Synaptic Transmission PDF - University of Central Lancashire

XY2141 Anatomy II Synaptic Transmission SGM104 Gillian Lewis [email protected] Last time… We looked at action Do you remember the potentials equation? Calculating the equilibrium potentials E (mV) = 58.log...

XY2141 Anatomy II Synaptic Transmission SGM104 Gillian Lewis [email protected] Last time… We looked at action Do you remember the potentials equation? Calculating the equilibrium potentials E (mV) = 58.log10 Co z Ci For sodium (Na+): Co/Ci 150/15=10 log10() log(10)=1 58x1=58 Valency z for Na is +1 58 58/1=+58 z So E (mV) =+58mV for the sodium ion  Calculating the equilibrium potentials Now it’s your turn!! At 200C: E (mV) = 58.log10 Co z Ci Co Ci Na+ 150mM 15mM K+ 5.5mM 150mM Cl- 125 9 Learning objectives The structure and functions of synapses Types of synapses: anatomical & functional. Synaptic transmission & neurotransmitters Fate of neurotransmitters. Electrical events at synapses (EPSPs & IPSPs). Properties of synaptic transmission and factors affecting them To start On a piece of paper or ipad Roles of synapses Lets build on this - worksheet The sequence of events at synapse 2. Synaptic Localised knob of the Acetylcholine circuit presynaptic molecule neurone released into the Synaptic cleft synaptic cleft Post synaptic neurone Receptor molecules ◼An action potential arrives at presynaptic Calcium ions cause synaptic vesicles to fuse with the presynaptic membrane, releasing acetylcholine into the membrane. Voltage gated calcium synaptic cleft. channels open, calcium ions enter  Empty synaptic 3. vesicles Acetylcholine 4. New localised circuit due to molecule fused to action receptor molecule potential Acetylcholine diffuses across the Sodium channels open - diffuse synaptic cleft and binds receptors into the postsynaptic membrane causing depolarisation and action potential. 5. 6. mitochondrion Choline mitochondrion molecule Reformed ethanoic acetylcholine in acid synaptic vesicle molecule Acetylcholinesterase breaks Choline and Acetyl Co A are used down acetylcholine -products to reform acetylcholine. Needs ATP diffuse back into the presynaptic neurone Synapses Where the information is transmitted between neurons 1) may be blocked in its transmission from one neuron to the next 2) may be changed from a single impulse into repetitive impulses 3) may be integrated with impulses from other neurons to cause highly intricate patterns  Anatomical types of synapses Axodendritic – synapses between the axon of one neurone and the dendrite of another Axosomatic – synapses between the axon of one neurone and the soma of another Other types of synapses include: – Axoaxonic (axon to axon) – Dendrodendritic (dendrite to dendrite) – Dendrosomatic (dendrites to soma)  Functional types of synapses There are two major types of synapses→ CHEMICAL AND ELECTRICAL Presynaptic neurone Presynaptic terminals many anatomical forms → small round or oval knobs separated from the postsynaptic neuronal soma by a synaptic cleft (200 to 300 angstroms (Å) wide) 2 important structures: vesicles and mitochondria voltage-gated calcium channels – The more channels opened, the more neurotransmitter released Postsynaptic neurone intracellular Binding component component Receptor Proteins 2 components - binding component – intracellular component that passes all the way through the postsynaptic membrane Receptor activation – Ionotropic → by gating ion channels directly – Metabotropic → by activating a “second messenger” Second messenger in postsynaptic neurone Required for prolonged changes in neurones G protein coupled receptors 1. Opening specific ion channels through the postsynaptic cell membrane 2. Activation of cAMP or cGMP 3. Activation of one or more intracellular enzymes 4. Activation of gene transcription Fast vs slow neurotransmission Electrical event on the postsynaptic neuron Excitatory post-synaptic potential [EPSPs] Inhibitory post-synaptic potentials (IPSPs) You need to know these terms How EPSPs differs from Action potential? Proportionate to the strength of the stimulus Can be summated If large enough to reach firing level → AP is produced  Integration of synaptic information Spatial summation – two or more presynaptic inputs arrive at a postsynaptic cell simultaneously Temporal summation – two presynaptic inputs arrive at the postsynaptic cell in rapid succession Facilitation –Neurone is close to the threshold for firing –Another excitatory signal required for AP –Large groups of neurones can respond quickly and easily Special Characteristics of Synaptic Transmission Fatigue of Synaptic Transmission Effect of Acidosis or Alkalosis on Synaptic Transmission Effect of Hypoxia on Synaptic Transmission Effect of Drugs on Synaptic Transmission Synaptic Delay Fatigue of Synaptic Transmission – Excitatory synapses are repetitively stimulated at a rapid rate→ fatigue→ decreases firing rate – Exhaustion or partial exhaustion of the stores of transmitters in the presynaptic