Conexinele, undele Conexinele, undele Conexinele, undele Conexinele, undele de calciu si de calciu si mielinizareamielinizarea

Dumitru Andrei IacobasDumitru Andrei Iacobasdiacobas@aecom.yu.edudiacobas@aecom.yu.edu

Joseph C. Arezzo, Professor: Electrophysiological analysis of cortical and subcortical mechanisms associated with sensorimotor processes in behaving monkeys; neurologic function in mutant mice.Thaddeus A. Bargiello, Professor: Molecular genetics and biophysics of gap junction channels; structure-function relationships and biological roles.Michael V.L. Bennett, Professor: Chemical and electrical synapses; structure-function studies of connexins and glutamate receptors; physiological roles analyzed by gene knock outs.Feliksas Bukauskas, Professor: Gap junction channel formation and gating.Reed Carroll, Associate Professor: Molecular mechanisms underlying synaptic plasticty.Pablo Castillo, Associate Professor: Synaptic transmission, modulation and plasticity; the properties of excitatory and inhibitory synapses in themammalian brain and the mechanisms of synaptic plasticity during developmentand in learning and memory.Kostantin Dobrenis, Assistant Professor: Novel approaches to treatment of diseases affecting the CNS; microglial biology: lineage, secretion, receptor systems, and interactions with neurons.Anne M. Etgen, Professor: Cellular and molecular mechanisms of steroid hormone action in brain; steroid receptors; steroid-monoamine interactions; steroids and amino acid neurotransmission.Donald S. Faber, Professor and Chair: Functional organization and adaptive properties of central synapses; mechanisms of action of neuromodulators; neural correlates of sensorimotor behavior and its plasticity.Anna Francesconi, Assistant Professor: Cellular and molecular mechanisms of neurotransmitter receptor trafficking; the role of lipid rafts in synaptic trafficking and signaling. David H. Hall, Professor: Correlative fine structure and serial section reconstruction at the electron-microscopic level; morphology of nervous system mutants of Caenorhabditis elegans.

Faculty with primary appointments in the DP Purpura Dept of Faculty with primary appointments in the DP Purpura Dept of Neuroscience and their research interestsNeuroscience and their research interests

Caenorhabditis elegans.Jean Hbert, Associate Professor: Genetic and molecular mechanisms required for neural stem and progenitor cells to generate the forebrain in development, and regenerate it in adulthood.Dumitru Andrei Iacobas, Assistant Professor: Comparative genomics and mathematical modeling of intercellular signaling in normal, transgenic and diseased nervous structures. Bryen Jordan, Assistant Professor: Exploring synaptic function and activity-dependent synapse-to-nucleus signaling.Kamran Khodakhah, Professor: Dendritic integration and neuronalcomputation; the role of calcium in regulation of excitability and synapticplasticity.Adam Kohn, Assistant Professor: Visual neuroscience; cortical plasticity.Jos Luis Pea, Assistant Professor: Neural bases of behavior and Neural coding. Alberto Pereda, Professor: Modulation in the central nervous system; synaptic plasticity; properties and plasticity of electrical synapses.Diana Pettit, Associate Professor: Dendritic physiology and modulation of synaptic transmission.Dominick P. Purpura, Distinguished Professor and Dean Emeritus: Dendritic and cortical development.Eliana Scemes, Associate Professor: Odelia Schwartz, Assistant Professor: Sensory coding; computational neuroscienceRoy Sillitoe, Assistant Professor: Development of topographic circuits in the cerebellum; pattern formation; mouse molecular genetics; comparative neuroanatomy David C. Spray, Professor: Biophysics of gap-junction channels; regulation of gap-junction gene expression; membrane trafficking of gap-junction proteins; physiology of gap junctions in neurons and cardiovascular systems.Elyse S. Sussman, Associate Professor: Cognitive Neuroscience - evoked potential analysis of cortical activity underlying auditory perception, attention, memory, and speech in children and adults.Vytautas K. Verselis, Professor: Structure-function studies of gap junction channels; voltage gating, and permeation.Steven U. Walkley, Professor: Pathobiology and treatment of genetic neurological diseases; cerebral cortical development; ganglioside function in neurons.R. Suzanne Zukin, Professor: Regulation of NMDA receptor trafficking, gating and expression in synaptic plasticity; calcium-permeable AMPA receptors in synaptic plasticity and neuronal death; molecular mechanisms of neuronal death in ischemia, epilepsy and Alzheimer's disease; estrogen neuroprotection in animals models of stroke; regulation of AMPA receptor mRNA trafficking and targeting to synapses and relevance to Fragile X Syndrome.

