Lecture 8 (4a) - Hippocampus, levels of understanding, optogentics Flashcards
Hippocampus
for new memories
• first affected in Alzheimer’s
• people don’t remember before age 6-7 because hippocampus not mature enough
Episodic memory
memory of events - what, when, where
H.M. case
most of his hippocampus was removed after severe epilepsy - drug resistant
consequences
• cannot form new memories
• old memories preserved
Alzheimer’s disease symptoms
early stages: difficulty remembering recent events while old memories are less affected
Alzheimer’s disease anatomy
the hippocampus is commonly the first affected structure
Older memories
don’t require the hippocampus
Newly formed memories
require the hippocampus
Different levels of understanding
- systems
- networks/neurons
- synapses/molecule
Human share DNA with rodents
80%
A rat learns, then
lesion the hippocampus –> can’t remember
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
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
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
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
AMPA
glutamate opens channel, sodium in
NMDA
- open channel, Mg out,
- 2nd messenger = Ca cells
- genes to transcribe
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
On postsynaptic cell terminal, AMPA receptors
allow rapid influx of Na+
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
Hippocampus LTP, LTD
LTP = long term potentiate
LTD = long term depress
(remove AMPA receptor)
Summary - the hippocampus is a key structure for
memory at all levels:
• systems
• networks/neurons
• synapses/molecule
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
Posterior hippocampus
larger in taxi drivers
• anterior hippocampus is smaller in taxi drivers
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
Astrocytes
support tissue
The adult brain constantly creates new neurons in certain regions - 2 sites
dentate gyrus of the hippocampus
olfactory bulbs
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
How can we manipulate our memory?
with optogenetics
Optogenetics
precisely controlling neural activity using light
• use light bc it’s fast
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)
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
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)
Researchers shoot laser beams into the brains of living mice to
activate and manipulate their memories
Therapeutic optogenetics application for the future
- cocaine addiction
- Parkinson disease
- OCD
