PSYC 3333 Neurotransmitters (1) PDF

PSYC 3333 Physiological Psychology Unit II  Quick Review & Preview Unit I Unit II History of Neuroscience Glial Cells What happens to a neurotransmitter types, location, functions...

PSYC 3333 Physiological Psychology Unit II  Quick Review & Preview Unit I Unit II History of Neuroscience Glial Cells What happens to a neurotransmitter types, location, functions (NT) once released? Neurons Neurotransmitters (NT) the cell wall, specialized proteins, parts Overview and functions Types of receptors Neural Communication The big 6: resting membrane potential, the action Acetylcholine potential, saltatory conduction, Dopamine, Norepinephrine, Serotonin neurotransmitter release Glutamate, γ-amino-butyric acid Nervous System brain structure & function Neurobiology of Learning & Memory Lecture Outline (today) The fate of a NT what happens to a NT once released? Types of receptors Overview & Introduction to NTs Acetylcholine  What happens to a NT? 1. Wiring Transmission  NT crosses synapse and acts on ligand-gated receptor of post-synaptic dendrite causing EPSP (and AP) or IPSP 2. Reuptake Transporters  Specialized proteins on pre-synaptic terminal button pulls NT back into pre-synaptic terminal button and recycles it 3. Enzymatic Degradation  Specialized enzymes break down NT 4. Pre-synaptic Autoreceptors  Receptors located on pre-synaptic terminal button 5. Volume Transmission  NT’s float away from synapse and act on distant receptors  Synaptic Transmission & Neurotransmitters are Neurotransmitters synthesized in soma Pumps/ Transporters Terminal button Autoreceptor Synapse Enzymes Post-synaptic neuron What are these? Post-Synaptic Receptors 2 different types  Types of Receptors: Ionotropic vs Metabotropic Ion influx Ionotropic 4 to 5 protein subunits ion channel located in the protein receptor NT binds to receptor inside ion channel opens ions move either in or out of the cell  Types of Receptors: Ionotropic vs Metabotropic Metabotropic Single protein But winds in and out of cell wall Metabolic process Ion channel located distantly in cell wall Slower transmission  Metabotropic Receptors/GPCRs K+ Synapse Ion Channel Post-synaptic G neuron G-Protein Cellular effects Kinases 2nd messenger Effector Enzyme ATP  What happens when NT binds to receptor? Depends on the NT-receptor combo Some are excitatory Depolarization & AP in post-synaptic cell Excitatory Post-Synaptic Potential (aka EPSP) Some are inhibitory Hyperpolarization & no AP in post-synaptic cell Inhibitory Post-Synaptic potential (aka IPSP)  Now on to neurotransmitters Each neurotransmitter has its own receptors ionotropic vs metabotropic what happens when a ligand binds to it? excitatory or inhibitory Neurotransmitters (NTs) how are they made what kind of receptors do they have & how many Where is it used in the brain What is each NT used for What disorders are associated with each NT (if any) Drugs that influence each NT system  Neurotransmitter Sampler Class Example - Acetylcholine Dopamine, Norepinephrine, Monoamines Serotonin Amino Acid Glutamate, GABA Peptides Opioids, etc. Gas NO, CO Lipid Anandamide NTs: What to know 1. Synthesis  How is each NT made 2. What type of receptors for each NT? How many? 3. What are the enzymes that destroy (degrade) each NT? 4. Where is each NT used?  Major pathways 5. What is each NT used for? 6. Disorders associated with each NT? 7. Any drugs along the way that work at any of the above?  Acetylcholine (ACh) Acetyl Co-A + Choline Choline Acetyltransferase Acetylcholine Terminal button Acetylcholine esterase ACh Synapse N M Post-synaptic ACh Receptors neuron (nicotinic vs muscarinic) Playing with ACh systems: curare & sarin Acetyl Co-A + Choline Choline Acetyltransferase Curare Terminal button Sarin ACh AChE Synapse Sarin Post-synaptic M N neuron ACh Receptors (nicotinic vs muscarinic)  ACh: Location/Pathways In the Brain Outside the Brain Autonomic nervous system Cell bodies in nucleus basalis Project to cortex Neuromuscular junctions ACh: Behavioral Functions/Disorders Movement Learning and memory ACh antagonists Morris Water Maze (MWM) Nucleus Basalis of Meynert Cell bodies produce ACh 1st structure lost