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 CYTOARCHITECTURE OF CEREBRAL CORTEX www.itk.ppke.hu Neurobiológia alapjai (Agykéreg szerkezete) ZSOLT LIPOSITS Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu CELLULAR COMPOSITION OF THE CEREBRAL CORTEX THE CEREBRAL CORTEX CONSISTS OF THE ARCHICORTEX (HIPPOCAMPALFORMA-TION), PALEOCORTEX (OLFACTORY AREAS) AND NEOCORTEX THE NEOCORTEX IS COMPRISED OF SIX SUPERIMPOSED LAYERS. THERE AREABOUT 1010 NEURONS IN THE CEREBRAL CORTEX THE CORTEX IS BUILT UP BY PRINCIPAL, PYRAMIDAL NEURONS, INHIBITORY INTER-NEURONS AND GLIA CELLS THERE ARE VARIATIONS IN THE CYTOARCHITECTURE OF THE CORTEX. THE PRIMA-RYSENSORY CORTEX IS GRANULAR, THE PRIMARY MOTOR CORTEX IS RATHER AGRANULAR IN NATURE THE INCOMING SUBCORTICAL AND CORTICAL AFFERENTS HAVE SPECIAL TERMINA-TIONPATTERNS. THEY TRANSFER THE INFORMATION TO INTERNEURONS, THAT RE-LAY IT FURTHER TO PRINCIPAL CELLS NEURONS INTERACTING LOCALLY ARE ORGANIZED IN COLUMNS CALLED CORTICAL MODULES Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu ORGANIZATION OF NEURONS IN CORTICAL LAYERS F 1. MOLECULAR LAYER 2. EXTERNAL GRANULAR LAYER 3. EXTERNAL PYRAMIDAL LAYER 4. INTERNAL GRANULE LAYER 5. INTERNAL PYRAMIDAL LAYER 6. MULTIFORM LAYER NEURONS FIBERS Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu HISTOLOGY OF CEREBRAL CORTEX CORTICAL SECTIONS STAINED BY CONVENTIONAL HEMATOXYLIN-EOSIN (A) AND TOLUIDINE BLUE (B). NOTE, THE THICK LAYER IV IN THE VISUAL CORTEX (C) ctx%20CV A B nissl2 I. II. III. IV. V. VI. C Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu THE PYRAMIDAL NEURON C A B CELL BODY APICAL DENDRITE DENDRITIC TREE BASAL DENDRITES AXON COLLATERAL AXON AS IT IS SHOWN IN PICTURE A DRAWN BY RAMON Y CAJAL, THE CEREBRAL CORTEX IS RICH IN PYRAMIDAL NEURONS OF DIFFERENT SIZES. FIGURE B DEPICTS A GOLGI-IMPREGNATED PYRAMIDAL NEURON. NOTE, THE RAMIFICATIONOFTHE BASAL AND APICAL DENDRITES. FIGURE C ILLUSTRATES THE MAIN STRUCTURAL DOMAINS OF THE SPINY, PYRAMIDAL NEURON Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu FEATURES OF INTERNEURONS THERE ARE SEVERAL KINDS OF INHIBITORY INTERNEURONS CLASSIFIED BASEDON THEIR STRUCTURAL, ELECTROPHYSIOLOGICAL AND CHEMICAL PROPERTIES. THE RICH PHENOTYPE OF THEM IS DEPICTED IN FIG A. THE MOST KNOWNREPRESENTATIVESOF INTERNEURONS ARE THE BASKET, CHANDELIER, STELLATE, RETZIUS-CAJALAND MARTINOTTICELLS. FOR A DEEPER INSIGHT SEE NATURE REVIEWS NEUROSCIENCE , VOLUME 9, 2008, 565. INTERNEURONS ESTABLISH SOPHISTICATED CIRCUITS WITH PRINCIPAL NEURONS (B) AND RELAY THE INFORMATION BROUGHT IN BY SPECIFIC AND NON-SPECIFIC AFFERENTS TOPYRAMIDAL CELLS Cerebral Cortex.tiff A B Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu PROPERTIES OF CORTICAL INTERNEURONS Physiological features • Passive or subthreshold parameters: resting membrane potential; membrane time constants; input resistance; oscillation and resonance; rheobase and chronaxie; rectification • Action potential (AP) measurements: amplitude; threshold; half-width; afterhyperpolarization; afterdepolarization; changes in AP waveform during train. • Dendritic back-propagation • Depolarizing plateaus • Firing pattern: oscillatory and resonant behaviour; onset response to depolarizing step; steadystate response to depolarizing step • Response to hyperpolarizing step: rectification; rebound • Spiking recorded extracellularly: phase relationship to oscillations; functional response specificity; cross-correlation and other dynamics • Postsynaptic responses: spontaneous and evoked; ratio of receptor subtypes; spatial and temporal summation; short-and long-term plasticity; gap