Neurotransmitter Systems Chapter 6 PDF

Neurotransmitter Systems Chapter 6   Discuss the criteria neurotransmitters have to meet  Learn about the experimental methods that allow us to study whether neurotransmitters meet those criterion  Understand the main categories of neurotrans...

Neurotransmitter Systems Chapter 6   Discuss the criteria neurotransmitters have to meet  Learn about the experimental methods that allow us to study whether neurotransmitters meet those criterion  Understand the main categories of neurotransmitters Learning and their functions  Discuss the difference between transmitter-gated ion objectives channels and G-protein-coupled receptors  To frame things: we’ll be talking about exactly what a neurotransmitter *is*, how we figured that out, and how it generally works in the nervous system   Neurotransmitters are chemical keys that open receptor(protein) locks.  Three classes of neurotransmitters  Amino acids, amines, and peptides  Many different neurotransmitters, each sending a different “message” Overview of  Defining particular transmitter systems neurotransmitter  By the molecule, synthetic machinery, packaging, reuptake systems and degradation, and action  Acetylcholine (Ach)  First identified neurotransmitter  Nomenclature (-ergic)  Cholinergic and noradrenergic   A molecule can be called a neurotransmitter if it meets these 3 How can you tell criteria / if you can prove the molecule is: 1. Synthesized and stored in presynaptic neuron if something is a 2. Released by presynaptic axon terminal distinct 3. When applied extraneously/”artificially”, mimics postsynaptic neurotransmitter cell response produced by “natural” release of neurotransmitter from the presynaptic neuron ?   There are several techniques to localize transmitters and transmitter- synthesizing enzymes within certain neurons:  Immunocytochemistry—localize molecules to cells using antibodies Studying neurotransmitter systems   There are several techniques to localize transmitters and transmitter- synthesizing enzymes within certain neurons:  Immunocytochemistry—localize molecules to cells using antibodies Studying neurotransmitter systems   There are several techniques to localize transmitters and transmitter- synthesizing enzymes within certain neurons:  In situ hybridization—Localize synthesis of protein or peptide to a cell (detect mRNA) Studying neurotransmitter systems   Transmitter candidate: synthesized and localized in terminal and released upon stimulation  Determined through immunocytochemistry & in situ hybridization  CNS contains a diverse mixture of synapses that use different neurotransmitters – how do you isolate one?  Brain slices are used as a model. Studying  Kept alive in vitro → stimulate synapses, collect and measure released chemicals neurotransmitter  New methods such as optogenetics allow us to turn on specific systems synapses!   Qualifying condition: Molecules evokes same response as neurotransmitter.  Microiontophoresis : assess postsynaptic Studying actions neurotransmitter  Apply tiny amount of neurotransmitter externally & study effects systems  Microelectrode: measures effects on membrane potential   Neuropharmacological analysis also tells us a lot about the actions of neurotransmitters  Agonists and antagonists  ACh receptors: opens when  Nicotinic, muscarinic  Glutamate receptors  AMPA, NMDA, and kainate Studying neurotransmitter systems   Neuropharmacological analysis also tells us a lot about the actions of neurotransmitters  Agonists and antagonists  ACh receptors  Nicotinic, muscarinic  Glutamate receptors  AMPA, NMDA, and kainate Studying neurotransmitter systems   Ligand-binding methods  Identify natural receptors using radioactive ligands – visual analysis of receptor localization  Ligand can be agonist, antagonist, or chemical neurotransmitter.  Example: opiate receptors Studying neurotransmitter systems   Molecular analysis—receptor protein classes  Transmitter-gated ion channels  GABA receptors  5 subunits, each made with 6 different subunit polypeptides  G-protein-coupled receptors Studying neurotransmitter systems   Evolution of neurotransmitters  Neurotransmitter molecules  Amino acids, amines, and peptides  Ach is an exception – it’s a special chemical derived from the mitochondria during cellular respiration  Dale’s principle – more common  A neuron has only one neurotransmitter.  Co-transmitters – less common Neurotransmitter  Two or more transmitters released from one nerve terminal  An amino acid or amine plus a peptide chemistry   Acetylcholine (ACh) is the neurotransmitter found at Cholinergic neuromuscular junctions  All cholinergic neurons contain (ACh) an enzyme called choline acetyltransferase (ChAT), which neurons is required to synthesize ACh  ChAT is therefore a good way to mark cholinergic cells   Catecholiminergic neurotransmitters are powerful  Involved in movement, mood, attention, and visceral function  Tyrosine: precursor for three amine neurotransmitters that contain catechol group  Dopamine Cate-  Norepinephrine  Epinephrine (adrenaline) cholaminergic neurons   Serotonin (5-HT) producing neurons are called serotonergic  Amine neurotransmitter Serotonergic  Derived from tryptophan (5-HT)  Regulates mood, emotional behavior, sleep neurons  Selective serotonin reuptake inhibitors (SSRIs)—antidepressants   Glutamate, glycine, and GABA  Differences among amino acidergic neurons are quantitative, not qualitative. Amino  Glutamic acid decarboxylase (GAD) acidergic  Key enzyme in GABA synthesis  Good marker for GABAergic neurons neurons  GABAergic neurons are major source of synaptic inhibition in the CNS.   ATP excites some neurons, Other neuro- binds to purinergic receptors.  