Memory and Hippocampus

Question 1

Declarative Memory

Answer 1

As you can understand from the name, you can talk about this memory, It is expressible by language( unlike Procedural Memory -You can’t explain how you ride a bike, you just do) and It is available to consciousness (You have an access to it).

Question 2

Semantic and Episodic Memory

Answer 2

Semantic Memory : Facts
Episodic Memory : Personal experiences in life (They fell like mental time-traveling, your autobiographical memories are great examples for episodic memory. These memories have specific spatio-temporal context.
* Semantic and episodic memory does not have to be completely separate from each other.
*(Fun fact for me) : Knowing your name is part of your semantic memory because you don’t remember when and where you’ve learned your name. You just know it.

Question 3

Entorhinal Cortex

Answer 3

• -> It is where the synaptic inputs come to Dentate Gyrus. This area provides the major cortical input to hippocampus. Not only Dentate Gyrus, but also CA3 gets input from Entorhinal Cortex.
• -> Neurons in this area are modulated by surrounding and orientation. (MEC and LEC is related to this)

Question 4

Hippocampus Basics

Answer 4

1 - It looks like a sea-horse (Hippokampus - It is a Greek name. Hippos (horse) and Kampos (sea monster)
2- It is very important for “declarative memory” and “spatial orientation”.
3- Dysfunction causes “anterograde amnesia”. You can’t form new memories. Therefore it is highly related to declarative memory formation and memory consolidation.
4- Adult Neurogenesis is observed in hippocampus ! ( (London Taxi drivers experiment)
5- It has 3 parts (head,tail,body)

Question 5

Medial Entorhinal Cortex (MEC)

Answer 5

This area includes different cells types:

• Cells that code border, head-direction and object-vector ( animal’s distance and direction to objects) and “grid cells”.
• Grid cells in MEC are “where cells” . Which means, these cells are repeatedly firing while animal is exploring the area. They code the general setting and influenced by the distant landmarks by creating a specific firing pattern.
• In MEC, Grid cells have regular, stable firing patterns.
• MEC input promotes place-field stability for Granule Cells.

Question 6

LEC (Lateral Entorhinal Cortex)

Answer 6

Neurons in this area represent “object related spatial feature”. It means, in this area Grid cells encode “What” information.
Since this area encodes object information, grid patterns are much more variant and influenced by closer landmarks.
LEC input helps to discriminate between separate temporal instances
** What I understand from this is that, grid cells in MEC help animal to encode the the contextual information about a maze (You are in the A maze not in the B maze) and grid cells in LEC help animal to encode specific objects in the maze (you are east side of the A maze) that can be used as a cue for the navigation in the maze.
**Also, overlapping MEC input and varying LEC input used as a pattern separation in Dentate Gyrus in terms of differentiating what happened in the same maze (MEC input) in different times (LEC input)

Question 7

Difference between Place Cells and Grid Cells

Answer 7

-Firstly, Grid cells are found in the Entorhinal Cortex. (Mostly in the Medial Entorhinal Cortex)
They fire repeatedly and they have “multiple” firing locations !!
Grid cells create virtual map of the area that animal is exploring.
-Place Cells have one firing area, which is called “Place Field”. They are found in Hippocampus ( Mostly CA3 and DG regions).
They fire when animal enters in a specific location in the environment. They encode the information about the specific spatial context where memory took place in.
They show firing-stability but they are subject to change due to contextual factors (remapping).
** While grid cells are always actively mapping the area, place cells tend to be more stable and encode the information about where you are standing. If you change your place (go other side of the same maze or similar maze,) there will be a different pattern of firing of the place cells . Therefore place field changes, too (remapping). But this does not happen if you are sent to another maze which is completely different from the first maze.

Question 8

Cornu Ammonis

Answer 8

• It is the area between Dentate Gyrus and Subiculum. (It is very close to the Dentate Gyrus, remember keep this information)
• It looks like a C and it is divided into 3 areas : CA1, CA2 and CA3. (CA3 is very important for memory encoding, consolidation and retrieval !)
• There is alveus and fimbria top of it. (Just look at the picture :)

Question 9

Dentate Gyrus

Answer 9

• It has “Tooth-row like appearance” (Because of that it is named as “Dentate” Gyrus )
• It has Granule cells and Mossy Fibers
• It gets input from MEC and LEC .
• Dentate Gyrus shows adult neurogenesis the most !!
• It has a role in : Pattern Separation (Cognitive discrimination of similar representations in the brain), Pattern Completion (Retrieval of complete stored memory input by activation of related input patterns), Binding of information to spatial context (I think this is about place cells).

