Limbic system & hippocampus Flashcards
What is the limbic system?
A series of anatomically connecte CORTICAL & SUBCORTICAL STRUCTURES that collectively play a role in the way we experience & repond to:
- Emotional
- Social
- Motivational
stimuli, as well as learning & memory
What are the 3 componenets of an emotional state?
- Autonomic responses
- Subjective feelings
- Cognition
Give examples of autonomic responses
What is the main area that controls this?
Increased HR or sweating
Hypothalamus
What are subjective feelings?
What is the main area that controls this?
Unconscious
Amnygdala, cingulate gyrus
What is cognition?
What is the main area that controls this?
Conscious thougths about the experience
Cortex
What are the subcortical structures of the limbic system?
- Amygdala & stria terminalis
- Hypothalamus
- Septa nuclei
- Olfactory bulbs
- Hippocampus
- Thalamus (anterior)
(This is in order, rememember it in this order & u are good)
What are the cortical structures of the limbic system?
- Cingulate gyrus
- Parahippocampal gyrus
- Orbitofrontal cortex
- Sensory association cortices
What is the “king of the limbic structures”
The Amygdala!
What is the role of the Amygdala?
Fear, strong emotions (e.g. anger), including pleasure
Where is the Amygdala located?
It is located in the temporal lobe, it is the most anterior aspect of the temporal lobe
(abt the size of an almond so pretty small)
What connection comes out of the amygdala & where does it go to?
The stria terminalis comes out of the amygdala
Projects to hypothalamus & nuelcues accumbens
What is the stria terminalis & where is it located?
It is a white matter structure
It follows the pathway of the fornix, moves in a posterior direction & shifts superiorally & it begins to move anterirorally, curling up & over the thalamus
What does the stria terminalis make connections to?
Part of the basal ganglia called the nucleus accumbens & the hypothalamus
What is the hypothalamus role in the limbic system?
Autonomic NS regulation, aggression, as well as endocrine functions:
(- Temp
- Hunger
- Weight
- Sleep
- Reproduction)
What does the Septal nuclei do?
Regulates hypothalamic aggression
(Now known that they regulate the hypothalamus → brain has so many built in mechanisms for reversing aspects of control
This makes sense bc if something goes wrong somewhere the brain has ways of overcoming & compensating this.)
Where is the Olfactory bulb located?
In the human brain they’re tucked up beneath the frontal lobes
(Massive in the rodent brain for obvious reasons)
Where does the olfactory bulb in the limbic system connect to & why is this important?
Important in limbic system
Have connections to the Amygdala –> bc smells can be correlated w emotion & memory
Where is the hippocampus loacted & what does it connect to?
In temporal lobe & has a lot of connections w the Amygdala (in rodents pretty large)
What is the role of the hippocampus in the limbic system?
Role in emotion & helps us to navigate around our environment
If u move in a posterior direction thru temporal lobe, what does the hippocampus become?
The fornix
Where is the cingulate gyrus found?
Found next to the cingulate sulcus that runs along the middle of the brain, parallel with the corpus callosum
Now please go over the structures of the limbic system & where they are located on the brain!!!
High chance you will be asked to label some of these
What are the 2 structures that are connected to the hippocampus?
The fornix & mammillary bodies
As we move in a posterior direction from the hippocampus, what is found here?
The fimbria
(Just means fringe = on the fringe of the hippocampus)
What is the crus?
It is the main part of the fornix (past the fimbria)
(They are the legs of the crus = latin for leg)
What happens at the fornix body?
The 2 legs (crus) connect & form the commisural fibre
Share info here
What happens at the colum of the fornix?
Once fornix has connected in the middle it will divide into the columns
These make connections to the mammillary bodies
What are the 6 key structures making up the fornix?
- Hippocampus
- Fimbria
- Crus
- Fornix body (commisural)
- Column
- Mammillary bodies
(These are in order, remember them in this order)
What is the septal nuclei a good landmark for?
For where the fornix seperates into the mammillary bodies
(Located in the middle between the lateral ventricles)
Pls study the structures of the limbic systems brain scan
Key structures will probs be asked to label them
What is the role of the cingulate gyrus?