Mielina, Oligodendrocitele si Reteaua de Mielina, Oligodendrocitele si Reteaua de canale intercelulare intre astrocite si canale intercelulare intre astrocite si

oligodendrociteoligodendrocite

Orthmann-Murphy, J. L. et al. J. Neurosci. 2007;27:13949-13957

MATERIE CENUSIE,MATERIE CENUSIE,MATERIE ALBA,MATERIE ALBA,

MIELINAMIELINA

Topologia SNCTopologia SNC

Mielinizarea SNC este alterata la bolnavii ODDDMielinizarea SNC este alterata la bolnavii ODDD

Encefalomielita Experimentala Encefalomielita Experimentala Autoimuna (EAE)Autoimuna (EAE)

Imagini de microscopie confocala

a unor sectiuni transversale prin

maduva soarecilor sanatosi si

EAE. A-B. Marcarea tripla pentru Cx43 (verde), axoni distrofici (rosu) si monocite (albastru). C-D. Marcare dubla: Cx43 (verde) si astrocite

(rosu). Tesutul soarecilor EAE prezinta zone cu nivel redus de Cx43, imunoreactivitate, distrofie axonala, monocite si astrocite hipertrofice monocite si astrocite hipertrofice (stelute albe in D).

Iacobas DA, Scemes E, Spray DC. (2004). Gene expression alterations in connexin null mice extend beyond the gap junction. Neurochem. Intl., 45(2-3), 243-250.

Brand-Schieber E, Werner P, Iacobas DA, Iacobas S, Beelitz M, Lowery SL, Spray DC, Scemes S. (2005). Connexin43, the major gap junction protein of astrocytes, is down regulated in an animal model of multiple sclerosis. J Neurosci Res. 80:798-808.

Iacobas DA, Iacobas S, Werner P, Scemes E, Spray DC (2008). Alteration of transcriptomic networks in adoptive-transfer experimental autoimmune encephalomyelitis. Front Integr Neurosci. 1:10. doi:10.3389/neuro.07/010.2007

Diferentierea Diferentierea oligodendrociteloroligodendrocitelor

Iacobas S, Iacobas DA, Spray DC. (2007). Transcriptomic changes in an oligodendroglial cell line following differentiation in vitro. NEURON GLIA BIOLOGY, 2, S51

Studiul interactiunii Studiul interactiunii oligodendrocitelor cu oligodendrocitelor cu

astrociteleastrocitele

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DIFF

ISOLATED AGONIST ONLY AGONIST+GJC

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SEMNALIZAREA PRIN SEMNALIZAREA PRIN UNDE DE CaUNDE DE Ca2+2+

Propagarea undelor de calciu in astroglioma cells (1321N1) transfectate cu P2Y2R w/o Cx43

Iacobas DA, Suadicani SO, Spray DC, Scemes E (2006). A stochastic 2D model of intercellular Ca2+ wave spread in glia. Biophys J. 90(1): 24-41.

Jonctiune distanta Jonctiune distanta Canal Canal intercelular intercelular -- Conexon Conexon conexinaconexina

O familie de ~20 de proteine care asigura la vertebrate continuitatea citoplasmaticacontinuitatea citoplasmatica intre celule prin formarea de canale intercelulare de jonctiune distanta (gap junction channels).

Conexinele sunt topologic asemanatoare cu inexinele de la organismele nevertebrate si panexinele.

Canalele intercelulare pot asigura continuitatea continuitatea transcriptomicatranscriptomica intre celulele cuplate prin difuzia de: - Ioni si molecule de semnalizare (Ca2+, IP3, cAMP) care pot modula exprimarea genelor prin modificarea fosforilarii unor factori de transcriere- Antigeni cu masa moleculara < 1.8kD - ARN de interferenta

(Spray DC, Iacobas DA, Iglesias R, Scemes E. (2008). Biophysics and transcriptomics of hemichannels and their genes. In Purinergic Signal. 4(Suppl 1): 1-210).

