Synaptic Transmission: Chemical Signaling in the Brain

\ Release of Neurotransmitters at the Synapse

  • Neurotransmission: how cells of the nervous system communicate across the synapse to each other or to targets (such as muscle cells of the heart)   * Neurotransmitters: chemicals released in neurotransmission   * Released from presynaptic receptor -- to postsynaptic receptor     * Change of chemical concentration at the postsynaptic    * Synaptic cleft     * Space between pre and postsynaptic cells   * Synaptic Vesicles     * Just inside the presynaptic cell     * Neurotransmitters are packaged here     * Neurotransmitter is released into the cleft by exocytosis

Type of Neurotransmitters

  • Acetylcholine   * The excitatory neurotransmitter in the PNS     * Causing muscle contractions when released at the neuromuscular junction (between the nervous system and muscular system)
  • Monoamines   * dopamine, epinephrine, norepinephrine, serotonin, melatonin     * Catecholamines: dopamine, epinephrine, norepinephrine       * Formed from the amino acid sequence tyrosine   * Dopamine     * Critical information-carrying molecule in the brain’s reward systems     * The target of drugs of addiction     * The main neurotransmitter in schizophrenia 
  • Amino Acids   * Glutamate     * The most common excitatory transmitter in the CNS   * Aspartate: excitatory   * GABA (gamma-aminobutyric acid): inhibitory   * Glycine: inhibitory
  • Peptide Neurotransmitters   * Ex: cholecystokinin, somatostatin, neuropeptide Y
  • Retrograde Transmitters   * Nitric Oxide and Carbon Monoxide   * Can carry signals   * Making the signals easily diffuse through cell membranes because they are gases   * Produced by the dendrites and crossing the synapse backward     * To affect the presynaptic cell’s axon     * Reverse of normal
  • Most neurons release one peptide neurotransmitter in addition to one or a few smaller neurotransmitters (acetylcholine, monoamines, amino acids)

Receptors

  • Receptors: specialized proteins in the membrane   * Where the neurotransmitters bind after being released into the synapse
  • Postsynaptic receptors   * Ionotropic receptors: transmit a signal to another cell by causing a direct flow of ions into or out of the cell     * Way of opening a temporary pore in the membrane for the flow of ions       * When closed, receptor protein blocks the flow of ions       * When opened (or gated), by the right type of neurotransmitter, the protein changes shape and provides a pore in the membrane     * Allowing a certain type of ion through       * Ex: receptor binds to GABA neurotransmitter and chloride ions can pass through   * Metabotropic receptors: transmit signals to another cell by causing more indirect changes inside the cell by a cascade of signals     * G-coupled protein receptor (second-messengers coupled)       * Associated with the inside face of the postsynaptic membrane       * Function: relay information from neurotransmitter receptors to proteins inside the cell         * Which relay and transform the signal     * Second Messengers       * Modulate the activity of neighboring ion channels       * Activate or deactivate enzymes within the cell       * Change which genes are expressed within the cell       * About half of all medical drugs target these receptors

 

  • Clean up in the synaptic cleft (1 of 3 done)   * Degradation: neurotransmitter molecule is broken apart by other molecules   * Diffusion: neurotransmitter moves out of the synapse (down its chemical concentration gradient)   * Reuptake: specialized protein transporters in the membrane selectively pull the neurotransmitter back into the cell (either pre or postsynaptic) or into the neighboring cell      * (most common)

Postsynaptic Potentials

  • What happens after the neurotransmitters bind and ions flow in or out of the postsynaptic cell?   * There is a voltage difference because of ion concentrations in and out of the cell   * The outside of the cell is usually more positive than the inside     * Resting Membrane Potential = -70 mV   * Excitatory Postsynaptic Potential (EPSP)     * when positive ions flow through the receptor into the cell (reducing the difference between inside and out)   * Inhibitory Postsynaptic Potential (IPSP)     * Allowing positively charged potassium to flow out of the cell or negatively charged chloride into the cell       * + out, - in     * When the voltage difference between inside and out becomes larger
  • Postsynaptic changes in membrane potential funnel down to the Soma   * Summarizes the signal
  • Inhibitory vs Excitatory    * Neurotransmitter isn’t either but the action of the receptor with the transmitter determine the effect
  • Electrical Synapses (gap junctions)   * Allow the direct passage of signal from one cell to the next   * Less common

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  • Axon hillock is where spikes are initiated

How an Action Potential Travels

  • Sodium (Na^+) and Potassium (K^+) play key roles in making action potentials
  • When a cell is at rest   * High concentration of Na^+ outside of the cell and lower inside   * Low concentration of K^+ outside of the cell and higher inside
  • Voltage-Gated ion channels   * Triggered by rise in membrane potential beyond threshold   * Sodium ion channels open     * Sodium flows into the cell       * Driven by concentration gradient       * Driven by electrical gradient (more - inside attracting +)     * Influx of sodium depolarizes the membrane and triggers the opening of potassium channels   * Potassium channels open     * Potassium ions flow out of the cell       * Following concentration gradient and electrical gradient       * Repolarizing         * Making the inside more negative again   * Traveling of an action potential     * The rapid voltage change spreads far enough down the membrane to cause the neighboring voltage-gated sodium channel to open up and cause the same cycle     * Cycle of depolarization and repolarization goes down the axon   * Refractory Period     * After an action potential      * Sodium channels are more resistant to opening -- so the potential can’t go both ways       * Cannot move back to a location where it has already occurred -- must go forward   * Calcium and Chloride ions are also used in action potentials
  • Bando MItsugoro   * Tetrodotoxin molecules block the pore of the voltage-gated sodium channel     * Without the sodium channel, there is no action potentials and no communication

Myelinating Axons to Make the Action Potential Travel Faster

  • Myelin sheaths are in segments   * In between is nodes of Ranvier     * Where ions outside the cell can most easily flow in and out   * Difficult for ions to cross the membrane where the sheath is
  • Saltatory Conduction   * Action potentials leap from node to node instead of flowing through axon   * Depolarization at one node will be large enough to open sodium channels on the next node   * Vastly increases the travel speed (conduction velocity)   * Decreases energy expenditure     * Less ions moving around -- less energy needed to replace them

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Action Potentials Reach Terminals and Cause Neurotransmitter Release

  • The change of voltage in the axon terminals   * Opens voltage-gated calcium channels     * Causing rapid entry of calcium ions from outside the cell     * Calcium ions cause vesicles filled with neurotransmitter to fuse with the terminal membrane       * Causing neurotransmitter to spill out into synaptic cleft

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