Psych 5

• Otto Loewi (1921)


  First isolation of a chemical messenger
• Frog heart experiment


  • Acetylcholine: works in peripheral and central nervous system
  • Activates skeletal muscles in the somatic nervous system (SNS) and may excite or inhibit internal organs in the autonomic nervous system (ANS)

  
• Epinephrine (EP, or adrenaline)


  Acts as a hormone to mobilize the body for fight or flight during times of stress and as a neurotransmitter in the central nervous system
• Norepinephrine (NE, or noradrenaline)


  Found in the brain and in the parasympathetic division of the autonomic nervous system; Accelerates heart rate in mammals
• Neurotransmitters


  • Chemical released by a neuron onto a target with an excitatory or inhibitory effect
  • Have distinctive shapes that allow them to interact with distinctive receptors
  • Outside the CNS, many of these chemicals circulate in the bloodstream as hormones
  • Have distant targets
  • Action slower than that of a neurotransmitter

  
• Chemical Synapse


  • Junction where neurotransmitters are released from one neuron to excite or inhibit the next
  • Most synapses in mammalian nervous system are chemical

  
• Presynaptic membrane


  Where the action potential terminates to release the chemical message
• Postsynaptic membrane


  Receiving side of the synapse, where excitatory or inhibitory postsynaptic potentials are generated

  
• Synaptic cleft


  Gap where neurotransmitters travel from presynaptic to postsynaptic membrane

  
• Tripartite synapse


  Functional integration and physical proximity of the presynaptic membrane, postsynaptic membrane, and their intimate association with surrounding astrocytes

  
• Anterograde synaptic transmission


  Process that occurs when a neurotransmitter is released from a presynaptic neuron and binds to a receptor on the postsynaptic neuron

  
• Neurotransmission in Five Steps

  1. Neurotransmitter synthesized inside the neuron

  2. It is packaged and stored within vesicles at the axon terminal

  3. It is transported to the presynaptic membrane and released into the cleft due to an action potential

  4. It binds to and activates receptors on the postsynaptic membrane

  5. It is degraded or removed to deactivate it

  
• Neurotransmitter Synthesis


  • In axon terminal
  • In cell body
  • Peptide
  • Lipid
  • Gaseous
  • Ion

  
• Synaptic vesicle


  Small membrane-bound spheres that contain one or more neurotransmitters
• Storage granule


  Membranous compartment that holds several vesicles containing neurotransmitter(s)
• Neurotransmitter Release


  1. At the terminal, the action potential opens voltage-sensitive calcium (Ca2+) channels

  2. Ca2+ enters the terminal and binds to the protein calmodulin, forming a complex

  3. The complex causes some vesicles to empty their contents into the synapse and others to get ready to empty their contents

  4. Exocytosis

  
• Transmitter-activated receptors


  Protein embedded in the membrane of a cell that has a binding site for a specific neurotransmitter

  
• Ionotropic receptor


  • Associated with pores that open to allow ions through the cell membrane
  • May have excitatory action (allow Na+ in)
  • May have inhibitory action (allow K+ out or Cl- in)

  
• Metabotropic receptor


  Embedded membrane protein with a binding site for a neurotransmitter linked to a G protein

  
• Second messengers


  • Can bind to a membrane-bound channel
  • Alters ion flow
  • Initiate a reaction incorporating intracellular protein molecules into the cell membrane
  • Formation of new ion channels
  • Bind to sites on the cell's DNA to initiate or cease the production of specific proteins

  
• Autoreceptor


  • Self-receptor in a neuronal membrane, which responds to the same transmitter released by the neuron
  • Part of a negative feedback loop allowing the neuron to adjust its own output
  • Can be either ionotropic or (rarely) metabotropic

  
• Neurotransmitter Deactivation


  1. Diffusion: spreads out into extracellular environment away from the synaptic cleft

  2. Degradation: enzymes in synaptic cleft break down the neurotransmitter

  3. Reuptake: brought back into presynaptic axon terminal

  4. Astrocyte uptake: nearby astrocytes take up neurotransmitter

  
• Synapse Variation


  • Synapses vary in location, structure, function, and target
  • Connections to the dendrites, cell body, or axon of a neuron, transmitters can control the actions of the neuron in various ways

