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

2020 ◽  
Author(s):  
John H. Harkness ◽  
Angela E. Gonzalez ◽  
Priyanka N. Bushana ◽  
Emily T. Jorgensen ◽  
Deborah M. Hegarty ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Active Phase ◽  
Autism Spectrum ◽  
Diurnal Rhythms ◽  
Oxidative Stress Marker ◽  
Perineuronal Nets ◽  
Diurnal Changes ◽  
Strong Trend ◽  
Fast Spiking

ABSTRACTPerineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) inhibitory interneurons are vital for providing excitatory:inhibitory balance within cortical circuits, and this balance is impaired in disorders such as schizophrenia, autism spectrum disorder, and substance use disorders. These disorders are also associated with altered diurnal rhythms, yet few studies have examined the diurnal rhythms of PNNs or PV cells. We measured the intensity and number of PV cells and PNNs labeled with Wisteria floribunda agglutinin (WFA) in the rat prelimbic medial prefrontal cortex (mPFC) at Zeitgeber times (ZT) ZT0, 6, 12, and 18. We also measured the oxidative stress marker 8-oxo-deoxyguanosine (8-oxo-dG). Relative to ZT0, the intensities of PNN and PV staining 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 time points (ZT6,12,18), in both PV cells and non-PV cells. To examine corresponding changes in inhibitory and excitatory inputs, we measured GAD 65/67 and vGlut1 puncta apposed to PV cells with and without PNNs. Relative to ZT6, there were more excitatory puncta on PV cells surrounded by PNNs at ZT18, but no changes in PV cells devoid of PNNs. No changes in inhibitory puncta were observed. 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 co-labeled PV/PNN cells containing the transcription factor orthodenticle homeobox 2 (OTX2), which maintains PNNs, showed a strong trend toward an increase from ZT6 to ZT18. These diurnal fluctuations in PNNs and PV cells are expected to alter cortical excitatory:inhibitory balance and provide new insights into treatment approaches for diseases impacted by imbalances in sleep and circadian rhythms.

scholarly journals 014 Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A7-A8
Author(s):  
Barbara Sorg ◽  
John Harkness ◽  
Angela Gonzalez ◽  
Priyanka Bushana ◽  
Emily Jorgensen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Diurnal Rhythms ◽  
Oxidative Stress Marker ◽  
Perineuronal Nets ◽  
Diurnal Changes ◽  
Strong Trend ◽  
Fast Spiking ◽  
Diurnal Fluctuations ◽  
Alcohol And Drug Abuse

Abstract Introduction Perineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) interneurons provide excitatory:inhibitory balance within cortical circuits. This balance is impaired in several disorders that are also associated with altered diurnal rhythms, yet few studies examined diurnal rhythms of PNNs or PV cells. Methods 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, 6, 12, and 18. To examine changes in inhibitory and excitatory inputs to PV cells, we measured GAD 65/67 and vGLUT1 puncta apposed to PV cells with and without PNNs. Whole-cell slice recordings in fast-spiking (PV) cells with PNNs was conducted to determine the ratio of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:N-methyl-D-aspartate receptor (AMPA:NMDA) at ZT18 vs. ZT6. Finally, the number of PV cells and PV/PNN cells containing orthodenticle homeobox 2 (OTX2), which maintains PNNs, was also assessed. Results Relative to ZT0, the intensities of PNN and PV labeling were increased in the dark compared with the light phase. The intensity of 8-oxo-dG was decreased from ZT0 at all times. 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. There was an increased AMPA:NMDA ratio at ZT18 vs. ZT6. The number of PV cells and PV/PNN cells containing OTX2 showed a strong trend toward an increase from ZT6 to ZT18, with no differences in non-PV-containing cells. Conclusion Diurnal fluctuations in PNNs and PV cells alter cortical excitatory:inhibitory balance. Detailed understanding of how these fluctuations are regulated should provide new insights into treatments for diseases impacted by disturbances in sleep and circadian rhythms. Ongoing studies are examining diurnal fluctuations in downstream signaling after PNN removal. Support (if any) Washington State University Alcohol and Drug Abuse Research Program, NIH GM134789 (JHH); NIH DA033404 (BAS), DA040965 (BAS, TEB, SAA); NIH NS078498 (JPW); NIH P30 NS061800 (SAA); and Agence Nationale de la Recherche ANR-18-CE16-0013-01 (AP and AAD).

