Limbic System Flashcards
Limbic System
Structures
Consists of interconnected cortical and subcortical brain structures:
-
Limbic lobe:
- uncus
-
parahippocampal gyrus
- formation of spatial memory
-
cingulate gyrus
- autonomic functions
- pain related emotions
- cognitive and attentional processing
-
hippocampus
- consolidation of long term memories
-
amygdala
- emotion, aggression, fear
- medial temporal gyrus
-
Orbitofrontal cortex
- emotion, memory, decision making
- Anterior insular cortex
-
Thalamus
- medio-dorsal nucleus
- anterior nucleus
-
Hypothalamus
- regulation of ANS via hormones
- ∆ BP, HR, hunger, thirst, sexual arousal, sleep/wake
-
Mammillary bodies
- formation of memory
- Septum
-
Nucelus accumbens
- reward, aversion, pleasure, addiction
- Ventral pallidum
Papez Circuit
Areas involved in expression and experience of emotion.
Added hippocampus, anterior nucleus of thalamus, most of hypothalamus, and mammillary bodies in addition to limbic structures.
Hippocampus → bodily expression of emotion.
Limbic system → mediating autonomic functions.
Limbic System
Circuits
Involved in memory, emotion, reward, motivation, goal directed behavior, and various autonomic functions.
3 most important circuits:
-
Memory circuit
⟾ involves hippocampus -
Emotion circuit
⟾ involves amygdala -
Reward circuit
⟾ involves nucleus accumbens and ventral tegmental area (VTA)
Extensive reciprocal connections between circuits.
Dysfunction associated with psychiatric disorders including schizophrenia, OCD, anxiety, depression, PTSD, and mania.
Memory
Definition
Memory = ability to store, retain, and retrieve information.
Divided into short term/working memory & long term memory.
Long term memory subdivided into declarative and procedural memory.
Short-term / Working Memory
- recall of recent events for a short time
- recall of moment-to-moment results of mental processing
- recall of info needed to accomplish a specific task
- prefrontal cortex plays a central role
Declarative Memory
The ability to store and recall info for days, years, or lifetime.
Type of long term memory:
-
Explicit / Declarative
- memory of facts and events
- prefrontal cortex → working memory buffer
- hippocampus involved in consolidation
- Also involves MD thalamus, basal forebrain, other limbic structures
- storage spread over associative cortical areas
- storing and recalling is conscious
- episodic memory → specific moment in time and place
- semantic memory → fact knowledge without context
Procedural Memory
The ability to store and recall info for days, years, or lifetime.
Type of long term memory:
-
Implicit / Non-declarative / Procedural
- memory for procedures and abilities
- motor skills
- habits
- conditioning
- emotional association
- priming
- storing and recalling is unconscious
- dependent on striatum, cerebellum, amygdala, brainstem, spinal motor outputs, and neocortex
- memory for procedures and abilities
Memory Classification
Summary
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Anmesia
A loss or disruption of memory.
Divided into 2 components:
-
Anterograde amnesia:
- impaired memory for info acquired after onset of memory loss
-
Retrograde amensia:
- impaired memory for info acquired before onset of memory loss
- less common
Hippocampus
Overview & Blood Supply
-
C-shaped in horizontal and coronal sections
- hippocampus proper named Ammon’s horn
-
Blood supply
- mainly from posterior cerebral artery
- hippocampal head partly from anterior choroidal artery
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Hippocampus
Location
Found in medial surface of temporal lobe next to inferior horn of lateral ventricle.
Anterior end near amygdala.
Caudal end near splenium of corpus callosum.
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Hippocampus
Efferents
Hippocampal pyramidal neurons:
- Axons exit via fimbria of fornix
- Curve around and continue as crus and body of fornix
- At anterior commissure, fibers split into pre and post commissural fibers
- Precommissural fibers → septum
- Postcommissural fibers → descend ventrally as columns of fornix → mammillary bodies
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Hippocampus
Structures
Hippocampal formation refers to 3 structures:
- Hippocampus proper (Cornu Ammonis)
- Dentate gyrus
- Subiculum
Hippocampus proper and dentate gyrus arranged as 2 interlocking C-shaped structures in cross section.
Contains rows of glutamatergic pyramidal cells and sparse GABAergic interneurons.
