Neurotransmitters - Nervous System Lecture Slides PDF

Nervous System, Cont. Neurotransmitters, Neurotransmitter receptors, Neural pools, Interpretation of APs Objectives Distinguish between spatial and temporal summation Give examples of excitatory and inhibitory neurotransmitters, and describe how they function De...

Nervous System, Cont. Neurotransmitters, Neurotransmitter receptors, Neural pools, Interpretation of APs Objectives Distinguish between spatial and temporal summation Give examples of excitatory and inhibitory neurotransmitters, and describe how they function Describe different types of neurotransmitter receptors Describe classes and functions of neurotransmitters Identify and explain function of different types of neural circuits Neurotransmitter Receptors NTs released from presynaptic cell NTs bind to receptors Postsynaptic cell membrane 1+ binding sites Binding  ion channels open EPSP IPSP Ionotropic Ionotropic Receptors Contains NT binding site & ion channel Same protein Ligand-gated channel Excitatory NTs Cation channels Why? Inhibitory NTs Anion (Cl-) channels Why? Ion Channels Selective based on size and charge Selectivity: only (+) ions can pass (Na+ and K+) Shape of AP depends on [Na+]outside % of the normal extracellul ar concentrat ion Shown here are action potentials recorded when the external medium contains 100%, 50%, or 33% of Na+. Metabotropic Receptors NT binding site, no ion channel Indirect connection to ion channel G protein mechanism G protein direct activation or second messenger Inhibitory NTs Linked to opening K+ or Cl- channels How does this inhibit? G protein Activation may Postsynaptic Effects of Same NTs Same NT can be excitatory or inhibitory How? Receptor structure & cell type Same signal molecule  induces different responses in different target cells Example: Acetylcholine (ACh) Excitatory: binds to ionotropic receptors  cation receptors open  EPSP Inhibitory: binds to metabotropic receptors  K+ channels open  IPSP Removal of NTs 1. Enzyme degradation E.g., acetylcholinester ase 2. Diffusion Synaptic cleft 3. Uptake by cells Neurotransmitter transporters Spatial and Temporal Summation Avg neuron: 1,000 – 10,000 synapses Trigger zone  1,000s points of communication Integration Summation of postsynaptic potentials Spatial summation # neurons Membrane coverage Temporal summation EPSP lasts 15 ms Spatial and Temporal Summation Postsynaptic cell receiving many signals EPSP = IPSP  no net change 1 Na+ : 1 Cl- EPSP If excitatory effects > inhibitory Below threshold IPSP If inhibitory effects > excitatory Hyperpolarization Nerve impulse If EPSP > threshold How is summation modulated? Stimulus Encoding All impulses are the same strength/size How is stimuli of differing intensities detected? The key: Frequency of APs! Frequency at trigger zone Initiated by graded potentials Stronger stimulus  higher frequency Number of neurons Recruitment More neurons stimulated  stronger signal detected Stop and think… How can one neurotransmitter have opposite (ultimate) functions? What are different ways graded potentials can be strengthened? What would be an effect of a blocked neurotransmitter transport protein? Neural Pools Large groups of neurons associated with a particular function E.g., Heart rate, breathing rate, limb movement, smell Discharge zone More synapses per postsynaptic cell Spatial summation Synapses where input neuron can cause AP Facilitated zone Not generate AP in postsynaptic cell by itself Facilitates (“has a vote”) Input neuron needs help for AP How? Differential regulation Neural Circuits (neural pathways) 1. Diverging One neuron  many downstream neurons E.g., motor output from brain  thousands of muscle fibers 2. Converging Many neuron  fewer neurons (as low as one) E.g., influence of signals on respiration Brain, blood chemistry, vessel stretch receptors Integrated in respiratory center  output breathing pattern Neural Circuits (neural pathways) 3. Reverberating Linear, some axons send signals to earlier neurons (feedback loop) A B C Repetitive effect until one fails to fire or is D inhibited E.g., inspiration (activation of diaphragm) Circuit continues for 2 secs (time takes to inhale) 4. Parallel After-Discharge One neuron  parallel series of neurons  one output Parallel series have diff # neurons Signals arrive at end at diff times Signal propagates after stimulus stops Neurotransmitters (NTs): 1. Acetylcholine (ACh) Neuromuscular junctions 2. Amino Acids GABA E.g., GABA (gamma-aminobutyric acid): inhibitory; Glutamate: excitatory 3. Biogenic Amines (monoamines) Amino acids without carboxyl group (-COOH) Emotional behavior Associated with mental illness Some drugs bind to receptors E.g., LSD Neurotransmitters (NTs): 4. Purines ATP Adenosine (inhibitor in brain) E.g., caffeine blocks this NT 5. Gases Nitric oxide (NO) Carbon monoxide (CO) Neuropeptid 6. Neuropeptides Cholecystokini eY 2 – 40 AAs n Some are hormones Associated with pain pathways Endorphins (reduce pain signals) E.g., childbirth, runner’s high E.g., CCK, substance P, endorphins, enkelphins Neuromodulators Do not directly cause EPSPs or IPSPs Hangs around synapse Affects strength of transmission Presynaptically Synthesis Release Degradation Reuptake Postsynaptically Changing sensitivity of membrane Drugs of Abuse - Effects Chemicals similar to reward system NTs E.g., Cocaine Blocks dopamine reuptake proteins Over stimulation of dopamine effects Repeated doses  body releases less  withdrawals E.g., MDMA 3,4-Methyl​enedioxy​methamphetamine (MDMA), commonly known as ecstasy Targets serotonin-releasing neurons Rush of serotonin and other NTs Dopamine, norepinephrine Damages neurons Problems sleeping, memory loss, Drugs of Abuse - Effects https://learn.genetics.ut ah.edu/content/addictio n/mouse/ Next: Reflexes, spinal cord, spinal tracts