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Book ; Online: Neuromodulation of Executive Circuits

Gonzalez-Burgos, Guillermo / Lambe, Evelyn K. / Gulledge, Allan T. / Puig, M. Victoria

2016

Abstract: High-order executive tasks involve the interplay between frontal cortex and other cortical and subcortical brain regions. In particular, the frontal cortex, striatum and thalamus interact via parallel fronto-striatal loops that are crucial for the ... ...

Abstract	High-order executive tasks involve the interplay between frontal cortex and other cortical and subcortical brain regions. In particular, the frontal cortex, striatum and thalamus interact via parallel fronto-striatal loops that are crucial for the executive control of behavior. In all of these brain regions, neuromodulatory inputs (e.g. serotonergic, dopaminergic, cholinergic, adrenergic, and peptidergic afferents) regulate neuronal activity and synaptic transmission to optimize circuit performance for specific cognitive demands. Indeed, dysregulation of neuromodulatory input to fronto-striatal circuits is implicated in a number of neuropsychiatric disorders, such as schizophrenia, depression, and Parkinsons disease. However, despite decades of intense investigation, how neuromodulators influence the activity of fronto-striatal circuits to generate the precise activity patterns required for sophisticated cognitive tasks remains unknown. In part, this reflects the complexity of the cellular microcircuits in these brain regions (i.e. heterogeneity of neuron subtypes and connectivity), cell-type specific expression patterns for the numerous receptor subtypes mediating neuromodulatory signals, and the potential interaction of multiple signaling cascades in individual neurons. This Research Topic includes 10 original research articles and seven review articles addressing the role of neuromodulation in executive function at multiple levels of analysis, ranging from the activity of single voltage-dependent ion channels to computational models of network interactions in cortex-striatum-thalamus systems
Keywords	Neurosciences. Biological psychiatry. Neuropsychiatry ; Science (General)
Size	1 electronic resource (257 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020091137
ISBN	9782889197071 ; 2889197077
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Strength of Excitatory Inputs to Layer 3 Pyramidal Neurons During Synaptic Pruning in the Monkey Prefrontal Cortex: Relevance for the Pathogenesis of Schizophrenia.

Gonzalez-Burgos, Guillermo / Miyamae, Takeaki / Nishihata, Yosuke / Krimer, Olga L / Lewis, David A

Biological psychiatry

2023 Volume 94, Issue 4, Page(s) 288–296

Abstract: Background: In schizophrenia, layer 3 pyramidal neurons (L3PNs) of the dorsolateral prefrontal cortex exhibit deficits in markers of excitatory synaptic inputs that are thought to disrupt the patterns of neural network activity essential for cognitive ... ...

Abstract	Background: In schizophrenia, layer 3 pyramidal neurons (L3PNs) of the dorsolateral prefrontal cortex exhibit deficits in markers of excitatory synaptic inputs that are thought to disrupt the patterns of neural network activity essential for cognitive function. These deficits are usually interpreted under Irwin Feinberg's hypothesis of altered synaptic pruning, which postulates that normal periadolescent pruning, thought to preferentially eliminate weak/immature synapses, is altered in schizophrenia. However, it remains unknown whether periadolescent pruning on L3PNs in the primate dorsolateral prefrontal cortex selectively eliminates weak excitatory synapses or uniformly eliminates excitatory synapses across the full distribution of synaptic strengths. Methods: To distinguish between these alternative models of synaptic pruning, we assessed the densities of dendritic spines, the site of most excitatory inputs to L3PNs, and the distributions of excitatory synaptic strengths in dorsolateral prefrontal cortex L3PNs from male and female monkeys across the periadolescent period of synaptic pruning. We used patch-clamp methods in acute brain slices to record miniature excitatory synaptic currents and intracellular filling with biocytin to quantify dendritic spines. Results: On L3PNs, dendritic spines exhibited the expected age-related decline in density, but mean synaptic strength and the shape of synaptic strength distributions remained stable with age. Conclusions: The absence of age-related differences in mean synaptic strength and synaptic strength distributions supports the model of a uniform pattern of synaptic pruning across the full range of synaptic strengths. The implications of these findings for the pathogenesis and functional consequences of dendritic spine deficits in schizophrenia are discussed.
MeSH term(s)	Animals ; Male ; Female ; Haplorhini ; Schizophrenia ; Pyramidal Cells/physiology ; Prefrontal Cortex ; Synapses/physiology ; Neuronal Plasticity ; Dendritic Spines/physiology
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2023.01.019
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Article ; Online: Differential gene expression between callosal and ipsilateral projection neurons in the monkey dorsolateral prefrontal and posterior parietal cortices.

