2011.10.14.. 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 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BEVEZETÉS A FUNKCIONÁLIS NEUROBIOLÓGIÁBA INTRODUCTION TO FUNCTIONAL NEUROBIOLOGY www.itk.ppke.hu By Imre Kalló Contributed by: Tamás Freund, Zsolt Liposits, Zoltán Nusser, László Acsády, Szabolcs Káli, József Haller, Zsófia Maglóczky, Nórbert Hájos, Emilia Madarász, György Karmos, Miklós Palkovits, Anita Kamondi, Lóránd Erőss, Róbert Gábriel, Kisvárdai Zoltán Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu RetinaImre Kalló & Róbert GábrielPázmány Péter Catholic University, Faculty of Information Technology I. Photoreception; receptor cells nourished by pigment epithelium II. Connectivity and function of horizontal, bipolar and amacrinecells. III. Ganglion cells and the visual pathway. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu Anatomy of the visual organ. Eyeball.tif Optic disc  Optic nerve  Fovea centralis  Retina  Sclera  Choroid  Ciliary body  Posterior chamber  Anterior eye chamber Aqueous humour  Cornea Pupil  Iris  Suspensory ligaments of the lens  Vitreous humour  Lens  Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu Anatomy of the visual organ. Thehumanvisualorganisapaired,light-proof„box”(eyeballs)withanadjustablediameterpinhole(pupil)onthefrontside.Lightispassingthroughtransparentmediainfront(i.e.tear,cornea,aqueoushumor)andbehind(i.e.thelens,vitreoushumor)thepupiltoreachtheinnerlayeroftheeyeball(retina),wheretheenergyoflightisconvertedtochemico-electricimpulses.Lightfromobjectslocatedbetween25cmtofardistancesisfocusedontotheretinabytheadjustmentoflensconvexity.Theinvertedimageoftheobjectsprojectedtotheretina,howevercanbeprocessedathighresolutiononlyatthecentralfovea,wherelightreachestheconereceptorcellsdirectly. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu Histology of the retina 10 histologicallydistinguishable layers 4 layers of cell bodies (nuclei) 1 layer of pigment cells 1 layer of receptor cells 2 layers of neurons 2 layers of synapses Vertical ”through pathway” Horizontal influence on the information processing retinasema Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu Connectivity of basic cell types of the retina Retina1.tif Retina_connectivity.jpg Rods and cones Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu Path of the light in the eye Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu Photoreceptors Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu Photoreceptor cells: anatomy Duplex retina Rods one (or maybe two) types similar morphology long outer segment closed endomembrane system Cones three, four types –wave-length sensitivity varies from group to group open endomembrane system rodcone Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu Synapses established by the photoreceptor cells I. gabaem2 Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu Synapses established by the photoreceptor cells II. Inner segment Photoreceptor cell terminal „Ribbon” synapse Two pools of synaptic vesicles Presynaptic markers (eg. bassoon, rib eye) Postsynaptic triad cone.jpg diad.jpg Dendrite of the bipolar cells in the middle, processes of horizontal cells laterally „Invaginating” and „flat” connections Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu Photoreceptor cells Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 www.itk.ppke.hu Types of photoreceptor cells Class of cells Types of cells Subtypes Notes PhotoreceptorCells Rods Uniform There are green and red light-sensitive rods in amphibians Cones Cones sensitive for short wave-lengthlight There are UV-sensitivecones in certain species Cones sensitive for long wave-lengthlight Two (green and red) subgroups of cones in primates Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 www.itk.ppke.hu Outer segment events: photochemical reaction Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 www.itk.ppke.hu Outer segment events: sodium channels close -hyperpolarization Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 www.itk.ppke.hu Absorbance maximum of photoreceptor cells Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 www.itk.ppke.hu Light sensitivity of photoreceptors Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 www.itk.ppke.hu Microanatomy of bipolar cells Orientation of bipolar cells: dendritic tree is towards the photoreceptor cells, axon is in the inner plexiform layer (IPL) It connects the external and internal parts of the retina It is crucial for processing the visual information 10 different types of bipolar cells are known in vertebrates xen57dhtlm Photoreceptors Outer plexiform layer Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 www.itk.ppke.hu Types of bipolar neurons Rod-bipolar cells: there are only in mammals Significance: visual reception at low light intensity circumstances Cone-bipolar cells: their