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Regionalized loss of Parvalbumin interneurons in the cerebral cortex of mice lacking RET-independent GFRα 1

Citation

Canty, A and Dietze, J and Harvey, M and Enomoto, H and Milbrandt, J and Ibanez, CF, Regionalized loss of Parvalbumin interneurons in the cerebral cortex of mice lacking RET-independent GFRα 1, Journal of Neuroscience, 29, (34) pp. 10695-10705. ISSN 0270-6474 (2009) [Refereed Article]

DOI: doi:10.1523/JNEUROSCI.2658-09.2009

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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Canty, A (Associate Professor Alison Canty)
ID Code:69927
Year Published:2009
Web of Science® Times Cited:40
Deposited By:Medicine
Deposited On:2011-05-25
Last Modified:2011-05-25
Downloads:0

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