Minimal Change in the cytoplasmic calcium dynamics in striatal GABAergic neurons of a DYT1 dystonia knock-in mouse model

Sadahiro Iwabuchi; Jin-Young Koh; Kai Wang; K W David Ho; N Charles Harata

doi:10.1371/journal.pone.0080793

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Minimal Change in the cytoplasmic calcium dynamics in striatal GABAergic neurons of a DYT1 dystonia knock-in mouse model

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Minimal Change in the cytoplasmic calcium dynamics in striatal GABAergic neurons of a DYT1 dystonia knock-in mouse model

Sadahiro Iwabuchi, Jin-Young Koh, Kai Wang, K W David Ho and N Charles Harata

PloS one, Vol.8(11), pp.e80793-e80793

2013

DOI: 10.1371/journal.pone.0080793

PMCID: PMC3834333

PMID: 24260480

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Abstract

DYT1 dystonia is the most common hereditary form of primary torsion dystonia. This autosomal-dominant disorder is characterized by involuntary muscle contractions that cause sustained twisting and repetitive movements. It is caused by an in-frame deletion in the TOR1A gene, leading to the deletion of a glutamic acid residue in the torsinA protein. Heterozygous knock-in mice, which reproduce the genetic mutation in human patients, have abnormalities in synaptic transmission at the principal GABAergic neurons in the striatum, a brain structure that is involved in the execution and modulation of motor activity. However, whether this mutation affects the excitability of striatal GABAergic neurons has not been investigated in this animal model. Here, we examined the excitability of cultured striatal neurons obtained from heterozygous knock-in mice, using calcium imaging as indirect readout. Immunofluorescence revealed that more than 97% of these neurons are positive for a marker of GABAergic neurons, and that more than 92% are also positive for a marker of medium spiny neurons, indicating that these are mixed cultures of mostly medium spiny neurons and a few (~5%) GABAergic interneurons. When these neurons were depolarized by field stimulation, the calcium concentration in the dendrites increased rapidly and then decayed slowly. The amplitudes of calcium transients were larger in heterozygous neurons than in wild-type neurons, resulting in ~15% increase in cumulative calcium transients during a train of stimuli. However, there was no change in other parameters of calcium dynamics. Given that calcium dynamics reflect neuronal excitability, these results suggest that the mutation only slightly increases the excitability of striatal GABAergic neurons in DYT1 dystonia.

Dystonic Disorders - genetics

Calcium - metabolism

Cholinergic Neurons - metabolism

Cells, Cultured

Cytoplasm - metabolism

Mice, Transgenic

Dystonia Musculorum Deformans - genetics

Corpus Striatum - metabolism

Action Potentials

Animals

Interneurons - metabolism

Heterozygote

Mice

GABAergic Neurons - metabolism

Mutation

Disease Models, Animal

Details

Title: Subtitle: Minimal Change in the cytoplasmic calcium dynamics in striatal GABAergic neurons of a DYT1 dystonia knock-in mouse model
Creators: Sadahiro Iwabuchi - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America
Jin-Young Koh
Kai Wang
K W David Ho
N Charles Harata
Resource Type: Journal article
Publication Details: PloS one, Vol.8(11), pp.e80793-e80793
DOI: 10.1371/journal.pone.0080793
PMID: 24260480
PMCID: PMC3834333
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 2013
Academic Unit: Molecular Physiology and Biophysics; Biostatistics; Otolaryngology
Record Identifier: 9983997344502771

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