8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realisedwith the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BASICS OF NEUROBIOLOGY SYNAPTIC COMMUNICATION www.itk.ppke.hu Neurobiológia alapjai (Szinaptikuskommunikáció) ZSOLT LIPOSITS Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu SYNAPTIC COMMUNICATION NEURONAL SIGNALS ARE TRANSMITTED FROM ONE NEURON TO THE NEXT THROUGH INTERNEURONALJUNCTIONS CALLED SYNAPSES THE TERM OF SYNAPSE WAS GIVEN BY CHARLES SHERRINGTON NEURONAL STRUCTURES APPROACH EACH OTHER AND ESTABLISH CLOSE CONNEC-TIONS BY THE JUXTAPOSITION OF THEIR CELL MEMBRANE-COVERED PARTS.THE INTERACTING ELEMENTS ARE IN CONTIGUITY THERE ARE TWO DIFFERENT TYPES OF SYNAPSES: THE CHEMICAL SYNAPSE AND THE ELECTRICAL SYNAPSE THE CHEMICAL SYNAPSE IS THE DOMINANT FORM OF COMMUNICATION IN THE CNS OF HUMANS. CHEMICAL SUBSTANCES CALLED NEUROTRANSMITTERS MEDIATE THE INFORMATION FROM ONE CELL TO THE OTHER. THE SYNAPSING ELEMENTS ARE SEPARATED BY THE SYNAPTIC CLEFT IN CASE OF ELECTRICALSYNAPSES THE EXTRACELLULAR SPACE NARROWS AND THE INTERACTING MEMBRANES GET COUPLED BY GAP JUNCTIONS. AT THE GAPS,THE INTERACTING ELEMENTS ARE IN CONTINUITY, ALTHOUGH THE OPENING OF THE PORES IS REGULATED. Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu CHEMICAL SYNAPSE PRINCIPAL OF ONE WAY CONDUCTION. IT MEANS THAT THE INFORMATION TRANSFER BETWEEN THE SYNAPSING ELEMENTS OCCURS IN ONE DIRECTION SPREADINGEXCLUSIVELY FROM THE PRESYNAPTIC STRUCTURE TO THE POSTSYNAPTIC ELEMENT THE HUMAN BRAIN POSSESSES ABOUT 1014TO 5 ×1014 SYNAPSES MAIN CHARACTERISTICS OF CHEMICAL NEUROTRANSMISSION INCLUDE: 1. THE SYNTHESIS OF THE CLASSIC NEUROTRANSMITTERS TAKES PLACE IN THE PRESYNAPTIC AXON TERMINAL 2. THE CLASSIC AND PEPTIDE NEUROTRANSMITTERS ARE STORED IN SYNAPTIC VESICLES AND GRANULES FORMING A RELEASABLE POOL OF BIOACTIVE MESSENGER SUBSTANCES 3. UPON ACTIVATION OF THE PRESYNAPTIC ELEMENT, THE NEUROTRANSMITTERS ARE RELEASED INTO THE SYNAPTIC CLEFT 4. BINDING AND RECOGNITION OF NEUROMESSENGERS BY SPECIFIC RECEPTORS OF TARGET STRUCTURES 5. TERMINATION OF THE SYNAPTIC EVENTS, INACTIVATION OF TRANSMITTERS Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu SCHEMATIC STRUCTURE OF THE CHEMICAL SYNAPSE PRESYNAPTIC ELEMENT POSTSYNAPTIC STRUCTURE GLIAL PROCESS TIGHT JUNCTION CALCIUM CHANNEL SYNAPTIC VESICLE PEPTIDERGICGRANULE RE-UPTAKE PUMP SYNAPTIC CLEFT TRANSMITTER RECEPTORS POSTSYNAPTIC PROTEINS THE DARK BLUE ARROW INDICATES THE DIRECTION OF ONE-WAY CONDUCTION Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu CELLULAR EVENTS OF SYNAPTIC INFORMATION TRANSFER THOUSANDS OF AXON BOUTONS TERMINATE ON THE DENDRITIC TREE AND SOMATA OF TARGET NEURONS CARRYING EXCITATORY AND INHIBITORY SIGNALS THE INTEGRATED MEMBRANE POTENTIAL REACHING THE THRESHOLD EVOKES AN ACTION POTENTIAL IN THE PRESYNAPTIC CELL WHICH IS PROPAGATED TOWARD ITS AXON TERMINAL THE ACTION POTENTIAL OPENS THE VOLTAGE-GATED CALCIUM CHANNELS IN THE TERMINAL ALLOWING THE INFLUX OF CALCIUM CALCIUM ACTIVATES THE PROTEIN MACHINERIES OF SYNAPTIC VESICLE DOCKING RESULTING IN THE EXOCYTOSIS OF VESICLES THE