scholarly journals Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Bhanu P. Tewari ◽  
Lata Chaunsali ◽  
Susan L. Campbell ◽  
Dipan C. Patel ◽  
Adam E. Goode ◽  
...  
Keyword(s):  
Membrane Capacitance ◽  
Perineuronal Nets ◽  
Fast Spiking

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 Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels

2021 ◽  
Author(s):  
Sharon R. Stevens ◽  
Colleen M. Longley ◽  
Yuki Ogawa ◽  
Lindsay H. Teliska ◽  
Anithachristy S. Arumanayagam ◽  
...  
Keyword(s):  
Cell Adhesion Molecules ◽  
Protein Complexes ◽  
Cytoskeletal Proteins ◽  
Intrinsic Excitability ◽  
Binding Motif ◽  
Perineuronal Nets ◽  
Dramatic Reduction ◽  
Fast Spiking ◽  
Firing Properties ◽  
Necessary And Sufficient

ABSTRACTNeuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv+ fast-spiking interneurons in mouse and human. We identify AnkR-associated protein complexes including cytoskeletal proteins, cell adhesion molecules (CAMs), and perineuronal nets (PNNs). We show that loss of AnkR from forebrain interneurons reduces and disrupts PNNs, decreases anxiety-like behaviors, and changes the intrinsic excitability and firing properties of Pv+ fast-spiking interneurons. These changes are accompanied by a dramatic reduction in Kv3.1b K+ channels. We identify a novel AnkR-binding motif in Kv3.1b, and show that AnkR is both necessary and sufficient for Kv3.1b membrane localization in interneurons and at nodes of Ranvier. Thus, AnkR regulates Pv+ fast-spiking interneuron function by organizing ion channels, CAMs, and PNNs, and linking these to the underlying β1 spectrin-based cytoskeleton.

scholarly journals Perineuronal Nets Enhance the Excitability of Fast-Spiking Neurons

eNeuro ◽  
2016 ◽  
Vol 3 (4) ◽  
pp. ENEURO.0112-16.2016 ◽  
Author(s):  
Timothy S. Balmer
Keyword(s):  
Spiking Neurons ◽  
Perineuronal Nets ◽  
Fast Spiking

scholarly journals Perineuronal Nets and Metal Cation Concentrations in the Microenvironments of Fast-Spiking, Parvalbumin-Expressing GABAergic Interneurons: Relevance to Neurodevelopment and Neurodevelopmental Disorders

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1235
Author(s):  
Jessica A. Burket ◽  
Jason D. Webb ◽  
Stephen I. Deutsch
Keyword(s):  
Nmda Receptor ◽  
Neurodevelopmental Disorders ◽  
Metal Cations ◽  
Autism Spectrum ◽  
Perineuronal Nets ◽  
Gabaergic Interneurons ◽  
Perineuronal Net ◽  
Reactive Metal ◽  
Protective Function ◽  
Fast Spiking

Because of their abilities to catalyze generation of toxic free radical species, free concentrations of the redox reactive metals iron and copper are highly regulated. Importantly, desired neurobiological effects of these redox reactive metal cations occur within very narrow ranges of their local concentrations. For example, synaptic release of free copper acts locally to modulate NMDA receptor-mediated neurotransmission. Moreover, within the developing brain, iron is critical to hippocampal maturation and the differentiation of parvalbumin-expressing neurons, whose soma and dendrites are surrounded by perineuronal nets (PNNs). The PNNs are a specialized component of brain extracellular matrix, whose polyanionic character supports the fast-spiking electrophysiological properties of these parvalbumin-expressing GABAergic interneurons. In addition to binding cations and creation of the Donnan equilibrium that support the fast-spiking properties of this subset of interneurons, the complex architecture of PNNs also binds metal cations, which may serve a protective function against oxidative damage, especially of these fast-spiking neurons. Data suggest that pathological disturbance of the population of fast-spiking, parvalbumin-expressing GABAergic inhibitory interneurons occur in at least some clinical presentations, which leads to disruption of the synchronous oscillatory output of assemblies of pyramidal neurons. Increased expression of the GluN2A NMDA receptor subunit on parvalbumin-expressing interneurons is linked to functional maturation of both these neurons and the perineuronal nets that surround them. Disruption of GluN2A expression shows increased susceptibility to oxidative stress, reflected in redox dysregulation and delayed maturation of PNNs. This may be especially relevant to neurodevelopmental disorders, including autism spectrum disorder. Conceivably, binding of metal redox reactive cations by the perineuronal net helps to maintain safe local concentrations, and also serves as a reservoir buffering against second-to-second fluctuations in their concentrations outside of a narrow physiological range.