terminals – Protection factor for overactivity Effect of Acidosis or Alkalosis 1. Alkalosis: – Increases neuronal excitability. – Causes cerebral epileptic seizures (Increased excitability cerebral neurons) 2. Acidosis: -Depresses neuronal activity - Causes a coma (e. g. severe diabetic or uremic acidosis)  Effect of Hypoxia on Synaptic Transmission Cessation of oxygen - cause complete in excitability of some neurones Effect of Drugs on Synaptic Transmission Psychostimulant vs depressant  Synaptic delay Is the minimum time required for transmission across the synapse - 0.5 ms Discharge of transmitter substance by pre- synaptic terminal Diffusion of transmitter to post-synaptic membrane Action of transmitter on its receptor Action of transmitter to ↑ membrane permeability Increased diffusion of Na+ to ↑ post- synaptic potential Neurotransmitters  Characteristics of NT’s Is a chemical molecule Must be endogenously synthesized From presynaptic neurone After electrical stimulation→ chemical must be released and produce a response in its target cell Response must be mimicked by exogenous application of the chemical Chemical must be endogenously removed at the synapse Categories of Nt’s Conventional small molecules 1.1. Amines - ACh and monoamines 1.2. Amino acids 1.3. Purines 2. Neuropeptides 3. Unconventional NT’s 1.1. Amines- ACH Excitatory response nAChRs are ionotropic receptors mAChRs are metabotropic GPCRs only neurotransmitter that is utilized at the neuromuscular junction PSN→ from all preganglionic and most postganglionic neurones SNS→ from all preganglionic neurones Basal forebrain → neuromodulatory functions in memory, arousal, and reward 1.1. Amines- Biogenic amines-Catecholamines DOPAMINE Brainstem and hypothalamus→ projections thoughout the brain Executive functions, motivation, arousal, reward, and motor control metabotropic GPCRs (5 subtypes) NOREPINEPHRINE & EPINEPHRINE Pons→ cortical and subcortical regions of the brain, the brainstem and to the spinal cord Sleep and dreaming, attentiveness, memory, and emotion SNS – postganglionic sympathetic neurones→including pupil constriction, gut motility….. – preganglionic sympathetic neuros → blood vessel constriction 1.1. Amines- Biogenic amines-Serotonin SEROTONIN Reticular formation → throughout the brain and spinal cord Regulation of mood, reward, anger, aggression, anxiety, sleep, nausea, sexuality, sensorimotor functions including pain processing, and memory 5HT3R → ionotropic receptors The rest are metabotropic receptors 1.1. Amines- Biogenic amines-Histamine HISTAMINE Hypothalamus→ mainly cortex and spinal cord Modulation of the circadian cycle and sleep metabotropic receptors (4 subtypes)  1.2 Amino acids GLUTAMATE Excitatory synaptic transmission Nearly in every region of the brain Relaying of sensory information, encoding of information, brain motor control and coordination, formation and retrieval of memories, emotion, spatial recognition, and consciousness. Ionotropic receptors and Metabotropic receptors Gamma-amino-butyric acid GABA Inhibitory synaptic transmission Motor control, sensorimotor processing, anxiety, emotions, learning and memory, pain, and sleep. Ionotropic receptor- GABAa Metabotropic receptor -GABAb 2. Neuropeptides Vast list of neuropeptides Most located in the hypothalamus neocortex and hippocampus→ GABAergic neurons Co-transmitters → cosecreted with a neurotransmitter and alter the response 1. Neuromodulators – alter the amount of neurotransmitter released 2. Neurohormones – secretory cells into the blood neuroendocrine regulation, analgesia, food and water intake, thermoregulation, circadian rhythms….  Example of Neuropeptides OPIODS PEPTIDES endogenous opioid peptides are the endorphins, enkephalins, and dynorphins Inhibitory effects (sometimes excitatory by inhibition of GABA) Analgesia→ pain processing But also, in reward systems, mood control, and drug addiction Metabotropic receptors → µ, δ, and κ opioid receptors  3. Unconventional NT’s Gasotransmitters- Nitric oxide- localized to the postsynaptic neuron NOS is activated by Ca2+/calmodulin following Glu activation of NNMDA receptors Inhibitory effect Endocannabinoids- anandamide and 2-arachidonoylglycerol- 2 EC’s receptors → CB1 and CB2 Activation CB1→ inhibition of NT release Regulation of appetite, eating and feeding behavior, sleep, pain relief, motivation, and pleasure. Drugs modify NT for treatment. Parkinson's disease –dopamine L-dopa Amphetamines -ADHD Agonists –antagonists Cocaine Create a table of NTs Neurotransmitter function Problems with excess or deficit E.g. Dopamine Motivation, arousal, Parkingson’s disease reward, and motor control  Guyton and Hall textbook of medical physiology. Hall, John E. (John Edward), 1946. 2021; Fourteenth edition / John E. Hall, PhD, Michael E. Hall, MD, MS.; Guyton and Hall textbook of medical physiology. Physiology Costanzo, Linda S., 1947. 2018; Sixth edition. Essentials of modern neuroscience Amthor, Frank, author. 2020