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Hippocampus Proper
(Cornu Ammonis)
Divided into 4 Cornu Ammonis areas:
CA1, CA2, CA3, and CA4
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Hippocampus
Layers
Entorhinal cortex (neocortex) contains 6 layers.
Hippocampus proper and dentate gyrus (archicortex) contains 3 layers.
Transition occurs within subiculum.
-
Hippocampus proper:
- polymorphic layer
- pyramidal layer
- molecular layer
-
Dentate gyrus:
- polymorphic layer
- granular layer
- molecular layer
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Hippocampus
Molecular Layer
Molecular layer is most superficial layer in entorhinal cortex (neocortex).
Becomes deepest layer in hippocampus proper.
Returns to most superficial layer in dentate gyrus.
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Hippocampus
Polymorphic Layer
Polymorphic layer is deepest layer within neocortex.
Considered an output layer.
Becomes most superficial layer in hippocampus proper.
Returns to deepest layer in dentate gyrus.
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Hippocampus
Internal Loop
Information to be consolidated into long term memory:
cortical association areas → entorhinal cortex → internal circuit loop
1) Entorhinal cortex via perforant path ⟾ dentate gyrus granule cells
2) Dentate gyrus granule cells via mossy fiber system ⟾ CA3 pyramidal neurons
3) CA3 via Schaffer’s collaterals ⟾ CA1 pyramidal neurons ⟾ subiculum
4) Subiculum ⟾ entorhinal cortex & cortical association areas for storage
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Hippocampus
External Loop
Pyramidal neurons in CA3, CA1, and subiculum receive inputs from entorhinal cortex.
Send axons in alveus which exit to form fornix
Fornix ⟾ septum and mammillary body
Mammillary body via mammillothalamic tract (MTT) ⟾ anterior nucleus of thalamus
⟾ cingulate gyrus
⟾ entorhinal cortex and cortical association areas for storage.
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Memory Consolidation
Involves hippocampus, entorhinal cortex, and various medial temporal structures.
Process unclear but classic hypothesis:
- structures temporarily store complete copy of memory
- memory gradually duplicated over time to various neocortical storage sites
- temporal lobe lesion ⟾ anterograde amnesia
- some retrograde amnesia seen
- info still in medial temporal region at time of lesion lost
- some retrograde amnesia seen
Spatial Memory
Hippocampus likely involved in storing and processing spatial memory.
- Rodents:
- Hippocampal neurons called “place cells” have spatial firing fields
- as animal moves along circular track, different cells fire at different locations
- creates a spatial or contextual map
- serves as framework for event memories created in that environment
- Hippocampal neurons called “place cells” have spatial firing fields
- Humans:
- Also have place cells
- hippocampus most activated during learning and recalling of specific routes
Flashbulb Memory
Highly detailed, exceptionally vivid “snapshot” of the moment and circumstances in which a piece of surprising and consequential new was heard.
Hippocampus
Long Term Potentiation
LTP extensively studied in hippocampus.
Model of synaptic plasticity and sustained ∆ in neural transmission.
Likely cellular basis of memory formation.
LTP results from high frequency stimulation of afferent pathways:
- Perforant path (PP) ⟾ granule cells of dentate gyrus
- Mossy fibers (MF) ⟾ pyramidal cells of CA3
- Schaffer collaterals (SC) ⟾ CA1 in hippocampus proper
Causes long-lasting ↑ in synaptic strength.
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Hippocampal Lesion
Results in Kluver-Bucy Syndrome
-
Anterograde amnesia
⟾ inability to transfer new short-term memory into long term memory-
explicit or declarative memory affected
- semantic memory ⟾ conscious memory of facts
- episodic memory ⟾ conscious memory of events
-
explicit or declarative memory affected
-
Short-term or working memory intact
- can keep info in memory for several seconds
-
Implicit or non-declarative memory intact
- can form motor skill, pattern recognition, habits, conditioning, emotional association, priming
- retain learning for as long as normal subjects
Hippocampus
in
Alzheimer’s Disease
- hippocampus among 1st damaged
- memory problems and disorientation among 1st symptoms
-
CA1 region particularly affected
- extracellular plaques
- intracellular tangles
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Hippocampal
Ischemia
Hypothalamus very susceptible to ischemia.
Selectively attacks CA1.
See pyramidal cell death d/t ischemia or stroke.
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Hippocampus
&
Seizures
Hippocampus very electrically excitable.
