5. Limbic System anatomy,physiology and related pathology

Limbic system anatomy, physiology and pathology with crystal clear concepts...

1. NB1.23: Apply knowledge of the neuroanatomical organization of the
neocortex and limbic cortex to understand the regulation of learning,
memory, emotions, and higher cortical functions.
Givenaclinicalvignette,scenario,table,graph,ordiagram,studentsshouldbeableto:
NB1.23.1.Describethestructuresofthelimbicsystem,toincludehippocampus,amygdala,and
functionallyrelatedstructures.
NB1.23.2.Comparetheroleofpost-tetanicpotentiation(PTP)insynapticplasticityandshort-term
memorywiththeroleoflong-termpotentiation(LTP)inlong-termmemory.
NB1.23.3.DescribehippocampalfunctionusingthePapezcircuitanditsroleinlong-term
potentiation(LTP)andexplicitlong-termmemory,includingtheneuronalmechanismsinvolvedinLTP.
NB1.23.4.Comparethemechanismsofextrinsic(declarative)andintrinsic(procedural)memory,to
includetherolesofthePapezcircuitaswellasthecerebellumandstriatum.

2. NB1.23: Apply knowledge of the neuroanatomical organization of the
neocortex and limbic cortex to understand the regulation of learning,
memory, emotions, and higher cortical functions.
NB1.23.5.Describehowshort-termmemoriesaretranslatedintolong-termmemoriesusingthe
hippocampusandPapezcircuitwithreferencetolocationsoflesionsassociatedwithmemoryloss
(includingKorsakoff’ssyndromeandAlzheimerdisease).
NB1.23.6.Differentiateanterogradeandretrogradememoryandtherolesofdeclarative(extrinsic)
andproceduralmemory(intrinsic)inanterogradeandretrogradeamnesia.
NB1.23.7.Describehowtheamygdalainteractswiththecerebralcortextoproducecognitive
emotionalbehaviorswithreferencetoKluver-Bucysyndrome.
NB1.23.8.Describetheroleofthehypothalamusinexpressingtheoutputofthelimbicsystem,to
includestress-relatedactivationofthehypothalamic-pituitary-adrenal(HPA,CRH,cortisol)axisand
thesympatheticbranchoftheautonomicnervoussystem.

3. Limbic system
❖The term "limbic" was used originally to describe gyri that form a ring
or border(limbus is Latin for border) on the medial surface of the
cerebral hemispheres, around the corpus callosum and rostral
brainstem.
❖Limbic system includes cortical & subcortical brain structures located
mainly in the medial and inferior regions of the cerebral hemispheres.
❖Limbic system is involved in emotion, motivation, olfaction and
emotional association (behavior) with memory by its
interconnections between hypothalamus and neocortex

4. Limbic Lobe

5. ➢Thelimbiclobecomprisesaringofcortexonthemedialsurface
ofthebrain,whichspansacrossaspectsofthefrontal,parietal,
andtemporallobes.
➢Itconsistsoftheparahippocampalgyrus,thecingulategyrus,
andacontinuationofthecingulategyrusanteriorlyand
inferiorly,calledthesubcallosalgyrus.Thesecorticalareasare
interconnectedbyasubcorticalfiberbundlecalledthe
cingulum.
➢Thesubcorticalstructuresofthelimbicsystemincludes
hippocampus,amygdala,hypothalamus,septalnuclei,anterior
nucleusofthalamusandNucleusaccumbens

6. ➢Therearetwohippocampi,locatedin
eachhemisphereofthebrain.Theyare
seahorse-shapedandarestructures
mainlyassociatedasbeingthememory
centersofourbrains.
➢Episodicmemoriesareformedinthe
hippocampusandthenfiledawayinto
long-termstoragethroughoutother
partsofthecerebralcortex.
➢Thehippocampusalwaysplaysarolein
spatialnavigationandhasalsobeen
associatedwithlearningandemotions.
Hippocampus

7. ➢The hippocampus is also known as a site
where neurogenesis occurs –this means
that new nerve cells are made here from
adult stem cells (other one is Olfactory
receptors)
➢Due to the hippocampus’s involvement
in memory, damage to this area can lead
to severe memory impairments.
➢Damage can also be detrimental to
spatial memory, for instance,
remembering directions to locations
that should be familiar to the individual.
Hippocampus

8. ➢The amygdala is an almond-shaped structure,
located right next to the hippocampus. The
main function of the amygdala is in emotional
responses, including feelings of happiness, fear,
anger, and anxiety.
➢This area is also key for the formation of new
memories. The amygdala interacts with the
hippocampus by attaching emotional content to
memories.
➢‘Fear learning’ is also an element of the
amygdala.

