LTD Mechanisms

Question 1

What is LTD? (2)

Answer 1

• Long term depression
• When synapses become less efficient at transmitting signals

Question 2

What is the circuitry of the cerebellum? (2)

Answer 2

• Climbing fibres form many synapses with a single Purkinje cell
• Parallel fibres synapse with many Purkinje cells, only forming one synapse with each Purkinje cell

Question 3

What happens in the Purkinje cell when there is a stimulation of a climbing fibre on its own? (3)

Answer 3

• Large depolarisation in the Purkinje cell because climbing fibres form many synapses with a single Purkinje cell
• AMPA receptors are activated causing depolarisation
• Activates voltage-gated Ca2+ channels = Ca2+ influx

Question 4

What happens in the Purkinje cell when there is a stimulation of a parallel fibre on its own? (3)

Answer 4

• Small depolarisation in the Purkinje cell because a parallel fibre forms a single synapse with many Purkinje cells
• AMPA receptors activated causing small depolarisation
• mGlutR activated leading to small increase in pKC activity

Question 5

What is the output of the cerebellum?

Answer 5

Output to the DCN via Purkinje fibres

Question 6

What is the DCN?

Answer 6

Deep cerebellar nuclei

Question 7

What happens in a Purkinje cell when you stimulate a parallel fibre and a climbing fibre at the same time? (3)

Answer 7

• Ca2+ influx from the climbing fibre stimulation potentiates the activity of pKC
• pKC phosphorylates AMPA receptor GluR2 subunit (different from LTP) so AMPA receptors in the parallel fibre synapse are endocytosed
• Causes a decrease in the EPSP = LTD in the parallel fibre : Purkinje cell synapse

Question 8

Which receptors are in the synapse between the climbing fibre and Purkinje cell?

Answer 8

AMPA receptors

Question 9

Which receptors are in the synapse between the parallel fibre and Purkinje cell? (2)

Answer 9

• Metabotropic glutamate receptors
• AMPA receptors

Question 10

What happens when metabotropic glutamate receptors are activated on Purkinje cells? (3)

Answer 10

• Activates Phospholipase C (PLC)
• Causes production of IP3 and DAG
• IP3 causes increase of intracellular calcium
• DAG activates protein kinase C (pkC)

Question 11

What is the effect of endocytosis inhibitors on LTD?

Answer 11

Prevents LTD

Question 12

Which cells in the cerebellum are involved in LTD? (3)

Answer 12

• Purkinje cells
• Climbing fibres
• Parallel fibres

Question 13

Where does LTD occur in the hippocampus?

Answer 13

The CA3 : CA1 synapse in the hippocampus (same synapse as LTP)

Question 14

How is NMDA receptor activation linked to LTP and LTD? (2)

Answer 14

• Low frequency stimulation of NMDA receptors causes LTD
• High frequency stimulation of NMDA receptors causes LTP

Question 15

How does LTP and LTD both occur in the hippocampus? (4)

Answer 15

• Hippocampal LTD requires phosphatases, LTP requires kinases
• Small increases in Ca2+ (from low frequency stimulation) activates phosphatases which decrease AMPA-R efficacy = LTD
• Large increases in Ca2+ (from high frequency stimulation) activates kinases which increase AMPA-R efficacy = LTP
• Balance between the two