Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
122 Cards in this Set
- Front
- Back
|
What does the hippocampus do? |
Helps us store memories |
|
|
What does hippocampal damage do? |
Destroys our ability to store new declarative memories (we can still do muscle memory and such) |
|
|
Where are memories stored? |
Their main association cortices. Ex: amygdala, frontal lobe, cerebellum |
|
|
What lobe is the hippocampus touch? |
The medial temporal lobe |
|
|
What is at the ends of the hippocampus? |
Amygdala |
|
|
What is the architecture of the hippocampus? |
CD |
|
|
Where is Ca1? |
C (top) |
|
|
Where is Ca3? |
C (left) |
|
|
Where is DG? |
D |
|
|
Where does information come into the hippocampus? |
DG |
|
|
Where does information leave the hippocampus?
|
C
|
|
|
What cortex does information enter the hippocampus through? |
Entorhinal Cortex |
|
|
How does information travel through the hippocampus? |
Entorhinal Cortex then follows axons down the perforate path and branches around the D..
Mossy fibers are the interneurons from DG to C. Output is the neurons in Ca1 or Ca3; they get info from mossy fibers and take it out of the hippocampus. |
|
|
How does information travel from DG to C? |
Mossy fibers |
|
|
How do we add memories? Connections Hypothesis |
(Hardware) Add a memory by adding neuronal connections. Ex: a neuron for knowing Holly, another neuron for associating her with something, etc. |
|
|
How do we add memories? Connections Hypothesis: Problems? |
Would this take too long? You can change electrical activity much faster. |
|
|
How do we add memories? Electrical Activity Hypothesis |
(Software) Electrical stuff moving through and the patterns of activity are our memories. |
|
|
How do we add memories? Third Hypothesis |
Some memories are connections and some are electrical! |
|
|
Memory Test & Hypothesis Support |
Remembering images we saw vs. similar images. In doing this activity we probably did not make drastic neuronal change. At most we probably could have made a small change to our synapse strengths. Our network activity (electrical) could have easily changed though! Supports the electrical activity hypothesis. |
|
|
What happens when we electrocute the brain? Hypothesis Support |
Peoples memories are not entirely wiped, which should happen if memory is only encoded by electrical activity. Instead, people only lose memories from around that time. This shows electrical activity is probably important for working memory, but it is connectivity that builds long term memories and even probably still most of the short term memory. |
|
|
Would memory have to be electrical or connective to body swap? |
Memories would have to be solely electrical so we could move activity from one brain to another. So not really possible since most of our memory seems to be based in connectivity. |
|
|
What is an organotypic culture? |
A hippocampal slice. |
|
|
Hippocampal Slice Experiment |
Stimulate perpherant path with an electrode. Record in DG. Send an AP down PP, small EPSP in DG. High Freq. Stimulate PP, EPSPs temporally integrate to threshold. Another AP down PP, now EPSP in DG is bigger. This stronger EPSP will persist for hours/days; this phenomena is known as LTP. |
|
|
High frequency stimulation occurs only at 1 of the 3 synapses... |
Only synapse 1 has LTP input specificity. |
|
|
If a single AP occurs while you are holding voltage at -40mV... |
LTP still occurs at the synapse that had the AP. |
|
|
If you high frequency stimulate one and three has a single AP then... |
you have LTP at one and three because one makes 3 cooperate with depolarization (associativity). |
|
|
If you have a single AP at 1 and at 3... |
no LTP occurs. |
|
|
NMDA receptor is responsible for... |
LTP. |
|
|
If you knockout NMDA... |
you can't have LTP. There is some potentiation, but it is short. |
|
|
NMDA has to do with the... |
length of potentiation (not facilitation). |
|
|
What does NMDA channel have on it? |
Magnesium ions. |
|
|
What do the Magnesium ions on NMDA do? |
Block other ions. |
|
|
How do you remove the Magnesium from NMDA? |
If cell is depolarized at -40mV then the charge pushes the Magnesium away. |
|
|
What can occur once Magnesium is out of the way on NMDA? |
Calcium can come through and cause LTP. Calcium influx causes more AMPA receptors. |
|
|
More NMDA = |
More AMPA |
|
|
When can you have a silent synapse? |
When no AMPA receptors turn on when no NMDA receptors open. |
|
|
Spectrum of Changing the Brain: Add/Delete a Neuron |
Big and slow; requires protein synthesis at least to add. |
|
|
Spectrum of Changing the Brain: Add or Subtract whole Axons or Dendrites |
Big and slow; requires protein synthesis at least to add. |
|
|
Spectrum of Changing the Brain: Change size or # of Synapses |
Middle; no protein synthesis required
|
|
|
Spectrum of Changing the Brain: Change properties of Cleft |
Middle Ex: Add molecule to prevent NT from crossing Could require protein synthesis if that molecule was a protein! |
|
|