sensitivity varies according to the wave-length Depolarizing cells (ON-type) Hyperpolarizing cells (OFF-type) Cells with special receptive field Class of cells Types of cells Subtypes Notes BipolarCells Rod-bipolar cells Uniform Bipolar neurons of amphibians receive afferents from both cones and rods.In a few species there are blue bipolars. ON-typecone-bipolar cells Manyalgroups OFF-type cone-bipolar cells Many algroups Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 www.itk.ppke.hu Bipolar neurons Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 www.itk.ppke.hu Neurochemistry of bipolar neurons rodbipollm Photoreceptors Rod-bipolars: PKC Cone-bipolars: OFF: recoverin ON: mGLUR6 Neurotransmitters used: Glutamic acid Axon terminals: L-type VGCCa Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 RB AII AII ON ON CB OFF OFF GC CB GC AII ON CB www.itk.ppke.hu Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 www.itk.ppke.hu Synaptic connections of bipolar cells in the inner plexiform layer I. bufoiplem2 Axons, ribbon synapses One terminal contains several ribbons, and establishes several outputs Every 8-10thsynapse of the inner plexiform layer is established by bipolar cells Postsynaptic diad Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 www.itk.ppke.hu Synaptic connections of bipolar cells in the inner plexiform layer II. EM_bipolar.jpg Bipolar axons terminals also receive afferents (from amacrine cells) Most of the output is glutamatergic, in contrast the inputs are GABAergic Axon terminals of the bipolar neurons contains both GABAAand GABABreceptors Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 www.itk.ppke.hu Synaptic connections of bipolar cells in the inner plexiform layer III. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 www.itk.ppke.hu Physiology of bipolar cells Hyperpolarising cells: AMPA and KA receptors, sign-conserving ”OFF”cells Depolarising cells: mGLUR6 receptors, sign-inverting ”ON”cells ON-OFF cells: only in non-mammal vertebrates Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 www.itk.ppke.hu Bipolar neurons are sensitive to the size of the enlightenedarea Bipolar response.jpg Transient response turns into sustained response Inhibition originating from the surrounding area decreases (see center/surround organisation) Saturation Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 www.itk.ppke.hu Microanatomy of the horizontal cells Class of cells Types of cells Subtypes Notes Horizontal Cells Cells with axon Uniform group Many species have also chromatic horizontal cells Cells without axon Uniform group calbhc Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 www.itk.ppke.hu Physiology and neurochemistry of the horizontal cells Horiz_Elektro_B.jpg Horiz_Elektro_A.jpg Hyperpolarizing and depolarizing cells Both cell types contain ionotropic glutamate receptors Neurotransmitter of the horizontal cells is GABA Histological marker of the horizontal cells is either PA or CaBP Lateral inhibition, centre-surround organization Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 www.itk.ppke.hu Light on center Center.jpg Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 www.itk.ppke.hu Light on surround Surround.jpg Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 www.itk.ppke.hu Cells of the inner part of the retina I. Class of cells Types of cells Subtypes Notes Amacrine Cells Cells with widedendritic field- cells with narrowdendritic field Severalsubgroups from morphological, physiological and neurochemical point of view The secondcolumn lists classification categories Cells with axon- cellswithout axon Cells generating action potential – cells generating only local potential change Cells located in normal position – Cells displaced Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 www.itk.ppke.hu Bipolar cells Amacrine cells Ganglion cells Glial cells: Müller-cells (K-sipho model) A>A, B>A, A>B, B>G and A>G synapses High complexity Cells of the inner part of the retina II. 5htaccomsema Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 www.itk.ppke.hu Microanatomy of amacrine cells I. diapozitivok 118 diaforaz Cells with narrow and wide dendritic tree About 20-30 different cell types Mosaic organization within the retina Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 www.itk.ppke.hu whamacrhrp There are cells without axons, as well as ones with multiple axons (poliaxonal cells) Diffuse network of processes Many different neurotransmitters, frequent co-localisations Sublayers in the inner plexiform layer (uni-, bi-, tri-and multistratified cells) Microanatomy of amacrine cells II. