Basal Ganglia Basal Forebrain

Septal Nuclei

Brainstem


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Hypothalamus (1893 Wilhelm His)

Anatomy

Below the thalamus

Optic chiasm rostrally & midbrain

tegmentum caudally

Forms floor & ventral wall of the 3rd

ventricle

Landmarks - Optic chiasm, median

eminence, Infundibulum, Pituitary,

tuber cinereum, mammillary

bodies, hypothalamic sulcus,

anterior commissure,

Continuous with posterior pituitary

via infundibular stalk


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Nuclei

Regions anterior to posterior

Preoptic

Anterior (supraoptic)

Middle (tuberal)Posterior (mammillary)

Regions medial to lateral

Periventricular

Periventricular nuclei

Medial hypothalamic

Preoptic area Medial preoptic nucleus

Anterior (supraoptic) nucleus Anterior hypothalamic nucleus

Supraoptic nucleus

Paraventricular nucleus

Suprachiasmatic nucleus

Middle (tuberal) area Arcuate nucleus

Ventromedial nucleus Dorsomedial nucleus

Posterior (mammillary) area Medial mammillarynucleus

Intermediate mammillary nucleus

Lateral mammillary nucleus

Posterior hypothalamic nucleus

Lateral hypothalamic

Lateral preoptic nucleus

Lateral hypothalamic nucleus

Medial & lateral nuclei separated by fibres

from the fornix passing to the mammillary

bodies


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Portal Circulation &

Neuroendocrine FunctionPeriventricular nuclei secrete releasing or

inhibiting peptides & dopamine (prolactin

release inhibiting factorPIF) into the portal

circulation at the median eminence.

These peptides travel to the anterior pituitary

& control secretion anterior pituitary hormones

Paraventricular & supraoptic nuclei produce

arginine vasopressin (AVP) or ADH & oxytocin &

project to the posterior pituitary

The hypophysial arteries are both branches

of the internal carotid artery


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Neuroconnections

Mainly paraventricular nuclei

project to reticular formation &

preganglionic neuron of both

parasympathetic & sympathetic

divisions of the autonomic

nervous system

Limbic-hypothalamic

interconnections important inemotional influences on the

autonomic pathways


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FunctionsHomeostasis

Circadian regulation (suprachiasmatic n.)

Appetite (lateral hypothalamus +, VMN -)

Water intake

Endocrine regulation

Autonomic regulation

Motivation & emotional behaviour

Sexual development

(Review the anterior pituitary functions)


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Limbic Cortex Hippocampal Formation

Amyglala Complex

Olfactory Cortex (Olfaction)

Diencephalon

Basal Ganglia

Basal Forebrain

Septal Nuclei Brainstem


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Olfactory Cortex

Anatomy

Components of olfactory system: Olfactory bulb, olfactory tract, medial & lateral striae,

primary olfactory cortex (piriform & periamygdaloid cortex), entorhinal cortex (anterior portion

of the parahippocampal gyrus, Brodmanns area 28), perirhinal cortex, orbitofrontal olfactory

area

Olfactory bulb & tract are in the olfactory groove (between rectus gyrus & orbitofrontal gyrus)

Neurons

Olfactory receptor neuron passes through the cribriform plate

Axons called olfactory nerves synapse in olfactory bulb with mitral cells & tufted cells in the

glomeruli

Mitral & tufted cells project to olfactory areas

Collaterals in the olfactory tract synapse with other neurons in the anterior olfactory nucleus.