Spectrum of Changing the Brain: Changing # of NT per vesicle or # of vesicles released or # of NT receptors |
Smaller and Faster; possible protein synthesis required to build vesicles and definitely needed for more receptors |
|
|
Spectrum of Changing the Brain: Alter Threshold via VGNaCh |
Smaller and Faster; protein synthesis needed for increasing # of receptors |
|
|
Spectrum of Changing the Brain: Change Network or Circuit Activity |
Smaller and Faster; probably doesn't require protein synthesis |
|
|
Early vs. Late LTP Timeframes |
Early LTP = two or three hours (short) Late LTP = can last a couple days |
|
|
Does LTP require protein synthesis? |
Late LTP does. If there is no protein synthesis than the LTP is short lived. This is why we do not need protein synthesis for short term memory. |
|
|
Where do proteins for Late LTP go? |
Dendritic spines. |
|
|
How do we get proteins in soma to just ONE SPINE for LTP? |
Golgi outposts + Synaptic tagging |
|
|
What does a synaptic tag indicate? |
It indicates the spine needs a new protein, and this tag grabs proteins going by. |
|
|
Does the tag itself require protein synthesis? |
No |
|
|
Do new synapses occur with LTP? |
Yes |
|
|
How soon do new synapses occur? |
Within 8-12 hours of LTP. (imaging before and after 8 hours shows appearance of 2 new synapses) |
|
|
How often are we making synapses? |
Pretty much constantly. |
|
|
Is it easier to make pre or post synaptic terminals? What does this mean for ease of altering axons vs. dendrites? |
Easier to make postsynaptic terminals because dendrite it closer to cell than end of axon. This means modify dendrites rather than axons if you have the option. |
|
|
What is memorable to a mouse? |
Environment |
|
|
Accessing a Memory Experiment (2 stages) |
2 Mice Add TRE so when neurons fire, FOS turns on which turns on TRE turning on yellow fluorescent proteins in active neurons. tTA and TRE allow us to turn yellow on and off as we choose so that we can label a specific memory (engram). Dox = no labeling. Results: Home cage with Dox = no labeling Home cage w.o Dox = 2% new memories (less likely to make memories in familiar environment) Feared cage w.o Dox = 6% of all neurons in DG light up. This means this 6% of neurons will always become active in this environment now (its a memory made). Seizure = 98% neurons light up Re-Activating a Memory: Use optogenetics by expressing channel rhodopsin in the 6% of neurons. Re-activate this neurons with light and see if mouse remember the room! We know the mouse is remembering the room because it will show fear by freezing up (we have shocked the mouse every time it was in the new room to create this fear). The mouse did freeze up, so we assume we have re-activated the memory! |
|
|
Fos Promotor |
An immediate early gene where when neurons start firing it becomes active within a few minutes. |
|
|
What happens when mice go into a new room? |
Their neurons start firing and FOS turns on. |
|
|
A memory snapshot is called an... |
engram. |
|
|
What kind of disease is Alzheimer's? |
Progressive Fatal Disease |
|
|
What is Alzheimer's characterized? |
Dimentia: memory loss, confusion NOT psychotic tendencies |
|
|
What is Alzheimer's related to? |
Aging. |
|
|
Is Alzheimer's just a natural result of aging? |
No! Not everyone over 90 gets Alzheimer's and most of the oldest people in the world DON'T have it! |
|
|
What are the symptoms of people with Alzheimer's? |
Their association areas are affected. (their movement, vision, smell, language, emotions, procedural memory, base functions, etc. are all fine) |
|
|
Are plaques extra/intraceullular? |
extra |
|
|
Are tangles extra/intraceullular? |
intra (within the neuron) |
|
|
Are plaques and tangles specific to Alzheimer's brains? |
No. Common to, but can also appear in non-Alzheimer's brains. |
|
|
What do plaques and tangles correlate with in Alzheimer's patients? |
They correlate with the association areas (the areas that Alzheimer's effects!). |
|
|
What is APP? |
Amyloid precursor protein; will result in amyloid plaques. |
|
|
What kind of protein is APP? |
Transmembrane |
|
|
What is the function of APP? |
We need this protein, but we do not know exactly what it does normally. |
|
|
What portion of APP is dangerous? |
The transmembrane portion called amyloid beta. Proteases chop it out and the fragments cause aggregations that are the core of amyloid plaques. |
|
|
What proteases cut amyloid beta out? |
Beta-secretace (BACE) is the bad protease. Beta to gamme = bad results. (gamma can be good or bad) |
|
|
Which of the proteases protects us? |
Alpha |
|
|
What is a secretase? |
A protease that can cut within a membrane. |
|
|
What is presenilin? |
It is part of the protease complex that cuts out beta amyloid. |
|
|
Clinical Trial: Protease |
Destroy BACE. However, people think while BACE can be a cause, it is probably not the precipitating event. |
|
|
Amyloid Beta and LTP |
When you add high levels of beta amyloid to a mouse's brain then its LTP curve will come back down to baseline to show it forgot whatever happened (did not make a memory). This shows amyloid beta is sufficient to interfere with LTP in high quantities. |
