Chronic Stress Alters Synaptic Inhibition/Excitation Balance of Pyramidal Neurons But Not PV Interneurons in the Infralimbic and Prelimbic Cortices of C57BL/6J Mice

Overview

Journal eNeuro

Specialty Neurology

Date 2024 Aug 15

PMID 39147579

Authors

Diana Rodrigues

Catia Santa

Bruno Manadas

Patricia Monteiro

Affiliations

Soon will be listed here.

Abstract

The medial prefrontal cortex (mPFC) plays a pivotal role in regulating working memory, executive function, and self-regulatory behaviors. Dysfunction in the mPFC circuits is a characteristic feature of several neuropsychiatric disorders including schizophrenia, depression, and post-traumatic stress disorder. Chronic stress (CS) is widely recognized as a major triggering factor for the onset of these disorders. Although evidence suggests synaptic dysfunction in mPFC circuits following CS exposure, it remains unclear how different neuronal populations in the infralimbic (IL) and prelimbic (PL) cortices are affected in terms of synaptic inhibition/excitation balance (/ ratio). Here, using neuroproteomic analysis and whole-cell patch-clamp recordings in pyramidal neurons (PNs) and parvalbumin (PV) interneurons within the PL and IL cortices, we examined the synaptic changes after 21 d of chronic unpredictable stress, in male mice. Our results reveal distinct impacts of CS on PL and IL PNs, resulting in an increased / ratio in both subregions but through different mechanisms: CS increases inhibitory synaptic drive in the PL while decreasing excitatory synaptic drive in the IL. Notably, the / ratio and excitatory and inhibitory synaptic drive of PV interneurons remained unaffected in both PL and IL circuits following CS exposure. These findings offer novel mechanistic insights into the influence of CS on mPFC circuits and support the hypothesis of stress-induced mPFC hypofunction.

References

Park J, Moghaddam B . Impact of anxiety on prefrontal cortex encoding of cognitive flexibility. Neuroscience. 2016; 345:193-202. PMC: 5159328. DOI: 10.1016/j.neuroscience.2016.06.013. View

Arnsten A . Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. 2009; 10(6):410-22. PMC: 2907136. DOI: 10.1038/nrn2648. View

Croft D, OKelly G, Wu G, Haw R, Gillespie M, Matthews L . Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Res. 2010; 39(Database issue):D691-7. PMC: 3013646. DOI: 10.1093/nar/gkq1018. View

McKlveen J, Morano R, Fitzgerald M, Zoubovsky S, Cassella S, Scheimann J . Chronic Stress Increases Prefrontal Inhibition: A Mechanism for Stress-Induced Prefrontal Dysfunction. Biol Psychiatry. 2016; 80(10):754-764. PMC: 5629635. DOI: 10.1016/j.biopsych.2016.03.2101. View

Shepard R, Page C, Coutellier L . Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders. Neuroscience. 2016; 332:1-12. DOI: 10.1016/j.neuroscience.2016.06.038. View

Furman O, Tsoory M, Chen A . Differential chronic social stress models in male and female mice. Eur J Neurosci. 2021; 55(9-10):2777-2793. DOI: 10.1111/ejn.15481. View

Woo J, Kwon S, Kim E . The NGL family of leucine-rich repeat-containing synaptic adhesion molecules. Mol Cell Neurosci. 2009; 42(1):1-10. DOI: 10.1016/j.mcn.2009.05.008. View

Schwabe L, Wolf O . Socially evaluated cold pressor stress after instrumental learning favors habits over goal-directed action. Psychoneuroendocrinology. 2010; 35(7):977-86. DOI: 10.1016/j.psyneuen.2009.12.010. View

Cerqueira J, Mailliet F, Almeida O, Jay T, Sousa N . The prefrontal cortex as a key target of the maladaptive response to stress. J Neurosci. 2007; 27(11):2781-7. PMC: 6672565. DOI: 10.1523/JNEUROSCI.4372-06.2007. View

10.

Kaiser T, Ting J, Monteiro P, Feng G . Transgenic labeling of parvalbumin-expressing neurons with tdTomato. Neuroscience. 2015; 321:236-245. PMC: 4769998. DOI: 10.1016/j.neuroscience.2015.08.036. View

11.

Selten M, van Bokhoven H, Nadif Kasri N . Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders. F1000Res. 2018; 7:23. PMC: 5760969. DOI: 10.12688/f1000research.12155.1. View

12.

McEwen B, Eiland L, Hunter R, Miller M . Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology. 2011; 62(1):3-12. PMC: 3196296. DOI: 10.1016/j.neuropharm.2011.07.014. View

13.

Radley J, Morrison J . Repeated stress and structural plasticity in the brain. Ageing Res Rev. 2005; 4(2):271-87. DOI: 10.1016/j.arr.2005.03.004. View

14.

Ferguson B, Gao W . PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders. Front Neural Circuits. 2018; 12:37. PMC: 5964203. DOI: 10.3389/fncir.2018.00037. View

15.

Moghaddam B . The Complicated Relationship of Stress and Prefrontal Cortex. Biol Psychiatry. 2016; 80(10):728-729. DOI: 10.1016/j.biopsych.2016.09.008. View

16.

Ulrich-Lai Y, Herman J . Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009; 10(6):397-409. PMC: 4240627. DOI: 10.1038/nrn2647. View

17.

Kim S, Burette A, Chung H, Kwon S, Woo J, Lee H . NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat Neurosci. 2006; 9(10):1294-301. DOI: 10.1038/nn1763. View

18.

Hok V, Save E, Lenck-Santini P, Poucet B . Coding for spatial goals in the prelimbic/infralimbic area of the rat frontal cortex. Proc Natl Acad Sci U S A. 2005; 102(12):4602-7. PMC: 555486. DOI: 10.1073/pnas.0407332102. View

19.

Harris K, Shepherd G . The neocortical circuit: themes and variations. Nat Neurosci. 2015; 18(2):170-81. PMC: 4889215. DOI: 10.1038/nn.3917. View

20.

Fogaca M, Duman R . Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions. Front Cell Neurosci. 2019; 13:87. PMC: 6422907. DOI: 10.3389/fncel.2019.00087. View