Synapses Part 1
Synapses Part 1 NEUR 0010
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This 11 page Class Notes was uploaded by Eileen artigas on Tuesday September 27, 2016. The Class Notes belongs to NEUR 0010 at Brown University taught by Michael Paradiso in Fall 2016. Since its upload, it has received 6 views. For similar materials see Intro to Neuroscience in Neuroscience at Brown University.
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Date Created: 09/27/16
Synaptic Transmission- the process of information transfer at a synapse Synapse- the specialized junction where one part of a neuron contacts and communicates with another The term synapse was coined by electro physiologist Sherrington from Greek synapto- to clasp What do different types of synapses look like? Electrical synapse- direct transfer of ionic current from one cell to the next, - occur at specialized gap junctions - narrow gap is spanned by clusters of special proteins called connexons - - connexons span from one cell to another- ions and small molecules pass through pore - the channel allows ions to pass directly from the cytoplasm of one cell to the cytoplasm of the other - bidirectional - electrically coupled - because most electrical synapses are bidirectional, when the second neuron generates an action potential, it will In turn produce a PSP (postsynaptic potential) in the first neuron - found where normal function requires high synchronicity - most common during early embryonic stage, smooth and muscle cells, liver cells, glandular cells - usually used by glial cells, not so much by neurons Chemical synapse- (Bernard Katz experiment) o the info in the presynaptic cell is passed to the post-synaptic cell by virtue of a chemical signal o Term synapse coined by Sherrington , from greek synapto “to clasp” o Comprise the majority of synapses in the brain o Synaptic cleft separates presynaptic and post synaptic membranes o The presynaptic side of the synapse is usually an axon terminal and contains dozens of small membrane-enclosed spheres called synaptic vesicles o Synaptic vesicles store neurotransmitters o Many axon terminals also contain larger vesicles called secretory granules Synaptic Arrangements If post synaptic membrane is on a dendrite, btwn axon and dendrite, the synapse is axodendritic If post synaptic membrane is on cell body, btwn axon and cell body,the synapse is said to be axosomatic Synapses forming on axon- axoaxonic Neuromuscular Junction- Motor neuron making synapse on skeletal muscle Specialized type of synapse where a nerve cell makes a synapse onto a muscle cell (instead of previous examples where nerve cells synapse with other nerve cells) Muscle- excitable tissue Synaptic junctions exist outside of the synapse Chemical synapses also occur between the axons of motor neurons of the spinal cord and skeletal muscle (neuromuscular junction) Synaptic density- made up of proteins and carbohydrates, keep synapse in place Parts of a Chemical Synapse - Mitochondria- providing energy for terminal bouton - Synaptic vesicles- membrane-bound bubbles, contain the chemicals signal (NT) that will be release by action potential - Gap (20-50 nm) - Synaptic Density- Proteins and carbohydrates that hold the whole thing together, keep synapse in place What happens at synapse? A Form of Signal Conversion. From Pre-Synaptic Cell- 1. an electrical signal (action potential) travels down the axon 2. arrives at terminal bouton? 3. And that electrical signal is turned into chemical signal (neurotransmitter) To Post-Synaptic Cell- 1. Chemical signal travels to post synaptic cell and converted back to electrical signal in the form of a depolarization or hyperpolarization Four stages of synaptic transmission 1. Synthesis and packaging of NT (or chemical signal) 2. Release of neurotransmitter from presynaptic cell 3. Action on the post-synaptic cell (how does chemical singal get converted into hyperpolarization, depolarization) 4. Termination of the signal NT Fall Into Various Classes - Amino acids (have amine group and carboxylic acid group) o Glutamate o Glycine o GABA (gamma- aminobutyric acid) - Monoamines o Seratonin o Acetylcholine - Catecholamines (have catechol group) o Dopamine (DA) o Norepinephrine (NE) o Epinephrine (Adrenaline) - Peptides (made up of strings of amino acids) o Synthesis and Packaging of Neurotransmitter For most NT, everything needed to synthesize and package NTis found in terminal bouton (except peptide NT) Synthesized in the terminal bouton Packaged in tiny membrane-bound vesicles (can be clear or dense-core vesicles, depending on what type of NT is packaged within them) What are the criteria for classification as a neurotransmitter? Many substances have been proposed to be NT but don’t satisfy all criteria. 1. Synthesized by some biochemical process and stored in vesicles in presynaptic cell 2. Electrical stimulation of a cell causes release 3. Elicits an effect on neuron (depolarization, hyperpolarization of a cell) 4. Method of termination (removal of NT) How are neurotransmitters made/ synthesized? Amino acids are the basis of most NT (either amino acids or derivative of amino acids or peptides- strings of amino acids) Synthesized in various levels of complexity Enzymes (proteins that catalyze chemical reactions) in terminal boutton Examples a. Precursor into a product- Glutamate (itself a NT) can be converted to GABA by enzyme glutamic acid decarboxylase b. One enzyme acting on two products to make a single NT- Enzyme choline acetyltransferase (ChAT) takes Acetyl CoA and Cholineto make NT Acetylcholine c. Multi-enzymatic processes- more than one enzyme is involved (tryptophan acted on by tryptophan hydroxylase (enzyme) to make 5- HTP (not NT) then 5-HTP decarboxylase removes a carboxyl group and you form serotonin d. Catacholamine Pathway (4 enzymes involved) - start with tyrosine, tyrosine hydroxylase, dopa, dopa decarboxylase, dopamine, dopamine betahydraxylase, norepinephrine, (PNMT), epinephrine Packing of Neurotransmitters -NT’s synthesized in cytosol, but have to be packaged into vesicles for storage where