L19 Synaptic plasticity

Question 1

what are the different types of memory

Answer 1

Explicit- includes declarative memory:

1)facts

and

2) events

Implicit- non-declarative money:

1) procedural memory: skills and habits
2) Classical conditioning: Skeletal musculature
3) Classical conditioning- emotional responses

Question 2

where are the areas that the different types of memory found in the brain

Answer 2

Explicit: Medial temporal lobs; diencephalon

Implicit: Procedural
memory :

striatum

classical-skeletal musculature: cerebellum

Emotional responses: Amygdala

Question 3

describe; how do we learn

Answer 3

• Learning: the response of the brain to environmental events and involves adaptive changes in synaptic connectivity which will in turn alter behaviour.

Question 4

describe the Donald Hebb cell assembly theory

Answer 4

1) Reciprocal connections exist between neurons; forming a cell assembly
2) An external stimulus is applied
3) Activation of the cell assembly by a stimulus
4) Reverberating activity continues activation after the stimulus is removed
5) Hebbian modification strengthens the reciprocal connection between neurons that are active at the same time
6) The strengthened connections of the cell assembly contain the engram for the stimulus
7) After learning, partial activation of the assembly leads to activation of the entire representation of the stimulus
8) Circle/cell assembly is formed

Question 5

summarise Hebb’s rule

Answer 5

-When an axon of cellAis near enough to excite a cellBand repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firingB, is increased

=

Strengthening and weakening synaptic connections in the brain provide a means by which learning occurs and memories can be formed.

Question 6

describe the rules of synaptic modification

Answer 6

1) Neurons that fire together wire together

2) Neurons that fire out of sync lose their link.

Question 7

read over slide 13 for an example of rules of synaptic modification

Answer 7

how was it?

Question 8

why is the hippocampus regularly tested and what is it used to study

Answer 8

shape and anatomy means pathways can be easily distinguished and recorded from electrophysiologically

used to study Long term potentiation (LTP)

Question 9

what does LTP underlie

Answer 9

• mechanism underlying synaptic strengthening

Question 10

describe Temporal LTP

Answer 10

• Temporal: Summation of inputs reaches a stimulus threshold that leads to the induction of LTP. e.g. Repetitive stimulation (HFS)

Question 11

describe Associative LTP

Answer 11

Associative: simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways. (Spatial summation)
Coincidence detection
“Cells that fire together wire together”

Question 12

describe specific LTP

Answer 12

Specific: LTP at one synapse is not propagated to adjacent synapses (input specific).

Question 13

what occurs at the synapse during LTP

Answer 13

Glutamate release onto inactive cell
(membrane at resting potential)

AMPA receptor activated to create EPSP
NMDA receptor blocked by Mg2+ ion
Depolarization from AMPA activation
not sufficient to expel Mg2+

Glutamate release onto an active
Cell (membrane depolarized)

AMPA receptor activated
Mg2+ block on NMDA receptor relieved
Na+ through AMPA and NMDA channels
Ca2+ through NMDA channel

Question 14

what happens when Ca2+ enters through the NMDA channel

Answer 14

Ca2+ entry through the NMDA receptor leads to activation of:
Protein kinase C
Calcium calmodulin-dependent protein kinase II (CaMKII)

1) phosphorylates existing AMPA receptors, increasing their effectiveness
2) stimulates the insertion of new AMPA receptors into the membrane

Question 15

describe the before and after depolarisation correlation between the number of AMPA receptors and an EPSPs

Answer 15

1)Before:
Few AMPA receptors
Small EPSPs

2)After:
More AMPA receptors working more effectively
Larger EPSPs
LTP

Question 16

describe the activity of the CaMKII - molecular switch - which has sustained activity after repolarization

Answer 16

1)Ca2+ entry through the NMDA receptor leads to activation of
Calcium calmodulin-dependent protein kinase II (CaMKII)

2) CaMKII has autocatalytic activity - becomes phosphorylated
3) When phosphorylated is constitutively active - no longer requires Ca2+
4) Maintains phosphorylation, insertion of AMPA receptors etc. after the depolarizing stimulus has receded
5) Molecular switch which maintains increased excitability of neuron for minutes to hours

Question 17

what are the presynaptic events in a LTP

Answer 17

1)Postsynaptic neuron can feed back to presynaptic neuron by retrograde neurotransmitter - Nitric Oxide (NO)

2)Ca2+ through the NMDA channel
activates Nitric oxide synthase

3)NO diffuses from site of production and
activates guanylyl cyclase in the presynaptic
terminal

