{"id":1490,"date":"2023-02-14T17:40:02","date_gmt":"2023-02-14T15:40:02","guid":{"rendered":"https:\/\/psy.artamax.eu\/?page_id=1490"},"modified":"2024-03-12T20:31:47","modified_gmt":"2024-03-12T19:31:47","slug":"prof-dr-johannes-letzkus-laboratory-of-neocortical-circuits","status":"publish","type":"page","link":"https:\/\/physiology-freiburg.de\/de\/prof-dr-johannes-letzkus-laboratory-of-neocortical-circuits\/","title":{"rendered":"Prof. Dr. Johannes Letzkus – Labor f\u00fcr neokortikale Schaltkreise"},"content":{"rendered":"
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Labor f\u00fcr neokortikale Schaltkreise<\/h1>\n<\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/section>

Prof. Dr. Johannes Letzkus – Labor f\u00fcr neokortikale Schaltkreise<\/h2>\n

Informationen \u00fcber vergangene Erfahrungen und aktuelle Ziele sind ein zentrales Element aller h\u00f6heren Hirnfunktionen, aber unser Verst\u00e4ndnis dieser intern erzeugten Top-down-Signale in Gesundheit und Krankheit ist begrenzt. Wir nutzen eine Kombination aus Bildgebung, Elektrophysiologie, zelltypspezifischem Targeting, Optogenetik, viraler Verfolgung und Verhalten, um diese Mechanismen im auditorischen Kortex zu untersuchen.<\/p>\n

Curriculum Vitae<\/strong><\/a><\/p>\n

Kontact: johannes.letzkus@physiologie.uni-freiburg.de<\/a><\/p>\n<\/div><\/div><\/div><\/div><\/div>

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Forschung<\/h2>\n

Der Neokortex ist der gr\u00f6\u00dfte und leistungsf\u00e4higste Bereich des S\u00e4ugetiergehirns. Diese Region hat sich im Laufe der Evolution am st\u00e4rksten ausgedehnt und differenziert, vermittelt viele der F\u00e4higkeiten, die den Menschen von seinen n\u00e4chsten Verwandten unterscheiden, und spielt auch bei vielen psychiatrischen St\u00f6rungen eine zentrale Rolle. Alle h\u00f6heren kognitiven Funktionen des Neokortex werden dadurch erm\u00f6glicht, dass zwei unterschiedliche Informationsstr\u00f6me zusammengef\u00fchrt werden: ein „Bottom-up“-Stream, der Signale aus der Umgebung \u00fcbermittelt, und ein „Top-down“-Stream, der intern erzeugte Informationen weiterleitet, die unsere fr\u00fcheren Erfahrungen und aktuellen Ziele kodieren.
\nW\u00e4hrend sich jahrzehntelange Arbeiten mit der Verarbeitung sensorischer Bottom-up-Informationen befasst haben, steckt unser Verst\u00e4ndnis der intern erzeugten Informationen noch in den Kinderschuhen.<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/section>

Techniken<\/h2>\n<\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/section>

Unsere Arbeit zielt darauf ab, diese L\u00fccke zu schlie\u00dfen, indem wir die Mechanismen und Folgen der Top-down-Informationsverarbeitung im auditorischen Kortex aufkl\u00e4ren. Mit einer Kombination aus modernsten Ans\u00e4tzen (einschlie\u00dflich 2-Photonen- und 1-Photonen-Bildgebung, Elektrophysiologie, Optogenetik, virales Tracing und computergest\u00fctzte Analysen) und Verhaltensparadigmen gehen wir den folgenden Fragen nach:<\/p>\n

1) Welche hirnweiten Afferenzen \u00fcbermitteln welche Art von Top-down-Informationen an den Neokortex?<\/p>\n

2) Wie werden diese Top-Down-Signale von lokalen inhibitorischen Interneuronen umgesetzt, um die Schaltkreisfunktion flexibel anzupassen?<\/p>\n

3) Welche Aspekte der Informationsverarbeitung unterliegen der Top-down-Modulation?<\/p>\n

4) Wie optimiert die Top-down-Information die Gehirnfunktion f\u00fcr komplexe, naturalistische Verhaltensweisen?<\/p>\n

