Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional CCK-Positive Basket Cell Terminals on Pyramidal Cells

Simon Früh; Jennifer Romanos; Patrizia Panzanelli; Daniela Bürgisser; Shiva K Tyagarajan; Kevin P Campbell; Mirko Santello; Jean-Marc Fritschy

doi:10.1523/JNEUROSCI.1823-16.2016

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Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional CCK-Positive Basket Cell Terminals on Pyramidal Cells

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Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional CCK-Positive Basket Cell Terminals on Pyramidal Cells

Simon Früh, Jennifer Romanos, Patrizia Panzanelli, Daniela Bürgisser, Shiva K Tyagarajan, Kevin P Campbell, Mirko Santello and Jean-Marc Fritschy

The Journal of neuroscience, Vol.36(40), pp.10296 -10313

10/05/2016

DOI: 10.1523/JNEUROSCI.1823-16.2016

PMCID: PMC6705590

PMID: 27707967

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Abstract

Distinct types of GABAergic interneurons target different subcellular domains of pyramidal cells, thereby shaping pyramidal cell activity patterns. Whether the presynaptic heterogeneity of GABAergic innervation is mirrored by specific postsynaptic factors is largely unexplored. Here we show that dystroglycan, a protein responsible for the majority of congenital muscular dystrophies when dysfunctional, has a function at postsynaptic sites restricted to a subset of GABAergic interneurons. Conditional deletion of Dag1, encoding dystroglycan, in pyramidal cells caused loss of CCK-positive basket cell terminals in hippocampus and neocortex. PV-positive basket cell terminals were unaffected in mutant mice, demonstrating interneuron subtype-specific function of dystroglycan. Loss of dystroglycan in pyramidal cells had little influence on clustering of other GABAergic postsynaptic proteins and of glutamatergic synaptic proteins. CCK-positive terminals were not established at P21 in the absence of dystroglycan and were markedly reduced when dystroglycan was ablated in adult mice, suggesting a role for dystroglycan in both formation and maintenance of CCK-positive terminals. The necessity of neuronal dystroglycan for functional innervation by CCK-positive basket cell axon terminals was confirmed by reduced frequency of inhibitory events in pyramidal cells of dystroglycan-deficient mice and further corroborated by the inefficiency of carbachol to increase IPSC frequency in these cells. Finally, neurexin binding seems dispensable for dystroglycan function because knock-in mice expressing binding-deficient T190M dystroglycan displayed normal CCK-positive terminals. Together, we describe a novel function of dystroglycan in interneuron subtype-specific trans-synaptic signaling, revealing correlation of presynaptic and postsynaptic molecular diversity.

Interneurons - physiology

Muscarinic Agonists - pharmacology

Mice, Inbred C57BL

Male

Presynaptic Terminals - physiology

Excitatory Postsynaptic Potentials - drug effects

Gene Knock-In Techniques

Mice, Knockout

gamma-Aminobutyric Acid - physiology

Carbachol - pharmacology

Cholecystokinin - metabolism

Animals

Parasympathetic Nervous System - drug effects

Pyramidal Cells - physiology

Neural Cell Adhesion Molecules - metabolism

Dystroglycans - genetics

Female

Parasympathetic Nervous System - physiology

Mice

Dystroglycans - physiology

Details

Title: Subtitle: Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional CCK-Positive Basket Cell Terminals on Pyramidal Cells
Creators: Simon Früh - Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland, Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland
Jennifer Romanos - Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland, Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland
Patrizia Panzanelli - Department of Neuroscience Rita Levi Montalcini, University of Turin, 10124 Turin, Italy
Daniela Bürgisser - ETH Zurich, 8092 Zurich, Switzerland
Shiva K Tyagarajan - Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland, Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland
Kevin P Campbell - University of Iowa, Molecular Physiology and Biophysics
Mirko Santello - Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland, Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland
Jean-Marc Fritschy - Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland, Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland fritschy@pharma.uzh.ch
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.36(40), pp.10296 -10313
DOI: 10.1523/JNEUROSCI.1823-16.2016
PMID: 27707967
PMCID: PMC6705590
NLM abbreviation: J Neurosci
eISSN: 1529-2401
Publisher: Society for Neuroscience; United States
Grant note: U54 NS053672 / NINDS NIH HHS
Language: English
Date published: 10/05/2016
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984034100202771

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