Arion, Dominique / Enwright, John F / Gonzalez-Burgos, Guillermo / Lewis, David A

Cerebral cortex (New York, N.Y. : 1991)

2022 Volume 33, Issue 5, Page(s) 1581–1594

Abstract: Reciprocal connections between primate dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices, furnished by subsets of layer 3 pyramidal neurons (PNs), contribute to cognitive processes including working memory (WM). A different subset of ... ...

Abstract	Reciprocal connections between primate dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices, furnished by subsets of layer 3 pyramidal neurons (PNs), contribute to cognitive processes including working memory (WM). A different subset of layer 3 PNs in each region projects to the homotopic region of the contralateral hemisphere. These ipsilateral (IP) and callosal (CP) projections, respectively, appear to be essential for the maintenance and transfer of information during WM. To determine if IP and CP layer 3 PNs in each region differ in their transcriptomes, fluorescent retrograde tracers were used to label IP and CP layer 3 PNs in the DLPFC and PPC from macaque monkeys. Retrogradely-labeled PNs were captured by laser microdissection and analyzed by RNAseq. Numerous differentially expressed genes (DEGs) were detected between IP and CP neurons in each region and the functional pathways containing many of these DEGs were shared across regions. However, DLPFC and PPC displayed opposite patterns of DEG enrichment between IP and CP neurons. Cross-region analyses indicated that the cortical area targeted by IP or CP layer 3 PNs was a strong correlate of their transcriptome profile. These findings suggest that the transcriptomes of layer 3 PNs reflect regional, projection type and target region specificity.
MeSH term(s)	Animals ; Haplorhini ; Corpus Callosum ; Parietal Lobe ; Neurons ; Gene Expression
Language	English
Publishing date	2022-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhac157
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Article ; Online: Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets.

Arbabi, Keon / Jiang, Yiyue / Howard, Derek / Nigam, Anukrati / Inoue, Wataru / Gonzalez-Burgos, Guillermo / Felsky, Daniel / Tripathy, Shreejoy J

iScience

2023 Volume 26, Issue 8, Page(s) 107329

Abstract: Microglia are cells with diverse roles, including the regulation of neuronal excitability. We leveraged Patch-seq to assess the presence and effects of microglia in the local microenvironment of recorded neurons. We first quantified the amounts of ... ...

Abstract	Microglia are cells with diverse roles, including the regulation of neuronal excitability. We leveraged Patch-seq to assess the presence and effects of microglia in the local microenvironment of recorded neurons. We first quantified the amounts of microglial transcripts in three Patch-seq datasets of human and mouse neocortical neurons, observing extensive contamination. Variation in microglial contamination was explained foremost by donor identity, particularly in human samples, and additionally by neuronal cell type identity in mice. Gene set enrichment analysis suggests that microglial contamination is reflective of activated microglia, and that these transcriptional signatures are distinct from those captured via single-nucleus RNA-seq. Finally, neurons with greater microglial contamination differed markedly in their electrophysiological characteristics, including lowered input resistances and more depolarized action potential thresholds. Our results generalize beyond Patch-seq to suggest that activated microglia may be widely present across brain slice preparations and contribute to neuron- and donor-related electrophysiological variability
Language	English
Publishing date	2023-07-11
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107329
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Article ; Online: Mechanisms regulating the properties of inhibition-based gamma oscillations in primate prefrontal and parietal cortices.

