Lecture 19 Flashcards
What are the two ways messages are transmitted from one neuron to another? (2 types of synapses)
Electrical synapse
Chemical synapse
What happens in an electrical synapse?
Adjacent cells are joined by gap junctions and ions diffuse directly from 1 cell into the next
What are the advantages of electrical synapse?
Much faster
No delay for release, diffusion and binding of NT
What are the disadvantages of electrical synapse?
Cannot integrate information
Only quick propagation of the existing AP for a simultaneous response among multiple cells, similar to cardiomyocytes
What happens in a chemical synapse?
Gap between 2 neurons where information passes chemicals, in the form of neurotransmitter (NTs) molecules
What is the advantage of chemical synapse?
NTs released at the chemical synapse can be both excitation and inhibitory and their quantity can vary, allowing integration from multiple presynaptic neurons
What may a presynaptic neuron synapse with?
A dendrite, the soma, or the axon of a postsynaptic neuron
What size molecules are “classical” neurotransmitters?
Small
What are the 4 kinds of molecules that are the neurotransmitters?
Amino acids
Monoamines “biological amines”
Acetylcholine
ATP & it’s derivatives (adenosine)
What are the 3 types of amino acids and are they excitatory/inhibitory?
Glutamate - excitatory
Y-aminobutyric acid (GABA) - inhibitory
Glycine - inhibitory
Where are monoamines synthesized from?
Amino acids
What are the 5 monoamines?
Dopamine
Norepinephrine
Epinephrine
Serotonin
Histamine
What are the 3 catecholamines and where are they derived from?
Dopamine
Norepinephrine
Epinephrine
Derived from tryptophan
Where is serotonin (5-HT) derived from?
Tryptophan
Where is histamine derived from?
Histadine
Where are all of the 4 neurotransmitters derived from?
Carbohydrate substrates of intermediate metabolism
Where are peptides?
Short protein chains of 2-40 amino acids
(B endorphins, substance P)
What are modulators?
“Unconventional” neurotransmitters
(Gases like NO and CO)
What are the steps of the synthesis and release of the classical neurotransmitters?
- The enzymes are required for their synthesis are synthesized in the rough ER (neurosoma)
- They are transported to the Golgi apparatus
- In the Golgi apparatus, they are modified
- Soluble enzymes are transported along the axon to the nerve terminal by slow anterograde axonal transport via microtubules. The remaining enzymes are transported by fast anterograde axonal transport.
- The precursor needed for the synthesis of NTs is taken up via transporter proteins located in the plasma membrane of the nerve terminal. The NT is synthesized in the presynaptic nerve terminal from the precursor.
- The synthesized pool of the NT in the cytoplasm is take up into small vesicles by Vesicular MonoAmine Transported (VMAT)
- The appropriate stimulus results in the release of the NT by exocytosis
What are the two major enzymes responsible for catecholamine catabolism int he brain?
Cateschol-O-methylthransferase (COMT)
Monoamine oxidase A (MAOa)
What is epinephrine (adrenaline) synthesized from?
From norepinephrine within the adrenal medulla
What is the adrenal medulla?
Small glands associated with the kidneys
What are the 2 types of receptors that neurotransmitters bind to?
Ionotropic receptors
Metabotropic receptors
What are ionotropic receptors?
Ligand-gated ion channel receptors
What are metabotropic receptors?
G-protein coupled receptors
What are ionotropic receptors composed of?
3-5 protein subunits that form a pore
What do NTs binding to ionotropic receptors do?
They open the pore and directly induce ion fluxes
What do metabotropic receptors affect?
Affect channels by the activation of intermediate molecules called G-proteins
What can G-proteins activate?
The production of second messenger molecules
How does synaptic transmission finish? (3 ways)
Via NT transporters on the plasma membrane
Diffusion/Absorption
Degradation
Reuptake
What is diffusion/absorption?
NT diffuse away from the synaptic cleft and are returned to presynaptic neuron
What is degradation?
NT are degraded by enzymatic reactions in the synaptic cleft
What is reuptake?
NTs are taken back into the presynaptic neuron
What does the monoamine hypothesis of depression suggest?
Suggests that depression was associated with a deficiency of monoamines such as serotonin and norepinephrine
How well are the causes of depression understood?
They are poorly understood
What are the steps in how serotonin works in the synapse?
- Serotonin is produced directly in the neuron
- Vesicle membrane embedded transported protein transports serotonin into vesicles
- Vesicle releases serotonin into the synaptic cleft
- Serotonin binds to receptor and initiates a signal to the cell body of the post synaptic neuron
- Receptor clears. Serotonin is taken up by the presynaptic neuron, a glial cell of neuron leaves the cleft through diffusion.
- After reuptake, serotonin gets reloaded into vesicle or broken down
- MAO breaks down serotonin
Hero do neurons of the substantia nigra communicate with neurons of the basal ganglia?
By liberating the NT dopamine
What is this biochemical interaction responsible for?
Voluntary movement coordination of the body
Which NT is association with Parkinson’s disease and how?
Neurons of the substantia nigra degenerate
What happens with this degeneration?
Slowness or a sense of movement, rigidity and a resting tumor (especially in the hands and fingers)
What has been a central dogma for schizophrenia for decades?
The mesolimbic hypothesis