These project to the ipsilateral and contralateral olfactory bulb via the medial stria providing

feedback

Other neurons in the olfactory bulbperiglomerular cells & granule cells


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Dentate gyrus

Hippocampus

Subiculum

Amyglala Complex

Olfactory Cortex

Diencephalon Hypothalamus

Thalamus

Anterior nucleus

Mediodorsal nucleus


Habenula

Basal Ganglia

Basal Forebrain

Septal Nuclei

Brainstem

(Memory & Learning)


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Anatomy

Coronal section

Dentate gyrus (tooth-like bumps on the medial surface) Hippocampus

Subiculum (latinsupport)

Hippocampal formation is largest anteriorly (peshippocampus or hippocampal head)

Curves back along floor of temporal horn & tapers tohippocampal tail

This disappears as it curves under the splenium of thecorpus callosum

Indusium griseum - minor vestigial remnant ofhippocampal formation continues along the dorsum ofthe corpus callosum

Arterial supplyant 1/3 ant. Choroidal, post 2/3 PCA

Neurons & nuclei 3 layered archicortex

Embryologically folds x2 on self: Pial/gray matter surfaces of dentate & subiculum fuse

Ventricular/white matter surfaces of subiculum &parahippocampal gyrus fuse


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Neurons & nuclei

Dentate Gyrus

Molecular layer Granule cells (principal neurons)

Polymorphic layer

Hippocampus Molecular layer Pyramidal cell layer

Polymorphic layer

Subiculum Molecular layer

Pyramidal cell layer

Polymorpjic layer


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CA- Cornu Ammonis:Horn of the Ancient Egyptian ram

headed god Ammon

Molecular layers of

subiculum & denate are

apposed & form hippocampal

sulcus.

Axons of granule cells of

dentate are called mossy

fibres

CA 1-4 sectionsdifferent

pyramidal cell sectors.


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Neuroconnections Intrinsic circuitry

Perforant pathway Entorhinal cortex subiculum (through hippocampal sulcus)

dentate (granular layer) then axons/mossy fibresCA3

fornixor Schaffer collaterals synapse with CA1fornixor

subiculum fornixor entorhinal cortex

Alvear pathway

Entorhinal cortex CA1 & CA3 subiculum

Input & Output Connections

Entorhinal cortex - major relay between

association cortex & hippocampal formation

Subiculum - main source of output fibres from

the hippocampal formation to the fornix &

entorhinal cortex

Hippocampal commissureconnect

contralateral hippocampi


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Circuit of Papez

Hippocampal formation fornixmammillary bodiesanterior thalamic nuclei

internal capsulecingulate gyruscingulumparahippocampal gyrus

hippocampal formation


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Neurotransmitters

Cholinergic modulation:

Inputs from cholinergic neurons in the medial septal

nucleus, nucleus of the diagonal band (of Broca) & nucleus

basalis (of Maynert) arrive via the fornix.

Additional modulatory influence from brainstem

nuclei:

Noradrenergic

Dopaminergic

Serotonergic

GABAergic


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Function: Consolidation of declarative memory

Structures involved:

Medial temporal lobe structures Hippocampal formation

Adjacent parahippocampal gyrus

Medial diencephalic memory areas: Thalamic mediodorsal nucleus

Anterior nucleus, thalamus Internal medullary lamina

Mammillary bodies

Other diencephalic nuclei lining the 3rdventricle

White matter networks

+/- Basal forebrain & cholinergic projections

(Review long-term potentiationLTP)


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Amyglala Complex (Emotion)

Olfactory Cortex

Diencephalon

Basal Ganglia

Basal Forebrain

Septal Nuclei

Brainstem


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Neuroconnections

Mainly Efferent Subcortical

1. Stria terminalisCM nuclei septal nuclei hypothalamus

Also projects to parabrachial n., n. of solitary tract, dorsal motor n. of

vagus, PAG, ventral tegmental area, SN & parts of the reticular

formation

These control CV, resp & gastric responses to fear & stress-related

behaviors.2. Ventral amygdalofugal pathwayBL nuclei through substantia innominata

ACh neurons in basal forebrain (n. basalis of Meynert) septal n.,

hypothalamus, cingulate cortex, olfactory areas.

Other pathways project to the prefrontal & cingulate cortical areas,

basal forebrain & mediodorsal thalamus

Also projects to adjacent hippocampal formation (subiculum &

entorhinal cortex)emotion can therefore influence learning &

memory processes.


