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

Cell Bio & Developmental Genetics > Lecture 8 (4a) - Hippocampus, levels of understanding, optogentics > Flashcards

Flashcards in Lecture 8 (4a) - Hippocampus, levels of understanding, optogentics Deck (34):
1

Hippocampus

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

2

Episodic memory

memory of events - what, when, where

3

H.M. case

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

consequences
• cannot form new memories
• old memories preserved

4

Alzheimer's disease symptoms

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

5

Alzheimer's disease anatomy

the hippocampus is commonly the first affected structure

6

Older memories

don't require the hippocampus

7

Newly formed memories

require the hippocampus

8

Different levels of understanding

• systems
• networks/neurons
• synapses/molecule

9

Human share DNA with rodents

80%

10

A rat learns, then

lesion the hippocampus --> can't remember

11

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

12

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

13

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

14

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

15

AMPA

glutamate opens channel, sodium in

16

NMDA

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

17

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

18

On postsynaptic cell terminal, AMPA receptors

allow rapid influx of Na+

19

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

20

Hippocampus LTP, LTD

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

21

Summary - the hippocampus is a key structure for

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

22

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

23

Posterior hippocampus

larger in taxi drivers
• anterior hippocampus is smaller in taxi drivers

24

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

25

Astrocytes

support tissue

26

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

dentate gyrus of the hippocampus
olfactory bulbs

27

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

28

How can we manipulate our memory?

with optogenetics

29

Optogenetics

precisely controlling neural activity using light
• use light bc it's fast

30

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)

31

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

32

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)

33

Researchers shoot laser beams into the brains of living mice to

activate and manipulate their memories

34

Therapeutic optogenetics application for the future

• cocaine addiction
• Parkinson disease
• OCD