|
|
Ways to Clear Amyloid Beta |
Endocytosis + proteases (bring them in then destroy them) Molecular chaperones (change conformation to stop plaque formation) Extracellular proteases Microglia; glia can eat and destroy them instead of important neurons doing it Glymphatic system; glial cells circulate cerebral spinal fluid in the cleft to clear them out. Neurovascular clearance: get them into the blood to clear them via liver/kidney. |
|
|
Alzheimer's Theory: AB Clearing |
Maybe everyone has plaques, but some of us are better at clearing them than others so thats why only some people develop Alzheimer's from them. |
|
|
What is the goal of current Alzheimer's treatments? |
Trying to make synapses work better by making them more active. This treatment is not specific and does not relieve symptoms long term. (After a year of treatment, patients are in the same place as their untreated counterparts). |
|
|
What does Tau do? |
Associates with microtubules and is very important for keeping the axon in tact. |
|
|
What is the main component of Tangles? |
Tau |
|
|
What does Tau do? |
Folds in a weird way allowing it to be phosphorylized allowing it to make a dimer with itself so it can build into stacks (aggregates into polymers). This directly harms the axon (causes axon degeneration). |
|
|
What would preventing Tau from dimerizing do? |
Would allow us to make synaptic connections better. |
|
|
What is one of the first signs of Alzheimer's that Tau causes? |
White matter lesions. |
|
|
What kind of protein do we think Tau could be? |
A prion. |
|
|
What is a prion? |
A specific protein conformation that acts as a template to cause other proteins to change to that (harmful) conformation. |
|
|
What do prions act like? |
Infections |
|
|
What do we not understand still about prions? |
How they jump through synapses. |
|
|
Common Prion Diseases? (4) |
Kuru, mad cow, CJD, and Alzheimer's |
|
|
3 Things to Think of When you Hear Alzheimer's |
1. Amyloid hypothesis 2. Tau and prions 3. Clean up defects |
|
|
Is Alzheimer's genetic? |
Yes |
|
|
How do you get Alzheimer's? (percentages!) |
75% heritable 20% spontaneous 5% other mutations including amyloid precursor, APOE (clean up defect; majority of "other mutation" causes), and APOJ/PICALM (unknown mutations) |
|
|
What is APOE? |
The most common defect to lead to Alzheimer's.
It is a clean up defect. |
|
|
Default Network |
The association areas of the brain that are active while we are doing nothing (just sitting and thinking in "default mode"). This areas are the areas that atrophy in Alzheimer's. They get stuck in default mode and won't know things like what they just did or what they were going to do. |
|
|
What area of the brain does Parkinson's involve? |
Substantia Nigra |
|
|
What NT does Parkinson's involve?
|
Dopamine |
|
|
a-Synuclein |
Associated with Parkinson's |
|
|
What kind of disease is Parkinson's? |
Mitochondrial
|
|
|
CAG (Poly Q Repeats) |
Huntington's |
|
|
What kind of disease is Huntington's? |
Dominant Progressive
|
|
|
What does ALS affect? |
Motor Neurons |
|
|
What can traumatic brain injury cause? |
Chronic Traumatic Encephalopathy |
|
|
What do NMDA receptors make up a large portion of? |
The C of the CD. |
|
|
What happens if you knockout AMPA? |
EPSP amplitude is fine. |
|
|
What happens if you knock out NMDA? |
EPSP amplitude drops. |
|
|
What happens if you knock out CAMKII?
|
EPSP amplitude drops. |
|
|
What happens when one branch has HFS? |
LTP |
|
|
What happens when one branch has an AP while depolarization is occurring? |
LTP |
|
|
What happens when all three branches together have enough AP to be considered LTP? |
LTP |
|
|
Cooperativity |
LTP not from HFS (from AP + depolarization) |
|
|
Associativity |
LTP with HFS at one synapse and regular APs at nearby synapses. |
|
|
Silent Synapse |
A synapse that when stimulated provides no EPSP. |
|
|
What causes a silent synapse? |
Presence of NMDA but no AMPA receptors. |
|
|
No AMPA receptors = |
No glutamate reception, so no depolarization. |
|
|
How do you depolarize a synapse with no AMPA receptors?
|
Activate a neighboring synapse within the same cell; this allows the silent synapse's NMDA receptors to open letting calcium in. |
|
|
When do NMDA receptors normally open? |
When cell is depolarized from AMPA. |
|
|
Small Amount of Ca + CAMKII = |
Transient activation (like tapping a flashlight button). |
|
|
Lots of Ca + CAMKII = |
Keeps CAMKII active longer by phosphorylating it. This allows CAMKII to be the molecular memory that tells a synapse to stay strong. |
|
|
Where does the Ca that turns CAMKII on come from? |
Through open NMDA channels. |
|
|
What three things does CAMKII cause when it is on for the long term? |
1. Causes AMPA channels to be more conductive. 2. Locks AMPA channels in place on terminal membrane. 3. Changes transcription to cause really long term effects. |
|
|
AMPA receptors being on for a long time is... |
basically our memory. |
