Abstract
The maturation of inhibitory circuits during adolescence may be tied to the onset of mental health disorders such as schizophrenia. Neurotrophin signaling likely plays a critical role in supporting inhibitory circuit development and is also implicated in psychiatric disease. Within the neocortex, subcircuits may mature at different times and show differential sensitivity to neurotrophin signaling. We measured miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs) in Layer 5 cell-types in the mouse anterior cingulate (Cg) across the periadolescent period. We differentiated cell-types mainly by Thy1 YFP transgene expression and also retrobead injection labeling in the contralateral Cg and ipsilateral pons. We found that YFP− neurons and commissural projecting neurons had lower frequency of mIPSCs than neighboring YFP+ neurons or pons projecting neurons in juvenile mice (P21–25). YFP− neurons and to a lesser extent commissural projecting neurons also showed a significant increase in mIPSC amplitude during the periadolescent period (P21–25 vs. P40–50), which was not seen in YFP+ neurons or pons projecting neurons. Systemic disruption of tyrosine kinase receptor B (TrkB) signaling during P23–50 in TrkBF616A mice blocked developmental changes in mIPSC amplitude, without affecting miniature excitatory post synaptic currents (mEPSCs). Our data suggest that the maturation of inhibitory inputs onto Layer 5 pyramidal neurons is cell-type specific. These data may inform our understanding of adolescent brain development across species and aid in identifying candidate subcircuits that may show greater vulnerability in mental illness.
Highlights
Inhibitory circuits in the prefrontal cortex are known to synchronize the firing of excitatory projection neurons (Cardin et al, 2009; Sohal et al, 2009) as well as influence synaptic plasticity (Sakata et al, 2009), both of which are thought to modulate executive functions such as behavioral regulation, flexibility, and working memory (Gonzalez-Burgos et al, 2011; Le Magueresse and Monyer, 2013)
We found that while miniature excitatory post synaptic currents (mEPSCs) measures did not differ between YFP+ and YFP− neurons, YFP+ and Pons projecting neurons had a significantly higher miniature excitatory (mEPSCs) and inhibitory (mIPSCs) frequency compared to adjacent YFP− or COM projecting neurons
CELL TYPE SPECIFIC DIFFERENCES IN mIPSCs IN LAYER 5 OF THE CINGULATE CORTEX We first examined whether synaptic inputs differ between different types of projection neurons in Layer 5 of the Cg cortex
Summary
Inhibitory circuits in the prefrontal cortex are known to synchronize the firing of excitatory projection neurons (Cardin et al, 2009; Sohal et al, 2009) as well as influence synaptic plasticity (Sakata et al, 2009), both of which are thought to modulate executive functions such as behavioral regulation, flexibility, and working memory (Gonzalez-Burgos et al, 2011; Le Magueresse and Monyer, 2013). There are still conflicting reports whether local GABAergic circuits differentially regulate specific excitatory subnetworks in the frontal cortex (Lewis et al, 2005; Otte et al, 2010; Fino and Yuste, 2011; Packer and Yuste, 2011; Krook-Magnuson et al, 2012; Le Magueresse and Monyer, 2013; Lee et al, 2014a,b) In this context, it is unknown whether neurotrophin signaling acts to regulate the maturation of inhibition onto different neuron subtypes in a homogenous or specific fashion. Cell-type and circuit specific organization and vulnerability may be important for understanding the etiology of psychiatric disease
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.