Often the focus of epileptic seizures.
Presence of strong glutamatergic transmission contributes.
Temporal Lobectomy
Rhesus Monkeys
- Results in:
- visual agnosia ⟾ psychic blindness
- oral tendencies ⟾ examine surroundings with mouths
- hypermetamorphosis ⟾ compulsion to explore
- emotions dulled
- loss of normal fear
- placidity
- hypersexuality
-
Herpes simplex encephalitis most common cause in humans
- visual agnosia, hypersexuality, loss of fear/anger
- anterograde amnesia
- dementia
- distractibility
- seizures
Korsakoff’s Syndrome
Brain disorder caused by chronic alcoholism, malnutrition, and thiamine (B1) deficiency.
Likely damages medial thalamus, hippocampus, and mammillary bodies.
Major symptoms:
- anterograde amnesia
- retrograde amnesia
- confabulation ⟾ making up stories
Often occurs along with Wernicke encephalopathy:
- ataxia
- confusion
- vision changes
Memory Circuit
Summary
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Cortical Association Areas
Interacts with parahippocampal region for memory formation but mechanism unclear.
Prefrontal cortex
Temporal lobe
Parietal lobe
Cingulate gyrus
Olfactory bulb
Amygdala
Functions
- attaching emotional significance to incoming stimuli
- form/store implicit (non-declarative) memory associated with emotional events
- unconscious emotional responses
- conscious feelings
- modulation of attention
- involved in explicit memory via processing of emotional meaning
Amygdala
Altered Function
∆ in amydala function associated with:
- stress
- psychiatric conditions
- anxiety disorders ⟾ PTSD, phobias, panic
- depression
- schizophrenia
- autism
Amygdala
Damage
B/l temporal lobectomy ⟾ ∆ emotional behavior
tame and fearless
Animals ⟾ loss of fear conditioning
Humans ⟾ impaired perception of emotional stimuli & emotional expression
Electrical stimulation in humans ⟾ feelings of fear and apprehension
Amygdala
Location
Small almond-shaped subcortical structure.
Buried in anterior-medial portion of temporal lobe.
Near anterior end of hippocampus.
Found beneath uncus in CS @ thalamus.
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Amygdala
Nuclei
Deep group ⟾ responsible for collecting input from sensory corticies.
-
Lateral nucleus (LA)
- major input nucleus for sensory info
-
Basal nucleus (B)
- major input nucleus for contextual info from hippocampus
- Accessory basal nuclei
Dorsal group ⟾ receives projections from deep group & sends signal out to autonomic centers.
-
Central nucelus (CE)
- main output nucleus
- Medial nucleus
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Amygdala
Afferents
Receives 5 main types of input:
- Olfactory input
-
Sensory input from sensory thalamic relay nuclei
- vision, audition, gustation, somatosensation
- Contextual input from hippocampus
- Cortical input
- Visceral sensory input from hypothalamus and brainstem
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Amygdala
Efferents
Must be able to control ANS.
Projects to hypothalamus and brainstem autonomic centers incuding vagal nuclei and SNS neurons.
Fibers leave via 2 main pathways:
- Stria terminalis (ST) ⟾ hypothalamus
- Ventral amygdalofugal pathway (VAFP) ⟾ hypothalamus & MD thalamus
Also involved in mood and conscious emotional response to an event.
Has projections to cortical areas, hippocampus, medial striatum.
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Amygdala
Input Pathways
Visual, auditory, gustatory, and somatosensory inputs to amygdala via 2 pathways:
-
Short route:
- sensory thalamus (VPL, VPM, LGN, MGN) directly to amygdala
- shorter and faster
- provides low-level info about objects and events (crude representation)
- designed to start fight-or-flight response
- info processed at unconscious level
-
Long route:
- sensory thalamus ⟾ sensory cortex ⟾ amygdala
- slower d/t processing time
- provides more complex and accurate info
- confirms or denies a threat
Entire process occurs unconsciously.
Involves implicit processing and implicit learning.
Olfactor inputs directly from olfactory bulb and olfactory cortex.
