Chapter 5 and 6 - Neurotransmitters

Question 1

There are two different types of connections that form between
neurons…

Answer 1

Electrical synapses - allow communication across cells through the direct transfer of electrical current via gap junctions

Chemical synapses - allow communication across cell through chemical messengers called neurotransmitters

Question 2

Gap Junctions

Answer 2

At gap junctions, ions are pass from one cell directly into another cell.

• Ions do not pass though extracellular space
• Channels form bridges between cells (~1nm)
• Channels are often bidirectional

Cells are electrically coupled

Question 3

Chemical Synapse - Buttons and Synapses

Answer 3

Buttons - the buttonlike endings of the axon branches, which release chemicals into synapses

Synapses - the gaps between adjacent neurons across which chemical signals are transmitted

Question 4

Chemical synapse

Answer 4

Synaptic cleft: a 20-50nm gap between neurons

Allows transfer of stored chemicals
from the presynaptic neuron to the postsynaptic neuron

Parts:
Neurotransmitter molecules
Receptor site
Synaptic vesicle
Axon terminal
Synaptic cleft
Axon
Neural impulse
Receiving neuron

Question 5

General Mechanisms of a Neurotransmitter

Answer 5

EXOCITOSIS- Triggered by an influx of Ca++ at the axon terminal through voltage-gated Ca channels

1. Neurotransmitter molecules are synthesized from precursors under the influence of enzymes
2. Neurotransmitter molecules are stored in vesicles
3. Neurotransmitter molecules that leak from their vesicles are destroyed by enzymes
4. Action potentials cause vesicles to fuse with the presynaptic membrane and release their neurotransmitter molecules into the synapse
5. Released neurotransmitter molecules bind with autoreceptors and inhibit subsequent neurotransmitter release
6. Released neurotransmitter molecules bind to postsynaptic receptors
7. Released neurotransmitter molecules are deactivated by either reuptake or enzymatic degradation

Question 6

Removing NT from the Synapse

Answer 6

As long as NT is in the synapse, it is “active” – activity must somehow be turned off

Reuptake – ‘scoop up’ and recycle NT

Enzymatic degradation – a NT is broken down by enzymes

Question 7

Postsynaptic Potentials (PSPs)

Answer 7

Postsynaptic depolarizations →
Excitatory PSP (EPSP)
(generated by the opening of Na+ channels)

Postsynaptic hyper-polarizations =
Inhibitory PSP (IPSP)
(generated by the opening of Cl- channels)

EPSP and IPSP’s are graded (size varies)

Sum together and determine if the neuron will fire an ACTION POTENTIAL

Question 8

EPSPs and IPSPs

Answer 8

Graded – greater the stimulus, the greater the response

Travel passively from their site of origination

Decremental – they get smaller as they travel

1 EPSP typically will not suffice to cause a neuron to “fire”, release neurotransmitter, and pass on a message – summation is needed

Question 9

Shunting

Answer 9

A large IPSP downstream from EPSPs can act to shut down any potential action potential

This is known as ‘shunting’

Question 10

Synaptic Morphology

Answer 10

The shape (morphology) of synaptic connections can impact how tightly bound activity the two neurons are.

More densely connected neurons are more likely to show similar patterns of activity

Question 10

Neurotransmitters

Answer 10

Add in from updated slide

Question 11

Small-Molecule Neurotransmitters

Answer 11

1. Acetylcholine (Ach)
2. Monoamines (Catecholaminergic NTs, Serotonergic NTs)
3. Amino acids
4. Unconventional NTs
   (1. soluble gases)
   (2. endocannabinoids)

Question 12

Acetylcholine

Answer 12

Synthesized from Choline and Acetyl CoA by the enzyme choline acetyltransferase (ChAT)

Synthesized in the axon buttons

One of only a few NTs broken down by an enzyme (acetylcholinesterase; AChE)

Only NT released at neuromuscular junction

Also implicated in learning & memory – Alzheimer’s?

