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
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
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.
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
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.
Hippocampus Proper
(Cornu Ammonis)
Divided into 4 Cornu Ammonis areas:
CA1, CA2, CA3, and CA4
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
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.
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.
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
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.
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.
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
Hippocampal
Ischemia
Hypothalamus very susceptible to ischemia.
Selectively attacks CA1.
See pyramidal cell death d/t ischemia or stroke.
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
Memory Circuit
Summary
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.
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
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
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.
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.
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
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
Emotion Circuit
Summary
Ventral Tegmental Area (VTA)
Location
Found near midline in midbrain.
Next to substantia nigra and red nucleus.
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
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
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
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
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
Autoregulation of HPA-axis
↑ [cortisol]plasma ⟾ ⨂ hypothalamus/pituitary/adrenals ⟾ ↓ cortisol production via negative feedback
Central regulation of HPA/SAM
Corticolimbic, hypothalamic, and brainstem centers have regulatory influence on HPA/SAM axes.
Hippocampus mostly ⊖
Amygdala mostly ⊕
HPA-axis dysregulation
Chronic stress ⟾ prolonged cortisol secretion ⟾ ↓ glucocorticoid receptors ⟾ glucocorticoid resistance ⟾ inability to shutdown immune responses ⟾ ↑ [inflammatory cytokines]
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
Limbic System
Summary
