mapping synaptic connectivity in developing neuronal networks · project description | research /...

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Department of Biosystems Bio Engineering Laboratory Mattenstrasse 26 CH-4058 Basel www.bel.ethz.ch Project Description | Research / MSc project Mapping synaptic connectivity in developing neuronal networks Figure: Mapping neuronal networks at cellular and subcellular resolution (Image (left) courtesy of D. Jaeckel) n Background Dissecting the cellular mechanisms of neuronal dynamics and the role of specific neurons in controlling neuronal activity is fundamental to our understanding of how information is processed and stored in neural circuits. Despite recent methodological advances in the reconstruction and optical imaging of cellular networks, as well as stimulation of circuits, a systematic investigation of the intricate structure-function relationship of neuronal networks at the cellular scale in vivo remains cumbersome. Neuronal cultures in vitro, therefore, still provide a very attractive modelling system to access and control neuronal tissue and to address key principles of neuronal network organization, in particular, the symbiotic link between neuronal structure and intrinsic neuronal activity. n Key objectives The main goals of this project will be to (i) become familiar with the recent literature on methods for mapping neuronal connectivity at the cellular scale, (ii), to learn the basic procedures of preparing primary neuronal networks in vitro, (iii), to record from them using multielectrode arrays (MEAs) developed by the BioEngineering laboratory (BEL), (iv), to localize and precisely align the electrical footprint of neurons with an optical readout of neuronal activity and, (v), to systematically validate to which degree spontaneous and/or evoked neuronal dynamics are indicative of mono-synaptic principal-cell connectivity. Validating tentative synaptic connectivity and functional connectivity inference between cells using MEA technology may also include experiments using patch-clamp and monosynaptic restricted transsynaptic tracing with viruses. In sum, the project will provide the applicant with a great overview on current micro-connectomic research at BEL and contribute to a better understanding of the interplay between functional and structural connectivity in living neuronal networks. n Requirements The candidate should have a profound background in neuroscience, physics, engineering or a related scientific field; he/she should be willing to learning new experimental techniques as well as run analysis and to work in a vibrant inter-disciplinary environment. Some knowledge and coding experience in Matlab, Python or comparable programming languages is mandatory. The minimum duration of the project is 6 months.

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Page 1: Mapping synaptic connectivity in developing neuronal networks · Project Description | Research / MSc project Mapping synaptic connectivity in developing neuronal networks Figure:

Department of Biosystems Bio Engineering Laboratory Mattenstrasse 26 CH-4058 Basel www.bel.ethz.ch

ProjectDescription|Research/MScproject

Mappingsynapticconnectivityindevelopingneuronalnetworks

Figure:Mappingneuronalnetworksatcellularandsubcellularresolution(Image(left)courtesyofD.Jaeckel)

n BackgroundDissectingthecellularmechanismsofneuronaldynamicsandtheroleofspecificneuronsincontrollingneuronalactivityisfundamentaltoourunderstandingofhowinformationisprocessedandstoredinneuralcircuits.Despiterecentmethodologicaladvancesinthereconstructionandopticalimagingofcellularnetworks,aswellasstimulationofcircuits,asystematicinvestigationoftheintricatestructure-functionrelationshipofneuronalnetworksatthecellularscaleinvivoremainscumbersome.Neuronalculturesinvitro,therefore,stillprovideaveryattractivemodellingsystemtoaccessandcontrolneuronaltissueandtoaddresskeyprinciplesofneuronalnetworkorganization,inparticular,thesymbioticlinkbetweenneuronalstructureandintrinsicneuronalactivity.

n KeyobjectivesThemaingoalsofthisprojectwillbeto(i)becomefamiliarwiththerecentliteratureonmethodsformappingneuronalconnectivityatthecellularscale,(ii),tolearnthebasicproceduresofpreparingprimaryneuronalnetworksinvitro,(iii),torecordfromthemusingmultielectrodearrays(MEAs)developedbytheBioEngineeringlaboratory(BEL),(iv),tolocalizeandpreciselyaligntheelectricalfootprintofneuronswithanopticalreadoutofneuronalactivityand,(v),tosystematicallyvalidatetowhichdegreespontaneousand/orevokedneuronaldynamicsareindicativeofmono-synapticprincipal-cellconnectivity.ValidatingtentativesynapticconnectivityandfunctionalconnectivityinferencebetweencellsusingMEAtechnologymayalsoincludeexperimentsusingpatch-clampandmonosynapticrestrictedtranssynaptictracingwithviruses.Insum,theprojectwillprovidetheapplicantwithagreatoverviewoncurrentmicro-connectomicresearchatBELandcontributetoabetterunderstandingoftheinterplaybetweenfunctionalandstructuralconnectivityinlivingneuronalnetworks.

n RequirementsThecandidateshouldhaveaprofoundbackgroundinneuroscience,physics,engineeringorarelatedscientificfield;he/sheshouldbewillingtolearningnewexperimentaltechniquesaswellasrunanalysisandtoworkinavibrantinter-disciplinaryenvironment.SomeknowledgeandcodingexperienceinMatlab,Pythonorcomparableprogramminglanguagesismandatory.Theminimumdurationoftheprojectis6months.

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n ContactApplicantsshouldsubmitabriefletterofmotivation(halfapage)andanup-to-dateCVtoDrManuelSchroeter([email protected])andDrSergeySitnikov([email protected]).Pleasedonothesitatetocontactusifyouhaveanyqueries.