Altered Parvalbumin Basket Cell Terminals in the Cortical Visuospatial Working Memory Network in Schizophrenia

Fish, Kenneth N.; Rocco, Brad R.; DeDionisio, Adam M.; Dienel, Samuel; Sweet, Robert A.; Lewis, David A.

doi:10.1016/j.biopsych.2021.02.009

Cited by 25 publications

(14 citation statements)

References 94 publications

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“…Furthermore, an extensive postmortem transcriptional profiling study proved a significant reduction of signaling pathways associated with GABA-receptor signaling (Lanz et al, 2019). Additional studies identified subtype-specific disruptions of parvalbumin-expressing interneurons including basket cells (Curley and Lewis, 2012;Glausier et al, 2014;Fish et al, 2021) and chandelier cells (Woo et al, 1998;Pierri et al, 1999;Lewis, 2011) as well as of somatostatin-expressing interneurons including martinotti cells and non-martinotti cells (Lewis et al, 2008;Van Derveer et al, 2021). Less is known about the role of 5HT3 a R-expressing interneurons in schizophrenia.…”

Section: The Influence Of the Extracellular Matrix On Parvalbumin-exp...mentioning

confidence: 99%

Regulation of the E/I-balance by the neural matrisome

Mueller-Buehl

Wegrzyn

Bauch

et al. 2023

Front. Mol. Neurosci.

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In the mammalian cortex a proper excitatory/inhibitory (E/I) balance is fundamental for cognitive functions. Especially γ-aminobutyric acid (GABA)-releasing interneurons regulate the activity of excitatory projection neurons which form the second main class of neurons in the cortex. During development, the maturation of fast-spiking parvalbumin-expressing interneurons goes along with the formation of net-like structures covering their soma and proximal dendrites. These so-called perineuronal nets (PNNs) represent a specialized form of the extracellular matrix (ECM, also designated as matrisome) that stabilize structural synapses but prevent the formation of new connections. Consequently, PNNs are highly involved in the regulation of the synaptic balance. Previous studies revealed that the formation of perineuronal nets is accompanied by an establishment of mature neuronal circuits and by a closure of critical windows of synaptic plasticity. Furthermore, it has been shown that PNNs differentially impinge the integrity of excitatory and inhibitory synapses. In various neurological and neuropsychiatric disorders alterations of PNNs were described and aroused more attention in the last years. The following review gives an update about the role of PNNs for the maturation of parvalbumin-expressing interneurons and summarizes recent findings about the impact of PNNs in different neurological and neuropsychiatric disorders like schizophrenia or epilepsy. A targeted manipulation of PNNs might provide an interesting new possibility to indirectly modulate the synaptic balance and the E/I ratio in pathological conditions.

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Section: The Influence Of the Extracellular Matrix On Parvalbumin-exp...mentioning

confidence: 99%

Regulation of the E/I-balance by the neural matrisome

Mueller-Buehl

Wegrzyn

Bauch

et al. 2023

Front. Mol. Neurosci.

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“…The C57BL/6-Gad2 EM1(IRES-ICRE-PA)SMOC (named as Gad2-ires-Cre) mice were purchased from Institute of Model Zoology, Nanjing University with the Product Number of D000668, previously reported (Taniguchi H et al, 2011). It is well-known that GABA (g-aminobutyric acid) in mammals was synthesized by two glutamic acid decarboxylase (GAD) GAD67 and GAD65 (Fish KN et al, 2021). These two proteins were encoded by Gad1 and Gad2 genes.…”

Section: Animals and Mouse Breedingmentioning

confidence: 99%

Visualizing an convergence of three mitochondrial molecule mRNAs for DRP1/MFN2/UCP4 on soma of cerebellar Purkinje cells by RNAscope

