Lecture 6 Notes
Lecture 6 Notes Biol-K416
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This 7 page Class Notes was uploaded by Malissa Notetaker on Saturday October 1, 2016. The Class Notes belongs to Biol-K416 at Indiana University Purdue University - Indianapolis taught by Dr. Jason Meyer in Fall 2016. Since its upload, it has received 5 views. For similar materials see Cell & Molecular Neuroscience in Neuroscience at Indiana University Purdue University - Indianapolis.
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Date Created: 10/01/16
Cellular and Molecular Neuroscience Lecture 6 9/19/16 Topic: Synaptic Transmission How do neurons communicate with each other? ● Neurons can have synaptic signaling with multiple neurons ● How do neurons communicate with each other? ○ Two general classes ■ Electrical synapses ● Relatively rare, but are found in all nervous systems ● Permit direct, passive flow of electrical current from one cell to another ■ Chemical synapses ● Chemical Synapses ○ Space between pre and post synaptic neurons is larger synaptic cleft ○ Chemical synapses have small, membranebound organelles in presynaptic neuron known as synaptic vesicles ○ Vesicles are filled with neurotransmitters, which serve as the signal between two cells ○ Presynaptic neuron’s axon terminal is enlarged to increase surface area to increase contact ● How Chemical Synapses Work: 1. Transmitter is synthesized and then stored in vesicles 2. An action potential invades the presynaptic terminal 3. Depolarization of presynaptic terminal causes opening of voltage gated Ca2+ channels 4. Influx of Ca2+ through channels 5. Ca+2 causes vesicles to fuse with presynaptic membrane 6. Transmitter is released into synaptic cleft via exocytosis 7. Transmitter binds to receptor molecules in postsynaptic membrane 8. Opening or closing of postsynaptic channels 9. Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell 10. Removal of neurotransmitter by glial uptake or enzymatic degradation 11. Retrieval of vesicular membrane from plasma membrane Why make the neurotransmitter, then have the action potential? Much faster, can take a while to make NT Remember Ca2+ is found on axon terminals ● What is the criteria for identifying a NT? 1. NT is present within the presynaptic cell 2. NT must be released in response to presynaptic depolarization in a calciumdependent fashion 3. Specific receptors for the NT must be found on the postsynaptic cell ● What else can be released that are not NT? ○ Neuroprotective factor help in the survival of neurons ○ Hormones ○ Ions ● Production of smallmolecule NT ○ For efficient synaptic communication, NT must be removed from synapse ○ NT produced in axon terminals ○ Enzymes needed for synthesis produced in cell body and must be transported to terminals via slow axonal transport (~0.55.0 mm/day) ■ Continuously going so that there is a quick response ○ NTs synthesized in terminals are loaded into vesicles via transporter proteins ● Production of peptide NT ○ Neuropeptides are produced in the cell body, a long distance from the terminals ○ Neuropeptides are loaded into vesicles in the cell body and transported down the axon via fast axonal transport (~400 mm/day) ○ Transport is mediated via microtubule proteins that serve as a track for transport 1. Synthesis of NT precursors and enzymes 2. Transport of enzymes and peptide precursors down microtubule tracks 3. Enzymes modify precursors to produce peptide NT 4. NT diffuses away and is degraded by proteolytic enzymes ● Small NT > Neuropeptides in the body ● NT’s: ○ Ach small molecule NT, used for locomotion for muscles bc want fast response ○ GABA small molecule NT ○ epinephrine/norepinephrine small molecule NT ○ glutamate/ dopamine small molecule NT ● What is the most abundant protein when it comes to NT and loading into vesicles? ○ VSNARE ● How many VATPase are on vesicles? ○ 12 ● Role of calcium in transmitter secretion ○ Originally identified due to experiments in which neurons were exposed to TTX (blocks Na+, should prevent action pot.), and unusual prolonged action potentials were observed ■ Due to Ca2+ flowing through voltagegated Ca2+ channel in axon terminals ■ Amount of NT release is sensitive to the amount of Ca that enters terminal ● When the Ca2+ channel is blocked, no postsynaptic membrane potential is measured ● Mechanisms of Vesicle Priming and Fusion ○ SNARE proteins in vesicle are known as VSNAREs ■ Include synaptobrevin winds around and tightly binds ○ SNARE proteins in plasma membrane are known as TSNAREs ■ Include syntaxin and SNAP25 ○ SNARE proteins form a complex to bring two membranes together ○ Since SNARE proteins do not bind Ca2+, other proteins must do this job. Primarily due to synaptotagmin ■ Has domains that will sense Ca2+ ○ SNARE complexes pulls them so close together so that