Gonzalez-Burgos, Guillermo / Miyamae, Takeaki / Reddy, Nita / Dawkins, Sidney / Chen, Chloe / Hill, Avyi / Enwright, John / Ermentrout, Bard / Lewis, David A

Cerebral cortex (New York, N.Y. : 1991)

2023 Volume 33, Issue 12, Page(s) 7754–7770

Abstract: In primates, the dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices are key nodes in the working memory network. The working memory-related gamma oscillations induced in these areas, predominantly in layer 3, exhibit higher frequency ... ...

Abstract	In primates, the dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices are key nodes in the working memory network. The working memory-related gamma oscillations induced in these areas, predominantly in layer 3, exhibit higher frequency in DLPFC. Although these regional differences in oscillation frequency are likely essential for information transfer between DLPFC and PPC, the mechanisms underlying these differences remain poorly understood. We investigated, in rhesus monkey, the DLPFC and PPC layer 3 pyramidal neuron (L3PN) properties that might regulate oscillation frequency and assessed the effects of these properties simulating oscillations in computational models. We found that GABAAR-mediated synaptic inhibition synchronizes L3PNs in both areas, but analysis of GABAAR mRNA levels and inhibitory synaptic currents suggested similar mechanisms of inhibition-mediated synchrony in DLPFC and PPC. Basal dendrite spine density and AMPAR/NMDAR mRNA levels were higher in DLPFC L3PNs, whereas excitatory synaptic currents were similar between areas. Therefore, synaptically evoked excitation might be stronger in DLPFC L3PNs due to a greater quantity of synapses in basal dendrites, a main target of recurrent excitation. Simulations in computational networks showed that oscillation frequency and power increased with increasing recurrent excitation, suggesting a mechanism by which the DLPFC-PPC differences in oscillation properties are generated.
MeSH term(s)	Animals ; Receptors, GABA-A ; Prefrontal Cortex/physiology ; Pyramidal Cells/physiology ; Parietal Lobe ; Primates
Chemical Substances	Receptors, GABA-A
Language	English
Publishing date	2023-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhad077
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Article ; Online: The cytotoxicity effect of 7-hydroxy-3,4-dihydrocadalene from

Mendoza-Fuentes, Alan / González-Burgos, Elena / Aparicio Trejo, Omar Emiliano / Delgado-Lamas, Guillermo / Rodríguez-Chávez, José Luis / Pedraza-Chaverri, José / Gómez-Serranillos, M Pilar / Araiza-Olivera, Daniela

PeerJ

2023 Volume 11, Page(s) e15586

Abstract: Background: Heterotheca inuloides: Methods: Cell viability and proliferation were assayed by thiazolyl blue tetrazolium bromide (MTT) assay and Trypan blue dye exclusion assay. Cell migration measure was tested by wound-healing assay. Moreover, the ... ...

Abstract	Background: Heterotheca inuloides Methods: Cell viability and proliferation were assayed by thiazolyl blue tetrazolium bromide (MTT) assay and Trypan blue dye exclusion assay. Cell migration measure was tested by wound-healing assay. Moreover, the reactive oxygen species (ROS) and lipid peroxidation generation were measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay and thiobarbituric acid reactive substance (TBARS) assay, respectively. Furthermore, expression of caspase-3, Bcl-2 and GAPDH were analyzed by western blot. Results: The results showed that 7-hydroxy-3,4-dihydrocadalene inhibited MCF7 cell viability in a concentration and time dependent manner. The cytotoxic potency of semisynthetic derivatives 7-(phenylcarbamate)-3,4-dihydrocadalene and 7-(phenylcarbamate)-cadalene was remarkably lower. Moreover, Conclusion: Taken together, 7-hydroxy-3,4-dihydrocadalene is a promising cytotoxic compound against breast cancer
MeSH term(s)	Humans ; Female ; Asteraceae/chemistry ; Caspase 3/metabolism ; Reactive Oxygen Species/metabolism ; Breast Neoplasms/drug therapy ; Antineoplastic Agents/pharmacology ; Oxidative Stress ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism
Chemical Substances	Caspase 3 (EC 3.4.22.-) ; Reactive Oxygen Species ; Antineoplastic Agents ; Proto-Oncogene Proteins c-bcl-2
Language	English
Publishing date	2023-06-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.15586
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The cytotoxicity effect of 7-hydroxy-3,4-dihydrocadalene from Heterotheca inuloides and semisynthetic cadalenes derivates towards breast cancer cells