9. ➢Fearful memories can be formed after only a
few repetitions, which can result in avoidance
of certain fearful stimuli.
➢Therefore, the amygdala is also linked with the
fight-or-flight response, as stimulating activity
in the amygdala can influence the body’s
automatic fear response.
➢Damage to the amygdala can result in more
aggression, irritability, loss of control of
emotions, and deficits in recognizing emotions,
especially recognizing fear.

11. The hypothalamus’ most basic function is in
homeostasis(maintaining a steady internal state).
This region controls autonomic functions such as
hunger, thirst, body temperature, blood pressure,
heart rate, and sexual activity.
The hypothalamus also serves as an interface between
the nervous system and the endocrine system and in
the regulation of sexual motivation and behavior.
The hypothalamus also has a role in controlling the
body’s response to stress.
In order to control these many functions
hypothalamus integrates information from other parts
of the brain and is responsive to a variety of stimuli
such as light, odor, stress and arousal.

12. The Hypothalamus Coordinates Drive-Related Behaviors
(1)Interconnections with various cortical and
subcortical components of the limbic system
that coordinate motivated behaviors.
(2) Outputs that influence the pituitary gland
coordinating hormonal changes.
(3)Interconnections with various visceral and
somatic nuclei, motor and sensory, of the
brainstem and spinal cord.
If the hypothalamus is impaired, this can lead to aggressive behavior, feeling over-stressed,
hypothermia, hyperthermia, fatigue, weight gain/loss, and an active/under active sex drive.

13. Imaginebeingonacampingtripandsuddenlyencounteringabearinthewoods.The
processesoccurringinthecortex(e.g.,visualprocessingofthebear)informthelimbic
system.Thelimbicsystemattachesanemotionalresponse(viatheamygdala)tothebear
andrelaysthatinformationtothehypothalamus.Thehypothalamussubsequently
mediatesautonomicresponsestothedangeroussituationbyactivatingthesympathetic
nervoussystem(causingincreasedheartrate,increasedbloodpressure,etc.)
CingulateGyrus:
Thecingulategyrusconnectsthelimbicsystemtootherportionsofthecerebralcortex
suchasthefrontalcortex.Itprovidesaconnectionbetweenthedecision-makingprocesses
thatoccurintheprefrontalcortexandtheemotionalinformationprocessedbythelimbic
system.Tobringthebearbackintothepicture,thisinteractiontakesthefearofthatbear
andallowsyoutodecidehowtobesthandlethesituation(e.g.,runfaraway).
Interactionofdifferentcomponentsoflimbicsystem

14. Connections of Limbicsystem
1. Fornix–Hippocampus with Mammillary Body (part of Papez Circuit)
–Emotion & memory
2. Medial fore-brain bundle (MFB) –Hypothalamus to Olfactory cortex,
septum, mid brain, reticular formation, medulla & neo-cortex
–Behavior & motivation
3. The Papez Circuit:
→ Cingulate gyrus → Hippocampus → Fornix → Mammillary
body → Mammillo-Thalamic tract→ Ant. nucleus of thalamus →
Cingulate gyrus
–Formation of Emotion and consolidation of episodic memory

15. 4. Longitudinal Stria –Hippocampus with septal area
–Pleasure & Memory
5. Stria Terminalis –Amygdala with Ventromedial Nucleus of
Hypothalamus & Nucleus tractus solitarius
–Emotional control of food intake
6. Diagonal band of Broca –Amygdala with septal area
–Pleasure & Emotion
7. Direct Amygdalo–Hypothalamic Fibers –
–Emotion & Autonomic Functions
Connections of Limbic System

