8/8/2011. 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 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. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BASICS OF NEUROBIOLOGY HIPPOCAMPAL FORMATION Neurobiológia alapjai (Hippocampális rendszer) ZSOLT LIPOSITS www.itk.ppke.hu Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu CHARACTERISTICS OF THE HIPPOCAMPAL FORMATION THE HIPPOCAMPAL FORMATION IS PART OF THE LIMBIC SYSTEM OF THE BRAIN IT IS COMPOSED OF THE DENTATE GYRUS AND THE HIPPOCAMPUS (CORNU AMMO-NIS). THE COMPLEX STRUCTURE BELONGS TO THE ALLOCORTEX THE HIPPOCAMPUS IS DIVIDED INTO3 SECTORS: CA1 (SOMMER’S SECTOR), CA2 AND CA3. THERE ARE 3 CYTOARCHITECTURAL LAYERS IN THE HIPPOCAMPUS: THE MOLE-CULAR, THE PYRAMIDAL AND THE POLYMORPHIC (ORIENS) LAYERS THE DENTATE GYRUSCOMPRISESTHE MOLECULAR LAYER, THE GRANULE CELL LAY-ER AND THE HILUS. IN ITS SUBGRANULAR ZONE ADULT NEUROGENESIS OCCURS AFFERENTS ARRIVE VIA THE PERFORANT AND ALVEAR PATHS, EFFERENT FIBER PRO-JECTIONS LEAVE THE TEMPORAL LOBE VIA THE FORNIX SYSTEM. IT GIVESRISE TO BOTH ASSOCIATIVE AND COMMISSURAL EFFERENTS. THE HIPPOCAMPUS VIA THE LIMBIC CONNECTIONS IS LINKED WITH MULTIPLE BRAIN NETWORKS INFORMATION CONVEYED BY THE PERFORANT PATH IS PROCESSED IN A TRISYNAP-TIC INTRINSIC CIRCUIT WITHIN THE HIPPOCAMPAL FORMATION THE HIPPOCAMPUS HAS A PIVOTAL ROLE IN LONG TERM MEMORY AND SPATIAL NAVIGATION. IT IS VULNERABLE TO HYPOXIA, EXCITOTOXINS AND AMYLOID Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu MACROSCOPIC PROPERTIES OF THE HIPPOCAMPUS FOR A FIRST IMPRESSION, THE SUPERIOR VIEW OF A HORIZONTALLY SLICED BRAIN IS USEFUL. THE HIPPOCAMPUSIS A C-SHAPED, PAIRED STRUCTURE LOCATED IN THE TEMPORAL LOBE. ANTERIOR TO IT IS THE AMYGDALA, IN DORSAL DIRECTION THE LENTIFORM NUCLEUS IS A CLOSE NEIGHBOR. THE STRUCTURE PROTRUDES INTO THE INFERIOR HORN OF THE LATERAL VENTRICLE. ITS EFFERENT AND AFFERENT PATHS FORM THE FORNIX. IT BEGINS AS A THIN CRUS, CONTINUES AS CORPUS AND TERMINATES AS COLUMNSPLITTING INTO PRE-AND POST-COMMIS-SURAL COMPONENTS THAT TERMINATE IN THE SEPTUM AND HYPOTHALAMUS. FIBERS INTERCONNECTING THE TWO HIPPOCAM-PAL STRUCTURES FORM DAVE’S LYRE Gray748.png 2 1 3 4 1. LATERAL VENTRICLE2. HIPPOCAMPUS 3. FORNIX 4. COMMISSURA FORNICIS Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu DEVELOPMENT OF THE HIPPOCAMPAL FORMATION ILLUSTRATION OF THE DEVELOPMENTAL EVENTS OF THE TEMPORAL LOBE WITH SPECIAL REFERENCE TO THE ESTABLISHMENT OF THE HIPPOCAMPAL FORMATION. ARROWS POINT TO THE HIPPOCAMPAL FISSURE GYRUS DENTATUS HIPPOCAMPUS SUBICULUMAND ENTORHINALCORTEX TEMPORAL LOBE Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu A.CORONAL RADIOLOGICAL PICTURE DEPICTS THE BRAIN IN SITU. IN THE TEMPORAL LOBE (GREEN HIGHLIGHT), THE HIPPOCAMPAL FORMATION APPE-ARS (ENFRAMED). LENTIFORM NUCLE-US IS IN PINK HIGHLIGHT A B B.CORONAL SECTION THROUGH THE HUMAN HIPPOCAM-PAL FORMATION. THE ENTORHINAL CORTEX (1) SHOWS A GRADUAL STRUCTURAL TRANSITION TOWARD THE SUBI-CULUM( 2). THE HIPPOCAMPUS (3) WITH ITS 3 LAYERS IS APPARENT. NOTEAS THE HIPPOCAMPUS INVADES THE DENTATE GYRUS (4) THROUGH ITS HILUS. THE IMPORTANT HIPPOCAMPAL FISSURE (5) IS HIGHLIGHTED IN BLUE. A NEIGHBORING LANDMARK IS THE CHOROID FISSURE (6) 1 2 3 4 5 6 ORGANIZATION OF THE HIPPOCAMPAL FORMATION