Chapter 25

For long term memory what must be done

permanent synaptic modification

What is memory acquisition

initial stage of memory where information is encoded in the brain

How does memory acquisition happen

we alter neural firing patterns, this is for temporary memory

What is memory consildation

temporary synaptic modifications that are made permanenet

What must be done for memory consolidation

New gene expression and protein synthesis

How do we keep a facial memory

neurons in area IT become more selective over more exposure

How do neurons become more selective in area IT

They are stimulus selective and they make different firing pattern for each face

Does one neuron in area IT tells us a face

no

How do multiple neurons tell us a face in area IT

We have a distributed pattern of activity that there is a ratio of neuron firing, rate

if neuron 1,2,3 fire at medium, large, and small it mark
if neuron 1,2,3 fire at small, medium, and large, it is Mohab

Why is distributed patterns important in firing cells

that if one neuron dies that the other neurons can still create that memory

but memory does degrade not loss

What is the neural network model

memory is encoded in the pattern of activity across many neurons

What invertebrate was used to study memory

Aplysia

How does sensitization of withdrawal reflex work in aplysia

a shock is given to the tail, it activates the sertonin modulatory neuron, it synapse on sensory neuron

Sensory neuron stimulating cAMP and activates PKA in axon terminal

What does PKA do in the sensory neuron

makes the sensory neuron release more glutmate onto the motor neuron

How does long term sensization happen in the Aplysia

more PKA activation results in gene expression and protein synthesis, this happens in the presynaptic neuron

How is short-term memory altered

different patterns of synaptic transmission

Hippocampus receives input from what

Entorhinal cortex

What is the pathway from entorhinal cortex to the hippocampus

Perforent Path→Mossy fiber synapse→ Schaffer collateral synapse

What is the perforent path

Entorhinal cortex→dentate gyrus

What is mossy fiber synapse

Dentate gyrus→CA3

What is Schaffer collateral synapse

CA3→CA1

Does LTP and LTD happen in the hippocampus

yes

What did Bliss and Lomo figure out

high frequency electricau stimulation of excitatory pathway produces LTP in awake rats

this was the Perforent Path


LTP + LTD Schaffer Collateral

How long does LTP lasts

1 year

Is LTP input specific

yes, it gives LTP to the neurons that was fired

What is the key to LTP

activation of NMDA receptors

How are NMDA receptors stimulated

via glutamate which binds to AMPA also and then depolarizes the membrane to release the Mg+2 block and allow for NMDA receptors to open which allows Ca+2 to come in

What is spike timing dependent plasticity

the strength of synaptic connections between neurons is modified based on the timing of their action potentials

What does Ca+2 do when it enters via NMDA receptor

Activates Protein Kinase C and CamKII

What does a Kinase do in general

phosphorylates things

How is AMPA receptor affected by PKC and CaMKII

AMPA gets phosphorylated on the cell membrane

What does CaMKII do

it increases the amount of AMPA receptor on the cell surface

Why do postsynaptic neuron extend to presynaptic neuron

due to presence of new AMPA receptor

If LTP happens what else must happen

LTD

How does the brain determine whether we have a LTD or LTP in the HIPPOCAMPUS

LTD is due to weak depolarizes due to an input
LTP is due to strong depolarizes due to an input

(this is called the sliding modification threshold)

What happens if the depolarization is neither weak or strong

We don’t get an LTD or LTP

is LTD calcium dependent

yes

How does LOW Ca+2 cause LTD

Low Ca+2 activates protein phosphatase which de-phosphorlaytes AMPA receptor and other postsynaptic protein

Fun fact about AMPA receptors

½ of AMPA receptors turn over every 15 minutes

What is the steady state of AMPA receptors

each AMPA removed is replaced by a new one

What is the steady state after LTP/LTD

Non-GluR1 AMPA receptor is replaced with a new non-GluR1 Ampa receptor


LTP starts with GluR1 receptor which is converted to non-GluR1

What is the side effect of GluR1 knocked out mice

Imparied Hippocampal LTP and cerebellar LTD

What are the 3 types of fibers in the cerebellum

Climbing fiber, parallel fiber, and purkinje cells

What does the Climbing fibers do

They receive excitatory input from medulla and uses it to coordinate planned movement with sensory input

this helps with a wrong movement that u did

What do parallel fibers do

they receive input from cerebellar granule cells, they relay motor commands from the motor cortex to the cerebellum

What do the purkinkje cells do

they are the main cerebellar output

How does LTD take place at the cerebellum

it involved pairing climbing fibers with parallel fibers, such pairing alters the Purkinje cells

LTD in the Cerebellum vs LTP in the hippocampus

they have the same mechanism

It LTP and LTD frequency dependent

yes

What was the mouse box shock expierement

scientists recorded the schaffer collateral synapse of CA1 neuron, before and after the shock, the outcome was that there was highended EPSP of neuron

meaning they learned

What blocks LTP learning in hippocampus

NMDA antagonists

What is the composition of NMDA receptor

two NR1 and two NR2

from the NR2 (we have NR2A and NR2B)

What affects the function of the NMDA receptor

ratio of NR2A and NR2B subunits

Why is sliding modification threshold important

it maintains neuronal stimulus selectivity and memory

because too much LTP would impair learning

How do we get LTP in NMDA receptors

increasing NR2B subunits (which allows more Ca+2)

How do we get LTD in NMDA receptors

increasing NR2A subunits (which allows less Ca+2)

Is phosphorylation and regulation of receptor sub units permanent

No

How does CaMKII work

It’s like a clothpin, one section of regulatory and other region is catalytic, it’s typically seen closed, but it opens when Ca+2 bound calmodulin binds to it, it ecposes the catalytic region,

a large elevation of Ca+2 can result in autophosporylation which makes catalytic region stay on FOREVER!

What is the molecular switch hypothesis

How CamKII work, and how it keeps postsynaptic AMPA receptors phosphorylated which helps in long term memory

What protein is seen in Long term memory Consolidation

Protein Kinase M Zeta

What does Protein Kinase M Zeta do

It’s mRNA form is translated when strongs amount of LTP-induced Ca+2 comes in

The protein phosphorylates other proteins that regulate AMPA receptor insertion

phosprylates it’s own proteins involved in it’s own translation

this happens even in the absence of Ca+2

Why is do people think Protein Kinase M Zeta is seen in memory consoldiation

A PKMZ inhibitor can erase LTP and memories

What does CREB do

help in protein synthesis for long term memory

How does CREB work

CREB-2 binding blocks transcription and new protein synthesis

CREB 1 moves CREB 2 and allows for transcription and new protein synthesis

What is presistence of LTP depended on

whether presynaptic stimulation is stron enough to trigger a new protein syntehsis

How do we get protein synthesis from LTP

an epsp can lasts hours creates protein

What does the new proteins do

it helps with synaptic remodeling, via increasing dendrites

How is LTP kind of not input specfic

When having a weak LTP on one input followed with a strong Input from anohter neuron, it can make proteins to help both synapses out

this has a time frame of 2 hours