Selective cortical interneuron and GABA deficits in cyclin D2-null mice.
In contrast to cyclin D1 nulls (cD1-/-), mice without cyclin D2 (cD2-/-) lack cerebellar stellate interneurons; the reason for this is unknown. In the present study in cortex, we found a disproportionate loss of parvalbumin (PV) interneurons in cD2-/- mice. This selective reduction in PV subtypes was associated with reduced frequency of GABA-mediated inhibitory postsynaptic currents in pyramidal neurons, as measured by voltage-clamp recordings, and increased cortical sharp activity in the EEGs of awake-behaving cD2-/- mice. Cell cycle regulation was examined in the medial ganglionic eminence (MGE), the major source of PV interneurons in mouse brain, and differences between cD2-/- and cD1-/- suggested that cD2 promotes subventricular zone (SVZ) divisions, exerting a stronger inhibitory influence on the p27 Cdk-inhibitor (Cdkn1b) to delay cell cycle exit of progenitors. We propose that cD2 promotes transit-amplifying divisions in the SVZ and that these ensure proper output of at least a subset of PV interneurons.
Glickstein
Sara B
SB
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA.
Moore
Holly
H
Slowinska
Bozena
B
Racchumi
Joelle
J
Suh
Minah
M
Chuhma
Nao
N
Ross
M Elizabeth
ME
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism*; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics*; D005260:Female; D019940:Genes, bcl-1 / Q000502:physiology; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009928:Organ Specificity; D010320:Parvalbumins / Q000378:metabolism; D011247:Pregnancy; D013569:Synapses / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000172:deficiency* / Q000378:metabolism
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid