Memory Flashcards
Who was patient HM?
Patient HM had bilateral medial temporal lobectomy to treat his epilepsy. Medial lobes and underlying strutures removed (HIPPO AND SURROUNDING CORTEX)
- profound anterograde amnesia, and some retrograde but only recent.
He could hold a conversation, but if you left and returned he wouldn’t know you.
Working memory in tact (could perform digit task), but could not consolidate long term memory.
He could also improve on
1. the mirror drawing task,
2. pavlovian conditioning, and
3. priming
- but all of which he said he’d never done before and had no idea of them.
implies hippocampus is important for consolidation.
Explicit vs. implicit memory?
explicit: memories of events and things
(episodic and semantic)
implicit: skills and habits and whatnot
memory is not a unitary construct.
Who is patient KC?
Kent cochran who lost his medial temporal lobes, mostly to hippo but diffuse damage.
- amazing factual memory but no episodic memories.
DIfficult time imagining himself in the future.
What is LTP?
Long term potentiation.
Initially a methodology using electrodes and stimulating the brain. First activity measured at baseline, then a weak stimulus, then a really strong one, thereafter all the EPSPs are strong even when given the weak stimulus. Synapse strengthened by a strong stimulation.
Tetanus is the strong stimulus. Now cell is more sensitive to PSPs.
How does LTP work? What changes during LTP?
When you have a strong stimulation, Mg2+ is electrostatically pushed out, allowing for binding. NMDAr now lets in calcium which is a potent signalling agent which leads to LTP.
Functionally (immediate): calcium comes in and brings more receptors to the surface of membrane (more binding and sensitivity to glutamate)
Structural (slower, longer lasting): changes in gene expression/transcription. Produce more receptor proteins.
Grow size of membrane, grown new dendritic spine.
What dysfunctions are NMDAR receptors implicated with?
LTP is more prominent in memory areas like hippocampus, but not in all areas like cortex.
Epilepsy treatment is to diminsh NMDA receptors, they’re associated with the same brain regions as LTP.
Basically…
Lets Calcium into cell, and its a potent signalling agent, and too much of it can trigger apoptosis
- stroke in penumbra
- excitotoxicity in general
- tonic-clonic seizures.
Glutamate antagonists act on NMDR receptors. Such as alcohol, PCP, ketamine all lead to memory impairments.
What is Korsakoff’s syndrome?
Wernicke Korsakoff’s syndrome.
Medial diencephalic amnesia.
Thiamine (Vitamin B1) deficiency. causing severe brain damage. Anterograde amnesia with mild retrograde amnesia. - seen in heavy alcohol users. BECAUSE alcohol inhibits the Thyb1 transporter, allowing less apsorbtion of thyb1, and heavy drinkers consume less food.
- malnourishment and thy1 deficency lead to korsakoff. but it doesn happen in people JUST with thy deficency on its own. THose folks have more cognitive abilities, whereas the alcohol induced one looks like amnesics.
Can also be induced by damage to the thalamus (fencing accident)
SYmptoms: amnesia, sensorimotor problems, confusion, personality issues.
What is the neural circuit for explicit memory?
Involved PFC, medial temporal lobe structures, and medial thalamus. if you disrupt one of these regions you disrupt the loop and cause problems!! V important regions for consolidation.
What is alzheimers disease?
Most common form of dementia. over 40% of older adults will develop it.
Mild cognitive impairment is how its called at first.
Early symptoms: mild SELECTIVE impairments that occur randomly “where am i”
Later stages: confusino, irritability, anxiety, deterioration of speech.
Advanced stages: difficulty with control or responses (bladder, swallowing)
Used to not be able to confirm until after death, now we can with a combination of biomarkers.
Occasional early onset due to genetics but no “gene” for alzeihmers. Common for family members but also just a common disease.
First appears in medial temporal lobe then spreads to cortex.
What are the defining charictaristics of AD?
- Brain volume decrease due to cell death and fewer synapses.
- Neurofibrillary tangles.
- Amyloid plaques.
What are tau tangles?
Hyperphosphorylated tau tangles. Aggregates of tau that bind to themselves instead of the cytoskeleon.
Looks different than in CTE.
Intracelluar process.
What are amyloid plaques?
Beta amyloid protein (A beta) which is made smaller and clipped from amyloid precursor protein (APP).
Very present in ourselves but function kinda unknown. Used in forming synapses, maintaining strength.
Extracelluar process.
What is the time course of AD?
Amyloid plaques increase for a long time before it becomes clinical. then Tau comes after.
But overall, change in brain size is what you see 1st.
We need presymptomatic diagnoses.
What are the biomarkers for AD?
- Low Beta amyloid in cerebralspinofluid. (more plaques will stay in the brain then get flushed out)
- High tau: since its intracellualr, after cell death they are released, so levels would be higher.
- PET imaging of A beta
- PET imaging of tau, but not as good cause it doesn’t bind equally well.
- Structural MRI to measure hippocampal size
- FDG, fluorescent glucose scan. Will look hypoactive, less glucose in the brain.
- Bodyweight: loose weight before showing symptoms.
what are the theories of pathogenesis of AD?
- Amyloid cascade: buildup of amyloid causes everything. Cause problems with neuronal integrity, destroying synapses or neurons. leading to tau buildup. - good evidence for this.
Those with downs syndrome have elevated a beta and also have higher alziehmers diesase numbers.
problems: lots of people have high a beta. maybe its the inflammatory response?
more problem: if this was the truth, more a beta should lead to more decline, but it doesn’t. - Tau is the problem, but less likely cause it shows up later, and animals with high tau don’t get plaques, but those with plaques get tau.
- vasular hypothesis: poor blood flow to your brain. Cerebrohyproper function. OVerall less blood to brain, NOT a stroke. could be related.
- Pathogenic spread. PRION DISEASE. small proteins.
If you are exposed to a small amount of specific beta or tau, which causes change of shape in your brain = cascade of issues. Healthy betas will change themselves like a VIRUS.
