Abstract
SummaryCortical GABAergic interneurons are generated in large numbers in the ganglionic eminences and migrate into the cerebral cortex during embryogenesis. At early postnatal stages, during neuronal circuit maturation, autonomous and activity-dependent mechanisms operate within the cortex to adjust cell numbers by eliminating naturally occurring neuron excess. Here, we show that when cortical interneurons are generated in aberrantly high numbers—due to a defect in precursor cell proliferation during embryogenesis—extra parvalbumin interneurons persist in the postnatal mouse cortex during critical periods of cortical network maturation. Even though cell numbers are subsequently normalized, behavioral abnormalities remain in adulthood. This suggests that timely clearance of excess cortical interneurons is critical for correct functional maturation of circuits that drive adult behavior.
Highlights
Cortical interneurons are normally generated in large numbers during embryogenesis, and their excess is eliminated soon after birth through cell autonomous and activity-dependent mechanisms (Southwell et al, 2012; Wong et al, 2018)
Report ll insert in Figure 1A), and in order to identify the role of this transcription factor in this region, we generated a conditional mutant mouse lacking Cux2 in the medial GE (MGE) at early embryonic stages (Nkx21-Cre;Cux2fl/D) (Figure 1A; Figure S1A)
We refer to this model as the ‘‘early-conditional knockout’’ in which deletion takes place in progenitors residing in the ventricular zone (VZ) of the MGE prior to the onset of neuronal migration
Summary
Cortical interneurons are normally generated in large numbers during embryogenesis, and their excess is eliminated soon after birth through cell autonomous and activity-dependent mechanisms (Southwell et al, 2012; Wong et al, 2018). The embryonic ganglionic eminences (GEs) generate all the GABAergic interneurons found in the adult cortex (Bandler et al, 2017; Kessaris et al, 2014; Ma et al, 2013; Marın and Mu€ller, 2014; Wonders and Anderson, 2006). The medial GE (MGE) is the source of two major classes of interneurons that express parvalbumin (PV) or somatostatin (SST) (Fogarty et al, 2007; Kessaris et al, 2014; Wonders and Anderson, 2006). The different neurogenic niche origins of these two ‘‘cardinal’’ interneuron classes suggest that their generation may be subject to distinct regulation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