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Fear System
Amygdala works at subconscious level:
- identify potential threats
- initiate behavioral responses and autonomic reactions
- freeze, fight, or flight
- increases likelihood of surviving danger
1. See a spider
2. Info ⟾ thalamus
3a. Short route:
- crude representation of potential danger ⟾ amygdala
- lateral nucleus ⟾ central nucleus
- info processed subconsciously
- many outputs:
- hypothalamus, memory center, motor structures, reflex centers
- recognized as a threat (implicit memory store)
- fight-or-flight response initiated
3b. Long route:
- crude representation ⟾ visual cortex
- quality of representation improved d/t processing by primary and associative cortical areas (what & where regions)
- more complex and accurate representation of object ⟾ amygdala
- if threat confirmed, fight-or-flight strategy persued
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Associative Emotional Learning
Learn by associating situation, object, or event with an emotional experience.
Associative process for emotional memories occurs in amygdala.
Involves LTP-related synaptic plasticity.
Lesion of amygdala ⟾ loss of fear conditioning.
Modulation of Explicit Memory
- Events linked to strong negative emotional experience are better recalled
- Amygdala facilitates hippocampal consolidation of explicit memories tied to emtional situations
- Too much stress ↓ explicit memory performance
- maybe d/t stress hormones
- disrupts hippocampal and prefrontal pathways
- enhances amygdala’s contribution to fear
- maybe d/t stress hormones
Emotional Memory Storage
Emotional implicit memories (e.g fear) stored:
- directly in amygdala
- in adjacent regions requiring amygdala for access
Amygdala lesions abolishes emotional component of learned fear responses.
Face Fearfulness
-
Amygdala response ↑ as fearfulness ↑ and happiness ↓
- extract expression from eye shape
-
Perceive fearful expression faster than neutral or happy face
- happy face signals safety
- do not need immediate action
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Urbach-Wiethe
Disease
- Genetic disease causing b/l calcification & atrophy of anterior-medial temporal lobes
- Results in b/l destruction of amygdala
- Presenation:
- pt judges face showing fear to be much less intense
- unable to link visual representations of facial expressions with fear emotion
- no motor/sensory or intellect ∆
- no declarative memor ∆
- no language function ∆
- no difficulty recognizing people by faces
- can rapidly learn new faces
Amygdala
&
Autism
- Theory for social deficits
- Amygdala damaged
- Unable to link emotional meaning with stimuli
- Babies unable to connect faces with comfort/food
- Early social bonds needed for normal development not formed
- Pt w/ autism bad at judging emotional state of a person from a picture
- little amygdala activation
-
Eye-gaze processing deficit
- inability to use gaze to spontaneously to understand others
- Amygdala much smaller in size
Amygdala
&
PTSD
- In PTSD:
-
fragment of a experience“flashback” triggers full force of original emotion
- b/c implicit memory well preserved
-
fragment of a experience“flashback” triggers full force of original emotion
- Pt’s with PTSD show exaggerated amygdala responses to neg. stimuli by fMRI
-
Normal fear extinction d/t brain regulation of fear response
- Not forgetting emotional response
- Fear, stress, and trauma form permanent memories
- survival strategy
- Actual mech. for PTSD unknown
- Treat with psychotherapy or antidepressants
Amygdala
&
Prefrontal Cortex
Amygdala ↔ Neocortex
-
memory & imagination can cause emotional response
- promotes use of emotional info in cognitive processing
-
cortex → amygdala
- conscious thoughts can suppress emotional responses
- ability to stop initial reaction judged inappropriate
-
amygdala → cortex
- too much emotion from amygdala to working memory can disrupt prefrontal cortex function
- leads to bad decisions
- ex. stressful situations
-
amygdala → cortex >> cortex → amygdala
- anxiety often control thoughts
- thoughts have trouble supressing anxiety
Klüver-Bucy
Syndrome
Most commonly caused by herpes simplex encephalitis.