Mielina, Oligodendrocitele si Reteaua de Mielina, Oligodendrocitele si Reteaua de canale intercelulare intre astrocite si canale intercelulare intre astrocite si

oligodendrociteoligodendrocite

Orthmann-Murphy, J. L. et al. J. Neurosci. 2007;27:13949-13957

Negative Stain

Mutatii ale Cx32 in CMT1XMutatii ale Cx32 in CMT1X(X-linked form of Charcot-Marie-Tooth disease, known also as Hereditary Motor and Sensory Neuropathy

(HMSN), Hereditary Sensorimotor Neuropathy (HSMN), or Peroneal Muscular Atrophy)

240 known human mutations in Cx32 gene

The foot of a person with Charcot-Marie-Tooth. The lack of muscle, high arch, and hammer toes are signs of the genetic disease. This patient was diagnosed with CMT-1A.

(Spray DC, Iacobas DA. (2007) Organizational principles of the connexin-related brain transcriptome. J Membr Biol. 218(1-3):39-47)

Mutatii ale Cx43 in ODDDMutatii ale Cx43 in ODDD(Occulodental digital (Occulodental digital

dysplasmia)dysplasmia)

(Iacobas DA, Iacobas S, Urban-Maldonado M, Spray DC (2005). Sensitivity of the brain transcriptome to connexin ablation, Biochimica et Biofisica Acta. 1711: 183-196).

Mutatii ale Cx47 in boala Pelizaeus MerzbacherMutatii ale Cx47 in boala Pelizaeus Merzbacher--like, o like, o leukodistrofie care afecteaza mielinizarea SNCleukodistrofie care afecteaza mielinizarea SNC

Henneke M, Combes P, Diekmann S, Bertini E, Brockmann K, Burlina AP, Kaiser J, Ohlenbusch A, Plecko B,

Rodriguez D, Boespflug-Tanguy O, Grtner J. GJA12 mutations are a rare cause of Pelizaeus Merzbacher-like

disease. Neurology. 2007 Dec 9 [Epub ahead of print]

Undele regenerative sunt initiateprin sumarea unor evenimente multiple elementare elementare (blips/puffs)rezulate din CICR (calcium-inducedcalcium-release)

Functia proteinelor depinde de configuratie si distributia de sarcina electrica, ambele amplu modificate prin legarea Ca2+ sau a radicalilor fosfat. Protein kinasele, reprezentand 2% din genomul eukaryot, scot fosfatul din ATP si il leaga covalent de gruparile hidroxil ale residuurilor de serina, treonina sau tirozina. Prin abilitatea lor de a altera campurile electrostatice locale si configuratia proteinelor, Ca2+ si fosfatul se constitue in doua instrumente universale ale transformarii semnalelor unul in altul (signal transduction).

De ce CaDe ce Ca2+2+??

transduction).

Celulele cheltuiesc multa energie pentru a tine sub control [Ca2+] datorita gradientilor de concentratie mari intre citoplasma (~100 nM) si mediul inconjurator (~1mM), prin contrast cu Mg2+, a carui concentratie este aproape uniforma. O ratiune majora pentru care Ca2+ trebuie exclus din citosol este capacitatea sa de a precipita fosfatul.

Circuitul CaCircuitul Ca2+2+ si efectul modulator asupra unor functii celulare si efectul modulator asupra unor functii celulare

PMCA = plasma membrane calcium/calmodulin-dependent ATPase (4 isoforms: PMCA1-4)

SERCA = Sarco(endo)plasmic reticulum (SER) Ca2+ ATPases

Berridge et al. 2003 Nature Reviews 4, 517

NCX = Natrium-calcium exchanger(3 isoforms: NCX1-3)

