Memory and Amnesia

Marinos Koulouroudias

What we will cover

• Review anatomy of structures involved in memory

• Explain how Short- term memory works

• Understand the concepts of consolidation and long-

term potentiation

• Understand how amnesia emerges and list its causes

From our previews lecture on the Limbic system:

• We examined HM’s case and realised that the Limbic system is necessary for the transfer of experience into long- term memory and for its easy recall (even though it is not where memories are stored)

• Try talking yourself through the Papez circuit on the next slide:

Work out the sequence in which different structures are involved in Papez’s Circuit

How well did you do?

START HERE

Congratulations!

• You are firm on your way to the neuroanatomy hall of fame!

Introductory concepts

• Imagine you receive a hard blow on your head enough to render you unconscious:

• You will lose memory about what happened a few minutes before the insult and will (of course!!!) not make any new memories while you are unconscious

• However, you will not have lost either your ability to recall past memories or make new ones!

So, what’s your point?

My point is twofold:a) You require CONSCIOUSNESS to make new

memoriesb) Short term memory can be disrupted by

insults that affect the ongoing electrical activity in your brain.

If you disrupt that = no transfer to Long- term memory.

So, what’s the point of all that???

• Short- term memory (STM) is a product of on- going electrical activity in your brain

• Long- term memory (LTM) requires consciousness to be created from STM and is stored in a more reliable form=

modification of synapses.

Quiz

What is the name of the process where information stored in STM is transferred to LTM?

See next slide

Consolidation

Yeap, you’ve guessed it right!

Let‘s explore consolidation further

Key facts about consolidation

• Needs consciousness

• Arousal is important (likely in the form of Noradrenaline; the reason why you may remember every detail of an exciting encounter but none about this lecture!)

• Make sure you are confident at defining consolidation before moving on!

Mechanisms that optimize consolidation- Part 1: the phonological loop

Language is very important: We engage in an internal monologue when presented with new information that can be articulated, ie instructions (go buy bread, milk and cheese, remember number 123124523, the bones of the hand are the scaphoid, lunate…)

Constantly repeating these instructions in our head extends our STM and allows effective consolidation

An experiment (of sorts): Read the number in the first box, and follow the instructions, then go to the next slide and see if you can

remember the number given!

Input: Remember this number

47863159144

Phonological store: Now you are

encoding these numbers as

electrical activity, relating to how

they sound ‘four, seven…’

Articulatory process:

Now you are actually ‘saying’ them, either out loud or in ‘your

brain’, repeat it for at least 30

seconds

Now look again at this number(a different one)

79018523364

Close your eyes IMMEDIATELY and keep them closed for 30 seconds, DO NOT practice the number, you only have ONE go at remembering it.

And go to the next slide (hopefully you’ve read this before indefinitely closing your eyes).

How well did you do?

• Yeap I know, you did much better when you had the chance to rehearse the information

• This ability, conferred by the phonological loop allows you to consolidate better as well as enhance your STM!

Part 2: The visuospatial sketchpad

This encodes all the information that cannot be coded verbally

It is not as good as the phonological loop, as the lack of the ability to articulate or verbally code these information, means that we cannot rehearse it!

Less rehearsal, makes for an embarrassing performance!

No experiment for this one I’m afraid, look at Dr Millar’s lecture on the slide with the pig drawing and you will see what I mean.

Therefore

STM can either be rehearsed in the phonological loop or roughly mapped out in the visuospatial sketchpad, before being either discarded or consolidated as LTM

The anatomical location of the phonological loop

• It requires the a) Dorsolateral frontal lobes- they provide the

attention required to perform the rehearsalb) Wernicke’s area to store the ‘sound’ of what

you want to rememberc) Broca’s area to perform the articulatory process

(think about saying it or actually saying it)d) The arcuate fasciculus to connect Wernicke’s

and Broca’s

Try and label the structures mentioned in the previous slide

Something like this maybe?

Dorsolateral frontal

• The phonological loop is more prominent on the LEFT frontal lobe

• The visuospatial checkpad is more on the RIGHT frontal lobe

What happens if you lose the phonological loop?

• Damage to the left dorsolateral frontal lobe, leaves you with decreased digit span memory, so the lack of the ability to rehearse a long number, makes you worse at recalling it!

• Also deficits in attention (and exhibition of perseverance)

Ok got it!

• So we have STM that is formed by loops of electrical activity mostly in the frontal lobes, mediated either by the phonological loop (for stuff we can verbalise) and the visuospatial sketchpad (for stuff we cannot).

• Then if it is to be put into LTM, consolidation happens.

• So, how does consolidation happen???

As we said before:

• Consolidation= Synaptic modification, permanent.

• One of the main mechanisms of consolidation is Long- Term Potentiation

Long- term potentiation (LTP)

• What is it?

Fire and Wire- LTP

• That’s the main concept: Synapses that fire together, wire together

• If a neuron receives high frequency stimulation delivered at the same time by several axons, then its response to future stimulation by those axons is enhanced!

• In other words, they fired together so now they are wired together!

How does the ‘wiring’ take place in LTP?- draw a diagram while reading this outline

1) Glutamate released from pre-synaptic neuron2) Glutamate binds to AMPA receptors in post-

synaptic neuron that ‘opens up’ to let Na+ ions in3) If the release of glutamate is ‘strong’ enough the

NMDA receptor loses the Magnesium ion that acts as a sort of ‘gate-keeper’

4) Glutamate binds to the NMDA receptor and BOTH Na+ and Ca2+ enter the post synaptic neuron

This is what your diagram should look like, try talking it through and explain to yourself or a colleague

Then?

• Then all the Calcium that comes in starts doing fancy stuff so that in the future the post- synaptic neuron can be activated more easily, such as increasing how many glutamate receptors it has on its surface and changing its shape so that current flows more easily through it

• Therefore these two neurons fired together and now they are better wired together!!!

So where are memories kept stored using this mechanism?

• One memory is stored in many different locations in the association cortices, and it becomes conscious when a pattern of neuronal activity occurs, ie when all the ‘right’ neurons in different places fire up in a specific order!

Thinking of an apple

• Eliciting your memory of an apple, possibly parts of your visual association cortex lights up to remind you of what it looks like, then maybe the olfactory or gustatory areas to remind you of what it smells and tastes like etc

• All these combined together give you the conscious experience of ‘remembering’ an apple!

How do memories end up in the right places in our brain? And how do we retrieve them?

• The limbic system seems to be important in directing in what association cortex each bit of the memory should be stored

• The hippocampus and the amygdala as well as the thalamic nuclei (rem the Papez circuit) seem to be important in retrieving these memories

Summary!- go back and answer these questions

1) STM- what structures are involved? What is the phonological loop and what is its significance?

2) LTM- what structures are involved? What is consolidation? What is LTP?

Amnesia: Types

PROFOUND MEMORY LOSS

1) Anterograde= new events not transferred in LTM (case of HM)- (problem with consolidation)

2) Retrograde= inability to recall events that happened before the onset of the amnesia, but can form new memories

3) Dissociative= selective blocking out of traumatic memories

Amnesia: Aetiology

Anything that disrupts consciousness or the integrity of the structures of the areas involved in memory:1) Trauma2) Infection- meningitis, encephalitis3) Electrolyte imbalance4) Degeneration- eg due to alcohol5) Psychogenic etc etc etc

Thanks for Remembering!