Alan Mendoza-Fuentes / Elena González-Burgos / Omar Emiliano Aparicio Trejo / Guillermo Delgado-Lamas / José Luis Rodríguez-Chávez / José Pedraza-Chaverri / M. Pilar Gómez-Serranillos / Daniela Araiza-Olivera

PeerJ, Vol 11, p e

involvement of oxidative stress-mediated apoptosis

2023 Volume 15586

Abstract: Background Heterotheca inuloides, traditionally employed in Mexico, has demonstrated anticancer activities. Although it has been proven that the cytotoxic effect is attributed to cadinane-type sesquiterpenes such as 7-hydroxy-3,4-dihydrocadalene, the ... ...

Abstract	Background Heterotheca inuloides, traditionally employed in Mexico, has demonstrated anticancer activities. Although it has been proven that the cytotoxic effect is attributed to cadinane-type sesquiterpenes such as 7-hydroxy-3,4-dihydrocadalene, the mechanism of action by which these agents act in tumor lines and their regulation remain unknown. This study was undertaken to investigate for first time the cytotoxic activity and mechanism of action of 7-hydroxy-3,4-dihydrocadalene and two semi-synthetic cadinanes derivatives towards breast cancer cells. Methods Cell viability and proliferation were assayed by thiazolyl blue tetrazolium bromide (MTT) assay and Trypan blue dye exclusion assay. Cell migration measure was tested by wound-healing assay. Moreover, the reactive oxygen species (ROS) and lipid peroxidation generation were measured by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) assay and thiobarbituric acid reactive substance (TBARS) assay, respectively. Furthermore, expression of caspase-3, Bcl-2 and GAPDH were analyzed by western blot. Results The results showed that 7-hydroxy-3,4-dihydrocadalene inhibited MCF7 cell viability in a concentration and time dependent manner. The cytotoxic potency of semisynthetic derivatives 7-(phenylcarbamate)-3,4-dihydrocadalene and 7-(phenylcarbamate)-cadalene was remarkably lower. Moreover, in silico studies showed that 7-hydroxy-3,4-dihydrocadalene, and not so the semi-synthetic derivatives, has optimal physical-chemical properties to lead a promising cytotoxic agent. Further examination on the action mechanism of 7-hydroxy-3,4-dihydrocadalene suggested that this natural product exerted cytotoxicity via oxidative stress as evidenced in a significantly increase of intracellular ROS levels and in an induction of lipid peroxidation. Furthermore, the compound increased caspase-3 and caspase-9 activities and slightly inhibited Bcl-2 levels. Interestingly, it also reduced mitochondrial ATP synthesis and induced mitochondrial uncoupling. Conclusion Taken together, ...
Keywords	Cytotoxicity ; Cadalenes ; Breast cancer ; Oxidative stress ; Apoptosis ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Neuronal functional connectivity is impaired in a layer dependent manner near the chronically implanted microelectrodes.

Chen, Keying / Forrest, Adam / Gonzalez Burgos, Guillermo / Kozai, Takashi D Y

bioRxiv : the preprint server for biology

2023

Abstract: Objective: This study aims to reveal longitudinal changes in functional network connectivity within and across different brain structures near the chronically implanted microelectrode. While it is well established that the foreign-body response (FBR) ... ...

