MICE LACKING THE TRANSCRIPTIONAL COACTIVATOR PGC-1α EXHIBIT ALTERATIONS IN INHIBITORY SYNAPTIC TRANSMISSION IN THE MOTOR CORTEX

被引：24

作者：

Dougherty, S. E. ^{[1
]}

Bartley, A. F. ^{[2
]}

Lucas, E. K. ^{[1
]}

Hablitz, J. J. ^{[2
]}

Dobrunz, L. E. ^{[2
]}

Cowell, R. M. ^{[1
]}

机构：

[1] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA

[2] Univ Alabama Birmingham, Dept Neurobiol, Evelyn F McKnight Brain Inst, Civitan Int Res Ctr, Birmingham, AL 35294 USA

来源：

NEUROSCIENCE | 2014年 / 271卷

基金：

美国国家卫生研究院;

关键词：

peroxisome proliferator-activated receptor gamma coactivator 1 alpha; parvalbumin; inhibitory neurotransmission; motor cortex; interneuron; PARVALBUMIN-POSITIVE INTERNEURONS; SYNCHRONIZED GAMMA-OSCILLATIONS; BINDING PROTEIN PARVALBUMIN; SHORT-TERM PLASTICITY; MITOCHONDRIAL DYSFUNCTION; PERISOMATIC INHIBITION; ASSOCIATION ANALYSIS; RELEASE PROBABILITY; ENERGY-METABOLISM; KNOCKOUT MICE;

D O I：

10.1016/j.neuroscience.2014.04.023

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Peroxisome proliferator-activated receptor c coactivator 1 alpha (PGC-1 alpha) is a transcriptional coactivator known to regulate gene programs in a cell-specific manner in energy-demanding tissues, and its dysfunction has been implicated in numerous neurological and psychiatric disorders. Previous work from the Cowell laboratory indicates that PGC-1 alpha is concentrated in inhibitory interneurons and is required for the expression of the calcium buffer parvalbumin (PV) in the cortex; however, the impact of PGC-1 alpha deficiency on inhibitory neurotransmission in the motor cortex is not known. Here, we show that mice lacking PGC-1 alpha exhibit increased amplitudes and decreased frequency of spontaneous inhibitory postsynaptic currents in layer V pyramidal neurons. Upon repetitive train stimulation at the gamma frequency, decreased GABA release is observed. Furthermore, PV-positive interneurons in PGC-1 alpha -/- mice display reductions in intrinsic excitability and excitatory input without changes in gross interneuron morphology. Taken together, these data show that PGC-1 alpha is required for normal inhibitory neurotransmission and cortical PV-positive interneuron function. Given the pronounced motor dysfunction in PGC-1 alpha -/- mice and the essential role of

引用

页码：137 / 148

页数：12

共 49 条

[1] The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons [J].

Alberi, Lavinia ;

Lintas, Alessandra ;

Kretz, Robert ;

Schwaller, Beat ;

Villa, Alessandro E. P. .

JOURNAL OF NEUROPHYSIOLOGY, 2013, 109 (11) :2827-2841

[2] Differential activity-dependent, homeostatic plasticity of two neocortical inhibitory circuits [J].

Bartley, Aundrea F. ;

Huang, Z. Josh ;

Huber, Kimberly M. ;

Gibson, Jay R. .

JOURNAL OF NEUROPHYSIOLOGY, 2008, 100 (04) :1983-1994

[3] Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks [J].

Bartos, M ;

Vida, I ;

Frotscher, M ;

Meyer, A ;

Monyer, H ;

Geiger, JRP ;

Jonas, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :13222-13227

[4] Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks [J].

Bartos, Marlene ;

Vida, Imre ;

Jonas, Peter .

NATURE REVIEWS NEUROSCIENCE, 2007, 8 (01) :45-56

[5] Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity [J].

Caillard, O ;

Moreno, H ;

Schwaller, B ;

Llano, I ;

Celio, MR ;

Marty, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (24) :13372-13377

[6] Experience and activity-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period [J].

Chattopadhyaya, B ;

Di Cristo, G ;

Higashiyama, H ;

Knott, GW ;

Kuhlman, SJ ;

Welker, E ;

Huang, ZJ .

JOURNAL OF NEUROSCIENCE, 2004, 24 (43) :9598-9611

[7] Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington's disease following chronic energy deprivation [J].

Chaturvedi, Rajnish K. ;

Calingasan, Noel Y. ;

Yang, Lichuan ;

Hennessey, Thomas ;

Johri, Ashu ;

Beal, M. Flint .

HUMAN MOLECULAR GENETICS, 2010, 19 (16) :3190-3205

[8] Association analysis of the chromosome 4p15-p16 candidate region for bipolar disorder and schizophrenia [J].

Christoforou, A. ;

Le Hellard, S. ;

Thomson, P. A. ;

Morris, S. W. ;

Tenesa, A. ;

Pickard, B. S. ;

Wray, N. R. ;

Muir, W. J. ;

Blackwood, D. H. ;

Porteous, D. J. ;

Evans, K. L. .

MOLECULAR PSYCHIATRY, 2007, 12 (11) :1011-1025

[9] Identification of novel targets for PGC-1α and histone deacetylase inhibitors in neuroblastoma cells [J].

Cowell, Rita M. ;

Talati, Pratik ;

Blake, Kathryn R. ;

Meador-Woodruff, James H. ;

Russell, James W. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 379 (02) :578-582

[10] Localization of the transcriptional coactivator PGG-1α to GABAergic neurons during maturation of the rat brain [J].

Cowell, Rita Marie ;

Blake, Kathryn Rose ;

Russell, James W. .

JOURNAL OF COMPARATIVE NEUROLOGY, 2007, 502 (01) :1-18

← 1 2 3 4 5 →