Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex.

Affiliation

Harkness JH(#)(1)(2), Gonzalez AE(#)(1)(2), Bushana PN(3), Jorgensen ET(4), Hegarty DM(5), Di Nardo AA(6), Prochiantz A(6), Wisor JP(3), Aicher SA(5), Brown TE(4), Sorg BA(7)(8).
Author information:
(1)Department of Integrative Physiology and Neuroscience, Washington State University Vancouver, Washington, 98686, USA.
(2)Dow Neurobiology, Legacy Research Institute, 1225 NE 2nd Ave, Portland, OR, 97232, USA.
(3)Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University Spokane, Washington, 99202, USA.
(4)Department of Pharmaceutical Science, University of Wyoming, Laramie, WY, 82071, USA.
(5)Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, 97239, USA.
(6)Centre for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Labex MemoLife, 75005, Paris, France.
(7)Department of Integrative Physiology and Neuroscience, Washington State University Vancouver, Washington, 98686, USA. [Email]
(8)Dow Neurobiology, Legacy Research Institute, 1225 NE 2nd Ave, Portland, OR, 97232, USA. [Email]
(#)Contributed equally

Abstract

Perineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) interneurons provide excitatory:inhibitory balance, which is impaired in several disorders associated with altered diurnal rhythms, yet few studies have examined diurnal rhythms of PNNs or PV cells. We measured the intensity and number of PV cells and PNNs labeled with Wisteria floribunda agglutinin (WFA) and also the oxidative stress marker 8-oxo-deoxyguanosine (8-oxo-dG) in rat prelimbic medial prefrontal cortex (mPFC) at Zeitgeber times (ZT) ZT0 (lights-on, inactive phase), ZT6 (mid-inactive phase), ZT12 (lights-off, active phase), and ZT18 (mid-active phase). Relative to ZT0, the intensities of PNN and PV labeling were increased in the dark (active) phase compared with the light (inactive) phase. The intensity of 8-oxo-dG was decreased from ZT0 at all times (ZT6,12,18). We also measured GAD 65/67 and vGLUT1 puncta apposed to PV cells with and without PNNs. There were more excitatory puncta on PV cells with PNNs at ZT18 vs. ZT6, but no changes in PV cells without PNNs and no changes in inhibitory puncta. Whole-cell slice recordings in fast-spiking (PV) cells with PNNs showed an increased ratio of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:N-methyl-D-aspartate receptor (AMPA: NMDA) at ZT18 vs. ZT6. The number of PV cells and PV/PNN cells containing orthodenticle homeobox 2 (OTX2), which maintains PNNs, showed a strong trend toward an increase from ZT6 to ZT18. Diurnal fluctuations in PNNs and PV cells are expected to alter cortical excitatory:inhibitory balance and provide new insights into treatments for diseases impacted by disturbances in sleep and circadian rhythms.