5) Wie tragen St\u00f6rungen der Top-down-Prozesse zu Hirnleistungsst\u00f6rungen bei?<\/p>\n<\/div><\/div><\/div><\/div><\/div>

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Publikationen<\/h2>\n<\/div><\/div>
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Schroeder A1,2<\/sup>, Pardi MB, Keijser J, Dalmay T, Groisman AI, Schuman E, Sprekeler H, Letzkus, JJ2,3<\/sup><\/b> (2023). Inhibitory top-down projections from zona incerta mediate neocortical memory. Neuron<\/i><\/u>, in press.<\/a><\/p>\n

Pardi MB1<\/sup>, Schroeder A1<\/sup>, Letzkus <\/strong>JJ2<\/sup><\/b> (2023). Probing top-down information in neocortical layer 1. Trends in Neurosciences<\/u><\/em>, in press.<\/a><\/p>\n

Schroeder A1<\/sup>, Pardi MB, Keijser J, Dalmay T, Schuman E, Sprekeler H, Letzkus, JJ2,3<\/sup><\/b> (2022). Control of neocortical memory by long-range inhibition in layer 1. bioRxiv<\/i><\/u>, 022.2002.2007.479360.<\/a><\/p>\n

Schroeder A1<\/sup>, Letzkus JJ<\/strong>2,3<\/sup><\/strong> (2021). A neuropeptide making memories. Cell<\/u><\/em>, 184, 5501-5503.<\/a><\/p>\n

Pardi MB1<\/sup>, Vogenstahl J, Dalmay T, Spano T, Pu D, Naumann LB, Sprekeler H, Letzkus JJ2 <\/sup><\/strong>(2020). A thalamo-cortical top-down circuit for associative memory. Science<\/u>, <\/em>370, 844-848.<\/a><\/p>\n

Highlighted by<\/u>: Lewis S. (2020) Nature Reviews Neuroscience<\/u><\/em><\/a>.<\/p>\n

Hartung, J1<\/sup>, Letzkus JJ<\/strong>2 <\/sup><\/strong>(2021). Inhibitory plasticity in layer 1 \u2013 dynamic gatekeeper of neocortical associations. Current Opinion in Neurobiology<\/u><\/em>, 67, 26-33.<\/a><\/p>\n

Medina C1<\/sup>, de la Fuente V, tom Dieck S, Nassim-Assir, B, Dalmay T, Bartnik I, Lunardi P, de Oliveira Alvares L, Schuman EM, Letzkus JJ<\/strong>,Romano A2<\/sup> (2020). LIMK, Cofilin 1 and actin dynamics involvement in fear memory processing. Neurobiology of Learning and Memory,<\/u><\/em> 173, 107275.<\/a><\/p>\n

Dalmay T1<\/sup>, Abs E1<\/sup>, Poorthuis RB, Hartung J, Pu D, Onasch S, Lozano YR, Signoret-Genest J, Tovote P, Gjorgjieva J, Letzkus JJ2,3<\/sup><\/strong> (2019). A critical role for neocortical processing of threat memory. Neuron<\/u><\/em>, 104:1180-1194.<\/a><\/p>\n

Pardi MB1<\/sup>, Abs E, Letzkus JJ<\/strong>2,3<\/sup><\/strong> (2019). Disinhibition goes spatial. Neuron<\/u><\/em>, 101:994-996.<\/a><\/p>\n

Abs E1<\/sup>, Poorthuis RB1<\/sup>, Apelblat D, Muhammad K, Pardi MB, Enke L, Kushinsky D, Pu D, Eizinger MF, Conzelmann K-K, Spiegel I2<\/sup>, Letzkus JJ<\/strong>2,3<\/sup><\/strong> (2018) Learning-related plasticity in dendrite-targeting layer 1 interneurons. Neuron<\/u><\/em>, 100:684-699. <\/a><\/p>\n

Highlighted by<\/u>: Hou WH & Capogna M (2018) Neuron<\/u><\/em> 100, 516-519<\/a>.<\/p>\n