Endocannabinoids transmitter  Retrograde messengers candidates &  These molecules don’t meet the extracellular criteria for being called neurotransmitters (yet?) messengers   Fast synaptic transmission  Sensitive detectors of chemicals and voltage  Regulate flow of large currents  Differentiate between similar ions Transmitter- gated ion channels   The basic structure of transmitter-gated channels  Pentamer: 5 protein subunits form a pore  Example: nicotinic Ach receptor at neuromuscular junction Transmitter- gated ion channels  Weird things in other organisms -Higher Plants (and other organisms) do not have centrosomes!! -Some organisms during development do mitosis without cytokinesis: it creates a syncytium, or a bunch of nuclei sharing a cytoplasm. EXAMPLE: Droshophila development   The basic structure of transmitter-gated channels  Pentamer: 5 protein subunits form a pore  Example: nicotinic Ach receptor at neuromuscular junction Transmitter- gated ion channels   Amino acid-gated channels mediate most of the fast synaptic transmission in the CNS  They are pretty ubiquitous  Glutamate-gated channels  Mediate synaptic excitation  AMPA, NMDA, kainite Transmitter-  Some are voltage-dependent gated ion  Voltage-dependent NMDA channels channels   Amino acid-gated channels mediate most of the fast synaptic transmission in the CNS  They are pretty ubiquitous  GABA-gated and glycine-gated channels  GABA mediates most synaptic inhibition in CNS.  Glycine mediates non-GABA synaptic inhibition. Transmitter-  Bind ethanol, benzodiazepines, barbiturates (“depressants”) gated ion channels   G-protein-coupled receptors have three steps in transmission  Binding of the neurotransmitter to the receptor protein  Activation of G-proteins  Activation of effector systems  Basic structure of G-protein-coupled receptors (GPCRs)  Single polypeptide with 7 membrane-spanning alpha-helices G-protein- coupled receptors & effectors   G-protein-coupled receptors have three steps in transmission  Binding of the neurotransmitter to the receptor protein  Activation of G-proteins  Activation of effector systems  Basic structure of G-protein-coupled receptors (GPCRs)  Single polypeptide with 7 membrane-spanning alpha-helices G-protein- coupled receptors & effectors G-protein-  G-protein is short for guanosine triphosphate (GTP) binding protein coupled  There are many different types but they are all called G-proteins receptors &  Signal → from receptor to effector proteins effectors  1. Inactive: 3 subunits—, , and —“float” in membrane ( bound to GDP) 2. Active: bumps into activated receptor and exchanges GDP for GTP G-protein 3. G-GTP and G—influence effector operation proteins 4. G inactivates by slowly converting GTP to steps GDP. 5. G and G recombine to start the cycle again.   There are two ways the G-protein- G-protein- coupled receptor can ultimately bring about a change in the postsynaptic coupled neuron; one is a “shortcut” way and one is more complex effector  The “shortcut” pathway systems  From receptor to G-protein to ion channel—fast and localized   There are two ways the G-protein-coupled receptor can ultimately bring about a change in the postsynaptic neuron; one is a “shortcut” way and one is more complex  Second messenger cascades – the more complex (but powerful) way G-protein-  G-protein: couples neurotransmitter with downstream enzyme coupled activation effector systems   There are two ways the G-protein-coupled receptor can ultimately bring about a change in the postsynaptic neuron; one is a “shortcut” way and one is more complex  Second messenger cascades – the more complex (but powerful) way  G-protein: couples neurotransmitter with downstream enzyme G-protein- activation coupled  Push–pull method (different G-proteins stimulate or inhibit adenylyl cyclase) effector systems   There are two ways the G-protein-coupled receptor can ultimately bring about a change in the postsynaptic neuron; one is a “shortcut” way and one is more complex  Second messenger cascades – the more complex (but powerful) way  G-protein: couples neurotransmitter with downstream enzyme activation  Push–pull method (different G-proteins stimulate or inhibit adenylyl G-protein- cyclase) coupled  Some cascades branch into even more paths  G-protein activates PLC, generates DAG and IP3 activate different effector effectors systems   Some key words to know for G-protein-coupled receptor/effector system functionality:  Phosphorylation and dephosphorylation  Phosphate groups added to or removed from a protein G-protein-  Changes conformation and biological activity coupled effector systems   Some key words to know for G- protein-coupled receptor/effector system functionality: G-protein-  Signal amplification  This is kind of the whole point coupled of using G-protein-coupled systems effector  As the signals cascade down, systems they become amplified / stronger  Exponential increase-like effect   Some key words to know for G- protein-coupled receptor/effector system functionality: G-protein-  Divergence coupled  One transmitter activates more than one receptor subtype → greater effector postsynaptic response systems  Convergence  Different transmitters converge to affect same effector system.   Neurotransmitters  Transmit information between neurons  Essential link between neurons and effector cells Why do we care  Signaling pathways so much about  Signaling network within a neuron somewhat resembles brain’s neural network. neurotransmitter  Inputs vary temporally and spatially to increase and/or decrease drive. systems?  Delicately balanced  Signals regulate signals—drugs can shift the balance of signaling power. Quiz hint!  Categories of neurotransmitters A note about  Would y’all be ok having class in CSHP 223?  (Anatomy & physiology lab) next class  I have brain models in that classroom y’all can work with.   It’s 1 week from today  I recommend you begin studying now!  Neuroanatomy is very memorization-heavy so it’s in your best A note about interest to get the conceptual stuff down early so you have your first energy for memorization.  Format will be multiple choice, true/false, and short answer neuro exam questions  40 combined MC + T/F (2 pts each)  4 short answer (5 pts each) Questions?