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PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY 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 realised with 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. 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 1

Peter Pazmany Catholic University Faculty of Information Technology BASICS OF NEUROBIOLOGY Neurobiológia alapjai NEUROTRANSMITTERS I. (Neurotranszmitterek I.) ZSOLT LIPOSITS 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 2

DEFINITION AND CRITERIA OF NEUROTRANSMITTERS NEUROTRANSMITTERS ARE ENDOGENOUS BIOACTIVE SUBSTANCES SYNTHESIZED BY NEURONS. THEY ARE D FROM THE CELLS, ACT VIA SPECIFIC RECEPTORS COUPLED TO THE MEMBRANE OF POSTSYNAPTIC TARGET S AND MODIFY THE ELECTRIC AND METABOLIC CONDITIONS OF THE AFFECTED CELLS. CRITERIA OF CHEMICAL NEUROTRANSMITTERS: 1. THE OF THE CHEMICAL TRANSMITTER TAKES PLACE IN THE PRESYNAPTIC NEURON 2. THE SYNTHESIZED TRANSMITTER OR IT PRECURSOR IS STORED IN THE COMPARTMENT OF THE CELL, MOST FREQUENTLY IN AXON TERMINALS 3. OF THE NEUROTRANSMITTER INTO THE SYNAPTIC CLEFT UPON EXCITATION OF THE PRESYNAPTIC ELEMENT 4. BINDING OF THE TRANSMITTER TO ITS RECEPTOR/S/ THAT BELONG TO IONOTROPIC AND METABOTROPIC CLASSES 5. TERMINATION OF THE ACTION OF TRANSMITTERS AND ITS TRIGGERED MECHANISMS 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 3

CLASSIFICATION OF NEUROTRANSMITTERS THE NEUROTRANSMITTERS BELONG TO TWO MAIN CATEGORIES, THE CLASSIC AMINE TYPE AND THE NON-CLASSIC PEPTIDE TYPE GROUPS COMPARISON OF THE PRODUCTION OF CLASSIC AND NON-CLASSIC TRANSMITTERS TYPE CELL BODY AXON TERMINAL EXAMPLE AMINE PRODUCTION OF 1. SYNTHESIZING ENZYMES 2. VESICLES AXONAL TRANSPORT OF 1. SYNTHESIZING ENZYMES 2. VESICLES SUPPLY OF CONSTITUENTS: 1. FROM CELL BODY 2. LOCAL 3. RE-UPTAKE ACETYLCHOLINE GABA GLUTAMATE SEROTONIN NORADRENALINE PEPTIDE PRODUCTION OF 1. PEPTIDE PRECURSORS 2. CONVERTING ENZYMES 3. VESICLES AXONAL TRANSPORT OF VESICLES SUPPLY OF CONSTITUENTS FROM CELL BODY ENKEPHALIN DYNORPHIN SUBSTANCE P VASOPRESSIN SOMATOSTATIN CHOLECYSTOKININ 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 4

NAME RECEPTORS DOPAMINE 4-(2-AMINOETHYL)BENZENE-1,2-DIOL SYNTHESIZING ENZYMES: CELLULAR L-DOPA TYROSINE HYDROXYLASE (TH), DOPA DECARBOXYLASE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL OF SYNTHESIZING ENZYMES SYNAPTIC VESICLE VESICULAR MONOAMINE -2 (VMAT-2) BY EXOCYTOSIS, PRESYNAPTIC VIA AUTORECEPTORS (D2 FAMILY) BY MONOAMINE OXYDASE (MAO), CATECHOL-O-METHYL TRANSFERASE (COMT), DOPAMINE (DAT) D1-LIKE FAMILY: D1 AND D5 RECEPTORS, G PROTEIN-COUPLED D2-LIKE FAMILY: D2, D3 AND D4 RECEPTORS, G PROTEIN-COUPLED IN NUCLEI OF THE BRAIN STEM AND HYPOTHALAMUS, MESOLIMBIC, MESOCORTICAL, NIGROSTRIATAL, TUBEROINFUNDIBULAR DOPAMINERGIC SYSTEMS COGNITION, ATTENTION, MEMORY, PROBLEM SOLVING, REWARD, MOOD, PROLACTIN SECRETION, PARKINSON DISEASE, SCHIZOPHRENIA, AGING 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 5

DOPAMINERGIC NEURONS IN THE HYPOTHALAMUS DOUBLE IMMUNOCYTOCHEMICAL LABELING REVEALS BLACK, DOPAMINERGIC NEURONS CONTACTING BROWN, CORTICOTROPIN-RELEASING HORMONE-SYNTHE- SIZING NEURONS IN THE PARAVENTRICULAR NUCLEUS 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 6

NAME RECEPTORS NOREPINEPHRINE (NORADRENALINE, NE) 4-[(1R)-2-AMINO-1-HYDROXYETHYL]BENZENE-1,2-DIOL SYNTHESIZING ENZYME CELLULAR DOPAMINE DOPAMINE BETA-HYDROXYLASE TRANS-SYNAPTIC INDUCTION, GLUCOCORTICOIDS SYNAPTIC VESICLE VESICULAR MONOAMINE -2 (VMAT-2) BY EXOCYTOSIS, PRESYNAPTIC VIA AUTORECEPTORS (ALPHA-2) BY MONOAMINE OXYDASE (MAO), RE-UPTAKE BY NOREPINEPHRINE (NET) G PROTEIN-COUPLED RECEPTORS, ALPHA AND BETA TYPES IN THE BAIN: ALPHA 2 INHIBITS ADENYLYL CYCLASE, BETA 1 ACTIVATES IT CELL GROUPS IN THE CAUDAL PART OF THE BRAIN STEM ATTENTION, AROUSAL, STRESS, FEEDING, ANTI DEPRESSION DRUG DEVELOPMENT 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 7