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 www.itk.ppke.hu Neurochemistry of amacrine cells I. Most of the cells use GABA or glycine, show narrow dendritic tree, and establish multiple synapses – 90% of all amacrine cells major role is inhibition!!!! Cells with medium-sized dendritic tree: acethylcholine (4-6%) orientation-selectivity detection of movement ”starburst” cells: philogenetically conserved cells Neurochemical code system! gabalm GABA-IR Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 38 www.itk.ppke.hu Neurochemistry of amacrine cells II. Monoamines: DA, 5-HT Peptidergic cells: SP, NPY, CCK; most cases these peptide are present as co-transmitter with GABA or glycine Usually they are uni-or bistratified cells Their functions: neuromodulation, eg. light adaption xen5htwm thlmfluo Dopaminergic cell, km Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 www.itk.ppke.hu Neurochemistry of amacrine cells III.: Calcium binding proteins Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 www.itk.ppke.hu Physiology of amacrine cells Sustained and transient On, Off and On-Off Sublaminar distribution of the dendrites is in overlap with the axonal ramifications of the bipolar cells and the dendritic tree of the ganglion cells. Overlap of the morphological and physiological segregation Orientation selectivity fishacfiziolanat Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 www.itk.ppke.hu Amacrine cells I. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 www.itk.ppke.hu Amacrine cells II. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 43 www.itk.ppke.hu Amacrine cells III. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 www.itk.ppke.hu Amacrine cells IV. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 www.itk.ppke.hu Amacrine cells V. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 www.itk.ppke.hu Synapses of the inner plexiform layer xengchrpem gabaem6 Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 www.itk.ppke.hu Microanatomy of ganglion cells Mass filling, HRP injection in the eye Mozaics of cells Dendritic segregation of On and Off cells On-Off cells are present frequently, especially in lower vertebrates hrptoltes4 xengchrplm INL IPL Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 www.itk.ppke.hu Neurochemistry of ganglion cells Neurofilament proteins MAPs On the receiving side: ionotropic and metabotropic glutamate receptors (AMPA, NMDA) IP3 and RyR systems Calciumbinding proteins Neurotransmitter: glutamic acide, certain cells contain neuropeptides (SP, NPY, PACAP): target-specificity! ryr2 RyR-pozitíve GC IPL INL Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 www.itk.ppke.hu Physiology of ganglion cells I. Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 www.itk.ppke.hu Microphysiology of ganglion cells II. • Generation of spikes • Saturation, long-lasting after potentials • Plateau phase, oscillations •X, Y and W cells –anatomy can be brought in correspondence with electrophysiology characteristics Mosaics of ganglion cells, convergence! gcfiziol ON-cell OFF-cell Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 51 www.itk.ppke.hu Microphysiology of ganglion cells III. Tranzient ganglion cells can exhibit both ON and OFF characteristics Ganglion cells are under GABAergic inhibition. Inhibition is mediated through GABAA receptors. retina_alt_1_8 Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 52 www.itk.ppke.hu Centre-surround organization Dendritic field, receptive field Lateral inhibition Horizontal cells, GABA Amacrine cells, GABA and glycine On-centrum, off-centrum Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 53 www.itk.ppke.hu Communication with higher order visual centres Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 54 www.itk.ppke.hu Mozaic of developing retina • Development of central specialization begins already at early stage of ontogenesis. The extent of specialization may vary from animal to animal depending on the territory they occupy Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 55 www.itk.ppke.hu A special mozaic of ganglion cells Elephant: Perpendicular and horizontal specializations Horizontal is present to observe continously the trunk at the highest resolution Primates: central fovea -there are no rods at this site -bipolar cell-ganglion cell connection is in 1:1 Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 56 www.itk.ppke.hu Central mechanisms of vision binocular vision Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 57 www.itk.ppke.hu The lateral geniculate body (CGL, LGN) vis13 Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 58 www.itk.ppke.hu Receptive fields of CGL and V1 cells vis14 Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 59 www.itk.ppke.hu Retinal projection to the visual cortex vis10 Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 60 www.itk.ppke.hu Thank you for your attention Pelikán.jpg Introduction to functional neurobiology: Retina 2011.10.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 61 www.itk.ppke.hu RB AII AII ON ON CB OFF OFF GC CB GC AII ON CB