Chapter 5 and 6 - Neurotransmitters Flashcards
There are two different types of connections that form between
neurons…
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
Gap Junctions
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
Chemical Synapse - Buttons and Synapses
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
Chemical synapse
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
General Mechanisms of a Neurotransmitter
EXOCITOSIS- Triggered by an influx of Ca++ at the axon terminal through voltage-gated Ca channels
- Neurotransmitter molecules are synthesized from precursors under the influence of enzymes
- Neurotransmitter molecules are stored in vesicles
- Neurotransmitter molecules that leak from their vesicles are destroyed by enzymes
- Action potentials cause vesicles to fuse with the presynaptic membrane and release their neurotransmitter molecules into the synapse
- Released neurotransmitter molecules bind with autoreceptors and inhibit subsequent neurotransmitter release
- Released neurotransmitter molecules bind to postsynaptic receptors
- Released neurotransmitter molecules are deactivated by either reuptake or enzymatic degradation
Removing NT from the Synapse
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
Postsynaptic Potentials (PSPs)
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
EPSPs and IPSPs
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
Shunting
A large IPSP downstream from EPSPs can act to shut down any potential action potential
This is known as ‘shunting’
Synaptic Morphology
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
Neurotransmitters
Add in from updated slide
Small-Molecule Neurotransmitters
- Acetylcholine (Ach)
- Monoamines (Catecholaminergic NTs, Serotonergic NTs)
- Amino acids
- Unconventional NTs
(1. soluble gases)
(2. endocannabinoids)
Acetylcholine
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?
Monoamines
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
Amino Acid Neurotransmitters
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
Other NTs
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)
Receptor Mechanisms
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
Transmitter-Grated Ion Channels
“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
G-Protein Coupled Receptors
“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
Metabotropic Receptors
NT binds ➡️ G protein breaks away ➡️ Ion channel opened/closed and 2nd messenger synthesized
Drugs Effects on Synaptic Transmission
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”
Agonistic Drug Effects
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
Example: Agonists
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
Antagonistic Drug Effects
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
Example: Antagonists
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
