Exam 1 Week 2: ppt 9 Post-Synaptic Events

Question 1

what are three important structures found in post-synaptic membranes?

Answer 1

1. Neurotransmitter receptors
   
   • –Ionotropic
   • –Metabotropic
2. Ligand-gated ionic channels
3. Membrane associated intracellular second messenger systems for regulating ionic permeability & neuronal genomic & metabolic functions

Synaptic Gap separates the presynaptic and post-synaptic membrane and it is a 20-30 micron gap. The neurotransmitter after being released by the presynaptic membrane diffuses across the gap to bind to Neurotransmitter receptors on the Post-synaptic membrane. There are two main types of neurotransmitter receptors:

Ionotropic

Metabotropic

In addition there are Ligand-gated ionic channels along the post-synaptic membrane.

Also bound to the post-synaptic membrane are Membrane associated intracellular second messenger systems for regulating ionic permeability & neuronal genomic & metabolic functions

Question 2

What three functions can membrane-associated intracellular second messenger systems have?

Answer 2

1. regulate ionic permeability
2. neuronal genomic
3. metabolic functions

Also bound to the post-synaptic membrane are Membrane associated intracellular second messenger systems for regulating ionic permeability & neuronal genomic & metabolic functions

Question 3

Describe the two types of receptors

Answer 3

1. •Ionotropic receptors gate ion channels directly
2. •Metabotropic gate ion channels indirectly after activating a protein
   
   • –G-protein-coupled receptors
   • “Second messengers”

Question 4

How is the postsynpatic neuron able to specialize its response?

Answer 4

With specific postsynaptic receptors

• –Specificity - “Lock & Key” mechanism
• –Two major domains for response to receptor binding
  
  • These domains are:
    
    • Ionotropic receptors gate ion channels directly
    • Metabotropic gate ion channels indirectly after activating a protein such as G-protein-coupled receptors or via the G-protein-coupled receptors to activate “Second messengers”

Question 5

If a postsynaptic neuron in deprived of its synapses by injruy or disease …

Answer 5

•it can become denervated or develop hypersensitivity

Question 6

•Receptor number can be _______________ or _______________ in response to the amount of transmitter released

Answer 6

•Receptor number can be up-regulated or down-regulated in response to the amount of transmitter released

Question 7

What are Postsynaptic Potentials?

Answer 7

•PSPs are changes in the postsynaptic neurons membrane potential caused by ion channels interacting with a neurotransmitter from the presynaptic neuron. They are non-propigating

• – Excitatory postsynaptic potentials (EPSPs) are depolarizing
• –Inhibitory postsynaptic potentials (IPSPs) are hyperpolarizing

Inotropic receptors are bound to ionic channels (ligand-gated channels) which can produce post-synaptic potentials..

These post-synaptic potentials are either:

Excitatory postsynaptic potentials (EPSPs) are depolarizing

Inhibitory postsynaptic potentials (IPSPs) are hyperpolarizing

Question 8

•Post synaptic excitation (EPSP)

Answer 8

–Transmitter binds to its receptor and opens Na+ channels
–Produces graded depolarization - moves toward threshold so excitatory

Excitatory Post synaptic potentials (EPSPs) occur when Transmitter binds to its receptor and opens Na+ channels

The influx of Na+ Produces graded depolarization - moves toward threshold so excitatory. Thus called Excitatory Post-synaptic excitatory potential (EPSP)

Question 9

EPSP: Two types of summation

Answer 9

Spacial summation

Temporal summation

Question 10

Spacial Summation

Answer 10

to reach threshold ,many EPSPs must be added together, Summation. One form of summation is Spacial Summation (middle picture)

1. §Multiple neuronal inputs
2. §Near simultaneous input
3. §Algebraically sum EPSPs
4. §Produces > depolarization
5. §If enough temporal summation, potential reaches threshold to generate action potential

to reach threshold ,many EPSPs must be added together, Summation. One form of summation is

Spatial summation (middle picture). In spatial summation there needs to be Multiple neuronal inputs to the same area of post-synaptic neuron that arrive near simultaneously. The summative potential is basically the Algebraically sum of the EPSPs. This produces a greater depolarization than a single EPSP and if there is enough temporal summation, the potential reaches threshold to generate action potentials.

Question 11

–Temporal summation

Answer 11

The other form of EPSP Summation is called Temporal summation (bottom picture

1. Could be a single input
2. At a high enough frequency a new EPSP is formed prior to decay of previous EPSP
3. If high enough frequency, potential to reach threshold to generate action potential

The other form of EPSP Summation is called Temporal summation (bottom picture). This could occur through a single input which is activated at a high enough frequency so that a new EPSP is formed prior to decay of previous EPSP. If high enough frequency, there will be a summation of potential to reach threshold and generate action potentials.

Question 12

Combined Summation

Answer 12

Actually what is needed is a Combination of these two forms of summation.

1. 40-80 terminals simultaneous activating neuron to produce a 20 mV depolarization
2. Combination of spatial & temporal summation occurs
3. EPSPs potentials produced in the dendrites & cell body move by electrotonic spread not by regenerative conduction

Actually what is needed is a Combination of these two forms of summation. Basically what is needed is between 40-80 terminals simultaneous activating the same region of a neuron to produce a 20 mV depolarization. So when a

Combination of spatial & temporal summation occurs and threshold can be reached. EPSPs potentials produced in the dendrites & cell body move by electrotonic spread not by regenerative conduction so these inputs need to be very close to one another and close to the axon hillock.

