L19 Synaptic plasticity

Question 1

What are the types of memory

Answer 1

Explicit - declarative memory(medial temporal lobe, diecephalon) facts and events

Implicit - non-declarative memory(procedural memory skills and habits - striatum), classical conditioning - skeletal musculature(cerebellum), classical conditioning - emotional responses(amygdala)

Question 2

What is the donald hebb model for neural connections

Answer 2

• The reciprocal connections between neurons pre-exist
• Activation of the cell assembly by a stimulus
• Reverberating activity continues activation after the stimulus is removed
• Hebbian modification strengthens the reciprocal connections between neurons that are active at the same time
• The strengthened connections of the cell assembly contain the engram for the stimulus

Question 3

What did Hebb hypothesise

Answer 3

• If activation of the cell assembly persisted long enough, consolidation would occur by a ‘growth process’ that made these reciprocal connections more effective
• Neurons that fired together, wired together
• Subsequently, even if only a fraction of the cells of the assembly were activated by a later stimulus, the strengthened connections could cause the whole assembly to become active again, recalling the entire internal representation of the external stimulus

Question 4

What is associative long term potentiation

Answer 4

• If the activity of strong synapses is sufficient to trigger an action potential in the neuron, the dendritic spike will depolarise the membrane of dendritic spines, priming NMDA receptors so that any weak synapses active at that time will become strengthened

Question 5

What is the mechanism for long term potentiation in the hippocampus

Answer 5

• High frequency electrical stimulation of the perforant pathway(input)
• Record from cells within the dentate gyrus - subsequent perforant pathway stimulation results in increase in EPSP amplitude
• One HFS - LTP lasts hours
• Multiple HFS - LTP lasts days/months

Question 6

How do temporal, associative and specific summations work in long term potentiation

Answer 6

Temporal - Summation of inputs reaches a stimulus threshold that leads to the induction of LTP eg repetitive stimulation(HPS)

Associative - Simultaneous of a strong and weak pathway will induce LTP at both pathways(spatial summation) coincidence detection

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

Question 7

What normally happens at the synapse at resting potential when glutamate is released

Answer 7

• Glutamate release onto inactive cell
• AMPA receptor activated to create EPSP
• NMDA receptor blocked by Mg2+ ion
• Depolarisation from AMPA activation
• Not sufficient to expel Mg2+

Question 8

What happens when glutamate is released onto an active cell

Answer 8

• 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 9

What does Ca2+ entry through the NMDA receptor lead to

Answer 9

• 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 10

How does CaMKII maintain its activity

Answer 10

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

Question 11

How can the postsynaptic neuron feed back to presynaptic neuron

Answer 11

• By retrograde neurotransmitter - nitric oxide
• Ca2+ through the NMDA channel activates nitric oxide synthase
• NO diffuses from site of production and activates guanylyl cyclase in the presynaptic terminal
• Guanylyl cyclase produces the second messenger cGMP
• Signal transduction cascade leads to increased glutamate release from the synaptic button

Question 12

What prevents the consolidation of long term memories and LTP

Answer 12

• Protein synthesis inhibitors

Question 13

How does long-term potentiation change a synapse

Answer 13

• After long-term potentiation, a perforated synapse develops

Question 14

What causes long term depression

Answer 14

• Low frequency stimulation actually causes the opposite and rather than getting an increase in EPSP amplitude on further stimulation, you get a decrease j

Question 15

How does LFS cause LTD

Answer 15

• NMDA dependent process
• AMPA receptors are de-phosphorylated and removed from the membrane
• Prolonged low level rises in Ca2+ activate phosphatases rather than kinases

Question 16

What is AP5

Answer 16

• NMDA receptor antagonist
• Blocks hippocampal LTP
• Blocks learning

Question 17

Effect of alcohol on NMDA receptor

Answer 17

• NMDA receptor antagonist

- Blackouts and amnesia caused by drinking

Question 18

How does alcohol affect brain waves

Answer 18

• Alcohol disrupts hippocampal theta rhythms and disrupts short term memory

Question 19

What is korsakoff syndrome

Answer 19

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

Question 20

Effects of benzodiazepines on GABAa receptors

Answer 20

• Indirect agonist of GABAa receptors
• Binding increases the receptor affinity for GABA
• increase frequency of channel opening
• Anxiolytic and hypnotic drugs

Question 21

What is a side effect of anxiolytic and sedative drugs

Answer 21

• Anterograde amnesia

Question 22

Pathways of the basal forebrain bundle(part of the acetylcholine projections)

Answer 22

• Medial septum to hippocampus
• Basal nucleus to cortex
• Septum to hippocampus projection regulates theta waves

Question 23

Effect of scopolamine on muscarinic receptors

Answer 23

• Muscarinic receptor antagonist

- Suppresses theta waves and impairs spatial learning

Question 24

Effect of acetylcholinesterase inhibitors in alzheimer’s disease

Answer 24

• eg phyostigmine
• Boost cholinergic function
• Improves memory impairment

Question 25

What are some other learning processes which use LTP or similar mechanism

Answer 25

• Activity dependent synaptogenesis(development)

- Motor learning - eg riding a bike - cerebellar

Question 26

What is early phase LTP

Answer 26

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

Question 27

What is late phase LTP

Answer 27

lasts hours, days or months
• requires new protein synthesis and can involve morphological
• changes and the establishment of new synapses
• Ca2+ activated signal transduction cascades
• activate new protein synthesis from dendritically localized mRNAs
• filter back to the cell body to stimulate new gene transcription (CREB -mediated), protein synthesis and recruitment of new proteins to the synapse

Question 28

What is an effect of acetylcholinesterase inhibitors that has not yet been fully validated

Answer 28

• Controversial as to whether they improve memory