La proteinele specializate, legarea Ca2+ se face de catre atomii de oxigen ai gruparilor carboxil si carbonil (si uneori ai apei). In mod tipic, 6-7 atomi de oxigen inconjoara Ca2+ la ~2.5 intr-o configuratie de bipiramida pentagonala (Fig. A). Afinitatea domeniilor EF (ale paralvuminei) pentru Ca2+ variaza in limite largi (100.000x) in functie de o multime de factori, inclusiv de prezenta unor aminoacizi critici in zona de legare a Ca2+. Calmodulina (CaM1-4) este o proteina mica, prezenta peste tot, ce amplifica domeniul Ca2+ la scara proteica. Calmodulina s-a modificat foarte putin in cei peste 1,5 miliarde de ani de evolutie,

CalmodulineCalmoduline

putin in cei peste 1,5 miliarde de ani de evolutie, fiind transcrisa din trei locatii cromozomilale la om. Legarea Ca2+ modifica configuratia domeniilor calmodulinei care poate astfel sa ridice autoinhibarea unor proteine, sa remodeleze locusurile active si sa dimerizeze alte proteine. Sute de proteine contin locusuri de recrutare a calmodulinei. Reziduurile hidrofobice, de obicei continand metionina, se imfasoara in jurul regiunilor amfifatice ale proteinelor tinta (ex. alfa-helixurile din myosin light chain kinase (MLCK; in Fig. B si C) si calmodulin dependent kinasa II (CaMKII).

Clapham DE. (2007). Calcium signaling. Cell. 31(6):1047-58.

Inchiderea si deschiderea Inchiderea si deschiderea rezervoarelor ERrezervoarelor ER

Propagarea inductiva a semnalelor de Ca2+ prin stimularea receptorilor de

IP3 (CICR)

CICR: low [Ca2+] stimulates, high [Ca2+] inhibits] IP3R

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GENE EXPRESSIONGENE EXPRESSION

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PostPost--translationaltranslationalmodificationsmodifications

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One type of bricks + one type of adhesive countless types of buildings

Producerea si citirea microarrayProducerea si citirea microarray--urilorurilor

> 2.5M mouse ESTs> 4.5M human ESTs

Differential dye incorporationConfiguration change

Photo bleaching

PMT setting

Expression variability

Several transcripts per gene

Printing errors

Coat non-specific adsorption(background)

Intrachip normalization

Differential hybridization of labeled cDNAs

(foreground)

B measured outside spots, subtracted from FNon-uniform adsorption

Non-linear,Purity

Redundancy(Average?)

Homology with several genes(composite signal -> Specificity?)

Regulation,Control,Coordination

16 bit detectionNon-linearSaturation

cDNA microarraycDNA microarray

The 8-bit pseudo-color image of a 27k AECOM mouse chip used to analyze the gene

expression regulation in the brain of Cx36 KO mouse.

Iacobas DA, Urban M, Massimi A, Iacobas S, Spray DC. (2002) Hits and misses from gene expression ratio measurements in cDNA microarray studies. J. Biomol. Tech. 13(3), 143-157.

Iacobas DA, Urban M, Massimi A, Spray DC. (2002). Improved procedure to mine the spotted cDNA arrays. J Biomol Tech 13(1), 5-19.

Alteration in gene expression of eukaryotic Alteration in gene expression of eukaryotic translation initiation factors (eIFs) in heart after translation initiation factors (eIFs) in heart after

chronic hypoxia treatmentchronic hypoxia treatment

Profiles of gene expression and regulation of eIFs in 4 individual mice subjected to normoxia (N1N4), CCH (C1C4), and CIH (I1I4) for 1, 2, or 4 wk. Eachvalue is represented by a colored square. Duration of the treatment is indicated before the letter of treatment, (e.g., 1I2 = 1 wk CIH, 2nd mouse), while thegreen/red color of the square shows down/upregulation, with brighter colors for higher regulation. Note both the variability and the reproducible patternamong the mice subjected to the same treatment. Note also the darker colors of the normoxic values, since they were closer to the average used innormalization.

Iacobas DA, Fan C, Iacobas S, Haddad GG. (2008). Integrated transcriptomic response to cardiac chronic hypoxia: translation regulators and response tostress in cell survival. Funct Integr Genomics. 8(3):265-75.