Liu¹,

Luo²,

Wu³

et al. 2021

Preprint

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We know little about how mitochondrial dynamic are regulated in the Purkinje cells. To explore it, we first set up a transgenic mice in which Purkinje cells expressed tdTomato in the cerebellum of Gad2-cre;ZsGreen-tdTomatofl/fl mice. Secondly Double stainings verified tdTomato cells were Calbinin (CB)-positive Purkinje cells, but not colocalized either with astrocyte marker GFAP or with microglia marker Iba1. Thirdly, application of RNAscope in situ hybridization with the identification of mRNAs of mitochondrial fusion (Mfn2), calcium transporter (Mcu and Nclx) and uncoupling proteins (Ucp2 and Ucp4) were used onto Purkinje cells for specific spatial analysis. The RNAscope assay used a semi‑quantitative H scoring guideline to evaluate the staining results. The number of bins ranges from 0–4 according to the ACD scoring system. Moreover, ACD scoring system was used to calculate the overall H scores of Dendritic Weighted Formula (DWF) and Soma Weighted Formula (SWF). Our data for the first time demonstrated that Mfn2 mRNAs expression was evident in Prukinje cells with the H scores of DWF and SWF as 60 and 139, respectively. And few Ucp4 mRNAs expression was present in dendritic shafts of Prukinje cells with the H scores of DWF and SWF as 14 and 103, respectively. It should be noted that Mcu mRNAs, Nclx mRNAs, as well as Ucp2 mRNAs expression were only scattered on both soma and dendrites in Prukinje cells with the low H scores of DWF and SWF. Double RNAscope profiling of mitochondrial molecules showed The data showed Mfn1 mRNAs are present only in the soma of the Purkinje cells, instead of processes. Double RNAscope showed almost none of dots of Drp1 mRNAs was co-localized with dots of Mcu mRNAs, as well as almost none of dots of Ucp2 mRNAs was co-localized with dots of Mfn2 mRNAs. All of these results show the mitochondrial Drp1/Mfn2/UCP4 convergence on the Purkinje cells. Finally, a major focus of present research will be to develop new and more specific molecules that tune the activity of the Purkinje cells activate or inactivate and to address diseases for which such druglike molecules may open therapeutic windows for Purkinje cells-related manipulation in the clinic. The molecular identification of drug targets, mechanism of action, and structural basis of their activity will crucially enable preclinical development.

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“…The C57BL/6-Gad2 EM1(IRES-ICRE-PA)SMOC (named as Gad2-ires-Cre) mice were purchased from Institute of Model Zoology, Nanjing University with the Product Number of D000668, previously reported [8]. It is wellknown that GABA (g-aminobutyric acid) in mammals was synthesized by two glutamic acid decarboxylases (GAD) GAD67 and GAD65 [9]. These two proteins were encoded by Gad1 and Gad2 genes.…”

Section: Gad2-ires-cre Micementioning

confidence: 99%

Visualizing a Convergence of Three Mitochondrial Molecule mRNAs for Drp1/Mfn2/Ucp4 on Soma of Cerebellar Purkinje Cells by RNAscope

Liu

Luo

et al. 2021

Preprint

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We know little about how mitochondrial dynamics regulates in the Purkinje cells. To explore it, we first set up the Gad2-cre:ZsGreen-tdTomatofl/fl mice where Purkinje cells expressed tdTomato in the cerebellum. Secondly, double stainings verified tdTomato cells were Calbinin (CB)-positive Purkinje cells, but colocalized neither with astrocyte marker GFAP nor with microglia marker Iba1. Thirdly, application of RNAscope in situ hybridization with the identification of mRNAs of mitofusin 2 (Mfn2), calcium transporter (Mcu and Nclx) and uncoupling proteins (Ucp2 and Ucp4) were used onto Purkinje cells for specific spatial analysis. Our findings demonstrated that Mfn2 mRNAs expression was evident in Purkinje cells. And few expressions of Ucp4 mRNAs were presented in dendritic shafts of Purkinje cells. It should be noted that Mcu, Nclx, and Ucp2 mRNAs expression were only scattered on both soma and dendrites in Purkinje cells. The double RNAscope profiling of mitochondrial molecules showed Mfn1 mRNAs are presented only in the soma of the Purkinje cells. Double RNAscope showed none of Drp1 mRNAs were co-localized with Mcu mRNAs, as well as almost none of Ucp2 mRNAs were co-localized with Mfn2 mRNAs. All of these results showed the mitochondrial Drp1/Mfn2/Ucp4 convergence on the Purkinje cells. Finally, present research focuses on developing new and more specific molecules tuning the activity of the Purkinje cells activate or inactivate and opening therapeutic windows for Purkinje cells-related diseases. The molecular identification of potential drug targets, mechanism of action, and structural basis of their activity will crucially enable preclinical development.

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Altered Parvalbumin Basket Cell Terminals in the Cortical Visuospatial Working Memory Network in Schizophrenia

Cited by 25 publications

References 94 publications

Regulation of the E/I-balance by the neural matrisome

Regulation of the E/I-balance by the neural matrisome

Visualizing an convergence of three mitochondrial molecule mRNAs for DRP1/MFN2/UCP4 on soma of cerebellar Purkinje cells by RNAscope

Visualizing a Convergence of Three Mitochondrial Molecule mRNAs for Drp1/Mfn2/Ucp4 on Soma of Cerebellar Purkinje Cells by RNAscope

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