Navigation

Molecular Structure and Function of Chemical Synapses in the Retina

PI: Johann Helmut Brandstätter

Members

Issue

A main issue in the neurosciences concerns the mechanisms underlying the exchange of information between neurons. Communication among neurons is achieved via defined contacts, the synapses. Chemical synapses belong to the most important and interesting structures in the nervous system. A plethora of biochemical and biophysical reactions, responsible for information processing, takes place in the small area of chemical synapses. Synaptopathies = malfunctioning synapses are a reason for many neurological disorders and neurodegenerative diseases.

Focus

Research in our laboratory focuses on molecules and mechanisms that play a role in the development and the structural and functional organization of chemical synapses in the Central Nervous System (CNS). We want to understand how synapses form during synaptogenesis, how they mature, turnover and plastically change, how they release neurotransmitter presynaptically and bind neurotransmitter and process the signal postsynaptically. Molecules of interest include cytomatrix proteins at the active zone, proteins of the neurotransmitter exocytosis machinery, neurotransmitter receptors and their interacting molecules, clustering molecules, and various kinds of membrane channels.
With our studies we hope to contribute to a better understanding of the structure and function of chemical synapses in health and disease.

The mammalian retina – a model system in the neurosciences

The mammalian retina is the main experimental system used in our studies. The retina is part of the CNS and the clear structure, the highly detailed anatomy, the easy accessibility for experimental perturbations, and the presence of morphologically and functionally distinct types of chemical synapses – conventional and ribbon synapses – make the retina one of the most important model systems in the neurosciences. The retinal photoreceptor ribbon synapses, for example, are structurally and functionally specialized for the continuous release of neurotransmitter, which makes them the most complex type of chemical synapse found in the CNS.

Methods

In our experimental approach, we combine neuroanatomical, immunocytochemical, biochemical, molecular, cell biological and physiological methods to investigate the retinae of wildtype, mutant, and transgenic mice.

Selected Publications

  • Ryl M, Urbasik A, Gierke K, Babai N, Joachimsthaler A, Feigenspan A, Frischknecht R, Stallwitz N, Fejtová A, Kremers J, von Wittgenstein J, Brandstätter JH (2021) Genetic disruption of bassoon in two mutant mouse lines causes divergent retinal phenotypes. FASEB J. 2021 May;35(5):e21520. doi: 1096/fj.202001962R. PMID: 33811381
  • Gierke K, von Wittgenstein J, Hemmerlein M, Atorf J, Joachimsthaler A, Kremers J, Cooper BH, Varoqueaux F, Regus-Leidig H, Brandstätter JH (2020) Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice. Int J Mol Sci. 2020 Oct 22;21(21):E7848. doi: 10.3390/ijms21217848. PMID: 33105896
  • Müller TM, Gierke K, Joachimsthaler A, Sticht H, Izsvák Z, Hamra FK, Fejtová A, Ackermann F, Garner CC, Kremers J, Brandstätter JH*, Regus-Leidig H* (2019) A multiple Piccolino-RIBEYE interaction supports plate-shaped synaptic ribbons in retinal neurons. J Neurosci. 2019 Apr 3;39:2606-2619. doi: 10.1523/JNEUROSCI.2038-18.2019. (*shared corresponding authors). PMID: 30696732
  • Babai N, Gierke K, Müller T, Regus-Leidig H, Brandstätter JH, Feigenspan A (2019) Signal transmission at invaginating cone photoreceptor synaptic contacts following deletion of the presynaptic cytomatrix protein Bassoon in mouse retina. Acta Physiol (Oxf). 2019 Jun;226(2):e13241. doi: 10.1111/apha.13241. Epub 2019 Jan 12. PMID: 30554473
  • Eulenburg V, Knop G, Sedmak T, Schuster S, Hauf K, Schneider J, Feigenspan A, Joachimsthaler A, Brandstätter JH (2018) GlyT1 determines the glycinergic phenotype of amacrine cells in the mouse retina. Brain Struct Funct. 2018 Sep;223(7):3251-3266. doi: 10.1007/s00429-018-1684-3. Epub 2018 May 28. PMID: 29808289
  • Löhner M, Babai N, Müller T, Gierke K, Altorf J, Joachimsthaler A, Peukert A, Martens H, Feigenspan A, Kremers J, Schoch S, Brandstätter JH, Regus-Leidig H (2017) Analysis of RIM expression and function at mouse photoreceptor ribbbon synapses. J Neurosci. 2017 Aug 16;37(33):7848-7863. doi: 10.1523/JNEUROSCI.2795-16.2017. Epub 2017 Jul 12. PMID: 28701482
  • Babai N, Sendelbeck A, Regus-Leidig H, Fuchs M, Mertins J, Reim K, Brose N, Feigenspan A, Brandstätter JH (2016) Functional roles of Complexin 3 and Complexin 4 at mouse photoreceptor ribbon synapses. J Neurosci. 2016 Jun 22;36(25):6651-67. doi: 10.1523/JNEUROSCI.4335-15.2016. PMID: 27335398
  • Cooper B, Hemmerlein M, Ammermüller J, Imig C, Reim K, Lipstein N, Kalla S, Kawabe H, Brose N, Brandstätter JH*, Varoqueaux F* (2012) Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses. J Neurosci. 2012 Jun 6;32(23):8040-52. doi: 10.1523/JNEUROSCI.4240-11.2012. (*shared corresponding)
  • Reim K, Regus-Leidig H, Ammermüller J, El-Kordi A, Radyushkin K, Ehrenreich H, Brandstätter JH*, Brose N* (2009) Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4. J Cell Sci. 2009 May 1;122(Pt 9):1352-61. doi: 10.1242/jcs.045401. (*shared corresponding authors). PMID: 19386896
  • Regus-Leidig H, tom Dieck S, Specht D, Meyer L, Brandstätter JH (2009) Early steps in the assembly of photoreceptor ribbon synapses: The involvement of precursor spheres. J Comp Neurol. 2009 Feb 20;512(6):814-24. doi: 10.1002/cne.21915. PMID: 19067356
  • Specht D, tom Dieck S, Ammermüller J, Regus-Leidig H, Gundelfinger ED, Brandstätter JH (2007) Structural and functional remodeling in the retina of a mouse with a photoreceptor synaptopathy: plasticity in the rod and degeneration in the cone system. Eur J Neurosci. 2007 Nov;26(9):2506-15. doi: 10.1111/j.1460-9568.2007.05886.x. Epub 2007 Oct 23. PMID: 17970721
  • Reim K*, Wegmeyer H*, Brandstätter JH*, Xue M*, Rosenmund C, Dresbach T, Hofmann K, Brose N (2005) Structurally and functionally unique complexins at retinal ribbon synapses. J Cell Biol. 2005 May 23;169(4):669-80. doi: 10.1083/jcb.200502115. (*shared first authors). PMID: 15911881
  • tom Dieck S, Altrock WD, Kessels M, Qualmann B, Regus H, Brauner D, Fejtová A, Bracko O, Gundelfinger ED, Brandstätter JH (2005) Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex. J Cell Biol. 2005 Feb 28;168(5):825-36. doi: 10.1083/jcb.200408157. Epub 2005 Feb 22. PMID: 15728193
  • Dick O, tom Dieck S, Altrock WD, Ammermüller R, Weiler R, Garner CC, Gundelfinger ED, Brandstätter JH (2003) The presynaptic active zone protein Bassoon is essential for photoreceptor ribbon synapse formation in the retina. Neuron. 2003 Mar 6;37(5):775-86. doi: 10.1016/s0896-6273(03)00086-2. PMID: 12628168

Publications in PubMed