COgnitive, attentional & emotional processing
What is the role of the parahippocampal gyrus?
Memory encoding
What is the role of the fornix?
Projects to the mammillary bodies (from hippocampus)
What is the role of the mammilothalamic tract?
Projects to anterior nucleus of the thalamus
What si the James Lange theory (1884)?
Proposed that the physiological status of the body triggers the conscious experience of emotion
What is the Cannon Bard theory?
Proposed that the physiological state & emotional state were occuring simultaneously
(This came AFTER James Lange theory)
How did Cannon Bard prove his theory & disprove James Lange?
He & a PhD student got come cats & removed the cortex of the cats
Cats survived & seemed normal, however very subtle stimuli caused ‘sham rage’
PROVED: you don;t need cortex to experience emotion
What areas did Cannon Bard say mediate aggression?
The thalamus & hypothalamus mediate aggression & this process is potentiated when the cortex is lost (cat can’t mediate its behaviour)
What later proved Cannon Bard’s theory?
Swiss pyschologist stimulated cat’s hypothalamus
Cats exhibited sham rage again = solidifies Cannon’s theory
What did septal nuclei stimulating experiments generally find?
What conclusions were drawn from this?
That if u stimulated the septal nucleus u get a calm animal
Theory was septal nucleus was regulating hypothalamic control –> this was the case
How did a modern paper prove that the septal nuclei regulates hypothalamic aggression?
Used optogenetics
- Take a virus, remove its DNA + CHR2 DNA –> fuse CHR2 to yellow fluorescent protein & inject into septal nucleus
- The CHR2 receptor will DEPOLARISE cells when activated by LIGHT
- Light stimulation of the lateral septal nuclei STOPPED ATTACKS
(e.g. put a grp of male mice together & whenever the light was turned on the attack stopped)
Summarise the Papez circuit:
The cingulate gyrus recieves stimuli from the sensory association cortex
It projects to the parahippocampal gyrus & the hippocampus processes this info
Info is fed back to the cingulate via the mammillary bodies & anterior nucleus of the thalamus
What did Papez name his circuit & what did he centre his theory around?
He called it the limbic loop
He thought the hippocampus was at the centre of the limbic system (was very hippocampus focussed & built his theory around this)
What is the primary cause of Kluver-Bucy syndrome?
Herpesviral encephalitis
(Kluver-Bucy is extremely rare in humans)
List some symptoms of Kluver-Bucy syndrome:
- Placidity - poor response to emotional stimuli incl reduced fear
- Difficulty w memory
- Hypersexuality
- Visual agnosia - inability to recognise familiar objects or faces
- Hyperphagia - over eating, and/or the compulsion to place and/or examine objects w the mouth
How did Kluver & Bucy discover Kluver-Bucy syndrome?
Kluver & Bucy were removing temporal lobes of monkeys & they started exhibiting strange behaviours after this.
They were no longer afraid of anything & became rlly docile, hungry, putting odd things in their mouths & they were hypersexual
List the structures of the Papez circuit:
- Hippcoampus & parahippocampal gyrus
- Fornix (connects)
- Mammillary bodies & hypothalamus
- Anterior thalamic nuclei
- Cingulate gyrus
- Seonsory association cortex
4 main theories you need to know!
James-Lange theory
Cannon-Bard theory
Papez circuit
Kluver-Bucy syndrome
James-Lange theory –> Proposed cortex elicits a conscious emotional response after receiving physiologicla stimuli
Cannon-Bard theory –> proposed emotions & physiological states were a simultaneous process (importance of thalamus & hypothalamus)
Papez circuit –> attributed emotional expression to the structures in the circuit
Kluver-Bucy syndrome –> caused by removal of temporal lobes & it’s discovery supported Papez theory
What did Paul MacLean (1950s) do?
He expanded on the Papez circuit
& coined the limbic system
(He recognised that Papez’s circuit is still valid but has just added a few more branches –> more refined)
How did Paul MacLean expand on the Papez circuit?