Question 10

Engram

Answer 10

When you experience something, it changes your brain. (Synaptic plasticity). A distinct pattern is created specific to your memory, stored and re-activated during recall

Each and every memory [experience driven change] has a unique pattern (of course they overlap in some points) and this unique pattern is called “Engram”

It is a sequential co-activation pattern of several neurons and synaptic weights in a neuronal network.

Question 11

Neurons in CA areas ( Mostly CA3)

Answer 11

• CA3 is the sole target of Dentate Gyrus ( and it is the coolest area. If you are not sure about which CA you need to choose, just choose this one)
• Excitatory Pyramidal Cells (which gets input from Granule Cells in Dentate Gyrus through Mossy Fibers and/or from Entorhinal Cortex through Perforant Path) [there was a debate about whether CA3 needs Granule Cell input during retrieval, the answer is no but it would be better if it gets the input in terms of pattern separation)
• Inhibitory Local Interneurons : These neurons are stimulated by Granule Cell input and they inhibit excitatory pyramidal cell activity. Why? Because through excitation and inhibition, neuronal firing is synchronized.

Question 12

Dentate Gyrus Neurons

Answer 12

Granule Cells of course !!

It is the only cell type goes through neurogenesis and it produces approximately 700 neurons per year [Memorize the number, It seems important to Derek since he asked it in mock exam]

Corticosteroids [Necessary for the survival of the neurons of this area ]

Adult-born Granule cells are like youngsters. They show low threshold for excitability (especially 4-6 weeks after they’ve born) unlike Mature Granule Cells. Since Adult-born ones show enhanced intrinsic excitability, they have enhanced potential in synaptic plasticity which is important for discrimination of similar memories)

Axons of granule cells : “Mossy fibers”- Project information to CA3 pyramidal cells and inhibitory interneurons

Question 13

Hilus and Mossy Cells

Answer 13

MOSSY CELLS AND MOSSY FIBERS ARE DEFINITELY NOT THE SAME THING!

Hilus : Dentate Granule Cell Layer
+ It has “Mossy Cells “
+ Mossy Cells are Glutamatergic Interneurons in hilus.
+ Mossy Cells have excitatory synapses into interneurons and Granule cells (reinforcing loop)

Hilus also has :

• It has SOM+ interneurons.
• SOM+ cells are inhibitory cells and they inhibit Granule cell activity.

Question 14

Molecular Layer (ML) and Granule Cell Layer (GCL)

Answer 14

Molecular Layer :
1- In the Entorhinal Cortex, there two main areas which are MEC and LEC. There is a fiber called Perforant Path (PP) and this PP carries info from EC to Granule Cells, CA3 pyramidal cells and interneurons.
*PP caries the main input everywhere !

Granule Cell Layer :
2- Both mature and new-born granule cells in the Dentate Gyrus get the information coming from the EC and carry it to the CA3 pyramidal through Mossy Fibers. Also, Granule cells sends information to Mossy Cells and interneurons, too.
*There are PV+ (parvalbumin-containing) cells here and they limit GC activity- and if you are curious these PV+ are GABAergic inhibitory interneurons-

Question 15

Outdated Trisynaptic Loop Stuff

Answer 15

Once upon a time people assumed that information follows this direction : Entorhinal Cortex —> (through Perforant Path) Dentate Gyrus’s Granule cells –> (through Mossy Fibres) CA3 pyramidal cells–> (through Schaffer collateral) CA1.

FORGET IT. THIS IS NO LONGER VALID. TRISYNAPTIC LOOP IS A SCAM (why did we talk about something which is no longer valid ). There is more like a “paralel processing” rather than a linear one.

What is the new hypothesis ? : CA3 does not need Dentate Gyrus and gets input directly from the EC through PP. ( Actually CA3 does not need GC input during memory consolidation and retrieval. For someone, this was not enough and they tried to prove that CA3 does not need GC input even during the memory encoding ) .

BUT, GC improves mnemonic performance. So there is no need for it but if it is there, that is better.

Question 16

Mnemonic Performance improved by Granule Cells

Answer 16

• Memory updating ( Give food to rat in a maze, rat encodes this place as a great place to live, then give shock to rat so that it has to update its memory about this place as a non-safe environment)
• Pattern Separation
• Pattern Completion
• Timing (during retrieval of recent “ensembles” (cool way of saying memories) Granule cells are needed. They are re-activated.

In the article it is written that GC activity is needed during initial encoding and intrahippocampal encoding but disposable during recall. (But also GC activity enhances its precision !!)

