NEUR 0010 - Chapter6 Flashcards
What does a neurotransmitter system include?
The NT molecule itself, molecular machinery for transmitter synthesis, vesicular packaging, reuptake, degradation, and action
What does cholinergic mean? Noradrenergic? Glutamatergic? GABAnergic? Peptidergic?
Neurons/synapses that use/release ACh; NE; glutamate; GABA; peptides…. You get the picture.
What are the three requirements for a molecule to be considered a NT?
Synthesized/stored in presynaptic neuron; released by presynaptic axon terminal upon stimulation; when experimentally applied, must produce a response in the postsynaptic cell that mimics the response produced by the release of the NT from the presyn neuron
What are the two most common methods for determining if a molecule is a NT?
Immunocytochemistry and in situ hybridization
What is immunocytochemistry?
Used to anatomically localize particular molecules in particular cells; NT candidate chemically purified, injected into bloodstream to stimulate immune response, antibodies bind to it; remove antibodies and chemically tag, apply to brain tissue; chemical tags of antibody+NT candidate will highlight brain areas where the NT candidate goes
What is in situ hybridization?
Used to confirm that a cell synthesizes a particular protein/peptide; complementary strand of mRNA (probe) for a particular nucleic acid sequence; probe is chemically labeled, binds to mRNA strand (hybridization), applied to brain tissue section, wash away extra probes that didn’t stick; search for neurons that contain the labeled probe
How do you test that an NT is released from the presyn neuron upon stimulation?
Bath brain tissue slice in high K+ solution (causes big depolarization, stimulates NT release from terminal to tissue), then in Ca++ (allows release of NT candidate into tissue slice after depolarization)
Why is it difficult to test that an NT is released from the presyn neuron upon stimulation?
Because following the K+ bath/Ca++ application to test for release of the NT candidate, it’s hard to tell whether the release is a secondary consequence or not; also hard to distinguish because many synapses with different NTs intermingle in the CNS (but not in the PNS)
How do you verify that the NT candidate evokes the same response as that produced by the release of naturally occurring NTs from the presyn neuron?
Microionophoresis
What is microionophoresis?
NT candidates dissolved in solutions to acquire net electrical charge; fine tipped pipette filled with ionized solution, inserted near postsyn membrane; pass electrical current through pipette to eject ionized solution; measure effects by microelectrode
What is the relationship between different NTs and different receptors? What can bind to many/only one of the other?
A NT can bond to many different receptors, but a receptor can only bind to one NT; “no two NTs can bins to the same receptor”
What are the two subtypes of cholinergic receptors? Why are they named as such?
Nicotinic and muscarinic; named for the agonists of each type
What are the antagonists for nicotinic and muscarinic cholinergic receptors?
Curare for nicotinic, atropine for muscarinic
What are three main subtypes of glutamatergic receptors?
AMPA, NMDA, kainate (each named for the agonists)
Of the three main subtypes of glutamatergic receptors, what substances can bind to what receptors?
Glutamate can bind to all three, but AMPA/NMDA/kainate can only bond to their respective receptors
What is a ligand?
Any chemical compound that binds to a specific site on a receptor; ligand = “to bind”
What is the ligand-bonding method?
Studying receptors using radioactively labeled ligands; can be agonist/antagonist/chemical NT itself
What are the two main NT receptor protein groups?
Transmitter-gated ion channels, G-protein coupled receptors (metabotropic)
What are the three main methods of studying different receptor subtypes?
Neuropharmacological analysis (how receptors respond to different drugs); ligand-bonding methods (radioactively tagging ligands to observe behavior); molecular analysis (identifying protein structure that makes up the receptors)
What is ACh derived from, and why is that different from usual NTs?
From acetyl CoA (byproduct of cellular respiration) and choline (important for fat metabolism); usually, NTs are derived from amino acids/amines/peptides
What is Dale’s principle?
The idea that a neuron has only one NT associated with it; often violated by peptide NTs
What group of NTs usually violates Dale’s principle? Why?
Peptide NTs: peptide-releasing neurons usually release the peptide NT and ALSO an amino acid/amine NT
What are co-transmitters?
NTs released from one axon terminal (according to Dale’s principle, there should only be one released from a given neuron)
What NT is present at all neuromuscular junctions? What does that imply about its synthesis?
ACh; synthesized by all motor neurons in the CNS