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.

Senior researcher

Jens Hjerling-Leffler

Phone: +46-(0)8-524 869 74
Organizational unit: Jens Hjerling Lefflers group
E-mail: jens.hjerling-leffler@ki.se

More information at www.hjerling-leffler-lab.org.

Research

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 does 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.

Research Group

Carolina Bengtsson GonzalesPhD student
Jens Hjerling-LefflerSenior researcher
Jose Martinez LopezPostdoc
Hermany Munguba VieiraPhD student, Graduate Student
Ana Munoz ManchadoAssistant professor
Kasra NikoueiPhD student, Graduate Student
Nathan SkeneAssociated

Selected publications

Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq.
Muñoz-Manchado A, Bengtsson Gonzales C, Zeisel A, Munguba H, Bekkouche B, Skene N, et al
Cell Rep 2018 Aug;24(8):2179-2190.e7

Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics.
Harris K, Hochgerner H, Skene N, Magno L, Katona L, Bengtsson Gonzales C, et al
PLoS Biol. 2018 Jun;16(6):e2006387

Genetic identification of brain cell types underlying schizophrenia.
Skene N, Bryois J, Bakken T, Breen G, Crowley J, Gaspar H, et al
Nat. Genet. 2018 Jun;50(6):825-833

Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq.
Zeisel A, Muñoz-Manchado A, Codeluppi S, Lönnerberg P, La Manno G, Juréus A, et al
Science 2015 Mar;347(6226):1138-42

Novel Striatal GABAergic Interneuron Populations Labeled in the 5HT3a(EGFP) Mouse.
Muñoz-Manchado A, Foldi C, Szydlowski S, Sjulson L, Farries M, Wilson C, et al
Cereb. Cortex 2016 Jan;26(1):96-105