1. Neurotransmitters & Receptors

2. Sensory neuron Motor neuron Receptor potentialAction potential Synaptic potential Action potential

3. Excitatory Post-Synaptic Potential (EPSP)

4. Removal of neurotransmitter from the synapse 1.Reuptake 2.Enzymatic deactivation 3.Diffusion

5. Neurotransmitter binds to postsynaptic receptors and can Influence neurotransmitter-dependent channels: 1) Direct 2) Indirect

6. neurotransmitter-dependent channels 2. Metabotropic Receptors 1. Ionotropic Receptor

7. neurotransmitter-dependent channels 2. Metabotropic Receptors 1. Ionotropic receptor In all cases, the neurotransmitter does not pass from one neuron to another

8. Ionotropic Metabotropic Fast effect Only opens transmitter dependent channels Slow effect may open/close transmitter dependent channels

9. Neurotransmitters

10. Who is a neurotransmitter? Four criteria: 1.Synthesis in the neuron 2.Present in pre-synaptic terminals and released in a sufficient amount to influence a post-synaptic neuron/organ 3.When administered exogenously (drug)– mimics the effect of the endogenously neurotransmitter 4.A specific removal mechanism exists

11. Neurotransmitter: fast and local in the synapse Neuromodulator: more diffuse and modulating effect Neurohormones: through the blood stream – distant targets

12. Neurotransmitters Two basic effects: – EPSP – IPSP The receptor, NOT neurotransmitter, determines whether the post-synaptic effect of a neurotransmitter will be: Inhibitory or excitatory Direct or indirect

13. Two basic effects: – EPSP: Glutamate – IPSP: GABA (gamma-aminobutyric acid), Glycine Neurotransmitters

14. EPSP Glutamate Glutamate Ionotropic receptors: N-methyl D-aspartate (NMDA receptor) – non-selective for cations and opens Na +, K +, and Ca 2+ channels α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor) Na+ & K+ Kainate receptor

15. NMDA A Neurotransmitter and Voltage dependent channel Neurotransmitter dependent: Glutamate + Glycine  open the channel voltage dependent: Depolarization  Mg2+ is removed Channel open – late effect Involved in synaptic plasticity, learning & memory PCP: Does not normally block the channel

16. Two types of receptors: GABAa - Ionotropic receptor that opens Cl- channels (fast) GABAb - metabotropic receptor that opens K + channels (slow) GABA IPSP

17. GABAa Neurotransmitter dependent Cl- channel Muscimol – direct agonist Bicuculline – direct antagonist

18. But we have more than just two types of neurotransmitters Acetylcholine Monoamines – Catecholamines Epinephrine Norepinephrine Dopamine – Indolamines Serotonin Peptides – ex. opiods

19. Acetylcholine Muscular movement – Motor neuron – muscle synapse. Also in central nervous system – Important for learning/memory Treatment for Alzheimer In peripheral nervous system – Autonomic nervous system

20. Acetylcholine Two types of receptors: – Nicotinic – ionotropic – Na+ & K+ (and some Ca 2+ ) EPSP – Muscarinic – metabotropic – close K+ Slow EPSP  easier to generate action potential Name of the receptor – the drugs that activate it

21. Reuptake of choline by transporter – for recycling not removal Removal mechanism – AchE – breaks Ach apart

22. Another group of neurotransmitters are the Monoamines: Epinephrine Norepinephrine Dopamine Serotonin Modulate information processing: Very few neurons – but great divergence Metabotropic receptors – slow effect

23. Dopamine Norepinephrine Tyrosine L-Dopa Dopamine Norepinephrine Dopamine Beta-hydroxylase

24. Dopamine Movement, attention, learning, motivation Both inhibitory and excitatory – Depending on the receptor – All metabotropic (D 1, D 2, …..) Parkinson’s Disease – low dopamine (using L-Dopa can increase dopamine levels)

25. Norepinephrine Alertness and vigilance Both inhibitory and excitatory – But behavioral effect is usually excitatory

26. Serotonin At least 14 different receptors (5HT 1,5HT 2..) – 5HT 3 – ionotropic – Na+ & K+ Low levels of serotonin (due to stress, lack of proper sleep, poor diet/exercise) can lead to irritability, anxiety, fatigue, chronic pain, and even depression – SSRI – Specific Serotonin Reuptake Inhibitors (e.g. Prozac) tryptophan 5-HTP 5-HT

27. How can we modulate the effect of neurotransmitters? #1. Precursor (e.g. L-Dopa) #2. Inactivation of an enzyme needed for synthesis (e.g. blocking dopamine beta-hydroxylase) #3 Preventing storage (by inactivating the vesicle transporter)

28. #4 Stimulation of release from terminal button #5 Inhibition of release from terminal button #6 Receptor blockers #7 Stimulation of auto-receptors #8 Reuptake #9 Enzymatic deactivation

30. Chemicals that mimic the function of a neurotransmitter are called: Agonists Chemicals that disrupt the function of a neurotransmitter are called: Antagonists