There is no oneThere is no one--gene showgene show

Gene expression regulation in neonatal Gja1-/- (black bars), Gjb1-/- (white bars) and P10 Gja9-/- (grey bars) brains as compared to the brains of

neonatal or P10 wildtype mice A. Percent of regulated genes in functional categories. B. Percent of regulated genes in chromosomes. Note that the

regulated genes are distributed in all functional categories (not restricted to JAE, the primary function of all connexins) and in all chromosomes (not restricted to

chromosomes 10 locating Gja1, or chromosome X locating Gjb1, or chromosome 2 locating Gja9). Although significantly reduced as percentages, the regulated

genes in Gja1+/- and Gja9+/- (not shown) were also distributed in all functional categories and chromosomes. C. Average fold-change of functional gene

cohorts. Note that no cohort was significantly regulated in any of the connexin deficient brains. D. Standard deviation of the expression ratios within

functional gene cohorts. Note that while no cohort excepting RNA and SIG exceeded by little the cut-off in Gja9 null brain, all functional cohorts have been

significantly perturbed in Gja1 null and Gjb1 null brains. (Iacobas DA, Iacobas S, Spray DC (2007). Connexin-dependent transcellular transcriptomic networks inmouse brain. Prog Biophys Mol Biol. 94(1-2):168-184.)

Validation through other Validation through other platformsplatforms

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Adrb2 = adrenergic receptor-beta2Bsn = bassoonPclo = piccoloPlp = proteolipid protein (myelin)Sfn = stratifinSlc43a1 = solute carrier family 43, member a1Tekt2 = tektin-2

Iacobas DA, Iacobas S, Li WEI, Zoidl G, Dermietzel R, Spray DC. (2005). Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart. Physiol Genomics 20: 211-223.

Fan C, Iacobas DA, Zhou D, Chen Q, Gavrialov O, Haddad GG (2005). Gene expression and phenotypic characterization of mouse heart after chronicconstant and intermittent hypoxia. Physiol Genomics. 22: 292-307.

PanPan--glial transcriptomic syncytiumglial transcriptomic syncytium

Similarities and dissimilarities between brains deficient of Gja1, or Gjb1, or Gja9. A. Log-log plot of expression ratios in Gjb1-/- and Gja1-/- brains

( ) ( )2 2( , ) ( ) ( ) ( , ) ( ) ( ){ } { }{ } { }{ } { }

1 1,G H H G G H H Gtranscriptome i i cohort i i

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Similarities and dissimilarities between brains deficient of Gja1, or Gjb1, or Gja9. A. Log-log plot of expression ratios in Gjb1-/- and Gja1-/- brains

with respect to the wildtype brain. Note the remarkable overlap of the 3730 ratios computed for each of the two connexin deficient brains. B. Distribution offold-change distances on functional categories. Reduced (Euclidean) fold-change distance between altered transcriptomes with respect to thecorresponding wildtypes was calculated at the level of the entire trancriptome as well as at the level of each gene cohort:

C. Distribution of fold-change distances on chromosomal locations. Note that the fold-change distances between the Gja9-/- brain and Gja1-/- (black bars)and Gjb1-/- (grey bars) brains are over twice as large as that between Gja1-/- and Gjb1-/- (open bars) and the robustness of this observation for all functionalcategories and chromosomal locations.

Iacobas DA, Iacobas S, Spray DC (2007). Connexin43 and the brain transcriptome of the newborn mice. Genomics. 89(1), 113-123.

Spray DC, Iacobas DA. (2007) Organizational principles of the connexin-related brain transcriptome. J Membr Biol. 218(1-3):39-47.

Iacobas DA, Suadicani SO, Iacobas S, Chrisman C, Cohen M, Spray DC, Scemes E. (2007). Gap junction and purinergic P2 receptor proteins as a functionalunit: insights from transcriptomics. J Membr Biol. 217(1-3):83-91.

Iacobas DA, Iacobas S, Spray DC (2007). Connexin-dependent transcellular transcriptomic networks in mouse brain. Prog Biophys Mol Biol. 94(1-2):168-184.

