Jens Hjerling-Leffler group
Our research group is interested in the genetic and cellular mechanisms of the postnatal development and function of the brain with a particular interest in the inhibitory system. We apply advanced mouse genetics in combination with electrophysiology and modern molecular methods.
More information at www.hjerling-leffler-lab.org.
Genetic mechanisms controlling the emergence of higher cognitive function
Ever wondered why it might be a bad idea to lend your car to a teenager? Why do many forms of neuropsychiatric disorders including Schizophrenia, depression and bipolar-disorder have a late onset, typically late teens - early twenties? The goal of our lab is to study the cellular- and network-changes that occur after birth throughout to adulthood and which genetic programs that control these changes. We use our cell type-specific knowledge to further our understanding of genetically complex disorders with a focus on Schizophrenia.
Neural diversity – function
Since the days of Ramon y Cajal we have known that the forebrain inhibitory system exhibits a stunning diversity. A major research effort has gone into characterizing the morphology, marker expression and electrophysiological properties of the interneurons (see Rudy et al 2011). With modern genetics we are starting to get a molecular handle on this diversity in order to functionally target individual cell classes with agents revealing their connectivity as well as either driving their activity or silencing them. We have recently identified a number of novel classes of interneurons and are studying their role in the local and long-range circuitry.
Neural diversity – stability
Knowing the transcriptional state of cells gives many clues how cell classes are related to each other but even with state of the art techniques the data remains as “snapshots” of individual cells and does not tell us how these profiles can change over time. We are interested in what aspects of cell transcription and function are stable over time and which parameter are variable in response to the environment of the cells.
Postnatal Sox6 Regulates Synaptic Function of Cortical Parvalbumin-Expressing Neurons.
Munguba H, Chattopadhyaya B, Nilsson S, Carriço JN, Memic F, Oberst P, Batista-Brito R, Muñoz-Manchado AB, Wegner M, Fishell G, Di Cristo G, Hjerling-Leffler J
J Neurosci 2021 10;41(43):8876-8886
Editorial overview: Rare CNV disorders and neuropsychiatric phenotypes: opportunities, challenges, solutions.
Mulle JG, Sullivan PF, Hjerling-Leffler J
Curr Opin Genet Dev 2021 06;68():iii-ix
Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease.
Bryois J, Skene NG, Hansen TF, Kogelman LJA, Watson HJ, Liu Z, , , , Brueggeman L, Breen G, Bulik CM, Arenas E, Hjerling-Leffler J, Sullivan PF
Nat Genet 2020 05;52(5):482-493
Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq.
Muñoz-Manchado AB, Bengtsson Gonzales C, Zeisel A, Munguba H, Bekkouche B, Skene NG, Lönnerberg P, Ryge J, Harris KD, Linnarsson S, Hjerling-Leffler J
Cell Rep 2018 08;24(8):2179-2190.e7
Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics.
Harris KD, Hochgerner H, Skene NG, Magno L, Katona L, Bengtsson Gonzales C, Somogyi P, Kessaris N, Linnarsson S, Hjerling-Leffler J
PLoS Biol 2018 06;16(6):e2006387
Genetic identification of brain cell types underlying schizophrenia.
Skene NG, Bryois J, Bakken TE, Breen G, Crowley JJ, Gaspar HA, Giusti-Rodriguez P, Hodge RD, Miller JA, Muñoz-Manchado AB, O'Donovan MC, Owen MJ, Pardiñas AF, Ryge J, Walters JTR, Linnarsson S, Lein ES, , Sullivan PF, Hjerling-Leffler J
Nat Genet 2018 06;50(6):825-833
Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq.
Zeisel A, Muñoz-Manchado AB, Codeluppi S, Lönnerberg P, La Manno G, Juréus A, Marques S, Munguba H, He L, Betsholtz C, Rolny C, Castelo-Branco G, Hjerling-Leffler J, Linnarsson S
Science 2015 Mar;347(6226):1138-42
Novel Striatal GABAergic Interneuron Populations Labeled in the 5HT3a(EGFP) Mouse.
Muñoz-Manchado AB, Foldi C, Szydlowski S, Sjulson L, Farries M, Wilson C, Silberberg G, Hjerling-Leffler J
Cereb Cortex 2016 Jan;26(1):96-105