He added & recognised the importance of the:
- Orbitofrontal cortex
- Amygdala
- Nucleus accumbens
(He was undoubtedly influenced by all the experiments on the hypothalamus, amygdala & septal nuclei)
What did Paul MacLean realise about the amygdala?
That it is anatomically connected to the Hippocampus & the Hypothalamus (via the stria terminalis)
What did Paul MacLean realise about the parahippocampal gyrus?
He added connections between parahippocampal gyrus & the cingulate gyrus
Also between cingulate gyrus & sensory association cortices too
What do amygdala lesions produce in animals?
Tameness & fear
(This idea was used in experiments to understand its role & location in the limbic system)
What causes Urbach-Wiethe disease & what does it do?
Is a rare genetic disorder
Cause = calcification of the amygdala
Symptoms = Patients unable to recognise fearful faces
What does modern neuroimaging tell us about the amygdala?
The techniques confirm the Amygdala is active when ppl see fearful faces
What did fear conditioning experiments in rondents tell us?
(Amygdala)
Highlighted the importance of the Amygdala w respect to LEARNING to FEAR stimuli
(Also plays a role in other emotions: anger & pleasure)
What did LeDoux do?
He discovered the concept of fear conditioning
Used rodents & fear conditioned them - soem of them he lesioned the amygdala
What was LeDoux’s process of fear conditioning?
- Put rat in the box & play a loud scary sound –> rat experiences a little bit of an inc in BP & a little bit of freezing behaviour where they are very still & nervous
- Then they give the loud noise & pair it with a foot shock which stings a little. BP skyrockets & lots of freezing behaviour
- The more & more u do this you no longer need the shock, just the sound & the rat will experience the rise in BP & the freezing behaviour
What was the result of fear conditioning in rodents which LeDoux had lesioned their amygdala?
They would never learn to be afraid of tbe sound even after being shocked
(Showed us it’s important to be afraid of things)
Where do dopaminergic neurones in the midbrain project to?
The amygdala, Orbitofrontal cortex & nucleus accumbens
(Release dopamine to the limbic structures - part of the mesolimbic reward system)
What does dopamine mediate?
The pleasurable aspects of reward
Where are the dopaminergic neurones in the midbrain?
Located in the ventral tegmeantal area
(where our dopamine producing cells are in the substantia nigra)
What is the mesolimbic reward system?
A group of cells in the VENTRAL TEGMENTAL area (in substantia nigra) in the midbrain that produce dopamine
Projects to the amygdala, OFC & nucleus accumbens
Dopamine mediates the pleasureable aspects of reward
What does the dopamingergic mesolimbic reward system do?
(Same as the mesolimbic reward system jsut another name)
Modulates the pleasurable experience associated w reward
What are the 2 main types of memory?
- Declarative/explicit memory
- Nondeclarative/implicit memory
What is declarative/explicit memory?
- Semantic e.g. facts, ppl, places & things
- Episodic e.g. personal experience
What is nondeclarative/implicit memory?
- Procedures, skills, habits
- Conditioning
(Things we don’t have to think about actively - skills or habits that you have)
Who helped us to understand the types of memory?
HM
Surgeon was supposed to take out the hippocampus & the parahippocampal gyrus but it turns out the surgery was more anterior than thought so it also took out the amygdala & the posterior aspects of the hippocampus & parahippocampal gyrus were left in tact
He couldn’t form new memories - jsut procedural & semantic only
What area of HM’s brain was removed & what did this result in?
Area removed = hippocampus & para-hippocampal gyrus
Resulted in = anterograde amnesia
What memories was HM capable of?
Couldn’t form new memories but was capable of:
Acquisition of SEMANTIC & PROCEDURAL memories
What is the hippcoampus composed of?
- Dentate gyrus
- Subiculum
- Cornu Ammonis (CA)
(Shaped like a seahorse ;l
Where is the hippocampus located?
Medial anteriorr aspect of temporal lobe
What does the structure of the hippocampus look like & what are the parts?
Like 2 interlocking C shapes
1st = is the dentate gyrus
2nd = CA (Cornu Ammonis - don’t rlly need to know full name)
(Interlocking C shapes are actually a row of cell bodies)
How many CA regions are there?