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Cortical pathways


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Neurotransmitters

Basolateral nuclei - high [GABA receptors]Inhibitory

Benzodiazepines & other neuroleptics bind to these receptors

Serotonergic projections from the dorsal & medial raphe nuclei of thebrainstem

Targeted in depression SSRI

Dopaminergic from ventral tegmental area (central) of brainstem

Noradrenergic projections from locus ceruleus (central) of brainstem

Functions

Emotional significance to stimulifear, anxiety, aggression

Activity of septal areapleasure states

Neuroendocrine

Autonomic

Memory


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Limbic Cortex

Hippocampal Formation Amyglala Complex

Olfactory Cortex

Diencephalon


Nucleus accumbens (Rewards)

Ventral caudate & putamen

Ventral pallidum

Basal Forebrain Septal Nuclei

Brainstem


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Limbic Cortex Parahippocampal gyrus

Cingulate gyrus

Medial orbitofrontalcortex

Temporal pole

Anterior insula

Hippocampal Formation Dentate gyrus

Hippocampus

Subiculum

Amyglala Complex Olfactory Cortex

Diencephalon

Hypothalamus Thalamus

Anterior nucleus

Mediodorsal nucleus


Habenula


Nucleus accumbens

Ventral caudate &putamen

Ventral pallidum

Basal Forebrain

Septal Nuclei

Brainstem


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1. Epilepsy

Mesial temporal sclerosis (MTS)

Temporal lobectomy (90% cure in medically refractory MTS)

2. Limbic enceplalitis

The limbic cortex has immunological markers which are the

targets in certain conditions:

HSV 1 encephalitis

Limbic encephalitisparaneoplastic

3. Korsakoffspsychosis

4. Transient global amnesia5. TIA, stroke, ruptured ACA aneurysm (basal forebrain)

6. Traumatemporal pole contusions


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7. Early Alzheimers disease

8. Diffuse anoxia

9. Neoplasms (glioma, lymphoma, metastases)

10. Other Inflammatorysarcoidosis

11. Psychiatric:

Schizophrenia

OCD

Anxiety disorders

Mood disorders & depressionamygdala is the target of pharmacotherapy

Drug Addiction

Amphetamines & cocaine increase dopaminergic transmission to the nucleus

accumbens & the mesolimbic system

Alcohol, nicotine & heroin also do this in addition to other mechanisms.


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Quiz


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1. Define the Limbic system

2. List 4 components of the Limbic system

3. List 4 functions of the Limbic system

4. List 1 difference between CN I and other cranial nerves

5. What type of memory deficits would you expect in a patient with

bilateral hippocampal formation ressection? Give another location

where a lesion could produce similar memory deficits.

6. A nuclear complex in the temporal lobe that forms part of thelimbic system; its major functions concern autonomic, emotional

and sexual behaviour.

7. An axon tract, best seen from the medial surface of the divided

brain that interconnects the hypothalamus and hippocampus.

8. Outline Papez circuit9. How would you examine the Limbic system clinically?


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Answers:

1. Limbic system network of diverse cortical & subcortical structures

located mainly medially & ventrally & involved in the preservation

of self & species.

2. Slide 9

3. Homeostasis, olfaction, memory & emotion.

4. Projects directly to olfactory cortex without thalamic relay.

5. Declarative memory, anterograde amnesia & some retrogradeamnesia. Medial diencephalic structures.

6. Amygdala

7. Fornix

8. Hippocampal formation fornixmammillary bodies

anterior thalamic nuclei internal capsulecingulate gyruscingulumparahippocampal gyrus hippocampal formation

9. Mental status examination and look for signs of endocrine and

autonomic dysfunction.


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References

1. Blumenfeld H. Neuroanatomy through clinical cases. Sinauer Associates. Massachusetts.

2002.

2. Purves D., et al. Neuroscience Fifth Edition. Sinauer Associates Inc. 2012.

3. Pritchard T.C. & Alloway K.D. Medical Neuroscience First Edition. Integrated Medical

Sciences. 1999.

4. Swenson. Review of clinical & functional neurosciences. Dartmouth Medical School.2006.

5. Netter F.H. & Hansen J.T. et al. Atlas of Neuroanatomy & Neurophysiology Special

Edition. Icon Custom Communications. 2002.

The Limbic System[1]

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