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

  • 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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