Lec 2b Structure and Function of Cells. Cogs17 Cognitive Neuroscience UCSD

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1 Lec 2b Structure and Function of Cells Cogs17 Cognitive Neuroscience UCSD

2 THE SYNAPSE Communication between cells

3

4 VESICLE Double lipid membrane NTs Exocytosis

5 VESICLE Exocytosis Double lipid membrane EnergyRequiring Process NTs

6 Exocytosis Reclaimed empty vesicle to be re-filled with NTs 1 9 EnergyRequiring Process After NT has After the NTs havethe drifted into the cleft... 5

7 Functions of various proteins embedded in neuron membranes: Ion Gates Fusion Pores Receptor Sites Each is specialized for only one function

8 The Synapse GABA Double Lipid Membranes Synaptic Cleft Fusion Pore (releasing NT) Receptor Sites

9 The Synapse GABA NT is released into Synaptic Cleft where it floats around until it chances to bump against a Receptor Site that it fits

10 The Synapse What happens next depends on... ACh Enzyme

11 The Synapse When NT attaches to Receptor site, >> Ion gate opens Enzyme ACh

12 The Synapse Adding positively charged decreases polarity of post-synaptic cell, bringing it closer to its threshold for firing = Excitation Excitatory Post-Synaptic Potential Post-synaptic cell is HYPO-Polarized ACh

13 Hypo- (less) polarization

14 The Synapse GABA Enzyme

15 The Synapse Adding negatively charged Clincreases polarity of post-synaptic cell, pushing it farther from its threshold for firing = Inhibition GABA "IPSP" Inhibitory Post-Synaptic Potential Post-synaptic cell is HYPER-Polarized

16 Hyper- (more) polarization

17 Summation Multiple excitatory and inhibitory inputs converge on each cell

18 MNEMONIC: EPSP & IPSP EPSP = Excitatory Post-Synaptic Potential Cell is HYPO-Polarized When you are excited, you say O! IPSP = Inhibitory Post-Synaptic Potential Cell is HYPER-Polarized When you are inhibited, you say ER...

19 AFTER the Synapse... Enzyme GABA

20 AFTER the Synapse... Enzyme NT Ion Gate closes, NT detaches

21 AFTER the Synapse... Astro- may carry NT off, dispose into bloodstream NT Enzyme

22 AFTER the Synapse... NT Enzyme

23 AFTER the Synapse... Enzyme NT Enzyme may deactivate NT

24 AFTER the Synapse... Enzyme T Enzyme may deactivate NT NABA

25 AFTER the Synapse... NT Enzyme

26 AFTER the Synapse... PreSynaptic Cell may Re-Uptake NT NT Enzyme

27 AFTER the Synapse... PreSynaptic Cell may Re-Uptake NT NT Enzyme

28 MNEMONIC Neurotransmitter Binds to the post, but doesn t go in, floats back home to be used again.

29 Ionotrophic Synapse When NT attaches to Receptor site, >> Ion gate opens Enzyme ACh

30 Metabotrophic Synapse Enzyme 5HT Post-Synaptic Cell Ribosomes (for manufacturing proteins)

31 Metabotrophic Synapse Enzyme NT attaches, Receptor site changes it configuration inside Post-synaptic cell 5HT Releases a "G Protein" G Post-Synaptic Cell Ribosomes (for manufacturing proteins)

32 Metabotrophic Synapse Enzyme 5HT Presence of G-Proteins triggers production of "Second Messengers" G 2nd Post-Synaptic Cell Ribosomes (for manufacturing proteins)

33 Metabotrophic Synapse Enzyme 5HT Presence of G-Proteins triggers production of "Second Messengers" G 2nd Post-Synaptic Cell Second Messenger binds w/g-protein Ribosomes (for manufacturing proteins)

34 Metabotrophic Synapse Enzyme 5HT This complex then opens a separate Ion Gate from inside cell. G 2nd Post-Synaptic Cell Ribosomes (for manufacturing proteins)

35 Metabotrophic Synapse Enzyme 5HT This complex then opens a separate Ion Gate from inside the cell. Post-Synaptic Cell G 2nd Ribosomes (for manufacturing proteins)

36 Metabotrophic Synapse Enzyme 5HT This complex then opens a separate Ion Gate from inside the cell. Post-Synaptic Cell G 2nd Ribosomes (for manufacturing proteins)

37 Ionotrophic vs. Metabotrophic Rapid response Very short-lived For sending message along a pathway Slow response Long lasting For setting conditions (e.g. mood, attention)

38 Acetylcholine (ACh) GABA SOME NTs: Glutamate Serotonin (5HT) Dopamine Norepinephrine Epinephrine (Adrenalin) Substance P Endorphins Hormones Neurotransmitters All neuro-muscular junctions; Cortical arousal... Suppress cortical activity; Regulate anxiety... Most common + ; Learning, Perception, Schiz... Often a neuromodulator; Mood, Sleep, Percep... Reinforcement; Atten; Motor control (Parkinsons)... Arousal; Attention... Arousal; Attention... SOME FUNTIONS: Pain (damage, itch, extreme temp, etc) Counter effects of Substance P e.g. Testosterone, Estrogen, Oxytocin, Insulin, CCK, Cortisol, Adrenalin,...

