Memory Flashcards
Lecture 11
how is memory affected by retrograde amnesia?
- person can create new memories but forgets old ones
- can be temporally graded, remember super old memories but not more recent ones before injury
how is memory affected by anterograde amnesia?
person can’t create new memories but remembers old ones
who is patient HM
- had bilateral medial temporal lobes removed because of severe epilepsy (hippocampus, amygdala, part of temporal cortex)
- developed anterograde amnesia and had temporally graded retrograde amnesia
- but working memory was intact
what were patient HM’s symptoms (how did he perform on tasks)
- had severe anterograde amnesia but short term and working memory were intact
- could perform a digit span task with 6-7 digits
- but, when asked to remember things that can’t be actively rehearsed and repeated, he couldn’t (picture matching)
- got better at tasks they did multiple times, but had no memory of doing the task in the past
what was patient HM’s memory duration like?
- they had working (short-term) memory, and could learn motor skills
- they could not consolidate memory into long term storage
what is implicit vs. explicit memory?
- implicit memory - things we remember without being conscious of it
- ex. learning to ride a bike
- explicit memory - things that require effort to remember, need to be actively recalled
- ex. general facts about the world
what are the two types of explicit memory?
- episodic memory - personally experiences events
- semantic memory - facts and general knowledge
who is patient KC?
- had bilateral hippocampus lesions
- remembered general facts but couldn’t remember experiences he had
- semantic memory was intact but episodic memory was not
what is the hippocampal indexing theory?
- all sensory information and stimuli from the event gets indexed together in the hippocampus
- indexing required at first in order to generate recall from other areas
- connections are strong and are able to be associated with each other even without the hippocampus
what is long term potentiation?
- repetitive strengthening of synapses that enables a long-lasting increase in synaptic transmission
- performed in the hippocampus of rats
- use weak vs. strong stimuli and measure EPSPs via electrodes to create a strong neural connections
what happens during long term potentiation?
- EPSP causes glutamate to release into the synapse and bind to AMPARs and NMDARs
- magnesium blocks in NMDARs require a very strong positive charge/depolarization in order to open and allow sodium in
- stronger signals = more calcium = more AMPARs go to bind to more glutamate
- more sodium and calcium are let in for a stronger connection
what are the immediate short term changes (functional) associated with LTP?
AMPARs are recruited to the membrane to have more signals and stronger connection between neurons
what are the long-lasting, slower changes (structural) associated with LTP?
- it can make synapses stronger and able to make more connections
- can start second messenger signalling and changes in genes to create more AMPARs
- ability for stronger memories
how and why are NMDARs related to brain dysfunction?
- LTP is more prominent in memory-related areas
- also epilepsy because of excitable brain areas
- NMDAR activity allows calcium into the cell
- calcium is a potent signalling molecule but too much can trigger apoptosis
- alcohol, PCP, ketamine are NMDAR antagonists
- lose abilities to form memories
what is alzheimer’s disease?
- irreversible (no cure), progressive, neurogenerative disease
- most common cause of dementia
- appears first in the medial temporal lobe then progresses to the cortex
- occasional early onset (familial or genetic form of AD) but there is no single gene associated with AD
what are the symptoms of alzheimer’s disease?
cognitive and non-cognitive symptoms
- early symptoms - being “forgetful”, selective declines in memory
- later symptoms - confusion, irritability, anxiety, problems with speech
- advanced stage symptoms - difficulties with even simple responses or behaviours
what are the defining characteristics of AD?
- brain volume decreases
- neurofibrillary tangles
- amyloid plaques
what are neurofibrillary tangles?
- hyperphosphorylated tau aggregates
- causes structure of the neuron and their axons to break down
- cell degeneration and death
- is intracellular - happens within the cell
what are amyloid plaques?
- comprised of beta-amyloid proteins (A-beta Aβ) that stick to each other and create plaques (are meant to be broken down)
- beta-amyloid comes from amyloid precursor protein (APP)
- is extracellular - happens outside and around the neuron
what is the usual time course of AD in terms of amyloid plaques and neurofibrillary tangles?
- amyloid plaques form and neuronal integrity declines before symptoms even arise
- neurofibrillary tangles begin a little later on
what are the biomarkers for AD?
- low beta-amyloid levels in CSF (because they are not being broken down)
- high tau levels in CSF
- PET imaging of beta-amyloid levels (amyvid)
- PET imaging of tau/hyperphosphorylated tau
- decreases in hippocampal volume (MRI)
- decreases in brain metabolism
what are the main theories of pathogenesis for AD?
- amyloid cascade hypothesis
- neurofibrillary (tau) hypothesis
- vascular hypothesis
- pathogenic spread
- bacterial hypothesis (gum disease)
- fungal hypothesis
- autoimmune hypothesis
what is the amyloid cascade hypothesis for AD?
- as beta amyloids clump up in the brain, it stimulates other abnormalities in the brain
- causes tau to hyperphosphorylate
what is the neurofibrillary (tau) hypothesis for AD?
- idea that neurofibrillary tangles come first
- we now know beta amyloids come first
what is the vascular hypothesis for AD?
- some risk factors for AD are also risk factors for cardiovascular disease (hypertension, high cholesterol)
- we also see vascular problems in the brain in people with AD
what is the pathogenic spread hypothesis for AD?
- proteins get misfolded in the brain and cause dysfunction, also spread other misfolded proteins
- if this were true, we would have to see a transmission of misfolded proteins between neurons, but we aren’t yet
why do some scientists believe in the bacterial and fungal hypothesis for AD?
- lots of people with AD have also had bacterial infections (gum disease - gingivitis)
- found fungus in the brains of AD patients
what is the autoimmune hypothesis for AD?
- pathogen is detected, beta amyloid increases, is over produced, and attacks its own cells
- as beta amyloids clump, they signal even more immune response
what are some treatments for AD?
- cholinergic (ACh) agonists (acetylcholinesterase inhibitors) - prevents enzymes from breaking down signalling neurotransmitter
- NMDAR antagonist (memantine) - prevent too much calcium and cell death
- lithium - prevents over excitability that happens during mania
- aducanumab (aduhelm) - antibodies for beta-amyloid, has been discontinued
- lecanemab (leqembi) - antibodies for beta amyloid, has been recently approved
- physical exercise, environmental enrichment as disease prevention