16. Functions of Limbic system
“Brain for Emotion”
❖Amygdala: Involved in formation of emotion, anxiety, aggression, fear
conditioning, emotional memory and social cognition.
❖Hippocampus: Required for the formation of
Short term memory and long-term memories
❖Parahippocampal gyrus: Plays a role in the formation of spatial memory.
❖Mammillary body: Important for the formation of episodic memory
❖Septal area: The septal area is an important pleasure area of the brain.
❖Nucleus accumbens: Involved in reward, Pleasure and addiction;
(Pleasure center)
❖Hypothalamus: Regulates the autonomic nervous system via hormone
production and release. Secondarily affects and regulates blood
pressure, heart rate, hunger, thirst, sexual arousal and the circadian
rhythm sleep/wake cycle

17. Hippocampus → Fornix → Mammillary
body → Mammillothalamic tract→
Ant. nucleus of thalamus → Cingulate
gyrus → Hippocampus

18. Papez circuit begins and ends with the hippocampus and
functions to relay emotions and memories.
The hippocampus in the Papez circuit travels through the
fornix, which is a C-shaped bundle of fibers and is
considered the hippocampus’s major output.
The fornix relays hippocampal information to the
mammillary bodies, (parts of the hypothalamus) that are
important in forming episodic memories. The interactions
between the hippocampus and mammillary bodies are
particularly important for episodic memory, and the
latter’s destruction is associated with anterograde amnesia
as well as Korsakoff syndrome.
The mammillary body then sends outputs via the
mammillothalamic tract to the anterior nucleus of the
thalamus. The anterior nucleus of thalamus is associated
with emotional and memory information.

19. The anterior nucleus of the thalamus
relays the information cingulate gyrus via
the anterior limb of the internal capsule.
The cingulate gyrus is responsible for
emotion formation and processing, along
with learning and memory.
The information processed in the
cingulate gyrus then travels via the
cingulum fiber bundle to the entorhinal
cortex.
Entorhinal Cortex further processing the
memory information from the circuit
relays it back to the hippocampus via the
perforant pathway fiber bundle.

21. Damage to the Limbic System
•Damage to the limbic system is dependent on which region is affected.
•Amygdala damage could affect a person’s fear processing (especially in being unable
to recognize fearful situations), which could result in more risk-taking behaviors and
putting themselves in dangerous situations.
•Damage to the hippocampus could lead to deficits in being able to learn anything
new, as well as affecting memory.
•Hypothalamus damage can affect the production of certain hormones, including
those which can affect mood and emotion.

22. ❖Bilateral damage to the medial temporal lobes including
the hippocampus results in a profound loss of the ability
to acquire new information, known as anterograde
amnesia.
❖Anterogradeamnesia is evident early in Alzheimer’s
patients.
Anterograde Amnesia

23. What is Memory?
•Memory is defined as the acquisition, storage and retrieval of information.
•All animals learn things from their interaction with the environment.
•Human brain forms memories more effectively than others.
•Maximum behavioral flexibility and most efficiently adaptation to
environment
•Physiological basis of memory is neuronal plasticity

24. Types of Synaptic plasticity
(Important property of synapse)

25. Types of Synaptic plasticity
(Important property of synapse)
•1. Post-tetanic potentiation (PTP) –application of same stimulus
repeatedly increase the post-synaptic response which lasts up to 60s
(due to accumulation of Ca2+ in pre-synaptic terminals)
•2. Habituation(Post-tetanic Inhibition) –Is a simple form of learning.
With repeated stimulus gradual decrease post-synaptic response (due to
inactivation of Calcium channels in the pre-synaptic terminals).
Habituation is a classic example of nonassociative learning.
•3. Sensitization–Habituated stimulus when paired with a noxious stimulus
repeatedly cause augmented postsynaptic response (noxious stimulus
cause pre-synaptic facilitation)

26. •PTP is a short-lived increase in synaptic strength that occurs immediately
following a high-frequency stimulation of the presynaptic neuron.
•It is involved in short-term memory, which refers to the transient storage of
information for a brief period, typically lasting minutes to hours.
•PTP enhances the synaptic transmission, facilitating the transfer of signals
between neurons temporarily.
•However, it does not lead to lasting changes in the synaptic connections or
neural circuitry.
Post-tetanic potentiation

27. 4. Long-term potentiation (LTP) –
repeated stimulation of presynaptic
neuron enhance synaptic transmission
(Here changes take place in the post-
synaptic neuron).
It is prolonged & last for daysdue to
increase intracellular Ca2+ in the post-
synaptic neuron
Example –In hippocampus (helps in
memory formation).