24

VECTORS NONVECTORS NON--ADDITIVE SYNERGISTIC ADDITIVE SYNERGISTIC EFFECT ON TRANSIENT TRANSFECTIONEFFECT ON TRANSIENT TRANSFECTION

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COORDINATED COORDINATED TRANSCRIPTOMICSTRANSCRIPTOMICSHypothesisHypothesis:: genes whose products perform synergistic or antagonistic functions arecoordinately transcribed (and their transcripts coordinately translated) to maximize the efficiency ofthe functional pathway .

Prediction accuracy of the Prediction accuracy of the coordination analysiscoordination analysis

Expression coordination with Gja1 in the wildtype brain (A) and heart (B) predicts expression regulation in the Gja1 null

brain and heart. Note the significantly high proportions of genes whose regulation (dot circles) or lack of regulation (the mountains standing on the rectangle between -0.05 and 0.05 as coordination with Gja1 in wildtype and -1.5 and 1.5 as fold change in the Gja1 null tissue) was accurately predicted.

ExpressomeExpressome remodeling in remodeling in CxCx null brainsnull brains

Synergistic expression

Antagonistic expression

Part of the Cx43 expressome (20 transcription factors) in the WT brain and its alterations when Cx43, Cx36 or Cx32 are disrupted.

Note the substantial alterations and similarities between Cx43 null and Cx32 null brains, and the significantly smaller effect in Cx36 null brain, supporting the idea of the pan-glial transcriptomic continuity in the brain, independent of the neuronal transcriptomic network.

Role of Cx29, Cx45 and Cx47 in coordinating Role of Cx29, Cx45 and Cx47 in coordinating myelination genesmyelination genes

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TheThe averageaverage genegene isis synergisticallysynergistically expressedexpressed withwith 99..66 55..22 %%

Intercoordination Intercoordination of functional of functional classesclasses

TheThe averageaverage genegene isis synergisticallysynergistically expressedexpressed withwith 99..66 55..22 %%ofof thethe selectedselected distinctdistinct 40964096 genes,genes, antagonisticallyantagonistically expressedexpressedwithwith 88..77 55..33 %% ofof thethe selectedselected genesgenes andand independentlyindependentlyexpressedexpressed withwith 66..77 33..66 %% ofof thethe selectionselection.. InIn spitespite ofof closeclosecoordinationcoordination degreesdegrees ofof functionalfunctional classes,classes, individualindividual genesgenesexhibitexhibit aa highhigh diversitydiversity ofof theirtheir significantsignificant expressionexpressionintercoordinationintercoordination.. Thus,Thus, DldDld (ENE(ENE--O),O), OatOat (ENE(ENE--O),O), SlcSlc2727aa22(TIC)(TIC) andand PfdnPfdn22 (TWC)(TWC) havehave thethe highesthighest numbernumber ofof synergisticsynergisticexpressionsexpressions withwith thethe otherother genesgenes ofof thethe selectionselection ((1818..77%%),),DokDok11 (SIG)(SIG) hashas thethe leastleast synergisticsynergistic relationsrelations ((00..44%%),), CacnbCacnb11(SIG)(SIG) andand NrbpNrbp (TIC)(TIC) havehave thethe highesthighest numbernumber ofof significantsignificantantagonismsantagonisms ((1818..77%%)) whilewhile ManMan11bb (ENE(ENE--D)D) andand DdxDdx5050 (TRA(TRA--P)P)havehave thethe lowestlowest numbernumber ((00..33%%),), CtbpCtbp22 (SIG)(SIG) isis thethe mostmostindependentlyindependently expressedexpressed ((2323..88%%),), whilewhile 1414 genes,genes, includingincludingTnfsfTnfsf1313bb (CSD(CSD--G),G), WntWnt44 (SIG),(SIG), CogCog22 (TWC),(TWC), GfiGfi11 (UNK)(UNK) andandMrplMrpl3232 (RNA(RNA--MIT)MIT) areare thethe leastleast independentlyindependently expressedexpressed((33..00%%)).. PseudocolorsPseudocolors correspondcorrespond toto zz--axisaxis valuesvalues..

