Flashcards in Lecture 8 (4a) - Hippocampus, levels of understanding, optogentics Deck (34):
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Hippocampus
for new memories
• first affected in Alzheimer's
• people don't remember before age 6-7 because hippocampus not mature enough
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Episodic memory
memory of events - what, when, where
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H.M. case
most of his hippocampus was removed after severe epilepsy - drug resistant
consequences
• cannot form new memories
• old memories preserved
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Alzheimer's disease symptoms
early stages: difficulty remembering recent events while old memories are less affected
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Alzheimer's disease anatomy
the hippocampus is commonly the first affected structure
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Older memories
don't require the hippocampus
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Newly formed memories
require the hippocampus
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Different levels of understanding
• systems
• networks/neurons
• synapses/molecule
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Human share DNA with rodents
80%
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A rat learns, then
lesion the hippocampus --> can't remember
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System - memory at the behavioral level
• rat memory at behavioral level
• spatial memory
• clear platform in water - rats with memory of enironment
• before learning = swim around tank before finding platform
• after learning = goes right to platform
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Memory at the neuron level -
what does a neuron in the hippocampus do when the animal is navigating?
• a neuron was placed in a specific neuron of a rat
• the rat was placed in a box
• every time the rat reached the top right corner, the device made a sound, showing that the neuron was associated with this spot
• electrode in hippocampus near neuron action potential
• active = sound (top right corner)
tells animal where it is in space
• trajectory, each dot = action potential
• place cells code space
• place = code field
• neuron for 1 place
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Memory at the neuron ensemble level
neurons active during an experience are being fast replayed during sleep
• fast relay happening during a ripple event
• release of neurotransmitter, chemical communication
• 2 receptors - ion channels post-synaptic
- AMPA and NMDA
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In sleep (neuron)
• same sequence but faster pattern repetition
• in sleep, memory transferred to long term
• related bc hippocampus and neocortex in time ripple = memory transcript stored
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AMPA
glutamate opens channel, sodium in
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NMDA
• open channel, Mg out,
• 2nd messenger = Ca cells
• genes to transcribe
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Memory at the synapse level
Long-Term Potentiation (LTP)
a long lasting enhancement in signal transmission between neurons first discovered in the hippocampus of the rabbit
• high frequency of electrical stimulation of the presynpatic neurons mimicking "learning" will reinforce the future communication between those 2 neurons
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On postsynaptic cell terminal, AMPA receptors
allow rapid influx of Na+
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Strong depolarization of the cell by Na+ influx
displaces MG(2+), which was blocking the NMDA receptor
• which is then open to both Na+ and Ca (2+)
• Ca(2+) acts as a second messenger, triggering long term cellular change
--> new AMPA receptors - reinforcement of this particular synapse = MEMORY AT THE SYNAPSE LEVEL
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Hippocampus LTP, LTD
LTP = long term potentiate
LTD = long term depress
(remove AMPA receptor)
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Summary - the hippocampus is a key structure for
memory at all levels:
• systems
• networks/neurons
• synapses/molecule
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How driving in London changes he taxi driver's hippocampus
Hippocampi volumes are compared between taxis and control adult of the same age
Conclusion of the study
• the longer you are a taxi driver in London, the larger the post hippocampi are compared to normal
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Posterior hippocampus
larger in taxi drivers
• anterior hippocampus is smaller in taxi drivers
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Before, it was thought that we make no new neurons - but now rejected
we produce new neurons all our lives in dentate gyrus in hippocampus
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Astrocytes
support tissue
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The adult brain constantly creates new neurons in certain regions - 2 sites
dentate gyrus of the hippocampus
olfactory bulbs
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The hippocampus, a structure that you can "train)
technique - add BrDU (labelling the DNA of the dividing cells) in humans and mice
• the rats mae more neurons in a stimulating environment with exercise than they did in a plain cage
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How can we manipulate our memory?
with optogenetics
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Optogenetics
precisely controlling neural activity using light
• use light bc it's fast
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Optogenetic techniques use
light sensitive ion channels or opsins coming from the genomes of algae, archaea, and fungi
(originally in the eye spot of green algae)
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Principe of optogenetics
when light stimulates them, they will open and light cations like Na+ go through.
This influx of Na+ creates an action potential in the neuron
- this is not an natural action potential, but rather induced artificially by light
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Technique of optogenetics
when a virus that contans the DNA of Channel Rhodopsin is injected in the target area of the brain, this DNA will be transcribed and translated in neurons - only in neurons because a specific promoter has been inserted upstream of the DNA sequence coding for the channel
• Now researchers have an amazing tool to control at the speed of light (instantaneously) the neurons (activate or inhibate)
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Researchers shoot laser beams into the brains of living mice to
activate and manipulate their memories
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