(There is a weird disagreement about the role of GC on memory . Some people hate GC and some people defend it.) For the exam, you can think it as not necessary (contrary to the trisynaptic loop hypothesis) but good for some specific functions

Question 17

Storage of Long Term Memory

Answer 17

+ It is not stored in Hippocampus ! Hippocampus is important for memory encoding and consolidation but not the storage.
+ Memory stored in the Neocortex.
+ According to the experiment of Lashley ; It seems like memory is not stored in a one specific area in the cortex since lesions in different areas do not affect rat’s performance in the maze.

Question 18

Storage of Verbal Memory

Answer 18

Temporal association cortex

Disruption = Wernicke’s aphasia

Question 19

Recognition of Faces or other Complex Stuff

Answer 19

“Fusiform Face Area”
But it is not just limited with faces. As humans we perceive faces everyday and we are experts in the face recognition.
If you are expert in cars, bird types etc. this area will be active while you are looking at those objects and differentiating different birds from each other ( bird recognition ? )

Question 20

Perception and Memory Recall

Answer 20

fMRI studies showed that same cortical areas are activated during recall and perception. Which might be interpreted as sensory perception areas are also serve as a sensory memory storage units.

Question 21

Non-declarative Memory : Priming

Answer 21

What is this : Change in processing of a stimulus due to a previous encounter with the same or related stimulus with or without conscious awareness of it.

Related Anatomical Structure : Sensory Association Cortex

Cool info : Priming is resistant the brain injury, aging and dementia

Question 22

Non-declarative : Cerebellum and Procedural Memory

Answer 22

• -> Cerebellum processes procedural memory (like riding a bike) - It is involved in motor movement learning. It detects difference between intended behavior and the actual behavior (feedback loop) and corrects it through influencing the upper motor neurons. The corrected version is stored (this is motor movement learning)
• -> Cerebellum is where eye-blink conditioning is happening (This is interesting because most of the conditioning happens in the Basal Ganglia and Frontal Cortex !)

Question 23

Complex Motor Sequencing and Basal Ganglia & Prefrontal Cortex

Answer 23

Complex motor sequencing (like learning how to play an instrument and other complex stuff (like reading a memorized poem) depends in “Basal Ganglia” and “Prefrontal Cortex” activity.

Huntington Disease : Death of neurons in Striatum. People who have this disease have problems in learning new complex motor stuff. (mirror tracing task which they draw a star by looking at their reflection on the mirror or sequential finger movements etc.)

Question 24

Basal Ganglia and Reinforcement Learning

Answer 24

Reinforcement Learning depends on Basal Ganglia (substantia nigra) through dopaminergic signaling.

Question 25

Fear Conditioning

Answer 25

Amygdala Amygdala Amygdala

Everything related to fear : Amygdala

Question 26

Forgetting

Answer 26

• Synaptic Plasticity ; neurons don’t fire together don’t wire together
• Unused synaptic connections are dissolved in time to improve normal process of performance.
• Humans are tend to gradually forget what they’ve encoded in the Long Term Memory (Memories deteriorate over time)
  “We forget things that have no particular importance, that are unused or unrehearsed.”

Forgetting is normal, forgetting everything is not normal (Amnesia, Dementia)

Question 27

Amnesia : Pathological Forgetting

Answer 27

Anterograde Amnesia: You can’t form (encode) new memories (like in the case of Hippocampus damage)
Retrograde Amnesia :You forget your past (No retrieval)

Question 28

Dementia

Answer 28

–> It is a progressive illness affecting memory, cognitive abilities, social skills and personality.

–> The main cause of dementia : Aging

–> Alzheimer is the most common case (60-80 % of of all dementia cases)
+ Amyloid Plaques and Neurofibrillary tangles
+ Chromosome 21, gene encoding for amyloid precursor protein (APP)

Interesting fact : Down Syndrome is also related to chromosome 21 and people who have Down Syndrome have a risk of developing Alzheimer’s Disease earlier than the general population.

This is not a clinical neuroscience course so I don’t think there will be detailed questions about Alzheimer. The important thing is that it is the most common cause of dementia and definite diagnosis made after death through brain autopsy (?). It causes impairment on nearly every aspect of the person.

Question 29

Improve Your Memory Capacity

Answer 29

Give Emotional Meaning and built Associations : Brain forgets everything that seems meaningless. (Like random numbers in digit span- If you are a normal person you can’t remember more than 7-9 numbers) But if you give meaning to them you won’t forget. [I remember hippocampus produces 700 new neurons per year because 7 is my lucky number :) ]

Be motivated to remember !

If you assign absurd or sexual content, you remember stuff better

Sleep ! Consolidation happens during sleep and while you are sitting and doing nothing (Sharp-wave ripples, occurs in CA3 during immobility and sleep and important for memory consolidation)

Gingko, mental exercises like sudoku do not prevent Alzheimer. Eat well, exercise and don’t fall for these commercial stuff.