NEUROTRANSMITTER IS RELEASED INTO THE SYNAPTIC CLEFT THE NEUROTRANSMITTER ACTS ON THE POSTSYNAPTIC MEMBRANE ACTIVATING ION CHANNELS AND RECEPTOR-COUPLED INTRACELLULAR MESSENGER SYSTEMS AFTER THE ACTION, THE NEUROTRANSMITTER GETS INACTIVATED IN THE SYNAPTIC CLEFT BY BREAKDOWN OR UNDERGOES RE-UPTAKE Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu STRUCTURAL CLASSIFICATION OF CHEMICAL SYNAPSES THE INTERACTING NEURONAL ELEMENTS ESTABLISH A WIDE VARIETY OF SYNAPSES UTILIZING ALMOST ALL FORMS OF COMBINATION THE MOST FREQUENT TYPES OF SYNAPTIC COMMUNICATION INCLUDE: 1. AXO-DENDRITICSYNAPSE: AXON TERMINATING ON THE DENDRITICSHAFT 2. AXO-SPINOUSSYNAPSE: AXON TERMINATING ON DENDRITICSPINE 3. AXO-SOMATICSYNAPSE: AXON TERMINATING ON CELL BODY 4. AXO-AXONICSYNAPSE: AXON TERMINATING ON PRESYNAPTICAXON 5. DENDRO-DENDRITICSYNAPSE: DENDRITE COMMUNICATINGWITH DENDRITE BASED UPON THE CHARACTERISTICS OF THE PRE-AND POSTSYNAPTIC MEMBRANES SYNAPSES ARE CLASSIFIED INTO TWO CATEGORIES: I.ASYMMETRIC SYNAPSEII.SYMMETRIC SYNAPSE (GRAY TYPE 1) (GRAY TYPE 2) D A A Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu EXCITATORY SYNAPSES THEY RELEASE EXCITATORY NEUROTRANSMITTERS LIKE ACETYLCHOLINE, SEROTONIN, DOPAMINE, NORADRENALINEAND HISTAMINE EXCITATORY TRANSMITTERS INCREASE THE MEMBRANE’SPERMEABILITYYTONa+ THE SODIUM INFLUXRESULTS IN THE INCREASE OF THE RESTING MEMBRANE POTENTIAL: EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP) THE EXCITATORY POSTSYNAPTIC POTENTIALS ARE GRADED THE EPSP-S ARE SUBJECT OF SPATIAL AND TEMPORAL SUMMATION MECHANISMS THAT INCREASE THE PROBABILITY OF EVOKING ACTION POTENTIAL FIRINGIN THE POSTSYNAPTIC NEURON EXCITATORY SYNAPSES GENERALLY CARRY SPHERICAL SYNAPTIC VESICLES WITH 30-40 nm DIAMETER THE FORMED SYNAPTIC SPECIALIZATIONS ARE ASYMMETRIC IN NATURE WITH PROMINENT THICKENING OF THE POSTSYNAPTIC MEMBRANE Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu THE INHIBITORY SYNAPSE THE AXONS RELEASE INHIBITORY NEUROTRANSMITTERS LIKE GAMMA-AMINOBU-TYRIC ACID (GABA) AND GLYCINE. IN CERTAIN SYSTEMS AND DEVELOPMENTAL PERIODS, SOME NEUROTRANSMITTERS CAN ALSO ACT IN AN OPPOSITE MANNER INHIBITORY TRANSMITTERS OPEN POTASSIUM AND/OR CHLORIDE CHANNELS THE EFFLUX OF POTASSIUM AND/OR THE INFLUX OF CHLORIDE IONS RESULT IN THE DECREASE OF THE RESTING MEMBRANE (HYPERPOLARIZATION). THE VOLTAGE IS CALLED INHIBITORY POSTSYNAPTIC POTENTIAL (IPSP) THE INHIBITORY POSTSYNAPTIC POTENTIALS ARE ALSO GRADED THE IPSP-S ARE SUBJECT TO SPATIAL AND TEMPORAL SUMMATION MECHANISMS WITH OTHER IPSP-sAND WITH EPSP-s INHIBITORY SYNAPSES GENERALLY CARRY FLATTENED SYNAPTIC VESICLES THE FORMED SYNAPTIC SPECIALIZATIONS ARE SYMMETRIC IN NATURE. THEPRE-AND POSTSYNAPTIC MEMBRANE REGIONS ARE EQUAL IN THICKNESS Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu SPECIAL FEATURES OF SYNAPTIC COMMUNICATION SYNAPTIC DELAY. DELAY IN THE TRANSFER OF INFORMATION FROM ONE NEURON TO THE OTHER. IT IS ABOUT 0.5 MILLISECOND. PRIMARILY DUE TO THE DURATION OF ACTIONS IN THE SYNAPTIC CLEFT AND AT THE POSTSYNAPTIC MEMBRANE SYNAPTIC STRENGTH. IT IS DEFINED BY THE CHANGE IN TRANSMEMBRANE