  
• Gap Junctions


  • Electrical synapse where two neurons' intracellular fluids come into direct contact
  • Eliminates the delay in information flow in chemical synapses (saves ~5 ms per synapse)
  • Forms when connexin proteins in one cell membrane connect to a hemichannel in an adjacent cell membrane
  • Allows ions to flow between the two
  • Gated channels
  • Can vary in terms of pore size
  • Allows for selectivity based on molecule size
  • Can be part of "mixed synapses" where gap junctions at axon terminals synapse on dendrites and cell bodies

  
• Excitatory Synapses


  • Typically located on dendrites
  • Round vesicles
  • Dense material on membranes
  • Wide cleft
  • Large active zone

  
• Inhibitory Synapses


  • Typically located on cell body
  • Flat vesicles
  • Sparse material on membranes
  • Narrow cleft
  • Small active zone

  
• What Counts as a Neurotransmitter?

  • Carries a message from one neuron to another by influencing the voltage on the postsynaptic membrane
  • Changes the structure of a synapse
  • Communicates by sending messages in the opposite direction (retrograde)

  
• Classes of Neurotransmitters


  • Small-molecule transmitters
  • Peptide transmitters
  • Lipid transmitters
  • Gaseous transmitters
  • Ion transmitters
• Best-Known and Well-Studied Small-Molecule Neurotransmitters

  • Acetylcholine (ACh)
  • Dopamine (DA)
  • Norepinephrine (NE, or noradrenaline [NA])
  • Epinephrine (EP, or adrenaline)
  • Serotonin (5-HT)
  • Glutamate (Glu)
  • Gamma-aminobutyric acid (GABA)
  • Glycine (Gly)
  • Histamine (H)
  • Adenosine
  • Adenosine triphosphate (ATP)
• Neuropeptide


  • Short amino acid chain (fewer than 100 amino acids)
  • Can act as neurotransmitter or hormone
  • Usually assembled on neuron's ribosomes, packaged by Golgi bodies, and transported by the microtubules to axon terminals
  • Act slowly and are not replaced quickly

  
• Peptide Transmitter Families


  • Opioids
  • Neurohypophyseals
  • Secretins
  • Insulins
  • Gastrins
  • Somatostatins
  • Tachykinins

  
• Lipid Transmitters


  • Lipids (fatty molecules) act as messengers
  • Lipids are special in that they can freely diffuse through membranes
  • Makes traditional storage difficult
• Endocannabinoids (endogenous cannabinoids)


  Act on receptors at the presynaptic membrane; affect appetite, pain, sleep, mood, memory, anxiety, and the stress response
• Phytocannabinoids


  Obtained from the hemp plants Cannabis sativa and Cannabis indica
• Gaseous transmitters


  • Not stored in or released from synaptic vesicles
  • Synthesized in cell as needed
  • Another category that can easily cross cell membrane
• Ion transmitters


  • Recent evidence has led researchers to classify zinc (Zn2+) as a transmitter
  • Actively transported, packaged into vesicles (usually with another transmitter like glutamate) and released into the synaptic cleft
• Cholinergic neurons


  • Motor neurons
  • Main neurotransmitter is acetylcholine (ACh)
  • Excitatory at skeletal muscles
  • Produces muscle contractions
• Nicotinic acetylcholine receptor (nAChr)


  • Transmitter-activated ionotropic channel
  • When ACh or nicotine binds, large pore opens
  • K+ flows out and Na+ flows in simultaneously
  • Muscle fiber depolarizes
• Autonomic Nervous System


  • Complementary sympathetic (ramp-up) and parasympathetic (ramp-down) systems work together to regulate arousal
  • Both controlled by cholinergic neurons that leave the CNS at two levels of the spinal cord
  • More variety in which synapses are excitatory and inhibitory based on receptors present

  
• Enteric Nervous System


  • Detect mechanical and chemical conditions in the gastrointestinal system
  • System can act without CNS input
  • Makes use of 30+ transmitters in total, many the same as those used in the CNS
  • Serotonin and dopamine are especially important