Our research group is interested in the genetic and cellular mechanisms of the development and function of the brain´s inhibitory system. We apply advanced mouse genetics in combination with electrophysiology and traditional molecular methods. We are also developing a behavioral paradigm using cell specific pharmaco-genetics. The group has two major research interests:
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 changes that occur around or just after sexual maturation and which genetic programs that control these changes. We are currently studying a few promising candidate genes as well as performing functional large scale arrays in order to identify novel genetic programs.
Characterization of interneuron subtype function
Since the days of Ramon y Cajal we have known that the 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 novel class of interneurons and are developing and applying pharmaco -genetic tools to study their role in behavioral paradigms
For further information, please also see: http://www.hjerling-leffler-lab.org
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* and Linnarsson S1* (2015) Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science in press. †shared first authorship, *corresponding authors
Muñoz-Manchado AB†, Foldi C†, Szydlowski S†, Sjulson L, Farries M, Wilson C, Silberberg G, Hjerling-Leffler J. (2014) Novel Striatal GABAergic Interneuron Populations Labeled in the 5HT3aEGFP Mouse. Cereb Cortex . †shared first authorshipAug 21. pii: bhu179. [Epub ahead of print]
Jaglin XH., Hjerling-Leffler J., Fishell G., Batista-Brito R. (2012) The origin of neocortical nitric oxide synthase-expressing inhibitory neurons. Front Neural Circuits , 6:44
Lee S., Hjerling-Leffler J., Zagha E., Fishell G., Rudy B. (2010) The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors. J. Neurosci ., 30 (50) : 16796-808.
Miyoshi G., Hjerling-Leffler J., Karayannis T., Sousa VH., Butt SJ., Battiste J., Johnson JE., Machold RP., Fishell G. (2010) Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J. Neurosci. , 30 (5) : 1582-94.
Batista-Brito R., Rossignol E., Hjerling-Leffler J., Denaxa M., Wegner M., Lefebvre V., Pachnis V., Fishell G. (2009) The cell-intrinsic requirement of Sox6 for cortical interneuron development. Neuron. , 63 (4) : 466-81.
Andäng M., Hjerling-Leffler J., Moliner A., Lundgren TK., Castelo-Branco G., Nanou E., Pozas E., Bryja V., Halliez S., Nishimaru H., Wilbertz J., Arenas E., Koltzenburg M., Charnay P., Manira AE., Ibañez CF., Ernfors P. (2008) Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation. Nature , 451 (7177) : 460-4.
2012 Marie Curie Career Integration Grant (until 2016)
2011 VR (Swedish Research Council) Assistant Professorship Grant (until 2015)
2009 SSMF (Swedish Society for Medical Research) Long-term fellowship (until 2011)
2008 EMBO Long-Term Fellowship (until 2009)
2007 Hjärnfonden (Swedish Brain Foundation) Postdoctoral Stipend
2006 The Svedberg Lecture, Uppsala Universitet
2004 IASP Collaborative Research Grant. Named Beneficiary, between UCL and Karolinska.
2004 Royal Society International Joint Project 2004/R2-EU Europe (ESEP). Named Beneficiary