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

2021 ◽  
Author(s):  
John H. Harkness ◽  
Angela E. Gonzalez ◽  
Priyanka N. Bushana ◽  
Emily T. Jorgensen ◽  
Deborah M. Hegarty ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Perineuronal Nets ◽  
Diurnal Changes ◽  
Parvalbumin Neurons

scholarly journals Cocaine Exposure Modulates Perineuronal Nets and Synaptic Excitability of Fast-Spiking Interneurons in the Medial Prefrontal Cortex

eNeuro ◽  
2018 ◽  
Vol 5 (5) ◽  
pp. ENEURO.0221-18.2018 ◽  
Author(s):  
Megan L. Slaker ◽  
Emily T. Jorgensen ◽  
Deborah M. Hegarty ◽  
Xinyue Liu ◽  
Yan Kong ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Perineuronal Nets ◽  
Cocaine Exposure ◽  
Fast Spiking

The Role of the Medial Prefrontal Cortex in Moderating Neural Representations of Self and Other in Primates

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Masaki Isoda
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Critical Role ◽  
Autism Spectrum ◽  
Annual Review ◽  
Publication Date ◽  
Self And Other ◽  
Neural Representations ◽  
The Social

As a frontal node in the primate social brain, the medial prefrontal cortex (MPFC) plays a critical role in coordinating one's own behavior with respect to that of others. Current literature demonstrates that single neurons in the MPFC encode behavior-related variables such as intentions, actions, and rewards, specifically for self and other, and that the MPFC comes into play when reflecting upon oneself and others. The social moderator account of MPFC function can explain maladaptive social cognition in people with autism spectrum disorder, which tips the balance in favor of self-centered perspectives rather than taking into consideration the perspective of others. Several strands of evidence suggest a hypothesis that the MPFC represents different other mental models, depending on the context at hand, to better predict others’ emotions and behaviors. This hypothesis also accounts for aberrant MPFC activity in autistic individuals while they are mentalizing others. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Effects of cross-rearing with social peers on myelination in the medial prefrontal cortex of a mouse model with autism spectrum disorder

Heliyon ◽  
2017 ◽  
Vol 3 (11) ◽  
pp. e00468 ◽  
Author(s):  
Manabu Makinodan ◽  
Kazuki Okumura ◽  
Daisuke Ikawa ◽  
Yasunori Yamashita ◽  
Kazuhiko Yamamuro ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Mouse Model ◽  
Medial Prefrontal Cortex ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats

2020 ◽  
Author(s):  
Sarah Jacot-Descombes ◽  
Neha U Keshav ◽  
Dara L. Dickstein ◽  
Bridget Wicinski ◽  
William G. M. Janssen ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Rat Model ◽  
Postsynaptic Density ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Head Diameter ◽  
Density Area ◽  
Synaptic Ultrastructure

Abstract Background Deletion or mutations of SHANK3 lead to Phelan-McDermid syndrome and monogenic forms of autism spectrum disorder. SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered dendritic and spine morphology in the hippocampus, cerebellum and striatum have been associated with behavioral impairments in various Shank3-deficient animal models. Given the attentional deficit reported in these animals, our study explored whether deficiency of Shank3 in a rat model alters synaptic ultrastructure in the medial prefrontal cortex. Methods We used electron microscopy to determine the density of asymmetric synapses in layer III excitatory neurons of the medial prefrontal cortex in 5 week-old Shank3-homozygous knockout ( Shank3 -KO), heterozygous ( Shank3 -Het), and wild-type (WT) rats. We also measured postsynaptic density length, postsynaptic density area, and head diameter of dendritic spines at these synapses. Results All three groups had comparable synapse density and postsynaptic density length. Spine head diameter of Shank3 -Het rats, but not Shank3 -KO, was larger than WT rats. Shank3 -Het rats had wider head diameter in non-perforated synapses compared to WT and Shank3 -KO rats. The total postsynaptic density area was significantly larger in Shank3 -Het rats compared to Shank3 -KO and WT rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the medial prefrontal cortex of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan-McDermid syndrome. Limitations The Shank3 deletion in the rat model we used does not affect all isoforms of the protein and as such, would only model the effect of the mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, this study focused only on synaptic ultrastructure in male Shank3 -deficient rats. Conclusions We observed increased head diameter and postsynaptic density area in rats heterozygous for Shank3 deficiency. Further investigations of the mechanisms leading to altered synaptic ultrastructure in this animal model will enable us to understand better the role that Shank3 protein plays in autism spectrum disorder and Phelan-McDermid syndrome.

scholarly journals Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

2018 ◽  
Author(s):  
Mary L. Phillips ◽  
Holly A. Robinson ◽  
Lucas Pozzo-Miller
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Social Memory ◽  
Memory Deficits ◽  
Autism Spectrum ◽  
Innervation Pattern ◽  
Wild Type ◽  
Contributing Factors ◽  
Social Memories

SUMMARYInputs from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) have been implicated in several neuropsychiatric disorders. Here, we show that the long-range vHIP-mPFC projection is hyperactive in the Mecp2 knockout (KO) mouse model of the autism spectrum disorder Rett syndrome, which has deficits in social memory. Chronically mimicking vHIP-mPFC hyperexcitability in wild-type mice impaired social memory, whereas chronic inhibition of mPFC-projecting vHIP neurons in Mecp2 KO mice rescued social memory deficits; the extent of memory rescue was negatively correlated with the strength of vHIP input to the mPFC. Acute manipulations of the vHIP-mPFC projection also affected social memory in a specific and selective manner, suggesting that proper vHIP-mPFC signaling is necessary to recall social memories. In addition, we identified an altered vHIP-mPFC innervation pattern and increased synaptic strength onto layer 5 pyramidal neurons as contributing factors in aberrant vHIP-mPFC signaling in Mecp2 KO mice.

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