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

scholarly journals Perineuronal nets protect fast-spiking interneurons against oxidative stress

2013 ◽  
Vol 110 (22) ◽  
pp. 9130-9135 ◽  
Author(s):  
J.-H. Cabungcal ◽  
P. Steullet ◽  
H. Morishita ◽  
R. Kraftsik ◽  
M. Cuenod ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Perineuronal Nets ◽  
Fast Spiking

scholarly journals Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sharon Stevens ◽  
Colleen M Longley ◽  
Yuki Ogawa ◽  
Lindsay Teliska ◽  
Anithachristy Arumanayagam ◽  
...  
Keyword(s):  
Cell Adhesion Molecules ◽  
Protein Complexes ◽  
Cytoskeletal Proteins ◽  
Intrinsic Excitability ◽  
Binding Motif ◽  
Perineuronal Nets ◽  
Dramatic Reduction ◽  
Fast Spiking ◽  
Firing Properties ◽  
Necessary And Sufficient

Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv+ fast-spiking interneurons in mouse and human. We identify AnkR-associated protein complexes including cytoskeletal proteins, cell adhesion molecules (CAMs), and perineuronal nets (PNNs). We show that loss of AnkR from forebrain interneurons reduces and disrupts PNNs, decreases anxiety-like behaviors, and changes the intrinsic excitability and firing properties of Pv+ fast-spiking interneurons. These changes are accompanied by a dramatic reduction in Kv3.1b K+ channels. We identify a novel AnkR-binding motif in Kv3.1b, and show that AnkR is both necessary and sufficient for Kv3.1b membrane localization in interneurons and at nodes of Ranvier. Thus, AnkR regulates Pv+ fast-spiking interneuron function by organizing ion channels, CAMs, and PNNs, and linking these to the underlying b1 spectrin-based cytoskeleton.

scholarly journals Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking

2018 ◽  
Author(s):  
Hu Chen ◽  
Amy W Lasek
Keyword(s):  
Neuronal Excitability ◽  
Insular Cortex ◽  
Maladaptive Behaviors ◽  
Perineuronal Nets ◽  
Negative Consequences ◽  
Cellular Mechanisms ◽  
Alcohol Activation ◽  
Fast Spiking ◽  
Fundamental Insight ◽  
Insight Into

One of the most pernicious characteristics of alcohol use disorder is the compulsion to drink despite negative consequences. The insular cortex (insula) controls decision-making under conditions of risk or conflict and regulates maladaptive behaviors in the context of addiction. Cortical activity is tightly controlled by fast-spiking inhibitory interneurons that are often enclosed by specialized extracellular matrix structures known as perineuronal nets, which regulate neuronal excitability and plasticity. Using a mouse model of compulsive drinking in which alcohol was adulterated with the bitter tastant quinine, we demonstrate that disrupting perineuronal nets in the insula rendered mice more sensitive to quinine-adulterated alcohol. Activation of the insula, as measured by c-fos expression, occurred during aversion-resistant drinking and was further enhanced by elimination of perineuronal nets. These results provide fundamental insight into neuroanatomical and cellular mechanisms that control compulsive drinking.

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