junctions Morphological features • Soma: shape; size; orientation; other • Dendrite: arborization polarity; branch metrics; fine structure; postsynaptic element; other • Axon: initial segment; arbor trajectory; terminal shape; branch metrics; boutons; synaptic targets; other • Connections: chemical and electrical; source; location and distribution; other Molecular features • Transcription factors • Neurotransmitters or their synthesizing enzymes • Neuropeptides • Calcium-binding proteins • Receptors: ionotropic; metabotropic • Structural proteins • Cell-surface markers • Ion-channels • Connexins • Transporters: plasma membrane; vesicular • Others Summary of the the Petilla Interneuron Nomenclature Group Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu NEURONAL ASSEMBLY OF A CORTICAL MODULE 300 MICROMETER CORTICO-CORTICAL AFFERENT SPECIFIC AFFERENT THE CORTICAL COLUMN IS ABOUT 300 MICROMETER WIDE AND HAS THE HEIGHT OF THE CORTEX (2.5-3 mm). EACH HOSTS ABOUT FIVE THOUSAND NEURONS. THERE ARE APPROXIMATELY 2x106CORTICAL MODULES IN HUMANS. THE SYSTEM SPECIFIC AFFERENTS AND THE CORTICO-CORTICAL AFFERENTS FEED THE CORTICAL COLUMNS. THE FORMER FIBERS TERMINATE IN THE MIDDLE AREA, THE LATTER ONES IN THE SUPERFICIAL ZONE OF THE COLUMN. A FEW KINDS OF INTERNEURONS ARE SHOWN IN SOLID BLACK IN THE ORIGINAL FIGURE OF J. SZENTÁGOTHAI. CHANDELIER CELLS ARE HIGHLIGHTED IN GREEN. THEIR AXONS FORM AXO-AXONIC CONNECTIONS WITH PYRAMI-DAL NEURONS. AT THE TOP AND THE BASE OF THE COLUMN THE EXCITATION SPREADS LATERALLY, WHILE IN THE MIDDLE PART THE LATERAL INFORMATION FLOW IS LIMI-TED. THE OUTFLOW FROM THE COLUMN IS EXECUTED BY AXONS OF PYRAMID CELLS. LAYER III CELLS PROJECT TO CORTICAL REGIONS AS ASSOCIATIVE AND COMMISSURAL FIBERS, WHILE THE LARGE BETZ PYRAMIDAL NEURONS OF LAYER V ESTABLISH THE DESCENDING CONNECTIONS Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu COMMUNICATION AMONG CORTICAL MODULES F MIDLINE OF THE BRAIN A B FIGURE A SHOWS THE IPSI-AND CONTRALATERAL CONNECTIONS OF MODULES ESTABLISHING CORTICO-CORTICAL NETWORKS. INHIBITORY NEURONS OF ACTI- VE CORTICAL COLUMNS (HIGHLIGHTED IN YELLOW) ARE SURROUNDED BY INAC- TIVE ONES (RED HIGHLIGHT). THE COLLATERAL INHIBITION IS DUE TO BASKET CELLS. FIGURE B DEPICTS THE PROPOSED FUNCTIONAL SHAPE (DASHED LINE) OF THE MODULE Basics of Neurobiology: Cytoarchitecture of cerebral cortex CORTICAL AREA FUNCTION PREFRONTAL CORTEX PROBLEM SOLVING, EMOTION, COMPLEX THOUGHT MOTOR ASSOCIATION CORTEX COORDINATION OF COMPLEX MOVEMENT PRIMARY MOTOR CORTEX INITIATION OF VOLUNTARY MOVEMENT PRIMARY SOMATOSENSORY CORTEX RECEIVES TACTILE INFORMATION FROM THE BODY SENSORY ASSOCIATION AREA PROCESSING OF MULTISENSORY INFORMATION VISUAL ASSOCIATION AREA COMPLEX PROCESSING OF VISUAL INFORMATION VISUAL CORTEX DETECTION OF SIMPLE VISUAL STIMULI WERNICKE'S AREA LANGUAGE COMPREHENSION AUDITORY ASSOCIATION AREA COMPLEX PROCESSING OF AUDITORY INFORMATION AUDITORY CORTEX DETECTION OF SOUND QUALITY (LOUDNESS, TONE) MOTOR SPEECH CENTER(BROCA'S AREA) SPEECH PRODUCTION AND ARTICULATION 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu DIFFERENT FUNCTIONAL OUTPUTS OF CORTICAL MODULES OF DIFFERENT BRAIN REGIONS Basics of Neurobiology: Cytoarchitecture of cerebral cortex 8/8/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu LOCALIZATION OF CORTICAL FUNCTIONS n_petbrainfunc_5 restbrain n_petbrainfunc_3 A B C NON-INVASIVE, RADIOLOGICAL IMAGING TECHNIQUES (PET, FMRI) ALLOW THE LOCALI- ZATION OF SPECIFIC BRAIN FUNCTIONS IN WELL-DEFINED REGIONS. THE SCANS SHOW BRAIN ACTIVITIES UNDER NORMAL (A), THINKING (B) AND SOMATIC MOTOR (C) CONDITIONS