Abstract	Objective: This study aims to reveal longitudinal changes in functional network connectivity within and across different brain structures near the chronically implanted microelectrode. While it is well established that the foreign-body response (FBR) contributes to the gradual decline of the signals recorded from brain implants over time, how does the FBR impact affect the functional stability of neural circuits near implanted Brain-Computer Interfaces (BCIs) remains unknown. This research aims to illuminate how the chronic FBR can alter local neural circuit function and the implications for BCI decoders. Approach: This study utilized multisite Michigan-style microelectrodes that span all cortical layers and the hippocampal CA1 region to collect spontaneous and visually-evoked electrophysiological activity. Alterations in neuronal activity near the microelectrode were tested assessing cross-frequency synchronization of LFP and spike entrainment to LFP oscillatory activity throughout 16 weeks after microelectrode implantation. Main results: The study found that cortical layer 4, the input-receiving layer, maintained activity over the implantation time. However, layers 2/3 rapidly experienced severe impairment, leading to a loss of proper intralaminar connectivity in the downstream output layers 5/6. Furthermore, the impairment of interlaminar connectivity near the microelectrode was unidirectional, showing decreased connectivity from Layers 2/3 to Layers 5/6 but not the reverse direction. In the hippocampus, CA1 neurons gradually became unable to properly entrain to the surrounding LFP oscillations. Significance: This study provides a detailed characterization of network connectivity dysfunction over long-term microelectrode implantation periods. This new knowledge could contribute to the development of targeted therapeutic strategies aimed at improving the health of the tissue surrounding brain implants and potentially inform engineering of adaptive decoders as the FBR progresses. Our study's understanding of the dynamic changes in the functional network over time opens the door to developing interventions for improving the long-term stability and performance of intracortical microelectrodes.
Language	English
Publishing date	2023-11-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.06.565852
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Article ; Online: Regulation of redox status in neuronal SH-SY5Y cells by blueberry (Vaccinium myrtillus L.) juice, cranberry (Vaccinium macrocarpon A.) juice and cyanidin.

Cásedas, Guillermo / González-Burgos, Elena / Smith, Carine / López, Víctor / Gómez-Serranillos, María Pilar

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2018 Volume 118, Page(s) 572–580

Abstract: Blueberry and cranberry are fruits with high polyphenol content, particularly anthocyanins. As cyanidin derivatives have been identified as one of the most representative polyphenols in berry juices, cyanidin has been designated for a better comparison ... ...

Abstract	Blueberry and cranberry are fruits with high polyphenol content, particularly anthocyanins. As cyanidin derivatives have been identified as one of the most representative polyphenols in berry juices, cyanidin has been designated for a better comparison and understanding of the potential neuroprotection of juices obtained from two Vaccinium species. Neuroblastoma SH-SY5Y cells were previously treated with different concentrations of lyophilized blueberry juice, cranberry juice or cyanidin for 24 h and oxidative stress was then generated with hydrogen peroxide (100 μM) for 30 min. Cytoprotective properties of cranberry juice, blueberry juice or cyanidin were evaluated using different methodologies such as mitochondrial activity (MTT), TBARS and ROS production, antioxidant enzymes (CAT, SOD) and antioxidant properties (ORAC, FRAP). Results indicated that blueberry and cranberry juices as well as cyanidin increased mitochondrial activity and reduced intracellular ROS production and lipid peroxidation induced by hydrogen peroxide. Furthermore, these berry juices and cyanidin upregulated the activity of the antioxidant enzymes catalase and superoxide dismutase. Finally, in vitro antioxidant capacities were confirmed by ORAC and FRAP assays demonstrating the potential of cyanidin and cyanidin-containing products for pharmaceutical or nutritional applications to prevent oxidative stress in neuronal cells.
MeSH term(s)	Anthocyanins/pharmacology ; Antioxidants/pharmacology ; Blueberry Plants/chemistry ; Catalase/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Humans ; Mitochondria/drug effects ; Oxidation-Reduction ; Plant Extracts/pharmacology ; Superoxide Dismutase/metabolism ; Thiobarbituric Acid Reactive Substances/metabolism ; Up-Regulation/drug effects ; Vaccinium macrocarpon/chemistry
Chemical Substances	Anthocyanins ; Antioxidants ; Plant Extracts ; Thiobarbituric Acid Reactive Substances ; cyanidin (7732ZHU564) ; Catalase (EC 1.11.1.6) ; Superoxide Dismutase (EC 1.15.1.1)
Language	English
Publishing date	2018-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2018.05.066
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Article ; Online: Presynaptic Effects of N-Methyl-D-Aspartate Receptors Enhance Parvalbumin Cell-Mediated Inhibition of Pyramidal Cells in Mouse Prefrontal Cortex.