-
Damage to b/l hippocampi & temporal association cortices
- anterograde & graded retrograde amnesia
- dementia
- seizures
-
Damage to amygdala
- emotional deficits
- fearless
- decreased affect
- docile
- placid
- emotional deficits
-
Loss of decending cortical control over hypothalamus
- hyperphagia
- hypersexuality
- distractibility
-
Damage to “what” portion of visual pathway
- visual agnosia/psychic blindness
- can see but cannot recognize or interpret visual information
- inability to recognize faces/objects
- visual agnosia/psychic blindness
Emotion Circuit
Summary
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Reward Circuit
Overview
-
Promotes pleasure associated with certain actions
- Encourages repetition of behaviors
- May or may not be essential for survival
-
Involves:
- Ventral tegmental area ↔ Nucleus accumbens ↔ Prefrontal cortex, ventral pallidum, thalamus
- Reward ↔ Memory ↔ Emotion
- Major component from limbic structures
- motivation, goal directed behavior, memory, emotion, and autonomic functions
-
Rewarding experience or anticipation releases dopamine
- brain forms implicit (amygdala) and explicit (hippocampus) memories
- drugs of abuse ∆ release → addiction
Reward Circuit
Functions
-
Learning
- via positive reinforcement
-
Appropriate behavior
- taking rewards as goals of behavior
-
Positive emotion (hedonia)
- reward elicits pleasure and mood changes,
Reward Circuit
Associated Brain Processess
Involves:
- attention
- anticipation
- perception (visual and sensation)
- motivation
- emotion
- judgement
- movement coordination
- thinking and decision making
- short and long term memory
Reward Circuit
Neurontransmitters
- Dopamine → well-being, arousal, reward
- Opiods → reward and reinforcement
- Serotonin → behavioral inhibition
- GABA → inhibitory
- Glutamate → excitatory
- Ach → addiction to nicotine and other drugs
Ventral Tegmental Area (VTA)
Location
Found near midline in midbrain.
Next to substantia nigra and red nucleus.
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Ventral Tegmental Area (VTA)
Function
- Contains dopaminergic neurons
-
Origin of two major dopamine pathways:
-
Mesolimbic pathway
- VTA → nucleus accumbens
-
Mesocortical pathway
- VTA → prefrontal cortex
-
Mesolimbic pathway
- Rewarding activities activates VTA → dopamine release to all targets
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Nucleus Accumbens
Part of the ventral striatum (basal ganglia).
Important role in reward, pleasure, and addiction.
Part of the cortico-striato-thalamo-cortical loop.
- Includes a core and shell
- 95% of neurons are medium spiny neurons secreting GABA.
- main output neuron
- Large aspiny cholinergic interneurons fewer
-
N. accumbens activated by:
- dopaminergic afferents from VTA
- via mesolimbic pathway
- amygdala
- hippocampus
- prefrontal cortex
- dopaminergic afferents from VTA
-
Output:
-
inhibitory to ventral pallidum
- VP is also inhibitory
- ⟾ disinhibition of MD thalamus
- ⟾ excitation of prefrontal cortex
- ⟾ disinhibition of MD thalamus
- VP is also inhibitory
- inhibitory to substantia nigra and pontine reticular formation
-
inhibitory to ventral pallidum
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Reward Center
- N. accumbens is part of the “reward center”
- Direct relationship b/t [DA] released at VTA/NA synapse & rewarding effect
- Natural reinforcers (food, sex, eating) have some rewarding effect by ↑ DA transmission
-
Drugs of abuse tap into system
- produce reinforcing effect by ↑ DA transmission
- ∆ chemistry of system
Cocaine
Dopamine Reuptake Inhibitor
- prolonged ↑ [DA] at VTA/n. accumbens synapse
- causes rewarding effects
-
Tolerance
- repeated use → ↓ DA receptors → ↓ 2nd messenger signaling → tolerance
-
∆ sensitivity of reward system
- natural reinforcers less rewarding
-
Dependence
- cocaine use stops → low [DA] in reward circuit → withdrawal
- depression, insomnia, fatigue, restlessness
- cocaine use stops → low [DA] in reward circuit → withdrawal
-
Craving
- prefrontal cortex hyperresponsive to stimuli releated to drugs
- overstimulates nucleus accumbens
- promotes goal-directed behaviors for drug seeking → relapse
- Implicit emotional memories tied to drug use can activate prefrontal cortex and amygdala years later
Drugs of Abuse
Mechanisms
Directly or indirectly enhance DA signaling in nucleus accumbens.
-
Cocaine, amphetamines, related stimulants
- block DA reuptake
- increase DA release by VTA
-
Nicotine
- stimulates VTA release of DA
-
Alcohol and opiates
- inhibits local interneurons normally inhibitory to VTA
- indirectly promotes VTA release of DA
Drugs can also ∆ response of n. accumbens to glutamate input from other regions.