POTENTIAL RESULTING FROM ACTIVATION OF THE POSTSYNAPTIC NEUROTRANS-MITTER RECEPTORS FATIGUE OF SYNAPTIC TRANSMISSION. OVERSTIMULATION OF EXCITATORY SYNAPSES REPETITIVELY AT A RAPID RATE INDUCES A COMPENSATORY MECHANISM MANIFESTED IN A GRADUAL DECLINE OF DISCHARGES OF THE POSTSYNAPTIC NEURON POST-TETANIC FACILITATION. IN THE REST PERIOD AFTER A REPETITIVE, TETANIC STIMULATION THE SYNAPSE MIGHT BECOME EVEN MORE RESPONSIVE TO SUBSEQUENT STIMULATION THAN NORMALLY. IT MAY LAST FOR SECONDS OR MINUTES. THIS MECHANISM CONTRIBUTES TO SHORT TERM MEMORY STORAGE Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu SYNAPTIC TYPES IN SOME SPECIAL NETWORKS OF THE CNS BOUTON-TYPE SYNAPSE. THE AXON EXHIBITSSIGNIFICANTLY ENLARGED, SPHERICAL AXON TERMINALS, SO CALLED BOUTONS. INNERVATION OF SPINAL MOTONEURONS REPRESENTS THIS CONNECTION TYPE EN PASSANT SYNAPSE. THE AXON ESTABLISHES SEVERAL SYNAPSES ALONG ITS COURSE WITHOUT BRANCHING INTO AXON TERMINALS. DENDRITIC SPINESOF PURKINJE CELLS RECEIVE INFORMATION FORM GRANULE CELLS THIS WAY BASKET-LIKE SYNAPSE. THE TERMINATING AXONS FORMBASKET LIKE STRUCTURES AROUND THE BASE OF THE CELL AT THE AXON HILLOCK REGION. INNERVATIONOF PURKINJE CELLS BY BASKET NEURONS PARALLEL CONTACTS. THE AXONS CLIMB AND WIND AROUND THE INNERVATED CELL. CLIMBING FIBERS TERMINATE THIS WAY ON PURKINJE CELLS GLOMERULAR SYNAPSE. HAS A COMPLEX ARCHITECTURE IN WHICH MULTIPLE DENDRITES RECEIVE INFORMATION FROM THE SAME, TERMINATING LARGE-SIZED AXON. THE INTERACTING STRUCTURES FIT EACH OTHER LIKE COGWHEELS. SYNAPSES FORMED BY MOSSY FIBERS AND GRANULE CELL DENDRITES IN CEREBELLUM Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu ELECTRICAL SYNAPSE AT ELECTRICAL SYNAPSE SITES, THE INTERACTING NEURAL ELEMENTS ARE COUPLED BY GAP JUNCTIONS WITH EACH OTHER THE INTERCELLULAR SPACE (20 nm) REDUCES CONSIDERABLY IN SIZE AT THE GAPS (2.7nm) GAP JUNCTIONS ARE COMPOSED OFCONNEXONS. THE INTERACTING MEMBRANES PROVIDE HEMI-CONNEXONS FOR ESTABLISHING THE CHANNELS THE ELECTRICAL SYNAPSES TRANSMIT SIGNALS IN A BIDIRECTIONAL MANNER THERE IS NO SYNAPTIC DELAY IN THE INFORMATION TRANSFER THE OPENING OF THE PORE OF CONNEXONS IS REGULATED BY THE INTRACELLULAR CALCIUM LEVEL. HIGH CALCIUM CONCENTRATION CLOSES THE PORES CELLS COUPLED BY ELECTRICAL SYNAPSES CAN BE DETECTED BY INTRACELLULAR DELIVERY OF THE DYE, LUCIFER YELLOW. IT PASSES THROUGH THE PORES Nexusdemo CELLS (A, B) ESTABLISHING AN ELECTRICAL SYNAPSE (ARROW) A B A D C B Basics of Neurobiology: Synaptic communication 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu COMPARISON OF CHEMICAL AND ELECTRICAL SYNAPSES FEATURE ELECTRICAL SYNAPSES CHEMICAL SYNAPSES Distance between pre-and postsynaptic cell membranes 3.5 nm 30-50 nm Cytoplasmic continuity between pre-and postsynaptic cells Yes No Ultrastructural components Gap junction channels Presynaptic active zones and vesicles; postsynaptic receptors Agent of transmission Ionic current Chemical transmitter Synaptic delay Virtually absent Significant: at least 0.3 ms, usually 1-5 ms or longer Direction of transmission Usually bidirectional Unidirectional