Adolescent maturation of inhibitory inputs onto cingulate cortex neurons is cell-type specific and TrkB dependent
Open accessAbstract
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.
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In mice, the peripubertal increase in inhibition onto pyramidal cells is dependent on signaling through the TrkB receptor.
“In mice, this increase is dependent on signaling through the TrkB receptor (Vandenberg et al., 2015)”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Vandenberg et al., 2015
Inhibition onto pyramidal cells increases between juvenile and adolescent/adult groups in both mice and macaques.
“In contrast, inhibition onto pyramidal cells increases between juvenile and adolescent/adult groups in both mice and macaques (Delevich, 2014; Gonzalez-Burgos et al., 2015; Vandenberg et al., 2015).”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Vandenberg et al., 2015
Functional measures of excitatory AMPA and NMDA mediated currents in frontal cortex pyramidal neurons do not change between the juvenile and adolescent periods in macaques or mice.
“Functional measures of excitatory AMPA and NMDA mediated currents in frontal cortex pyramidal neurons do not change between the juvenile and adolescent periods in macaques or mice (Gonzalez-Burgos et al., 2008; Vandenberg et al., 2015)”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Vandenberg et al., 2015
In the frontal association cortex, measures of inhibitory neurotransmission onto pyramidal neurons increase from P21-25 to P40-50.
“In the frontal association cortex, measures of inhibitory neurotransmission onto pyramidal neurons increases from P21–25 to P40–50 (Vandenberg et al., 2015)”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Vandenberg et al., 2015
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- Authors
- Vandenberg, A., Piekarski, D. J., Caporale, N., Munoz-Cuevas, F. J., & Wilbrecht, L.
- Affiliations
- University of California, San Francisco (US)
- University of California, Berkeley (US)
- Corresponding author
- Wilbrecht, Linda
- Venue
- Frontiers in Neural Circuits
- Publisher
- Frontiers Media SA
- Published
- 2015-02-16
- Volume
- 9
- Pages
- 5-5
- ISSN
- 1662-5110 (ISSN-L)
- PMC
- PMC4329800
- OpenAlex
- W2000064453
- Cited by
- 22
- References
- 64
- Citations by year
- 2026: 2 · 2025: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 2
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neural Circuits (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Stryker
- National Institute of Mental Health (R01MH087542)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- adolescent brain development, inhibitory synapses, cingulate cortex, layer 5 pyramidal neurons, TrkB signaling, neurotrophin signaling, miniature inhibitory postsynaptic currents, cell type specificity, commissural neurons, schizophrenia vulnerability
- MeSH terms
- Aging, Animals, Female, Gyrus Cinguli, Male, Neural Inhibition, Neurons, Signal Transduction, Patch-Clamp Techniques, Excitatory Postsynaptic Potentials, Receptor, trkB, Mice, Inhibitory Postsynaptic Potentials, Neurogenesis
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