39 Agonists vs. Antagonists AGONIST ANTAGONIST Increases the likelihood of a Neurotransmitter having its effect (+ or -) Decreases the likelihood of a Neurotransmitter having its effect (+ or -) GABA GABA

40 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft What works as an Agonist vs. Antagonist often depends on how NT is typically processed in the cleft AChE ACh Post-Synaptic Cell

41 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft What works as an Agonist vs. Antagonist often depends on how NT is typically processed in the cleft AChE When ACh detaches from Receptor Site into cleft... ACh Post-Synaptic Cell

42 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft What works as an Agonist vs. Antagonist often depends on how NT is typically processed in the cleft Acetylcholine-Esterase, an Enzyme in cleft, AChE ACh will break down ACh Post-Synaptic Cell

43 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft What works as an Agonist vs. Antagonist often depends on how NT is typically processed in the cleft Acetylcholine-Esterase, an Enzyme in cleft, will break down ACh AChE ACh... into Acetate and Choline ACh Post-Synaptic Cell

44 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft What works as an Agonist vs. Antagonist often depends on how NT is typically processed in the cleft cells carry off Acetate, AChE to dispose in bloodstream ACh ACh Post-Synaptic Cell

45 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft What works as an Agonist vs. Antagonist often depends on how NT is typically processed in the cleft cells carry off Acetate, AChE to dispose in bloodstream ACh ACh Post-Synaptic Cell

46 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft Re-Uptake AChE ACh Post-Synaptic Cell

47 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft Re-Uptake The Choline is re-uptaken into the Pre-Synaptic cell for re-use AChE ACh Post-Synaptic Cell

48 Agonists vs. Antagonists Acetylcholine (ACh) in the Cleft Pre-Synaptic Cell Re-Uptake ACh The Choline is re-uptaken into the Pre-Synaptic cell for re-use AChE Post-Synaptic Cell

49 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft An AChE-Blocker is an ACh Agonist AChE AChE- Blocker ACh Post-Synaptic Cell

50 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft An AChE-Blocker is an ACh Agonist By preventing the break-down of ACh, the AChE-Blocker frees ACh to re-stimulate the Post-Syntatic cell AChE AChE- Blocker ACh Post-Synaptic Cell

51 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft An AChE-Blocker is an ACh Agonist By preventing the break-down of ACh, the AChE-Blocker frees ACh to re-stimulate the Post-Syntatic cell AChE AChE- Blocker ACh Post-Synaptic Cell

52 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft An Reuptake-Blocker is an ACh Antagonist AChE ACh ACh Post-Synaptic Cell

53 Agonists vs. Antagonists Pre-Synaptic Cell Acetylcholine (ACh) in the Cleft An Reuptake-Blocker is an ACh Antagonist AChE ACh ACh Choline alone cannot stimulate Post-Synaptic cell, so effectiveness of ACh reduced Post-Synaptic Cell

54 Agonists vs. Antagonists Serotonin (5HT) in the Cleft Pre-Synaptic Cell Re-Uptake Enzyme The typical pattern for 5HT in the cleft is different from that of ACh 5HT Post-Synaptic Cell

55 Agonists vs. Antagonists Serotonin (5HT) in the Cleft Pre-Synaptic Cell Re-Uptake Enzyme The typical pattern for 5HT in the cleft is different from that of ACh 5HT is re-uptaken whole. 5HT Post-Synaptic Cell

56 Agonists vs. Antagonists Serotonin (5HT) in the Cleft Pre-Synaptic Cell Re-Uptake Enzyme The typical pattern for 5HT in the cleft is different from that of ACh 5HT is re-uptaken whole. 5HT Post-Synaptic Cell

57 Agonists vs. Antagonists Serotonin (5HT) in the Cleft Pre-Synaptic Cell Re-Uptake Enzyme So, unlike in ACh, since 5HT is re-uptaken whole... 5HT Post-Synaptic Cell

58 Agonists vs. Antagonists Serotonin (5HT) in the Cleft Pre-Synaptic Cell Re-Uptake Enzyme So, unlike in ACh, since 5HT is re-uptaken whole......a Re-Uptake Blocker, like PROSAC, will, in this case, free 5HT to re-stimulate post-synaptic cell 5HT Prosac Post-Synaptic Cell

59 Agonists vs. Antagonists Serotonin (5HT) in the Cleft Pre-Synaptic Cell Re-Uptake Enzyme So, unlike in ACh, since 5HT is re-uptaken whole......a Re-Uptake Blocker, like PROSAC, will, in this case, free 5HT to re-stimulate post-synaptic cell Prosac 5HT Post-Synaptic Cell

60 Agonists vs. Antagonists Serotonin (5HT) in the Cleft Pre-Synaptic Cell Re-Uptake Prosac Enzyme So, unlike w/ach, this Re-Uptake Blocker is a 5HT Agonist 5HT Post-Synaptic Cell

61 Other Factors that Modify Function RNA DNA GENE TRANSCRIPTION Copies of segments of DNA (= RNA) are made, to code for protein production

62 Dendritization Increase # of dendritic spines

63 Availability of NT Components e.g. Choline (for making ACh) from milk or nuts & seeds via DIET... e.g. Tryptophan (for making 5HT) from turkey via administering DRUGS... e.g. L-DOPA (a Dopamine precursor) that crosses blood-brain barrier e.g. Fat-soluble drugs (heroin, canobinol, LSD) cross barrier and mimic NTs

64 Kinesin Molecules transporting NT to Terminal

65 EXCEPTIONS Auto-Receptor Inhibitory Neurotransmitter In cells with "Auto-Receptors" the presynaptic cell inhibits itself, as well as the post-synaptic cell (i.e. Limits how much NT presym will release)

66 EXCEPTIONS Axo-Axonal Synapses In brain, activity along Pain pathways provokes activity from Endorphin cells. Receptor sites on Terminal of pain cell responds to endorphins, reducing release of Substance P

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