| Title | Regionalized loss of parvalbumin interneurons in the cerebral cortex of mice with deficits in GFRalpha1 signaling. | | Author(s) | Canty AJ, Dietze J, Harvey M, Enomoto H, Milbrandt J, Ibáñez CF | | Institution | Department of Neuroscience, Division of Molecular Neurobiology, Karolinska Institute, S-171 77 Stockholm, Sweden. | | Source | J Neurosci 2009 Aug 26; 29(34):10695-705. | | MeSH | Action Potentials
Age Factors
Animals
Animals, Newborn
Brain Mapping
Caspase 3
Cell Death
Cerebral Cortex
Disease Models, Animal
Glial Cell Line-Derived Neurotrophic Factor Receptors
Glutamate Decarboxylase
Green Fluorescent Proteins
Homeodomain Proteins
Intermediate Filament Proteins
Interneurons
Maze Learning
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins
Neural Inhibition
Parvalbumins
Pentylenetetrazole
Seizures
Signal Transduction
Social Behavior
gamma-Aminobutyric Acid
| | Abstract | Inhibitory interneurons are crucially important for cerebral cortex function and behavior. The mechanisms controlling inhibitory interneuron diversification and allocation to distinct cortical areas remain poorly understood. GDNF (glial cell line-derived neurotrophic factor) and its receptor GFRalpha1 have been implicated in the development of GABAergic precursors but, because of the early lethality of null mutants, their roles in postnatal maturation and function of cortical interneurons are unknown. "cis-only" mutant mice lack GFRalpha1 only in cells that do not express the RET signaling receptor subunit and survive to adulthood. At birth, both null mutants and cis-only mice showed a specific loss of GABAergic interneurons in rostro- and caudolateral cortical regions but not in more medial areas. Unexpectedly, the adult cortex of cis-only mice displayed a complete loss of parvalbumin (PV)-expressing GABAergic interneurons in discrete regions (PV holes) interspersed among areas of normal PV cell density. PV holes predominantly occurred in the visual and frontal cortices, and their size could be affected by neuronal activity. Consistent with deficits in cortical inhibitory activity, these mice showed enhanced cortical excitability, increased sensitivity to epileptic seizure, and increased social behavior. We propose that GFRalpha1 signaling guides the development of a subset of PV-expressing GABAergic interneurons populating discrete regions of the cerebral cortex and may thus contribute to the diversification and allocation of specific cortical interneuron subtypes. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19710321 |
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