Approx 4
What is the order of the 2 interlockign C shapes in the hippocampus?
Inside to out
Dentate gyrus
CA4
CA3
CA2
CA1
What comes after the CA(1) region of the hippocampus (working outwards)?
The subiculum & then entorhinal cortex
How many layers does the hippocampal cortex have?
Only 3 layers (not 6)
(The CA & dentate gyrus have these 3 layers each)
What are the 3 cortex layers of the CA region called?
1 - Polymorphic
2 - Pyramidal (This is the layer that mkaes the charateristic C shape)
3 - Molecular
What are the 3 cortex layers of the dentate gyrus?
4 - Polymorphic
5 - Granular (Very densely packed in this layer)
6 - Molecular
What happens to the hippocampal cortex when you move out to the subiculum?
It transitions (from 3 layers) to the standard 6 layered entorhinal cortex
What is Long Term Potentiation (LTP)?
The cellular basis by which memories are stored = LTP
What was Bliss & Lomo’s experiment on LTP & what did they discover?
→ They had rabbits & put electrodes into the entorhinal cortex & electrically stimulating it via the perforant path
→ However the recording electrodes were placed in the CA1 region.
→ This showed that although they were stimulating the entorhinal cortex, they could read the postsynaptic responses in the CA1 region
→ The postsynaptic responses were lasting (long term) & enhanced (potentiated), called LTP
What did Bliss & Lomo’s experiment show?
That the brain is able to make changes in its organisation & in response to stimulation → the concept of plasticity
Has been suggested to be a cellular model by which memories are formed
What is the order of info being processed in the hippocampus?
→ Perforant path stimulates granular cells in the dentate gyrus
→This then stimulates the mossy fibres which project to the CA3 layer
→ CA3 layer has schaffer collaterals which project to the CA1 layer
→ Finally, the CA1 pyramidal cells project to the subiculum
What was the first evidence that the hippocampus plays a role in spatial memory?
Came from the discovery of PLACE CELLS
What are place cells?
Hippocampal cells that fire depending on the location of the organism in the environment
(aka GPS of the brain)
What area of the brain plays a role in spatial memory?
The hippocamus
How was it discovered that the hippocampus plays a role in spatial memory?
→ Had rats & used a plus maze & they put some tasty rat food in there, there’s things all around the room that they can see that they can use to navigate to the food
→ They put electrodes into the brains of rats & they could measure up to 50 cells at the same time.
→ They let the rat go round & get the food out the maze and what they noticed was when the rats were in certain locations in the maze, only certain cells would fire
→ e.g. in the second diagram (refer to lecture) when the rat was staying in the left side, cell C was firing, whereas when the rat was approaching his target, cell D was firing
What did lesion studied of the hippocampus show that it was important for?
Additional evidence that the hippocampus plays a role in COGNITIVE MAPS came from lesion studies
(Morris tested this)
What was the set up of Morris’ experiment on spatial memory?
- A vat with opaque liquid in like milk or something non toxic to rats & there’s an escape platform in there, the goal is to find the escape platform.
- There’s objects around the room & the rat will see these when on the escape platform, so when they repeat it the next day they’ll recognise the things in the room and remember where to go
- Use cues in the room to guide them to the platform (spatial nav) → called the Morris water maze
How did the Morris water maze work when the hippocampus was lesioned?
Normally the rat would be able to find the platform every time after 1 or 2 goes (could rememeber where it was)
When hippocampus was lesioned no matter how amny times the rat couldn’t remember & would swim around randomly until it found the platform
Where does adult neurogenesis occur in the hippocampus?
In the sub-granular zone of the dentate gyrus
(It is 1 of 2 brain structures that has the ability to generate new neurons)
Describe how adult neurogenesis can occur in the hippocampus:
→ Quiescent undifferentiated STEM CELLS (nesting, sox-2, GFAP) activate & give rise to fast PROLIFERATING cells (nestin, sox-2)
→ NEUROBLASTS (doublecortin) reflect the commitment towards NEURONAL LINEAGE
→ Immature neurons begin to MATURE & extend DENDRITES into the MOLECULAR LAYER & the AXONS project into the CA3 region
