Neurochemistry 2. Loewi s experiment

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1 Neurochemistry 2 Loewi s experiment Cengage Learning 2016

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4 AP reaches the axon terminal and activates voltage-gated Ca++ channels (3 major classes). Ca++ influx results in exocytosis of neurotransmitters into the synapse. In the synapse, neurotransmitters bind to post-synaptic receptors (ionotropic or metabotropic) EPSPs, IPSPs, or other biochemical changes

5 Major Events in Transmission at a Synapse Cengage Learning 2016

6 very common very common impt for presynaptic inhibition

7 Are you your connectome? Your brain contains billions of neurons, cells that send and receive messages through synapses, the connections between neurons. Over time, neurons and their networks can branch or wither, grow or retreat and get stronger or weaker. This process is directed by your genes and also shaped by your experiences, creating an intricate pattern of neural connectivity that is unique. Some scientists believe that a map of all your brain's connections, known as your connectome, could be used to simulate your consciousness.

8 You are a pattern of electrical signals. this is only partially true An operating room at Alcor. The clear box is used to prepare the patient's head for preservation. Part of the container in which Kim's preserved brain is stored. A third of the $80,000 fee Kim paid for preservation has been placed in a trust for future revival.

9 Brain Cryonics Do you think neuropreservation and then creating a digital replica of someone's connectome will be technically possible one day? Do you think this is a worthwhile goal? Would you donate money to someone like Kim? Would you consider doing this?

10 Neurotransmitters Most neurotransmitters are small; some peptides are large. Most small neurotransmitters are synthesized and packaged in the terminal buttons into synaptic vesicles, by Golgi complex Synaptic vesicles are moved to near presynaptic membrane. Peptides are synthesized in cell body, packaged into vesicles can be moved to terminal buttons also can be released from cell body and dendrites

11 MAJOR CLASSES OF NEUROTRANSMITTERS Amino Acids Monoamines SUB- CLASSES Catecholamines Indoleamines EXAMPLES Glutamate GABA Aspartate Glycine Dopamine Epinephrine Norepinephrine Serotonin Soluble gases Nitric oxide Modified AA Acetylcholine Neuropeptides NPY, AVP, OT

12 Synthesis of Neurotransmitters Cengage Learning 2016

13 Release & Diffusion of Transmitters Most individual neurons release 2 or more neurotransmitters Movement across the synaptic cleft takes less than 0.01 milliseconds (0.01 msec) Cengage Learning 2016

14 IONOTROPIC METABOTROPIC

15 Ionotropic Receptors neurotransmitter binding immediately opens ion channel (< 1 msec) effect is often very short-lasting glutamate, GABA acetylcholine Cengage Learning 2016

16 Cholinergic Pathways

17 Cengage Learning 2016 Acetylcholine Receptor

18 Acetylcholine Receptor

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20 Metabotropic Receptors neurotransmitter binding receptor changes shape intracellular portion of the receptor affects other proteins (2 nd messengers) sequence of slower biochemical events effects are often longer-lasting dopamine, norepinephrine, serotonin, and sometimes glutamate and GABA Cengage Learning 2016

21 Dopaminergic Pathways

22 Cengage Learning 2016 Metabotropic Receptors

23 Inactivation and Reuptake of Neurotransmitters Enzymes (e.g., MAO, AChE) inactivate neurotransmitters in synapse Also, presynaptic neuron can take up the neurotransmitter molecules and reuse them Specific membrane proteins facilitate reuptake Cengage Learning 2016

24 Negative Feedback Autoreceptors: presynaptic receptors that detect the amount of transmitter released and inhibit further synthesis and release Postsynaptic neurons: release chemicals that travel back to the presynaptic terminal and inhibit further neurotransmitter release Cengage Learning 2016

25 Electrical Synapses Some synapses operate electrically Faster than chemical synapses Gap junction: the direct contact of the membrane of one neuron with the membrane of another Cengage Learning 2016

26 Basic Neuropharmacology Agonists: mimic, replicate, or enhance activity of one or multiple neurotransmitters. Antagonists: block, attenuate, or inhibit activity of one or multiple neurotransmitters.

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28 Cengage Learning 2016 The Chemistry of Addiction

29 Should addiction be viewed as a brain disease? Arguments in favor of this? Arguments against this? What things could be considered addictive? Practical implications for people, perhaps someone you know?

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