in Alzheimer’s Monoamine NTs Catecholamines Dopamine (DA) Norepinephrine (NE) Indolamine Serotonin (5-HT)  Tyrosine Dopamine (DA) Tyrosine Dopa Hydroxylase Dopa Decarboxylase DA Reuptake Dopamine (DA) Transporters Terminal button Monoamine Oxidase Synapse & Psychostimulants Catechol – O – methyl transferase (COMT) Post-synaptic neuron DA Receptors (DA1-5) Dopaminergic Pathways & Behaviors 1. Nigro-striatal Pathway  Cell bodies originate in substantia nigra  Axons project and terminal buttons release DA in striatum  Movement 2. Meso-Cortical Pathway 1. Cell bodies originate in ventral tegmental area 2. Axons project and terminal buttons release DA in cortex 3. Motivation, emotion, executive function (evaluation of stimuli) 3. Meso-Limbic Pathway 1. Cell bodies originate in ventral tegmental area 2. Axons project and terminal buttons release DA in nucleus accumbens 3. Pleasure/displeasure (euphoria/dysphoria)  Tyrosine Norepinephrine (NE) Tyrosine Hydroxylase Dopa Dopa Decarboxylase Dopamine-beta- Dopamine Hydroxylase NE Transporters Terminal button MAO/COMT NE Synapse Post-synaptic neuron NE Receptors (NE alpha & beta)  Pathways: NE in CNS Cell bodies: Raphe nuclei of Pons & Medulla Locus Coeruleus projects to: Cortex Hippocampus Hypothalamus Thalamus Cerebellum Spinal Cord Other Forebrain regions  NE: Behavioral Effects Arousal and vigilance Stimulation of autonomic nervous system Cognition Memory consolidation Emotional experiences Disorders Attention disorders Mood disorders  Tryptophan Serotonin (5HT) Tryptophan Hydroxylase 5-Hydroxytryptophan 5HTP (5HTP) Decarboxylase 5HT Transporters 5 Hydroxytryptamine (5-HT) Terminal button MAO Synapse Post-synaptic neuron 5HT Receptors (5HT1-7)  5-HT: Pathways/Location Cell Bodies Projections Dorsal Raphe nucleus Cortex Median Raphe nucleus Caudate Putamen Nucleus Accumbens Thalamus & Hypothalamus Limbic System Hippocampus Amygdala Septal Area  5-HT: Behavioral Functions/Disorders Sleep/Wake cycles Mood Aggression Lower 5-HT levels correlate to increased aggression and increased impulsivity Lecture outline Finish up Glutamate & GABA Discussion on the neurobiology of learning & memory glutamate and its receptors how do neurons make memories?  Amino Acids Glutamate γ-amino-butyric acid (GABA) Excitatory Inhibitory 3 Ionotropic receptors (post-synaptic) 2 Receptors Kainate, AMPA, NMDA GABA-A 8 Metabotropic Ionotropic Family I: #1 & 5 GABA-B Family II: #2 & 3 metabotropic Family III: #4, 6, 7, & 8 NTs: What to know 1. Synthesis  How is each NT made 2. What type of receptors for each NT? How many? 3. What are the enzymes that destroy (degrade) each NT? 4. Where is each NT used?  Major pathways 5. What is each NT used for? 6. Disorders associated with each NT? 7. Any drugs along the way that work at any of the above? Amino Acids: Synthesis Glutamine (from glial cells) + glutaminase Glutamate + glutamate decarboxylase GABA Glutamate: Reuptake Transporters Excitatory Amino Acid Transporters (EAAT) 5 types (EAAT 1-5) Let’s focus on 1, 2, and 3 Glutamate Reuptake & Enzymatic Degradation EAAT 1 & 2 on astrocytes Take in Glu Glutamine synthetase Converts Glu to glutamine Glutamine sent to glutamatergic neuron Glutamate: Pathways Cell bodies in cortex project to: Striatum Hippocampus Intra-hippocampal pathways Glutamate: Behavioral Effects/Disorders NMDA blockers impairs MWM performance NMDA-KO mice show MWM performance deficits Over-expression of NMDA receptors produces “Doogie-Mice” GABA Receptors Two types GABA-A & GABA-B Activation of either produces hyperpolarization But via different processes GABA: Receptors GABA-A GABA-B Ionotropic Metabotropic Cl- entry opening K+ channels internal charge K+ efflux become more negative internal charge becomes more negative GABA: Enzymatic Degradation GABA aminotransferase (GABA-T) converts GABA back to Glutamate GABA pathways GABA used throughout the brain VTA GABA DA DA GABA Inside the Ventral DA Tegmental Area (VTA) DA GABA GABAergic neurons project onto GABAergic receptors located on DA neurons GABA: Behavioral Effects/Disorders Depends on the receptor type Anxiety (Panic Disorder) Pain modulation Sedative-hypnotic Anticonvulsant properties Hallucinations