1. NT’s, Receptors and their actions Cholinergic Receptors (receptors that respond to Ach) –Nicotinic –Muscarinic Adrenergic Receptors (receptors that respond to NE) –Alpha –Beta Other NT Dopamine, serotonin, GABA, Glutimate

2. Binding of NT to receptors on post synaptic membrane can cause EPSPs or IPSPs depending on the combination of NT and receptor at any given synapse.

3. Acetylcholine (ACh) Used extensively in PNS and in restricted areas of CNS Broken down by Achase Two types of receptors 1.Nicotinic 2.muscarinic Autonomic ganglia, Neuromuscular junctions Post ganglionic Parasympathetic neurons

4. Nicotinic (Cholinergic) Receptors — Activated by ACh: Ionotropic: activation directly leads to movement of ions across membrane Chemical (ligand) gated channels ACh bind receptors/gated channel  channel opens  Na+ flows in  depolarization Excitation (EPSP)

5. Fig. 7.27 Muscarinic (Cholinergic) Receptors—Activated by ACh: Metabotropic: binding of receptors directly leads to chemical reactions (metabolism) Activates a second-messenger; G-protiens ACh binds receptor  G protien is activated  G protien signals gated channel  next step varies If G protien opens K+ channels: ↑ K+ outflow  hyperpolarization  IPSP If G protein closes Ca+ or Na+ channels: ↓ Ca+/Na+ flow into cell  hyperpolarization  IPSP if G protein closes (blocks) K+ channels: ↓ K+ leaking  depolarization  EPSP Can also close K+ channel in other cases

6. Fig. 9.11 Or reduce Ca+ inflow

7. Norepinephrine (NE) and Epinephrine (E) Monoamine > catecholamine broken down by monoamine oxidases (MOA) Used in sympathetic post-ganglionic neurons and in some CNS areas.

8. Fig. 7.31 Adrenergic Receptors (NE, E) Metabotropic; binding of receptor initiates metabolic reactions NE binds receptor  G-protein activates  adenylate cyclase  cAMP  kinase  open/closes channel (and/or intracellular effects)  IPSP or EPSP or epinephrine And/or activates proteins within the cytoplasm, and/or initiates events in the nucleus Changes in nucleus

10. Fig. 9.1

11. Fig. 9.7

12. Fig. 9.10 muscarinic e.g., smooth muscle effects, increases digestive activity, slow heart rate, gland secretion

14. Receptor TypeNeurotransmitter Sensativity EffectorEffect on Effector NicotinicAchSkeletal muscle, adrenal medulla, post-gangioloic neurons of ANS Excitatory MuscarinicAch in PD-ANSCardiac muscle, smooth muscle, exocrine glands, some endocrine glands Excitatory or inhibitory Alpha-1Norepinephrine > epinephrine Most sympathetic target tissues excitatory Alpha-2Norepinephrine > epinephrine Digestive organsinhibitory Beta-1Norepinephrine = epinephrine Heartexcitatory Beta-2Epinephrine onlySmooth muscle of arterioles and bronchioles Inhibitory (i.e., leads to dilation)

15. Table 7.5 CASTOR BEANS

16. MM How various substances influence neuron and synaptic function

17. Review of ANS neurons and NT’s

18. Dopamine In CNS Can be excitatory or inhibitory 2 major dopamine systems in brain –Involved with motor control (involved with inhibiting muscles that should be relaxed/preventing overstimulation of skeletal muscle) Basal Nuclei (nigrostriatal system) –involved in behavior and emotional reward (“feel good” NT) Part of reward system that influences behavior (“is it worth it to choose a course of action) Most addictions activate this system, also risk taking behaviors Overactivity contributes to schizophrenia –Which is treated by anti-dopamine drugs Mesolimbic dopamine system 7-67

19. Serotonin In CNS (and enteric system/GI tract) Excitatory and inhibitory Involved in regulation of mood, behavior, appetite and cerebral circulation, muscle control, bone remodelling, reproductive behavior. Effects mood, perception, and behavior –Linked to depression LSD is structurally similar Ecstasy targets serotonin receptors SSRIs (serotonin-specific reuptake inhibitors) are antidepressants –e.g., Prozac, Zoloft, Paxil, Luvox –Block reuptake of serotonin, prolonging its action 7-66

20. GABA (gamma-aminobutyric acid) Inhibitory (opens Cl- channels) is most common NT in brain Inhibits neural pathways (so they are not over- active) Linked to anxiety levels (increased GABA reduces axiety) Barbituates & Benzodiazepines (Xanax and valium) are agonists of GABA receptors Alcohol also targets GABA receptors 7-69

21. Glutamate Glutamate most important excitatory NT in CNS Important in memory formation and learning Involved with excitotoxicity 7-69

22. Glycine Inhibitory (mostly within brainstem and spinal cord) Important in maintiaing proper balance of inhibition and excitation that controls skeletal muscle contraction –Opens Cl - channels which hyperpolarize –Strychnine blocks glycine receptors Causes spastic paralysis (over active stimulation/excitation of skeletal muscle) 7-69

23. Interesting concept—NOT fact checked