Nervous Tissue

1. Nervous Tissue Martini Chapter 12 Bio 103 Part 3

2. What happens after an Action Potential is Propagated? • The message must cross the synapse to reach it’s target. • electrical synapse • rare in CNS and PNS • 2 membranes locked together with gap junctions and the current flows across • chemical synapse

3. The Chemical Synapse • When the action potential reaches the synaptic terminal, neurotransmitters are released which cross the synapse bind to receptors on the postsynaptic membrane.

4. Neurotransmitter: a definition • Causes immediate local and temporary change in postsynaptic membrane potential • can cause excitatory or inhibitory changes

5. Neuromodulator: a definition • alters rate of neurotransmitter release by presynaptic neuron or changes the response of the postsynaptic cell to a neurotransmitter

6. Neurotransmitters and Neuromodulators • Be Aware: • there is not a clear distinction between neurotransmitters and neuromodulators and some molecules will fit into both categories • For this class, I will refer to all chemical signals as NEUROTRANSMITTERS!

7. Categories of Neurotransmitters • cholinergic (acetylcholine) • monoamines (biogenic amines) • amino acids • neuropeptides • dissolved gasses • lipids • purines

8. Mechanisms of Action Three Categories • receptor-mediated direct action • receptor-mediated indirect action • phospholipid diffusion indirect action

9. Mechanisms of Action • receptor-mediated direct action • NT binds with transmembrane protein receptor and opens a chemical-gated ion channel (IONOTROPIC EFFECT) • e.g., acetylcholine

10. Mechanisms of Action • receptor-mediated indirect action • NT binds to transmembrane protein receptor causing a sequence of protein interaction, usually phosphorylations (METABOTROPIC EFFECT) • Can lead to: • opening of ion channel • change in protein expression • change in cell metabolism • change in enzyme activity

11. Metabotropic Effects require a G-protein coupled receptor • first messenger • neurotrasmitter • g-protein • uses energy (GTP) • second messenger • usually enzyme is activated (via phosphorylation) setting off downstream cascade of events

12. Mechanisms of Action • phospholipid diffusion indirect action • gases like NO • diffuse across phospholipid bilayer and have direct effect on enzyme activity. • 2nd messengers can also be involved

13. Categories of Neurotransmitters • cholinergic (acetylcholine) • monoamines (biogenic amines) • amino acids • neuropeptides • dissolved gasses • lipids • purines

14. Monoamines • Dopamine • inhibition or excitation depending on brain region • metabotropic • made by neurons in the: • ventral tegmental area (VTA) • reward and drug abuse • substantia nigra • movement • when these neurons die you get Parkinson’s Disease

15. Monoamines • Norepinephrine(aka noradrenaline) • adrenergic system • metabotropic action • typically excitatory at postsynaptic membrane • released from brainstem throughout CNS and in PNS • Makes us stay awake and alert!

16. Monoamines • Serotonin • made by brainstem neurons and released all over CNS • metabotropic action • inadequate levels associated with depression • SSRI (serotonin-reuptake inhibitors) used to treat mood disorders (Fluoxetine, Paxil, Zoloft) • sexual side effects • don’t work for weeks and nobody understands why!

17. GABA (gamma aminobutyric acid) The major inhibitory neurotransmitter in the brain metabotropic & ionotropic Glutamate The major excitatory neurotransmitter in the brain metabotropic & ionotropic Amino Acids • Glycine • inhibitory neurotransmitter in the brain • ionotropic only • strychnine blocks these receptors • Asparate • excitatory neurotransmitter in the brain • metabotropic & ionotropic

18. Neuropeptides • small proteins that act at chemical synapses in the brain. • typically have metabotropic effects • the book says that these are usually neuromodulators, but that is not always the case

19. Neuropeptides • Opioids • endorphin, enkephalin, dynorphin • involved in pain regulation and emotion • bind to receptors that morphine acts on

20. INCREASE FEEDING NPY (brain) AGRP (brain) Ghrelin (gut) Orexin (brain) MCH (brain) DECREASE FEEDING MSH (brain) POMC (brain) insulin (pancreas) leptin (fat) CCK (gut) PYY (gut) Neuropeptides and Appetite:just to mention a few….

21. Gases • Nitric Oxide (NO) • diffuses across membranes to effect presynaptic neurons • involved in learning and memory

22. Lipids • Anandamide • binds to the endocannabinoid receptor • metabotropic effects • receptor named because that’s also where the active compound in marijuana acts • involved in euphoria, fear and anxiety, hunger

23. Purines • Adenosine • produces drowsiness • metabotropic action • caffeine blocks the receptor this neurotransmitter bind with!

24. Acetylcholine • First NT to be discovered and studied • Widespread • released at • all neuromuscular junctions with skeletal fibers • many CNS locations • all neuron--neuron PNS synapses • all neuromuscular/neuroglandular junctions in parasympathetic PNS • Primarily Ionotropic action

25. Acetylcholine • We will use the cholinergic synapse as an example • Be aware that this is how most chemical synapses work

26. Cholinergic Synapse Step 1 • An action potential depolarizes the synaptic knob.

27. Cholinergic Synapse Step 2 • voltage-gated Ca2+ channels open in response to the action potential and Ca2+ rushes into the synaptic knob • Ca2+ stimulates exocytosis of neurotransmitter vesicles containing ACh

28. Cholinergic Synapse Step 3 • ACh diffuses across the synaptic cleft and binds to its receptor on the postsynaptic membrane • The receptor, a chemically-gated Na+ channel, allows Na+ to rush into the postsynaptic neuron triggering a graded potential • When Ca2+ levels return to normal, ACh release ceases

29. Cholinergic Synapse Step 4 • Remaining ACh is broken down by the enzyme acetylcholinesterase (AChE) into choline and acetate. Choline is reabsorbed and reused by the presynaptic neuron

30. Synaptic Delay • It takes 0.5 msec after the arrival of an action potential for the effect of the neurotransmitter to be elicited at the postsynaptic neuron. • For this reason, reflexes usually only involve a few synapses between sensation and movement.

31. Synaptic Fatigue • When the synapse has fired often and runs out of neurotransmitters to release • The neurotransmitters must be synthesized and packaged into vesicles before the synapse can be active again.

32. Processing the Inputs • A postsynaptic neuron may receive input from thousands of synapses • input can be excitatory or inhibitory • The NET impact at the axon hillock determines a neurons response • will it fire an action potential or not

33. Postsynaptic Potentials • graded potentials that develop in the postsynaptic membrane following neurotransmitter binding: • Excitatory postsynaptic potential (EPSP) • Inhibitory postsynaptic potential (IPSP)

34. Summation • Adding up EPSPs and IPSPs in the membrane to determine the membrane potential 2 categories: • temporal summation • spatial summation

35. Temporal Summation • 1 synapse receives multiple action potentials in rapid succession • at cholinergic synapses, this causes ACh to be present in synapse longer, more Na+ gets across postsynaptic membrane

36. Spatial Summation • Simultaneously multiple action potentials stimulate different regions of the neuron. • Same overall effect as temporal summation: • more Na+ across membrane and stronger depolarization

37. Summation Leads to Action Potentials

38. Presynaptic Inputs • can facilitate (help) or inhibit the possibility of neurotransmitter release

39. Potentiation • The more a neuron is stimulated, the stronger the connection between those 2 neurons • Long-term potentiation • in the hippocampus (and elsewhere) synapses are strengthened by activity • theoretically, believed to be process underlying long-term memory