Poorthuis RB1<\/sup>, Muhammad K, Wang M, Verhoog MB, Junek S, Wrana A, Mansvelder HD, Letzkus JJ<\/strong>2,3<\/sup><\/strong> (2018) Rapid Neuromodulation of Layer 1 Interneurons in Human Neocortex. Cell Reports<\/u><\/em> 23:951-958.<\/a><\/p>\n

Mager T1<\/sup>, Lopez de la Morena D1<\/sup>, Senn V, Schlotte J, A DE, Feldbauer K, Wrobel C, Jung S, Bodensiek K, Rankovic V, Browne L, Huet A, Juttner J, Wood PG, Letzkus JJ<\/strong>, Moser T2<\/sup>, Bamberg E2<\/sup> (2018) High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics. Nature Commun.<\/u><\/em> 9:1750.<\/a><\/p>\n

Letzkus JJ1,2<\/sup><\/strong>, Wolff SB, Luthi A2,3<\/sup> (2015) Disinhibition, a Circuit Mechanism for Associative Learning and Memory. Neuron<\/u><\/em> 88:264-276.<\/a><\/p>\n

Karadottir RT1,2<\/sup>, Letzkus JJ<\/strong>2<\/sup><\/strong>, Mameli M2<\/sup>, Ribeiro C2<\/sup> (2015) Your ticket to independence: a guide to getting your first principal investigator position. Eur J Neurosci<\/u><\/em> 42:2372-2379.<\/a><\/p>\n

Wolff SB1<\/sup>, Grundemann J1<\/sup>, Tovote P, Krabbe S, Jacobson GA, Muller C, Herry C, Ehrlich I, Friedrich RW, Letzkus JJ<\/strong>2<\/sup><\/strong>, Luthi A2<\/sup> (2014) Amygdala interneuron subtypes control fear learning through disinhibition. Nature<\/u><\/em> 509:453-458.<\/a><\/p>\n

Highlighted by<\/u>: Ozawa T & Johansen JP (2014) Current Biology<\/u><\/em> 24, R690-693<\/a>.<\/p>\n

Senn V1<\/sup>, Wolff SB1<\/sup>, Herry C, Grenier F, Ehrlich I, Grundemann J, Fadok JP, Muller C, Letzkus JJ<\/strong>, Luthi A2<\/sup> (2014) Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron<\/u><\/em> 81:428-437.<\/a><\/p>\n

Poorthuis RB1<\/sup>, Enke L1<\/sup>, Letzkus JJ<\/strong>2<\/sup><\/strong> (2014) Cholinergic circuit modulation through differential recruitment of neocortical interneuron types during behaviour. The Journal of Physiology<\/u><\/em> 592:4155-4164.<\/a><\/p>\n

Letzkus JJ<\/strong>1,2<\/sup><\/strong>, Wolff SB1<\/sup>, Meyer EM, Tovote P, Courtin J, Herry C, Luthi A2<\/sup> (2011) A disinhibitory microcircuit for associative fear learning in the auditory cortex. Nature<\/u><\/em> 480:331-335.<\/a><\/p>\n

Highlighted by<\/u>: Flight MH (2011). Nat Rev Neurosci<\/u><\/em> 13, 72<\/a>.<\/p>\n

Kampa BM1<\/sup>, Gundlfinger A, Letzkus JJ<\/strong>, Leibold C (2011) Circuit mechanisms of memory formation. Neural Plast<\/u><\/em> 2011:494675.<\/a><\/p>\n

Ciocchi S1<\/sup>, Herry C1<\/sup>, Grenier F, Wolff SB, Letzkus JJ<\/strong>, Vlachos I, Ehrlich I, Sprengel R, Deisseroth K, Stadler MB, Muller C, Luthi A2<\/sup> (2010) Encoding of conditioned fear in central amygdala inhibitory circuits. Nature<\/u><\/em> 468:277-282.<\/a><\/p>\n

Froemke RC1,<\/sup>2<\/sup>, Letzkus JJ<\/strong>, Kampa BM, Hang GB, Stuart GJ (2010) Dendritic synapse location and neocortical spike-timing-dependent plasticity. Front Synaptic Neurosci<\/u><\/em> 2:29.<\/a><\/p>\n