Question 13

EPSP (electrical details)

Answer 13

–Single EPSP (top) is 250- 500 microvolts (μV) & cannot raise membrane potential to threshold
–30 mV depolarization needed in soma or 10 mV depolarization needed at axon hillock to produce action potentials

A Single EPSP (top illustration) produces a depolarization of about 250- 500 microvolts (μV) & cannot raise membrane potential to threshold. A 30 mV depolarization needed in soma or 10 mV depolarization needed at axon hillock reach threshold level to produce action potentials

Question 14

EPSP Summation: Distance from cell body and axon hillock

Answer 14

1. §Action potentials generated at axon hillock
2. §Synapses farther from cell body & axon hillock have less effect depolarization at axon hillock & AP generation
3. §Illustration shows size of somatic EPSP when synapse activated in different regions of a cortical pyramidal neuron
4. §EPSP generated in cell body would have depolarization of 270 microV (0.27 mV) at axon hillock
5. §EPSPs generated just 100-150 microM away from cell body - depolarization of 127 microV at axon hillock (< half at soma)
6. §EPSPs generated in distal dendrites have depolarization of 13 mv (< 1/20th at soma)
7. §If 40-80 simultaneous inputs to cell body of neuron to reach threshold, then up to 1,600 simultaneous inputs needed for distal dendrite synapses

The greater the distance the synapses are from the cell body & axon hillock, the more EPSPs are required to generate Action potentials at axon hillock. In otherwords Synapses farther from cell body & axon hillock have less effect depolarization at axon hillock and generating action potentials.

EPSPs generated just 100-150 microns away from cell body produce only a depolarization of 127 microVolts at axon hillock (which is < half at soma) EPSPs generated in distal dendrites have depolarization of 13 microVolts (< 1/20th of the size that would occur if the synapse was on the cell soma)

This Illustration shows size of somatic EPSP when synapse activated in different regions of a cortical pyramidal neuron. EPSP generated in cell body would have depolarization of 270 microV (0.27 mV) at axon hillock

So If 40-80 simultaneous inputs to cell body of neuron to reach threshold at the axon hillock, then up to 1,600 simultaneous inputs needed for distal dendrite synapses to produce enough depolarization at the axon hillock to reach threshold. So the closer a synapse is to the axon hillock the greater effect it will have on the excitability of the post-synaptic cell.

Question 15

IPSP

Answer 15

• •Inhibitory Post-synaptic Potential (IPSP)
• –Receptor bound by transmitter & opening of either Cl− or K+ channels
• –Influx of Cl− or efflux of K+ produces hyperpolarization
• –Inhibitory as moves membrane potential away from threshold
• –IPSPs disrupts EPSP summation by cancelling out EPSPs
• –IPSPs are relatively more powerful
  
  • §Takes 40-80 EPSPs to reach threshold but only a few IPSPs can prevent reaching threshold

Inhibitory Post-synaptic Potentials (IPSPs) are produced when the Receptor bound by transmitter opens either Cl− or K+ channels producing either an Influx of Cl− or efflux of K+ as both would produce a hyperpolarization. Since a hyperpolarization moves membrane potential away from threshold it is inhibitory – an Inhibitory Post-synaptic Potential (IPSP)

IPSPs disrupt EPSP summation by cancelling out EPSPs. IPSPs are relatively more powerful. If it takes 40-80 EPSPs to reach threshold but only a few IPSPs can prevent the membrane from reaching threshold. Theoretically if 80 EPSPs are need to reach threshold, one IPSP cancelling out one EPSP leaves only 79 and threshold would not be reached.

Question 16

Metabotropic receptors

Answer 16

One of two types of receptors that neurotransmitters can activate (the other is ionotropic)

• •All classes of neurotransmitter can bind to G-protein-coupled receptors
• •> 20 types exist
• •3 general steps
• •3 general actions

Metabotropic receptors are G-protein-coupled receptors. All classes of neurotransmitter can bind to G-protein-coupled receptors. More than 20 types of these receptors exist. These receptors generally have 3 general steps to activation and 3 general actions once activated

Question 17

Three General Steps for G-Protein-Coupled receptors (metabotropic)

Answer 17

1. –Binding of neurotransmitter to the receptor protein
2. –Activation of the G-protein
3. –Activation of an effector system

Question 18

G-Protein -Coupled recepor: Three General Actions

Answer 18

1. Direct modulation of ionophore
2. Second messenger cascades
3. Postsynaptic responses involving gene expression

Question 19

Direct modulation of ionophore

Answer 19

Direct modulation of ionophore is when a G-protein subunit binds to an ionic channel – ligand gated channel where the ligand is internal to the cell rather than external and opens the channel to ionic flux. In this picture it would be a K+ ion channel

Question 20

Second Messenger Cascades

Answer 20

Second messenger cascades would involve the G-protein subunit activating a second messenger enzyme such as adenylate cyclase. In this case the enzyme would produce cyclic-AMP which would activate a variety of protein kinases to produce a variety of metabolic effects.

Question 21

Postsynaptic response involving gene expression

Answer 21

Or activation of the G-protein could activate Postsynaptic responses involving gene expression. In this case the G-protein subunit would move to the nucleus directly to change DNA expression or RNA synthesis. Or as illustrated here this effect could be mediated through a second messenger system – in this case cyclic GMP.

Question 22

Three ways neurotransmitters can be inactivation

Answer 22

To stop the post-synaptic effect of transmitters, the transmitter must be removed from the gap by one of three mechanisms or a combination:

1. Diffusion away from the gap
2. Enzymatic degradation
3. Uptake/Reuptake of the transmitter by the presynaptic ending or neighboring glial cells

Question 23

Examples: 2 Enzymes that degrade Chatecholamines

Answer 23

§Monoamine oxidase (MAO)
§Catechol-O-methyl transferase (COMT)

Question 24

Examples: Enzyme that degrade Ach

Answer 24

–Acetylcholine is broken down by Acetylcholinesterase