there is no water and it is favorable for lipids to rearrange ■ Usually not favorable for lipids to rearrange and fuse bc of hydrophobic tails do not like the watery cytoplasm ● Neurotransmitter receptors on Postsynaptic Membrane ○ Two main types of receptor molecules found in membrane: 1. Ionotropic receptors or ligand gated ion channels contain a membranespanning domain that forms an ion channel 2. Metabotropic receptors do not have ion channels as part of their structure. Instead, they have an intracellular domain that affects channels through activation of intermediate known as Gproteins. Thus, these are also known as Gproteincoupled receptors. ● Excitatory and Inhibitory Postsynaptic Potentials ○ At many synapses, PSPs increase the probability of firing an action potential. These PSPs are known as excitatory postsynaptic potentials (EPSPs) ■ Depolarizes Na+, Ca2+ ○ At other synapses, PSPs decrease the probability of firing an action potential. These PSPs would be known as inhibitory postsynaptic potentials (IPSPs) ○ Most neurons receive input from both excitatory and inhibitory synapses ○ Example of an EPSP ■ At synapse that uses glutamate (binds to receptor, cation channels open) as NT, receptors will open cation channels (permeable to + charged ions) ■ When these synapses are activated, both Na+ and K+ CAN flow across membrane ● If EPSP is strong enough, converted into action potential ■ At resting membrane potential, most flow is due to Na+ influx ● Bc of concentration gradient ○ Example of an IPSP ■ At synapse that uses GABA as a NT, receptors will open channels permeable to Cl ions ● Hyperpolarizing response ● IPSP used as a “safe guard” ○ There can be EPSPs and IPSPs on the same neuron ● Summation of the postsynaptic potentials ○ If there are EPSPs and IPSPs, the net potential will be the sum of the two ○ Already have a negatively charged inside neuron, so easier to have + charged ions come in as opposed to charged ions coming in ○ Dependent on size of the ion ● Postsynaptic membrane permeability changes ○ Inwards flow of Na+ is depicted by downwards arc in pA ■ Duration varies, but amount of ions flowing through is the same ● Quantal theory of NT release ○ NT is released in relatively precise units known as quanta ○ Increments in the PSP response occur in units of reproducible and scalable size ■ Bc each vesicle has a certain amount ○ Thus, PSPs are likely due to the simultaneous release of many NT units ■ 1st release X ■ 2nd release 2X ● Postsynaptic membrane permeability changes ○ NT binding to receptor opens ion channels ○ When a few channels open at the same time, the postsynaptic current is additive ○ Physiologically, release of NT into synapse will activate many channels to produce a postsynaptic potential ○ Bc current flowing during the PSP is normally inward, causes the postsynaptic membrane to depolarize ● What happens after NT signaling? ○ After actions of NT, it must be cleared from the synapse ○ Means of removal include: ■ Diffusion away from synapse (slowest) ■ Reuptake into terminals or nearby glial cells ■ Degradation by enzymes (fastest) ● When vesicles become fused, membrane is continuous ● Synaptic Vesicle Cycle ○ Retrieved vesicular membrane passes through a number of intracellular compartments ○ Eventually used to make new synaptic vesicles ○ Originally, synaptic vesicles were made in the endoplasmic reticulum ● Structure of Electrical Synapses ○ Presynaptic neuron the upstream neuron that is the source of the signal ○ Postsynaptic neuron the downstream neuron that receives the signal ○ In electrical synapses, the two neurons are connected by intracellular proteins known as the gap junctions ○ Note: pre and postsynaptic neurons can change “places” with electrical but not chemical ● Gap Junctions of Electrical Synapses ○ Gap Junctions contain precisely aligned, paired channels known as connexons ■ Connexons are present in both the presynaptic and postsynaptic membranes ○ Connexons are composed of a special family of ion channel proteins known as connexins ■ Six presynaptic connexins align with six postsynaptic connexins ○ Connexon pores are much larger than most other channels, which allows larger substances to pass ○ Transmission through gap junctions can be bidirectional ■ Is also very fast ■ Why faster with chemical? Connected so no fusing vesicle into membrane, releasing contents, etc. ● Crayfish demonstration of electrical synapses ○ Postsynaptic electrical signal is observed within a fraction of a millisecond after it is found in the presynaptic cell ■ Such synapses in crayfish are essential for reflex behaviors such as those used to escape predators ○ Another purpose of electrical synapses is to synchronize activity in populations of neurons ■ Ex brainstem neurons that regulate breathing are synchronized through electrical synapses