Question 13

Monoamines

Answer 13

Synthesized from a single amino acid (tyrosine or tryptophan)

Effects tend to be diffuse

Have general modulating effects

Tend to activate or inhibit entire circuits of neurons that are involved in particular brain function

Norepinephrine, dopamine, serotonin

Catecholamines → synthesized from tyrosine

Indolamines → synthesized from tryptophan
(Serotonin – also called 5-hydroxytryptamine (5-HT))

DA in basal ganglia – involved in motor movement
DA in limbic system – involved in reward and pleasure
DA in frontal lobe – involved in STM and planning

Question 14

Amino Acid Neurotransmitters

Answer 14

Usually found at fast-acting directed synapses in the CNS

Glutamate – Most prevalent excitatory neurotransmitter in the CNS

GABA (gamma amino butyric acid)
◦ Synthesized from glutamate
◦ Most prevalent inhibitory NT in the CNS
◦ Alcohol; Epilepsy

Glycine

Glutamate (Glutamic acid decarboxylase ->) GABA

Question 15

Other NTs

Answer 15

Endorphins
◦ Endogenous “opioids”
◦ Produce analgesia
◦ Receptors were identified before the natural ligand was

Endocannibanoids (CB1)
◦ Released from postsynaptic neurons and effect pre-synaptic
neurons
◦ ‘retrograde messenger’

Nitric oxide (NO)
◦ Only reliably-evidenced ‘gas transmitter’
◦ Function and mechanism is yet to be determined

Adenosine triphosphate (ATP)
◦ More commonly known as the energy molecule
◦ Often packaged/released with other NTs (e.g., GABA)

Question 16

Receptor Mechanisms

Answer 16

Transmitter-gated ion channels:

• NTs act as ligands and bind to receptors that open ion channels in the cell membrane
• Bound receptor directly acts as cause for PSP

G-protein coupled receptors:

• NTs act as ligands and bind to receptors that cause a cascade of secondary effects
• Bound receptor does NOT directly cause PSP

Question 17

Transmitter-Grated Ion Channels

Answer 17

“Ionotropic receptors”

NT binds → associated ion channel opens or closes → PSP

Na+ channels opened → Na+ in → EPSP

Cl-/K+ channels opened → Cl- in/K+ out → IPSP

Question 18

G-Protein Coupled Receptors

Answer 18

“Metabotropic Receptors”

Effects are slower, longer-lasting, more diffuse, and more varied

Effects may be on:
- Other membrane channels
- RNA/Protein synthesis
- Other metabolic processes

Question 19

Metabotropic Receptors

Answer 19

NT binds ➡️ G protein breaks away ➡️ Ion channel opened/closed and 2nd messenger synthesized

Question 20

Drugs Effects on Synaptic Transmission

Answer 20

Many drugs act to alter neurotransmitter activity

AGONISTS → increase or facilitate NT activity

ANTAGONISTS → decrease or inhibit NT activity

Drugs may alter NT activity at any point in its “life cycle”

Question 21

Agonistic Drug Effects

Answer 21

Agnostic ➡️ ⬆️ or facilitate NT activity

Drug increases the synthesis of neurotransmitter molecules (eg. by increasing the amount of precursor)

Drug increases the number of neurotransmitter molecules by destroying degrading enzymes

Drug increases the release of neurotransmitter molecules from terminal buttons

Drug binds to autoreceptors and blocks their inhibitory effect on neurotransmitter release

Drug binds to postsynaptic receptors and either activates them or increases the effect on them of neurotransmitter molecules

Drug blocks the deactivation of neurotransmitter molecules by blocking degradation or reuptake

Question 22

Example: Agonists

Answer 22

Cocaine: Dopamine Agonist
- blocks reuptake - preventing the activity of the neurotransmitter from being “turned off”
- intense euphoria, stimulant
- high doses produce symptoms similar to schizophrenia

Benzodiazepines: GABA Agonist
- binds to the GABA molecule and increases the binding of GABA
- sedative, anxiolytic, muscle relaxant

Question 23

Antagonistic Drug Effects

Answer 23

Antagonist ➡️⬇️ or
inhibit NT activity

Drug blocks the synthesis of neurotransmitter molecules (eg. by destroying synthesizing enzymes)

Drug causes the neurotransmitter molecules to leak from the vesicles and be destroyed by degrading enzymes

Drug blocks the release of the neurotransmitter molecules from terminal buttons

Drug activates autoreceptors and inhibits neurotransmitter release

Drug is a receptor blocker; it binds to the postsynaptic receptors and blocks the affect of the neurotransmitter

Question 24

Example: Antagonists

Answer 24

Atropine – Ach Antagonist
- binds and blocks muscarinic receptors in CNS
- high doses disrupt memory, similar to AD

Botox – Ach Antagonist
- blocks release Ach at nicotinic receptors at NMJs
- paralyzes facial muscles - giving firm & stiff appearance