Herry C1<\/sup>, Ferraguti F, Singewald N, Letzkus JJ<\/strong>, Ehrlich I, Luthi A2<\/sup> (2010) Neuronal circuits of fear extinction. Eur J Neurosci<\/u><\/em> 31:599-612.<\/a><\/p>\n

Letzkus JJ<\/strong>1,2<\/sup><\/strong>, Stuart GJ2<\/sup> (2008) All asleep-but inhibition is wide awake. Neuron<\/u><\/em> 57:804-806.<\/a><\/p>\n

Kole MH1<\/sup>, Letzkus JJ<\/strong>1<\/sup><\/strong>, Stuart GJ2<\/sup> (2007) Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. Neuron<\/u><\/em> 55:633-647.<\/a><\/p>\n

Letzkus JJ<\/strong>1<\/sup><\/strong>, Kampa BM, Stuart GJ2<\/sup> (2007) Does spike timing-dependent synaptic plasticity underlie memory formation? Clin Exp Pharmacol Physiol<\/u><\/em> 34:1070-1076.<\/a><\/p>\n

Kampa BM1,<\/sup>2<\/sup>, Letzkus JJ<\/strong>, Stuart GJ (2007) Dendritic mechanisms controlling spike-timing-dependent synaptic plasticity. Trends Neurosci<\/u><\/em> 30:456-463. <\/a><\/p>\n

Letzkus JJ<\/strong>1<\/sup><\/strong>, Kampa BM, Stuart GJ2<\/sup> (2006) Learning rules for spike timing-dependent plasticity depend on dendritic synapse location. J. Neurosci.<\/u><\/em> 26:10420-10429.<\/a><\/p>\n

Kampa BM1,2<\/sup>, Letzkus JJ<\/strong>, Stuart GJ (2006) Cortical feed-forward networks for binding different streams of sensory information. Nature Neurosci.<\/u><\/em> 9:1472-1473.<\/a><\/p>\n

Kampa BM1<\/sup>, Letzkus JJ<\/strong>, Stuart GJ2<\/sup> (2006) Requirement of dendritic calcium spikes for induction of spike-timing-dependent synaptic plasticity. The Journal of Physiology<\/u><\/em> 574:283-290.<\/a><\/p>\n

Davie JT1<\/sup>, Kole MH, Letzkus JJ<\/strong>, Rancz EA, Spruston N, Stuart GJ, Hausser M2<\/sup> (2006) Dendritic patch-clamp recording. Nature Protocols<\/u><\/em> 1:1235-1247. <\/a><\/p>\n

Kuppers-Munther B1<\/sup>, Letzkus JJ<\/strong>, Luer K, Technau G, Schmidt H, Prokop A2<\/sup> (2004) A new culturing strategy optimises Drosophila primary cell cultures for structural and functional analyses. Dev Biol<\/u><\/em> 269:459-478. <\/a><\/p>\n

Kuppers B1<\/sup>, Sanchez-Soriano N, Letzkus J<\/strong>, Technau GM, Prokop A2<\/sup> (2003) In developing Drosophila neurones the production of gamma-amino butyric acid is tightly regulated downstream of glutamate decarboxylase translation and can be influenced by calcium. J Neurochem<\/u><\/em> 84:939-951. <\/a><\/p>\n

(1<\/sup>first author, 2<\/sup>corresponding author, 3<\/sup>lead author)<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/section>

Finanzierung<\/h2>\n<\/div><\/div>
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\"\"<\/a><\/div><\/div><\/div><\/div><\/div><\/div><\/section>\n<\/section>","protected":false},"excerpt":{"rendered":"Labor f\u00fcr neokortikale Schaltkreise Prof. Dr. Johannes Letzkus – Labor f\u00fcr neokortikale Schaltkreise Informationen \u00fcber vergangene Erfahrungen und aktuelle Ziele sind ein zentrales Element aller h\u00f6heren Hirnfunktionen, aber unser Verst\u00e4ndnis dieser intern erzeugten Top-down-Signale in Gesundheit und Krankheit ist begrenzt. 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