Introduction to Neuroscience 2100 (Campeau) Study Guide for Second Midterm Exam I. Neurochemistry: Who discovered neurotransmitters and how (what was Loewi's experimental design, and what was his interpretation)? •Otto Loewi discovered the neurotransmitter by using frog hearts in contact through water. Stimulate the vagus nerve in a donor heart, heart rate slows, then remove fluid sample. Add fluid to recipient heart and heart rate also slows. What are type I and type II synapses, and what are they typically associated with functionally? ! •Type I: asymmetrical synapse, usually excitatory (EPSPs) •Type II: symmetrical synapse, usually inhibitory (IPSPs) Where are neurotransmitters produced? (hint: remember the different types of NT - small and large) •Large, Dense-core vesicles (Peptides) are made in the cell body (Golgi Apparatus) and transported to axon terminals via microtubules. •Small, Clear Synaptic Vesicles (Amines and Amino-Acids) are synthesized in synaptic terminals using precursor and synthesizing enzymes. ! 1What is the sequence of steps leading to traditional neurotransmitter release from presynaptic terminals? •Arrival of action potential-terminal depolarization •Opening of voltage-gated calcium channels •Ca++ enters presynaptic terminal •Docking and fusion of vesicles to presynaptic membrane •Exocytosis: neurotransmitter release into synaptic gap How are neurotransmitters deactivated when they are released in the synapse (hint: there are 2 different mechanisms)? •Reuptake into presynaptic terminals or glial cells (ex. Amino acids-excitatory amino acid transporters) •Enzymatic degradation (ex. Acetylcholinestrase- AChE) What determines the effects of specific neurotransmitters (hint: it is NOT the neurotransmitter molecules)? •Postsynaptic receptors determine the effects of neurotransmitters. What are neurotransmitter receptors? •A membrane receptor protein that is activated by a neurotransmitter. What are different subtypes of NT receptors? •Catecholaminergic oDopamine oNorepinephrine oEpinephrine •Amino Acidergic oSerotonin •Cholinergic oNicotinic, Muscarinic •Glutamatergic oAMPA, ▪Selective to Na+ oNMDA, ▪Na+ K+ oKainate omGluR •Serotonergic What are the different major types of NT receptors? (hint: we described two major types in class, but we discussed a total of 4 major types) •Inotropic •Metabotropic •Enzyme-Linked •Intracellular ! 2What is the general protein structure of ionotropic receptors (remember to cover the different structural components responsible for gating and ion selectivity!) •Multimers made up of 4-5 protein subunits •Two functional domains: oExtracellular site that binds to Neurotransmitters oMembrane-spanning domain that forms an ion channel •What is the general protein structure of metabotropic receptors? •A G-protein-coupled receptor hose primary action is to stimulate an intracellular biochemical response •Three subunits: alpha, beta, and gamma •Extracellular domain that contains a neurotransmitter binding site and an intracellular domain that binds to G-proteins What are the different types of receptors based on location? What are the main criteria used to determine if a substance is a neurotransmitter? •Found in presynaptic terminal/neuron •Have enzymes for synthesis •Release from presynaptic terminals •Action on postsynaptic neuron (e.g. IPSP vs. EPSP) •Postsynaptic receptors •Deactivation (Uptake/Degradation) •Predictable pharmacological action (e.g. always IPSP or always EPSP) What are the synthetic and metabolic pathways for the neurotransmitter GABA? •(GAD) transforms glutamate into GABA, VGAT fills vesicles, membrane GABA transporters, mostly responsible for fast IPSPs, 30-40% of CNS neurons utilize GABA What are the synthetic and metabolic pathways for the catecholamine neurotransmitters? A. Dopamine: movement, attention, learning, reward - degeneration of Substantia Nigra in midbrain = Parkinson’s disease (loss of DA) schizophrenia (too much DA) B. Norepinephrine and epinephrine: released by the SNS and adrenals Control alertness/wakefulness; alarm Vesicular transporters concentrate all catecholamine’s in vesicles, and this system includes metabolic enzymes (MAOs) and membrane transporters for activation What are the major classes of neurotransmitters and some of their characteristics (fast or slow acting) and functions (what are "small" neurotransmitters?; what is the general function ! 3associated with those?; how are they generally deactivated?; you can ask yourself the same questions about the other classes of neurotransmitters!) What are retrograde messengers (hint: endogenous cannabinoids)? •They are synthesized in post-synaptic elements “de novo” upon second messenger stimulation. They have widespread inhibitory functions in the central nervous system. What are the similarities and distinction between traditional neurotransmitter release (glutamate, catecholamines) vs. some of the more recently discovered neurotransmitters (endocannabinoids, soluble gases)? •What is Dale's principle? •The hypothesis that a neuron releases the same neurotransmitter at all its synapses •Many neurons synthesize and release multiple neurotransmitters at their synapse What are the 3 main components of a "signaling system"? •A molecular signal •A receptor molecule •A target effector molecule (response) What are molecular signals? •Cell impermeant molecules: includes neurotransmitters (do not readily cross membranes) •Cell permanent molecules: includes steroid based molecules, thyroid hormone and retnoids •Cell associated molecules: cell membrane proteins to cell membrane receptor interactions of closely apposed cells What are receptor molecules? •Channel-linked receptors (ionotropic) •Metabotropic receptors (G-protein coupled receptors) •Enzyme linked receptors •Intracellular receptors What are the main effector cascades? •G-proteins and their targets •Second messenger targets •Nuclear messenger targets How do G-proteins activation regulate second messengers (cAMP, cGMP)? •Adenylyl cyclase is targeted by several types of activated alpha subunits (GTP) leading to increases or deceases in [cAMP] •Guanylyl cyclase performs a similar function for [cGMP] Do you remember one of the functions of activated βγ subunits? ! 4Which G-protein subunit is mainly responsible for the production of