Lecture 11 and 12 - LTP and LTD mechanisms

Question 1

with is a Hebbian synpase

Answer 1

• coordinated activity of a presynaptic terminal and a postsynaptic neuron to strengthen the synaptic connections between them

Question 2

recording the LTP phenomenon

Answer 2

use CA1 neuron and record from it and have presynaptic inputs of the neuron resulting in a response
- expect the EPSP with stable amplitude of change
- record many times and average should be the same

Question 3

what happens to the amplitude on average for LTP phenomenon?

Answer 3

amplitude on average becomes bigger to lead to a higher firing rate and other processes

Question 4

what does higher frequency result in for LTP phenomenon

Answer 4

• high frequency leads to higher and longer activity in postsynaptic neuron
• EPSP becomes bigger

Question 5

what happens when the neuron receives multiple inputs?

Answer 5

• get an increases in amplitude in input 1
• stimulate input 2 will remain the same
• there are places in the neuron where LTP is not shared

Question 6

what happens when two pathways converge on the same target?

Answer 6

• they can be strengthened if they fire together
• one pathway may be quite weak

Question 7

how to get an LTP phenomenon in both neurons

Answer 7

stimulate both neurons at the same time and both depolarise

Question 8

what is the synpase bwteen CA3 and CA1

Answer 8

glutaminergic

Question 9

what are the three classes of glutamate receptors?

Answer 9

NMDA, non-NMDA and mGlut
- NMDA and non-NMDA are ionotropic
- mGlut are metabotropic

Question 10

AMPA (non-NMDA) permeability

Answer 10

more permeable for sodium and potassium and is the main receptor for transmission of information

Question 11

NMDA permeability

Answer 11

permeable to calcium so does not depolarise the cell much but increases calcium concentration

Question 12

how does LTP occur? (CamK2)

Answer 12

NMDA opens and leads to increase in calcium concentration and activates kinases like CamK2 which is activated by calcium. Kinase phosphorylates different proteins which leads to increase in amplitude of EPSP

Question 13

magnesium dependent magnesium block in NMDA receptors

Answer 13

just glutamate alone is not enough, needs to depolarise the cell as well and leads to activation of the receptor as it removes magnesium

Question 14

weak vs strong activation (AMPA and NMDA)

Answer 14

if activation is weak only AMPA will open. If there is strong activation, the magnesium block is removed and the NMDA receptor is activated

Question 15

early vs late LTP

Answer 15

• early involves activated NMDA receptors with Camk2 self phosphorylation leading to AMPAification
• late involves gene expression with CREB2 binding to CRE

Question 16

cerebellum LTD circuitry inputs

Answer 16

positively charges mossy and climbing fibres

Question 17

cerebellum LTD circuitry outputs

Answer 17

negatively charges Purkinje fibres

Question 18

cerebellum LTD circuitry

Answer 18

mossy fibres send signal to granule cells (parallel fibres) which send signal to Purkinje fibres (by climbing fibres)

Question 19

what evokes LTD?

Answer 19

• paired Purkinje fibres and climbing fibres to a signle Purkinje cell

Question 20

which channels does cerebellar LTD mechanisms involve?

Answer 20

metabotropic Glu-R, AMPA-R, and voltage-activated Ca2+ channels

Question 21

cerebellar LTD mechanism

Answer 21

• protein kinase C phosphorylates AMPA GluR2 subunit
• reduces currents by endocytosis
• CF transmitter is glutamate
• AMPA-R internalisation triggered by phosphorylation

Question 22

what inhibits LTD?

Answer 22

Endocytosis inhibitors

Question 23

where does LTD occur in hippocampus?

Answer 23

CA3-CA1 synapse with LFS

Question 24

what dictates the probability of inducing LTP or LTD?

Answer 24

the degree of NMDA receptor activation

Question 25

what reduces AMPA-R efficacy?

Answer 25

small increases in calcium from NMDA-R triggering more phosphotase action

Question 26

what increases AMPA-R efficacy?

Answer 26

large increases in calcium activating more protein kinases