Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice

Karen Müller Smith; Devon M Fagel; Hanna E Stevens; Rebecca L Rabenstein; Maria Elisabetta Maragnoli; Yasushi Ohkubo; Marina R Picciotto; Michael L Schwartz; Flora M Vaccarino

doi:10.1016/j.biopsych.2007.09.020

Back

Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice

Journal article

Peer reviewed

Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice

Karen Müller Smith, Devon M Fagel, Hanna E Stevens, Rebecca L Rabenstein, Maria Elisabetta Maragnoli, Yasushi Ohkubo, Marina R Picciotto, Michael L Schwartz and Flora M Vaccarino

Biological psychiatry (1969), Vol.63(10), pp.953-962

2008

DOI: 10.1016/j.biopsych.2007.09.020

PMID: 17988653

View Online

Abstract

Motor hyperactivity due to hyper-dopaminergic neurotransmission in the basal ganglia is well characterized; much less is known about the role of the neocortex in controlling motor behavior. Locomotor behavior and motor, associative, and spatial learning were examined in mice with conditional null mutations of fibroblast growth factor receptor 1 (Fgfr1) restricted to telencephalic neural precursors ( Fgfr1 f/f;hGfapCre). Locomotor responses to a dopamine agonist (Amphetamine 2 mg/kg and Methylphenidate 10 mg/kg) and antagonists (SCH233390 .025 mg/kg and Haloperidol .2 mg/kg) were assessed. Stereological and morphological characterization of various monoaminergic, excitatory, and inhibitory neuronal subtypes was performed. Fgfr1 f/f;hGfapCre mice have spontaneous locomotor hyperactivity characterized by longer bouts of locomotion and fewer resting points that is significantly reduced by the D1 and D2 receptor antagonists. No differences in dopamine transporter, tyrosine hydroxylase, or serotonin immunostaining were observed in Fgfr1 f/f;hGfapCre mice. There was no change in cortical pyramidal neurons, but parvalbumin+, somatostatin+, and calbindin+ inhibitory interneurons were reduced in number in the cerebral cortex. The decrease in parvalbumin+ interneurons in cortex correlated with the extent of hyperactivity. Dysfunction in specific inhibitory cortical circuits might account for deficits in behavioral control, providing insights into the neurobiology of psychiatric disorders.

schizophrenia

Fgf

hyperactivity

GAD67

parvalbumin

Tourette Syndrome

Details

Title: Subtitle: Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice
Creators: Karen Müller Smith - Child Study Center, Yale University, New Haven, Connecticut
Devon M Fagel - Child Study Center, Yale University, New Haven, Connecticut
Hanna E Stevens - Child Study Center, Yale University, New Haven, Connecticut
Rebecca L Rabenstein - Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut
Maria Elisabetta Maragnoli - Child Study Center, Yale University, New Haven, Connecticut
Yasushi Ohkubo - Child Study Center, Yale University, New Haven, Connecticut
Marina R Picciotto - Department of Psychiatry, Yale University, New Haven, Connecticut
Michael L Schwartz - Department of Neurobiology, Yale University, New Haven, Connecticut
Flora M Vaccarino - Child Study Center, Yale University, New Haven, Connecticut
Resource Type: Journal article
Publication Details: Biological psychiatry (1969), Vol.63(10), pp.953-962
DOI: 10.1016/j.biopsych.2007.09.020
PMID: 17988653
NLM abbreviation: Biol Psychiatry
ISSN: 0006-3223
eISSN: 1873-2402
Publisher: Elsevier Inc
Language: English
Date published: 2008
Academic Unit: Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984004087302771

Metrics

30 Record Views

32 Times Cited - Web of Science

See more details