IN SITU Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu HIPPOCAMPUS REVEALED BY GOLGI IMPREGNATION A CORONAL SLICE (B) CUT FROM THE HIPPO-CAMPUS (A) WAS IMPREGNATED BY THE GOLGI TECHNIQUE. IT VISUALIZES THE CELLULAR CONSTITUENTS INCLUDING THE PYRAMIDAL NEURONS (C). THE DRAWING (D) OF C. GOLGI MADE ABOUT HIS PREPARATION REVEALS THE PYRAMIDAL LAYER OF THE HIPPOCAMPUS (1), THE ENTORHINAL CORTEX (2) AND THE DENTATE GYRUS (3) 3 ca1pyr hip7.jpg A B C 5 D 2 1 3 Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu LAYERS AND CELL TYPES OF THE HIPPOCAMPUS PRINCIPAL, PYRAMIDAL NEURONS AND INHIBI-TORY INTERNEURONS SUCH AS O-LM CELLS, BASKET CELLS AND BISTRATIFIED CELLS OCCUPY THE MAIN LAYERS OF THE HIPPOCAM-PUS. THE FIGURE ON LEFT SIDE SUMMARIZES THE PHENOTYPE, CHEMOTYPE AND CONNECTI-ONS OF INTERNEURONS THAT HAVE BEEN IDENTIFIED (J PHYSIOL, 2005 VOL. 562, 9-26) STR. LACUNOSUM- MOLECULARE STR. RADIATUM STR. PYRAMIDALE STR. ORIENS PYRAMIDAL NEURON O-LM CELL BASKET CELL BISTRATIFIED CELL hipcell type j Physiolgif.gif COURTESY OF P. SOMOGYI’SLABORATORY Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu HISTOLOGICAL AND CHEMICAL DISSECTION OF THE DENTATE GYRUS hip5.gif hip12.jpg Nature Reviews Neuroscience 7, 259-268, 2006 MOLECULAR LAYERGRANULE CELL LA YERHILUS GRANULE CELLS MOSSY FIBERS CA3 PYRAMIDAL CELLS Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu THE INTRINSIC CIRCUITS AND CONNECTIONS OF THE HIPPOCAMPAL FORMATION NUMBERS IN RED (1-3) INDICATE COMMUNICATION SITES OF THE TRI-SYNAPTIC CIRCUIT 1 2 3 DENTATE GYRUS CA3 CA1 CA2 SCHAFFER COLLATERAL ALVEUS MOSSY FIBER PERFORANT PATH SUBICULUM ENTORHINAL CORTEX EXTRINSIC AFFERENTS FORNIX Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu MAIN AFFERENT INPUTS ARRIVE FROM ENTORHINAL CORTEX VIA THE PERFORANT AND ALVEAR PATHS, THE SEPTUM, THE CONTRALATERAL HIPPOCAMPUS AND THE RETICULAR FORMATION. EFFERENTSARE SENT TO THE SOURCES OF AFFERENT INPUTS. THE FORNIX IS THE MAIN PROJECTING EFFERENT SYSTEM TO THESEPTUM, SUBSTANTIA INNOMINATA, ANTERIOR HYPOTHALAMUS AND THE MAMMILLARY BODY SEPTUM SUBICULUM ENTORHINAL AFFERENTS EFFERENTS AFFERENT AND EFFERENT CONNECTIONSOF THE HIPPOCAMPUS Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu INTEGRATION OF THE HIPPOCAMPUS WITHIN THE LIMBIC SYSTEM THE MAIN LIMBIC STRUCTURESARE HIGHLY INTEGRATED WITH EACH OTHER. A PROMINENT FOR- MATIONIS THE CIRCUIT (RING) OF PAPEZ. IT INVOLVES THE CONNECTIONS AND PROJECTIONS OF THE HIPPOCAMPALFORMATION WITH EMPHASIS ON THE LINK WITH THE MAMMILLARY BODY. THIS NUCLEUS PROJECTS VIA THE THALAMUS TO THE CINGULATE CORTEX THAT IS KNOWN TO FEED BACK TO ENTORHINAL CORTEX. A DESCENDING UNIT IS CALLED THE MAMILLOTEGMEN- TAL FASCICULUS ORIENTED MAINLY TO THE RAPHE NUCLEI AND THE RETICULAR FORMATION Basics of Neurobiology: Hippocampal formation 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu FUNCTIONAL CORRELATES OF THE LIMBIC SYSTEM PHYSIOLOGICAL CORRELATES 1. PLACE CELLS2.THETA RHYTHM3.SHARP WAVES 4.LONG TERM POTENTIATION (LTP)5.SHORT TERM POTENTIATION 6.LEARNING 7.SPATIAL MEMORY8.MORRIS WATER MAZE9.EMOTIONS 10.BEHAVIOR PATHOLOGICAL CORRELATES 1. ANXIETY2. DEPRESSION3.EPILEPSY 4. SCHIZOPHRENIA5.AMNESIA 6. KORSAKOFF’S PSYCHOSIS7.ABNORMAL SEXUAL ACTIVITY8.ABNORMAL APPETITE 9.AGING 10.ALZHEIMER DISEASE