Increased GABAergic function in mouse models of Huntington's disease: Reversal by BDNF

• DOI: 10.1002/jnr.20344
• Publication Date: 2004-11-12T20:46:53Z
• Authors: Carlos Cepeda; Amaal J. Starling; Nanping Wu; Oanh K. Nguyen; Besim Uzgil; Takahiro Soda; Veronique M. André; Marjorie A. Ariano; Michael S. Levine
• Keywords: Medium spiny neuron; Gamma-Aminobutyric Acid; Postsynaptic Current

Abstract Huntington's disease (HD) is characterized by loss of striatal γ‐aminobutyric acid (GABA)ergic medium‐sized spiny projection neurons (MSSNs), whereas some classes interneurons are relatively spared. Striatal provide most the inhibitory synaptic input to MSSNs and use GABA as their neurotransmitter. We reported previously alterations in glutamatergic activity R6/2 R6/1 mouse models HD. In present study, we used whole‐cell voltage clamp recordings examine GABAergic currents from slices these two compared those age‐matched control littermates. The frequency spontaneous was increased significantly transgenics starting around 5–7 weeks (when overt behavioral phenotype begins) continuing 9–14‐week‐old mice. A similar increase observed 12–15‐month‐old transgenics. Bath application brain‐derived neurotrophic factor, which downregulated HD, reduced but not mice at 9–14 weeks. Increased current densities also occurred acutely isolated animals. Immunofluorescence demonstrated expression ubiquitous α1 subunit receptors These results indicate that increases postsynaptic receptor function occur parallel progressive decreases inputs MSSNs. conjunction, both changes will severely alter outputs target areas involved movement. © 2004 Wiley‐Liss, Inc.