Pafundo, Diego E / Miyamae, Takeaki / Lewis, David A / Gonzalez-Burgos, Guillermo

Biological psychiatry

2018 Volume 84, Issue 6, Page(s) 460–470

Abstract: Background: Testing hypotheses regarding the role of N-methyl-D-aspartate receptor (NMDAR) hypofunction in schizophrenia requires understanding the mechanisms of NMDAR regulation of prefrontal cortex (PFC) circuit function. NMDAR antagonists are thought ...

Abstract	Background: Testing hypotheses regarding the role of N-methyl-D-aspartate receptor (NMDAR) hypofunction in schizophrenia requires understanding the mechanisms of NMDAR regulation of prefrontal cortex (PFC) circuit function. NMDAR antagonists are thought to produce pyramidal cell (PC) disinhibition. However, inhibitory parvalbumin-positive basket cells (PVBCs) have modest NMDAR-mediated excitatory drive and thus are unlikely to participate in NMDAR antagonist-mediated disinhibition. Interestingly, recent studies demonstrated that presynaptic NMDARs enhance transmitter release at central synapses. Thus, if presynaptic NMDARs enhance gamma-aminobutyric acid release at PVBC-to-PC synapses, they could participate in NMDAR-dependent PC disinhibition. Here, we examined whether presynaptic NMDAR effects could modulate gamma-aminobutyric acid release at PVBC-to-PC synapses in mouse PFC. Methods: Using whole-cell recordings from synaptically connected pairs in mouse PFC, we determined whether NMDA or NMDAR antagonist application affects PVBC-to-PC inhibition in a manner consistent with a presynaptic mechanism. Results: NMDAR activation enhanced by ∼40% the synaptic current at PVBC-to-PC pairs. This effect was consistent with a presynaptic mechanism given that it was 1) observed with postsynaptic NMDARs blocked by intracellular MK801, 2) associated with a lower rate of transmission failures and a higher transmitter release probability, and 3) blocked by intracellular MK801 in the PVBC. NMDAR antagonist application did not affect the synaptic currents in PVBC-to-PC pairs, but it reduced the inhibitory currents elicited in PCs with simultaneous glutamate release by extracellular stimulation. Conclusions: We demonstrate that NMDAR activation enhances PVBC-to-PC inhibition in a manner consistent with presynaptic mechanisms, and we suggest that the functional impact of this presynaptic effect depends on the activity state of the PFC network.
MeSH term(s)	Animals ; Dizocilpine Maleate/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Female ; Male ; Mice ; Organ Culture Techniques ; Parvalbumins ; Patch-Clamp Techniques ; Prefrontal Cortex/cytology ; Pyramidal Cells/drug effects ; Pyramidal Cells/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Synapses/metabolism ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Excitatory Amino Acid Antagonists ; Parvalbumins ; Receptors, N-Methyl-D-Aspartate ; gamma-Aminobutyric Acid (56-12-2) ; Dizocilpine Maleate (6LR8C1B66Q)
Language	English
Publishing date	2018-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2018.01.018
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