DA circuits more involved in “wanting” → incentive salience
Mu-opioid circuits more involved in “liking” → hedonic aspect
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Reward Circuit
Summary
- Pleasurable thoughts, memories, and activities activate VTA dopaminergic neurons
- DA released into reward circuit → activates GABA neurons in nucleus accumbens
- GABA neurons in n. accumbens inhibit GABA neurons in ventral pallidum
- GABA neurons in ventral pallidum inhibition on MD thalamic neurons decreased
- MD thalamic neurons disinhibited and excitation to prefrontal cortex increased
- Activation associated with pleasure and goal-directed behaviors
- Drugs of abuse tap into circuit and ↑ DA
-
Memories of past drug experiences & stress
- from amygdala, hippocampus
- can directly affect circuit
- promotes relapse
-
Prefrontal cortex influence over VTA & n. accumbens
- allows throughts to be rewarding
- way to exert cortical control over pleasure and goal directed behaviors
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Stress
HPA-axis & SAM-axis
Regulates metabolic, immune, and brain function in response to stressors.
-
Hypothalamic-Pituitary-Adrenal (HPA) Axis
- Stress ⟾ ⊕ paraventricular nucleus (PVN) of hypothalamus ⟾ CRH release
- CRH ⟾ anterior pituitary ⟾ ACTH release
- ACTH ⟾ adrenal cortex ⟾ cortisol release
- Anti-inflammatory and immunosuppressive actions
-
Sympathetic-Adrenal-Medullary (SAM) Axis
- Stress ⟾ ⊕ postganglionic SNS fibers⟾synaptic norepi release⟾adrenal medulla⟾ systemic norepi & epi release
- ∆ immune function
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Autoregulation of HPA-axis
↑ [cortisol]plasma ⟾ ⨂ hypothalamus/pituitary/adrenals ⟾ ↓ cortisol production via negative feedback
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Central regulation of HPA/SAM
Corticolimbic, hypothalamic, and brainstem centers have regulatory influence on HPA/SAM axes.
Hippocampus mostly ⊖
Amygdala mostly ⊕
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HPA-axis dysregulation
Chronic stress ⟾ prolonged cortisol secretion ⟾ ↓ glucocorticoid receptors ⟾ glucocorticoid resistance ⟾ inability to shutdown immune responses ⟾ ↑ [inflammatory cytokines]
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SAM-axis dysregulation
Acute activation of SAM-axis for fight-or-flight response
SNS fibers & circulating norepi/epi ∆ immune function including:
cell proliferation, cytokine/Ab production, cell trafficking
Chronic activation of SAM ⟾ dysregulaton of SAM effects on immune system
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Stress
&
Psychiatric Disorders
Stressful life events & HPA-axis dysfunction ∝ risk, onset, and course of pyshiactric orders.
- Chronic ± HPA/SAM function ⟾ ∆ regulatory feedback mechs ⟾ dysfunction
-
↑ cortisol common w/ depression, anxiety, substance abuse, psychosis
- normal neg. feedback mech impaired
-
toxic to limbic structures
- ex. ↓ hippocampus size
- impaired inhibition of HPA-axis
- memory loss
- ex. ↓ hippocampus size
-
HPA-axis functional tests with depression
- ↓ dexamethasone suppression
- ↓ CRF stimulation
Psychoneuroimmunology
Stress, emotion, disease ↔ ∆ immune system ↔ ∆ brain
- Stress
⟾ pro-inflammatory cytokines in children
⟾ risk of mental illness in adults
⟾ ⊕ neuroinflammation markers in limbic regions- Induces sick sx, depression, anxiety
- Ass. w/ bipolar d/o, schizophrenia, neurodegenerative diseases
- Bipolar & schizophrenia linked to:
- childhood autoimmune diseases
- maternal infecitons
- inflammation during pregnancy
- Targeting immune system for treatment of psychiatric d/o being studied
Depression
&
Inflammation
- Proinflammatory cytokines / bacterial endotoxins ⟾ sickness/depression ⟾ better w/ antidepressants
- Cytokines interact w/ depression pathways
- neuroendocrine & central neurotransmitter ∆
- similar to depression
- Severe depression w/ signs of immune activation & ↑ cytokines
- > inflammatory response to stress ⟾ > chance of developing depression
- Cytokines ↓ DA release ⟾ ↓ reward circuit ⟾ anhedonia & no motivation
- ↑ inflammation ⟾ ↑ activation of threat/anxiety circuits
Limbic System
Summary
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