Lecture 8 (4a) - Hippocampus, levels of understanding, optogentics

Question 1

Hippocampus

Answer 1

for new memories
• first affected in Alzheimer’s
• people don’t remember before age 6-7 because hippocampus not mature enough

Question 2

Episodic memory

Answer 2

memory of events - what, when, where

Question 3

H.M. case

Answer 3

most of his hippocampus was removed after severe epilepsy - drug resistant

consequences
• cannot form new memories
• old memories preserved

Question 4

Alzheimer’s disease symptoms

Answer 4

early stages: difficulty remembering recent events while old memories are less affected

Question 5

Alzheimer’s disease anatomy

Answer 5

the hippocampus is commonly the first affected structure

Question 6

Older memories

Answer 6

don’t require the hippocampus

Question 7

Newly formed memories

Answer 7

require the hippocampus

Question 8

Different levels of understanding

Answer 8

• systems
• networks/neurons
• synapses/molecule

Question 9

Human share DNA with rodents

Answer 9

80%

Question 10

A rat learns, then

Answer 10

lesion the hippocampus –> can’t remember

Question 11

System - memory at the behavioral level

Answer 11

• 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

Question 12

Memory at the neuron level -

what does a neuron in the hippocampus do when the animal is navigating?

Answer 12

• 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

Question 13

Memory at the neuron ensemble level

Answer 13

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

Question 14

In sleep (neuron)

Answer 14

• same sequence but faster pattern repetition
• in sleep, memory transferred to long term
• related bc hippocampus and neocortex in time ripple = memory transcript stored

Question 15

AMPA

Answer 15

glutamate opens channel, sodium in

Question 16

NMDA

Answer 16

• open channel, Mg out,
• 2nd messenger = Ca cells
• genes to transcribe

Question 17

Memory at the synapse level

Long-Term Potentiation (LTP)

Answer 17

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

Question 18

On postsynaptic cell terminal, AMPA receptors

Answer 18

allow rapid influx of Na+

Question 19

Strong depolarization of the cell by Na+ influx

Answer 19

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

Question 20

Hippocampus LTP, LTD

Answer 20

LTP = long term potentiate
LTD = long term depress
(remove AMPA receptor)

Question 21

Summary - the hippocampus is a key structure for

Answer 21

memory at all levels:
• systems
• networks/neurons
• synapses/molecule

Question 22

How driving in London changes he taxi driver’s hippocampus

Answer 22

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

Question 23

Posterior hippocampus

Answer 23

larger in taxi drivers

• anterior hippocampus is smaller in taxi drivers

Question 24

Before, it was thought that we make no new neurons - but now rejected

Answer 24

we produce new neurons all our lives in dentate gyrus in hippocampus

Question 25

Astrocytes

Answer 25

support tissue

Question 26

The adult brain constantly creates new neurons in certain regions - 2 sites

Answer 26

dentate gyrus of the hippocampus

olfactory bulbs

Question 27

The hippocampus, a structure that you can “train)

Answer 27

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

Question 28

How can we manipulate our memory?

Answer 28

with optogenetics

Question 29

Optogenetics

Answer 29

precisely controlling neural activity using light

• use light bc it’s fast

Question 30

Optogenetic techniques use

Answer 30

light sensitive ion channels or opsins coming from the genomes of algae, archaea, and fungi
(originally in the eye spot of green algae)

Question 31

Principe of optogenetics

Answer 31

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

Question 32

Technique of optogenetics

Answer 32

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)

Question 33

Researchers shoot laser beams into the brains of living mice to

Answer 33

activate and manipulate their memories

Question 34

Therapeutic optogenetics application for the future

Answer 34

• cocaine addiction
• Parkinson disease
• OCD