28. Long-term potentiation (LTP)
•LTP is a long-lastingenhancement of synaptic strength that arises
from repeated or sustained stimulation of the synapses.
•It is a fundamental mechanism underlying long-term memory, which
involves the persistent storage of information that can last for days,
weeks, or even a lifetime.
•LTP results in structural and functional modifications of the synapses,
including an increase in the number of neurotransmitter receptors
and changes in dendritic spines, leading to more efficient synaptic
communication and the formation of stable neural connections.

29. •5. Long-term depression (LTD):
Noted in the hippocampus but occurs
throughout the brain in the same fibers
as LTP.
LTD is the opposite of LTP.
It resembles LTP in many ways, but it is
characterized by a decrease in synaptic
strength. It is produced by slower
stimulation of presynaptic neurons and
is associated with a smaller rise in
intracellular Ca
2+
It may be part of the mechanism by
which learning occurs in the cerebellum.

30. Memory traces (Development of
new neuronal pathways)
•New pathways developed for transmission signals through the neural
circuits of brain due to neuronal plasticity –‘memory trace’
•Memory traces can develop both cortical & subcortical level
•Memory traces develop at the cortical level is associated with intellectual
memory & at subcortical level associated with habitual memory.

31. Neuronal basis
•Reverberating circuit theory –Reverberating circuit connects
cortex with sub-cortical & brain stem nuclei. Continuous
discharge for certain length of time (up to 1 hour) in this circuit,
even after the stimulus is withdrawn, cause formation of
memory.
•(Concussion of brain, damaging this circuit knock out the
formed memory)

32. Types of memory
Two types –
•◼Short term memory (Recent memory)
&
•◼Long term memory (Past memory)

37. Short term memory
Mechanism which mediates memories of recent events that occurred
seconds to hours or days before is short term memory (STM).
Short term memory is of two forms –
•1. Instantaneous memory (Immediate short-term memory) –amount
of information a person can respond or repeat back immediately
•2. Working memory–longer form of short-term Memory. It can be tested in
a clinical setting by asking the patient to rearrange a series of mixed numbers
in ascending order. A patient with intact working memory would be able to
reorganize 10, 1, 5, and 7 in ascending order (1, 5, 7, 10).
Short term memory is responsible for “consolidation of memory trace” , a
process that eventually encodes memory & become long term memory.

38. Forms of memory
•1. Explicit memory or Declarative memory or Conscious
memory or Recognition memory or Awareness memory
•2. Implicit memory or Non-declarative memory or Unconscious
memory or Reflexive memory or Habit memory

39. Long term memory
Mechanism which recall the memories of remote past is long term memory
(LTM).
•LTM can be recalled or assessed by many different associations.
Long term memory of two types –
1. Declarative memory or conscious memory –for events, facts, images &
propositions (for explicit memory)
2. Non-declarative memory or unconscious memory or Procedural memory
for procedures to do cognitive operations (for implicit memory)

41. Explicit memory
•Associated with consciousness & awareness.
•Formation depend upon Hippocampus & portion of medial
temporal lobe
Two forms –
•Episodic memory –memory for events
•Semantic memory –for words, rules & languages etc

42. Implicit memory
•Totally unconscious memory.
•Formation does not process through Hippocampus (through various
other areas).
•Encoding (pathway) involves striatum & cerebellum.
Includes –
•1. Non-associative learning –Habituation (negative memory) &
Sensitization (positive memory)
•2. Associative learning –Classical condition reflex, Operant
condition reflex, skills, habits & priming
Example –cycling, typing, driving etc.