they sit until AP causes them to be released - often some type of energy requiring process (proton gradient- transporter- drives NT into vesicle) because concentrating NT in vesicle against concentration gradient use transporter to drive concentration of NT into the vesicle Dale’s principle - States one neuron one neurotransmitter - Any given neuron will make one neurotransmitter - Not always true (look above at Catacholmine Pathway, along pathway, three NT’s used (dopamine, norepinephrine, epinephrine, process stops depending on genetic program of the cell) Neurotransmitter synthesis is tightly regulated -You don’t want to make excessive amounts of a neurotransmitter that you don’t need, but just the right amount needed handy How does it happen? Process called End Production Inhibition/ Feedback Inhibition End Product Inhibition/ Feedback Inhibition Think of NT synthesis as assembly line Specifically, think of Catacholamine Pathway Each of these enzymes is a person working to assemble the product for which they are responsible for. The rate at which you make the end product is dependent on the slowest person on the assembly line, that person is the rate limiting person. Control how much and how fast product is made by controlling the action of the rate-limiting enzyme. Most often, the rate-limiting enzyme is the first enzyme in pathway. When enough of a NT is made, it feeds back into the rate limiting enzyme and you stop making that NT. Inhibition is set or relieved depending on current concentration and demand. Peptide neurotransmitter synthesis is a little different - In most cases, everything you need to make a NT is found in the terminal bouton (enzymes, precursors) - Peptide NT- strings of amino acids, composed of various sequences of 20 amino acids used to made proteins in our bodies Where does synthesis of protein start? In nucleus DNA (sequence of string of amino acid coded in genome) RNA (transcribed to messenger RNA, translated into a protein by ribosomes) Protein Chemical structure of peptide- two amino acids, join carboxyl group and amino group to make a peptide bond How does peptide NT end up in a synaptic vesicle in terminal bouton? - DNA in nucleus - Messenger RNA sent out into cytoplasm - Grabbed onto by ribosomes (attached to rough ER) - Protein is now in loomin of ER - Protein buds off into Golgi apparatus (where large pieces are chopped up into smaller active pieces NT) - Packaged into secretory granule - Transported down axon by axoplasmic flow - Matures into synaptic vesicle in terminal bouton Neurotransmitter release - Otto Loewi- won nobel prize for demonstrating conclusively that chemical neurotransmission existed o Experiment o Took two frog hearts (which beat spontaneously if you take the out of the animal and keep it oxygenated, special conditions, etc. o There’s a nerve that goes into the frog heart called the vagus nerve o If you stimulate this nerve, the beating rate would slow down o Set up two frog hearts, connected them to a solution called ringers (buffer solution containing everything cells need to survive) connected the two hearts through a tube which had a valve, o Beat rate of each heart could be measured o Heart one is beating spontaneously o Stimulate vagus nerve with valve closed o Heart 1 slows, heart 2 keeps beating along o Repeats experiment with valve open (liquid can flow from heart one to heart two) o Stimulate vagus nerve o Heart number 2 beats and minutes later also slows o Concluded something was being released from vagus nerve in heart 1 into heart 2, having same effect on heart 2, (would HAVE TO BE some sort of chemical substance) o Named the substance “Vagus Stuff”, later found to be acetylcholine, part of sympathetic nervous system, what controls your heart rate o Later found “Accelerance Stuff”, later found to be epinephrine o Proved chemical neurotransmission exists Neurotransmitter release (cont.) - Triggered by the arrival of the action potential in the axon terminal bouton, depolarization causes voltage-gated calcium channels in the active zones to open - Vesicles fuse with membrane and release their content by a process called exocytosis - The membrane of the synaptic vesicle fuses to the presynaptic membrane at the active zone, allowing the contents to spill out into the synaptic cleft - The vesicle membrane is recovered by the process of endocytosis - SNARE proteins - SNARE proteins involved in the process of release - V-snares- found on vesicle - T-snares- (target snares) found on inner leaflet of synaptic bouton membrane - Synaptotagmin- calcium-sensing protein, binds calcium - When AP arrives at terminal bouton, there are voltage-gated calcium channels in the membrane of terminal bouton, - The voltage-gated calcium channels pop open in response to the AP arriving - Calcium conc. outside of cell much larger than in, rushes into cell down concentration gradient - Calcium then binds to synaptotagmin, causes a huge change in the conformation of the shape of the protein complex such that the vesicle then slams down onto membrane of terminal bouton and fuses with it - Thin of SNARE as spring, when calcium binds, it causes vesicle to be brought down, fusion, NT released - Process completely dependent on calcium entering - Once vesicles fuse, they pinch off and float away and recycle to be loaded again, you want that to happen or the terminal bouton would keep growing and growing Peptide neurotransmitter release is a little different - In this case, the calcium channels are farther away from where vesicles are anchored - More calcium needed to cause vesicles to fuse, more AP stimulation (than monoamine or catecholamine) Action on Post-Synaptic Cell Receptor molecules express on surface of post-synaptic cell Each NT has its own receptor molecule, great deal of specificity built into receptor molecule Receptors recognize very specifically their NT (lock and key fit) complementary protein structure in receptor Receptor recognizes 3D shape of NT Receptors itself have 3D shapes (we know thanks to structural biologists)
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