DISTRIBUTION OF CATECHOLAMINERGIC CELL GROUPS IN THE RODENT BRAIN 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 8

NAME Basics of Neurobiology: Neurotransmitters I. SEROTONIN 5-HYDROXYTRIPTAMINE (5-HT) SYNTHESIZING ENZYMES: CELLULAR TRYPTOPHAN TRYPTOPHAN HYDROXYLASE (TPH), AROMATIC L- AMINO ACID DECARBOXYLASE PRECURSOR CONCENTRATION, PHOSPHORYLATION OF TPH SYNAPTIC VESICLE VESICULAR MONOAMINE -2 (VMAT-2) BY EXOCYTOSIS, PRESYNAPTIC VIA AUTORECEPTORS (5-HT 1A ) RECEPTORS BY MONOAMINE OXYDASE (MAO), RE-UPTAKE BY SEROTONIN LIGAND-GATED ION CHANNEL (5-HT 3 ), G PROTEIN-COUPLED RECEPTORS (5-HT 1-2, 5-HT 3-7 ) RAPHE NUCLEI OF THE BRAINSTEM AGGRESSION, OBSESSIVE-COMPULSIVE BEHAVIOR, FEEDING, OBESITY, ANTI DEPRESSION DRUG DEVELOPMENT (SSRI) 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 9

NAME RECEPTORS ACETYLCHOLINE (ACh) 2-ACETOXY-N,N,N-TRIMETHYLETHANAMINIUM SYNTHESIZING ENZYME CELLULAR ESTER OF ACETIC ACID AND CHOLINE CHOLINE ACETYLTRANSFERASE ACTIVITY, ALLOSTERIC INHIBITION, PRECURSOR AVAILABILITY SYNAPTIC VESICLE VESICULAR ACh BY EXOCYTOSIS, MINIATURE END-PLATE POTENTIALS, QUANTAL ACETYLCHOLINESTERASE, CHOLINE NICOTINIC, IONOTROP, LIGAND-GATED ION CHANNEL, EXCITATORY MUSCARINIC, G PROTEIN-COUPLED, M1-M4 BASAL FOREBRAIN, HABENULA, BRAIN STEM LEARNING, MEMORY, ATTENTION, AGING, ALZHEIMER DISEASE 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 10

NAME RECEPTORS GLUTAMATE GLUTAMIC ACID SYNTHESIZING ENZYMES CELLULAR ALPHA-KETOGLUTARATE AND GLUTAMINE AMINOTRANSFERASE, GLUTAMINASE THE GLUTAMINE-GLUTAMATE CYCLE (GLIA- NEURON) SYNAPTIC VESICLE VESICULAR GLUTAMATE (VGLUT1-3) BY EXOCYTOSIS, PRESYNAPTIC VIA AUTORECEPTORS (mglur2, mglur3) NEURONAL AND GLIAL UPTAKE BY PLASMA MEMBRANE GLUTAMATE S IONOTROPIC, AMPA (GluR1-4), KAINATE (GluR5-7, KA1-2), NMDA (NR1, NR2A-2D) METABOTROPIC, G PROTEIN-COUPLED (mglur1-7) THROUGHOUT THE BRAIN LEARNING, PLASTICITY, LONG TERM POTENTIATION, NEUROTOXICITY 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 11

NAME HISTAMINE 2-(1H-IMIDAZOL-4-YL)ETHANAMINE HISTIDINE SYNTHESIZING ENZYMES L-HISTIDINE DECARBOXYLASE PRECURSOR AVAILABILITY CELLULAR SYNAPTIC VESICLE VESICULAR MONOAMINE -2 (VMAT-2) BY EXOCYTOSIS, AUTORECEPTORS HISTAMINE-N-METHYL TRANSFERASE, MAO-B RECEPTORS HISTAMINE RECEPTORS 1-4 TUBERO-MAMMILLARY NUCLEI OF THE CAUDAL HYPOTHALAMUS (E1-5) SLEEP-WAKING CYCLE, PSYCHOMOTOR PERFORMANCE 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 12

NAME RECEPTORS GABA GAMMA -AMINOBUTYRIC ACID SYNTHESIZING ENZYMES CELLULAR L-GLUTAMATE GLUTAMATE DECARBOXYLASE (GAD) ENDPRODUCT BY EXOCYTOSIS, PRESYNAPTIC INHIBITION GABA AMINOTRASNFERASE SYNAPTIC VESICLE VESICULAR GABA (VGAT) GABA A, CHLORIDE CHANNEL, WITH VARIOUS BINDING SITES (GABA, PICROTOXIN, BARBITURATE, BENZODIAZEPINE, STEROID) GABA B DIFFUSELY DISTRIBUTED CELL GROUPS IN THE ENTIRE NEUROAXIS GENERAL INHIBITION AND COUNTERBALANCING OF EXCITATORY ACTIONS, ROLE IN EPILEPSY, ANXIETY AND CONVULSION 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 13

NAME GLYCINE AMINOETHANOIC ACID SYNTHESIZING ENZYMES CELLULAR BY EXOCYTOSIS SERINE SERINE HYDROXYMETHYLTRANSFERASE ENDPRODUCT SYNAPTIC VESICLE NOT KNOWN RECEPTORS CONVERTED TO GLUTATHIONE, GLYCINE S CHLORIDE CHANNEL MOST STUDIES IN THE SPINAL CORD, BRAIN IS A RISING FIELD GENERAL INHIBITION AND COUNTERBALANCING OF EXCITATORY ACTIONS 11/25/2011. TÁMOP 4.1.2-08/2/A/KMR-2009-0006 14