43. Explicit memory Implicit memory
1. Declarative memory 1. Non-declarative
2. Conscious memory 2. Unconscious
3. Recognition memory 3. Reflexive memory
4. Awareness memory 4. Habit memory
5. Episodic & Semantic memory 5. Procedural memory
6. Encoding at Hippocampus 6. Encoding at cerebellum and
striatum

44. Mechanism of memory formation
•Memory first formed as Working memory which by consolidation
becomes short-term memory, which by associating different cues &
neuronal plasticity becomes Long term memory, which are
established in various areas of neo-cortex.
•Amygdala for emotional aspect of memory
•Formation of Long-term memory (LTM) –involves & connecting
all areas of neocortex.

46. Defects In Memory
1.Retrograde amnesia –Loss of memory of the events immediately
preceding (sometimes of many days) a Brain concussion or
electrical shock therapy
2. Anterograde amnesia –Defects In consolidation of Recent Memory
into LTM:
•➢Lesions of Papez circuit, Thalamus, Hippocampus, Mamillary
body, Temporal Lobe, Basal fore-brain etc.
•➢Cause –removal of hippocampus and the portions of temporal lobe

47. Defects In Memory
3. Confabulation –“Honest Lying”: they spontaneously
describe events that never occurred
–Lesion of ventro-medial frontal lobe
–An apparently reasonable but imagined memory that fills
in gaps in what is forgotten
4. De’javuphenomenon –strange feeling of familiarity in new
surroundings
–Occurs in Temporal Lobe Epilepsy

48. Kluver-Bucy syndrome
❖Bilateral lesions of the amygdala and hippocampus causes Kluver-Bucy
syndrome.
❖Salient features are:
1. Tameness
2. Loss of fear
3. Decreased aggressiveness
4. Oral tendency (excessive tendency to examine objects orally)
5. Change in dietary habits
6. Visual defects
7. Excessive sex drive
8. Placidity (calm and does not easily become excited, angry, or upset.)
9. Psychic blindness
10. Hypermetamorphosis(Excessive attentiveness to visual stimuli with a tendency to
touch every such stimulus regardless of its history or reward value)
11. Anterograde amnesia

49. Korsakoff Syndrome
❖Isa memory disorder that results from vitamin B1 deficiency and is
associated with alcoholism.
❖Often follows an acute presentation of Wernicke encephalopathy (which
presents with ocular palsies, confusion and Gait ataxia)
❖Wernicke-Korsakoff syndrome presents with lesions found in the
mammillary bodies and the dorsomedial nuclei of thalamus.
❖Anterograde amnesia and confabulation with ophthalmoparesisand
ataxia make up the classic presentation of Korsakoff syndrome.
Ataxia make up the classic presentation of Korsakoff syndrome.

50. Alzheimer Disease
❖Alzheimer disease results from neuronal degeneration, beginning in
the hippocampus, that exhibit neurofibrillary tangles and amyloid
plaques.
❖Patients with Down syndrome commonly present with Alzheimer’s in
middle age because chromosome 21 is one site of a defective gene.
❖Accounts for 60% of all cases of dementia, incidence increases with
age.
❖Insidious onset, progressive memory impairment, mood alterations,
disorientation, aphasia, apraxia, and progression to a bedridden state
with eventual death.
❖5 to 10% cases are hereditary, early onset, and transmitted as
autosomal dominant.

51. Alzheimer’s Disease
•Alzheimer’s disease –Dementia due to destruction of cholinergic neurons
in nucleus basalis of Meynertin the basal forebrain, hippocampus (CA1
neurons), corpus striatum of basal ganglia, etc.
•First affects episodic memory (hippocampus)
•Later, affects semantic memory, (cortical regions just outside
the hippocampus).
•May affect working memory,
–inability to remember what they were trying to do
–inability to retrieve the other information that are required
for the task.

56. Defects In Memory
•1. Destruction of Amygdala along with hippocampus causes Severe
generalized Amnesia
•2. Attention deficit and hyperactivity disorder (ADHD) –problem in
working memory
•3. Post-traumatic stress disorder (PTSD): exaggerated sense of
emotional memory
•4. Parkinson’s disease patients often lose their ability to acquire new
motor skills or habits: a deficit in their procedural memory.
•5. Dementia : Mental deterioration of organic or functional origin