BIOL 3322 1nd Edition Lecture 6 I. Chemical messagesa. Step 1 – synthesis and storage i. Synthesized in the axon terminal ii. Synthesized in the cell body iii. Synthesis – some neurotransmitters are transported from the cell nucleus to the terminal button. Others made from building blocks imported into the terminal are packaged into vesicles there.iv. Release – in response to an action potential the transmitter is released across the membrane by exocytosisv. Receptor action – the transmitter crosses the synaptic cleft and binds to a receptor vi. Inactivation – the transmitter is either taken back into the terminal or inactivated in the synaptic cleftb. Step 2 – neurotransmitter release i. Ca2+ ii. Calmoduliniii. Action potential reaches the voltage sensitive terminal it opens calcium channelsiv. Incoming Ca2+ ions bind to calmodulin forming a complexv. Complex binds to vesicles releasing some from filaments and inducing others to bind to the presynaptic membrane and to emty their contents by exocytosisc. Step 3 – receptor site activation i. Transmitter activated receptors ii. Autoreceptors – usually on cell body (thermostat for the cell)iii. Quantum iv. Dendrodendritic – dendrites send messages to other dendrites v. Axodendritic – axon terminal of one neuron synapses on dendritic spine of anothervi. Axoextracellular – terminal with no specific target. Secretes transmitter into extracellular fluid vii. Axosomatic – axon terminal ends on cell bodyviii. Axosynaptic – axon terminal ends on another terminal ix. Axoaxonic – axon terminal ends on another axon d. Step 4 – deactivation of the neurotransmitteri. Diffusion – carries away from cellii. Degradation – enzymatic degradation iii. Reuptake – transporter protein taken back into iv. Glial cells – transporter protein on neighboring glial cellv. Know slide 12II. Varieties of neurotransmitters These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.a. About 50 different kinds have been identified b. Some are inhibitory at one location and excitatory at other endc. More than one neurotransmitter may be active at a single synapsed. No simple one to one relationship between a single neurotransmitter and a single behavior III. 4 criteria for identifying neurotransmittersa. Chemical must be synthesized or present in neuron b. When released chemical must produce response in target cellc. Same receptor action must be obtained when chemical is experimentally placed on target d. There must be a mechanism for removal after chemicals work is doneIV. 3 classes of neurotransmitters a. Small – molecule transmitters i. Class of quick acting neurotransmittersii. Synthesized from dietary nutrients and packaged ready for use in axon terminalsiii. Examples: 1. Acetylcholine (Ach)2. Amines – dopamine (DA), norepinephrine (NE), Epinephrine (EP), Serotonin (5-HT)3. Amino Acids – Glutamate (Glu), Gamma-aminobutyric acid (GABA), Glycine (GLY)4. Acetylcholine synthesis a. Two important enzymes b. Choline acetyltransferace (ChAT)c. Acetate – acetyl coenzyme A 5. Breakdown of acetylcholine a. Enzyme – acetylcholinesterace (AChE)6. Sequential synthesis of three aminesa. Tyrosine – L-Dopa – dopamine – norepinephrine – epinephrine 7. Amino acid transmitters a. Glutamate – main excitatory transmitterb. GABA – main inhibitory transmitter8. Excitatory and inhibitory messagesa. Type 1 synapse b. Type 2 synapseb. Peptide transmittersi. Neuropeptide 1. A multifunction al chain of amino acids that act as a neurotransmitter2. Synthesized from mRNA on instructions from the cells DNA3. Do not bind ion channels; don not have direct effects on the voltage of the postsynaptic membrane c. Transmitter gasesi. Synthesized in cell, as needed ii. Easily crosses cell membrane iii. Example 1. Nitric oxide (NO)2. Carbon monoxide (CO)V. 2 classes of receptors a. Ionotropic receptor – binds transmitter and permits ions to cross; open gate and continuous flow of ionsb. Metabotropic receptor (G-protein) i. Transmitter binds & triggers G-protein ii. Alpha subunit is released from g-protein iii. Alpha subunit activates second messenger; which then activates DNA and/or forms new ion channeliv. Or – alpha subunit activates ionotropic receptor v. Know illustration on slide 29VI. 4 activating systems in the CNS a. Activating system i. Neural pathways that coordinate brain activity through a single neurotransmitterii. Cell bodies are located in a nucleus in the brainstem and their axons are distributed through a wide region of the brain iii. 4 systems:1. Cholinergic systema. Acetylcholine b. Active in maintaining waking electroencephalographic pattern ofthe cortex c. Thought to play a role in memory by maintaining neuron excitability d. Death of cholinergic neurons and decreases in Ach in the neocortex are thought to be related Alzheimers disease2. Dopaminergic system a. Dopamineb. Nigrostriatial pathwaysc. Active in maintaining normal motor behavior d. Loss of DA is related to muscle rigidity and dyskinesia in parkinsons diseasee. Mesolimbic pathways f. Dopamine release causes feelings of reward and pleasure g. Thought to be the neurotransmitter system most affected by addictive drugs h. Increases in DA activity may be related to schizophrenia3. Noradrenergic a. Norepinephrine b. Active in maintaining emotional tone c. Decreases in NE activity are thought to be related to depression d. Increases in NE are thought the be related to mania – overexcited behavior 4. Serotonergica. Serotonin b. Active in maintaining waking electroencephalographic patternc. Changes in serotonin activity are related to obsessive – compulsive disorder tics and schizophreniad. Decreases in serotonin activity are related to depression e. Abnormalities in brainstem 5-HT neurons are linked to disorders such as sleep apnea and