4)Guanylyl cyclase produces the
second messenger cGMP

5)Signal transduction cascade leads to increased
glutamate release from the synaptic button

Question 18

describe what occurs in a late phase LTP

Answer 18

1) Protein synthesis required for long-lasting LTP (days, months)
2) Protein synthesis inhibitors prevent the consolidation of long term memories and LTP
3) Stages of memory formation

4)Acquisition (training)
Consolidation
Recall (testing)

5)Protein synthesis inhibitor
injected just post-acquisition
(training) inhibits recall
- necessary for consolidation

6)CREB - cAMP Response Element Binding protein activated by phosphorylation by a number of kinases (PKA, CaMKII etc)

Question 19

describe the difference between early and late phase LTPs( starting with early) Part 1/2

Answer 19

1) lasts a minute to an hour
2) and can be explained by the actions of Ca2+ through the NMDA receptor and subsequent enhancement of AMPA receptor efficiency
3) presynaptic events etc.

Question 20

describe the difference between early and late phase LTPs( ending with late) Part 2/2

Answer 20

1) lasts hours, days or months

2) requires new protein synthesis
and can involve morphological
changes and the establishment
of new synapses

3) Ca2+ activated signal transduction
cascades:

A- activate new protein synthesis from
dendritically localized mRNAs

B-filter back to the cell body to
stimulate new gene transcription (CREB -mediated), protein synthesis
and recruitment of new proteins to the synapse

Question 21

describe what LTD is

Answer 21

Long Term Depression (LTD)=

-
Low frequency stimulation (LFS: 100x 1 Hz) actually causes the opposite and rather than getting an increase in EPSP amplitude on further stimulation you get a decrease

Same players involved:
-NMDA dependant process
-AMPA receptors are de-phosphorylated and
removed from the membrane

-prolonged low level rises in Ca2+ activate
phosphatases rather than kinases

Question 22

what do LTP and LTD reflect bidirectional regulation of

Answer 22

1. phosphorylation and

2. number of postsynaptic AMPA receptors

Question 23

what is the proof that changes in synaptic activity really lead to learning

Answer 23

in Rats:

1) NMDA receptor activity in the hippocampus essential for both LTP and spatial learning
2) AP5
- NMDA receptor antagonist

-blocks hippocampal LTP
blocks learning in the Morris Water Maze

3) conclusion: normal rat without AP5 learned uickly to find the way to escape the water maze

but

the rats with AP5 infused struggled to escape after multiple trials

Question 24

describe the studies done on humans in regards to LTP

Answer 24

Human inferotemporal cortex
removed during surgery
maintained in vitro

HFS - produced LTP

LFS - produced LTD

Question 25

what are the effects of acute and chronic alcohol on memory and learning

Answer 25

Alcohol -
NMDA receptor antagonist (as well as other sites)

Blackouts and amnesia caused by drinking

directly blocking normal LTP processes?

Alcohol disrupts hippocampal theta rhythms and disrupts short term memory.

Chronic alcoholism and associated nutritional deficiency can result to Korsakoff syndrome or psychosis: loss of recent memory, and tendency to fabricate accounts of recent events (confabulation).

Question 26

what are the effects of benzodiazepines on learning and memory

Answer 26

• Benzodiazepines

Indirect agonist of GABAA receptors:

- binding increases the receptor affinity for GABA 		- increase frequency of channel opening
- anxiolytic and hypnotic drugs

Side effect to anxiolytic and sedative properties:
- anterograde amnesia

Question 27

describe the effects of cholinergics/anticholinergics on learning and memory

Answer 27

Acetylcholine projections:

Basal forebrain bundle:
Medial septum to hippocampus
Basal nucleus to cortex

Septum to hippocampus projection regulates theta waves

Scopolamine (muscarinic receptor antagonist)
suppresses theta waves and impairs spatial learning

Question 28

describe the effects of cholinergics/anticholinergics on learning and memory in Alzheimers

Answer 28

Alzheimer’s disease

Acetylcholinesterase inhibitors
e.g. physostigmine
Boost cholinergic function
Improves memory impairments

Question 29

describe the effects of cholinergics/anticholinergics on learning and memory in a healthy brain

Answer 29

Controversial as to whether they improve memory
May increase attention

Most cognitive enhancing effects of both acetylcholinesterases and other cholinergic drugs, e.g. nicotine, seen in impaired subjects, i.e. Alzheimer’s patients, or in restoring performance of animals with lesions.

Question 30

name some other processes which use LTP

Answer 30

Activity dependent synaptogenesis (development)

Motor learning - e.g. riding a bike - cerebellar