Joseph C. Arezzo, Professor: Electrophysiological analysis of cortical and subcortical mechanisms associated with sensorimotor processes in behaving monkeys; neurologic function in mutant mice.Thaddeus A. Bargiello, Professor: Molecular genetics and biophysics of gap junction channels; structure-function relationships and biological roles.Michael V.L. Bennett, Professor: Chemical and electrical synapses; structure-function studies of connexins and glutamate receptors; physiological roles analyzed by gene knock outs.Feliksas Bukauskas, Professor: Gap junction channel formation and gating.Reed Carroll, Associate Professor: Molecular mechanisms underlying synaptic plasticty.Pablo Castillo, Associate Professor: Synaptic transmission, modulation and plasticity; the properties of excitatory and inhibitory synapses in themammalian brain and the mechanisms of synaptic plasticity during developmentand in learning and memory.Kostantin Dobrenis, Assistant Professor: Novel approaches to treatment of diseases affecting the CNS; microglial biology: lineage, secretion, receptor systems, and interactions with neurons.Anne M. Etgen, Professor: Cellular and molecular mechanisms of steroid hormone action in brain; steroid receptors; steroid-monoamine interactions; steroids and amino acid neurotransmission.Donald S. Faber, Professor and Chair: Functional organization and adaptive properties of central synapses; mechanisms of action of neuromodulators; neural correlates of sensorimotor behavior and its plasticity.Anna Francesconi, Assistant Professor: Cellular and molecular mechanisms of neurotransmitter receptor trafficking; the role of lipid rafts in synaptic trafficking and signaling. David H. Hall, Professor: Correlative fine structure and serial section reconstruction at the electron-microscopic level; morphology of nervous system mutants of Caenorhabditis elegans.

Faculty with primary appointments in the DP Purpura Dept of Faculty with primary appointments in the DP Purpura Dept of Neuroscience and their research interestsNeuroscience and their research interests

Caenorhabditis elegans.Jean Hbert, Associate Professor: Genetic and molecular mechanisms required for neural stem and progenitor cells to generate the forebrain in development, and regenerate it in adulthood.Dumitru Andrei Iacobas, Assistant Professor: Comparative genomics and mathematical modeling of intercellular signaling in normal, transgenic and diseased nervous structures. Bryen Jordan, Assistant Professor: Exploring synaptic function and activity-dependent synapse-to-nucleus signaling.Kamran Khodakhah, Professor: Dendritic integration and neuronalcomputation; the role of calcium in regulation of excitability and synapticplasticity.Adam Kohn, Assistant Professor: Visual neuroscience; cortical plasticity.Jos Luis Pea, Assistant Professor: Neural bases of behavior and Neural coding. Alberto Pereda, Professor: Modulation in the central nervous system; synaptic plasticity; properties and plasticity of electrical synapses.Diana Pettit, Associate Professor: Dendritic physiology and modulation of synaptic transmission.Dominick P. Purpura, Distinguished Professor and Dean Emeritus: Dendritic and cortical development.Eliana Scemes, Associate Professor: Odelia Schwartz, Assistant Professor: Sensory coding; computational neuroscienceRoy Sillitoe, Assistant Professor: Development of topographic circuits in the cerebellum; pattern formation; mouse molecular genetics; comparative neuroanatomy David C. Spray, Professor: Biophysics of gap-junction channels; regulation of gap-junction gene expression; membrane trafficking of gap-junction proteins; physiology of gap junctions in neurons and cardiovascular systems.Elyse S. Sussman, Associate Professor: Cognitive Neuroscience - evoked potential analysis of cortical activity underlying auditory perception, attention, memory, and speech in children and adults.Vytautas K. Verselis, Professor: Structure-function studies of gap junction channels; voltage gating, and permeation.Steven U. Walkley, Professor: Pathobiology and treatment of genetic neurological diseases; cerebral cortical development; ganglioside function in neurons.R. Suzanne Zukin, Professor: Regulation of NMDA receptor trafficking, gating and expression in synaptic plasticity; calcium-permeable AMPA receptors in synaptic plasticity and neuronal death; molecular mechanisms of neuronal death in ischemia, epilepsy and Alzheimer's disease; estrogen neuroprotection in animals models of stroke; regulation of AMPA receptor mRNA trafficking and targeting to synapses and relevance to Fragile X Syndrome.