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Article ; Online: Fear memory recall involves hippocampal somatostatin interneurons.

Zichó, Krisztián / Sos, Katalin E / Papp, Péter / Barth, Albert M / Misák, Erik / Orosz, Áron / Mayer, Márton I / Sebestény, Réka Z / Nyiri, Gábor

PLoS biology

2023 Volume 21, Issue 6, Page(s) e3002154

Abstract: Fear-related memory traces are encoded by sparse populations of hippocampal principal neurons that are recruited based on their inhibitory-excitatory balance during memory formation. Later, the reactivation of the same principal neurons can recall the ... ...

Abstract	Fear-related memory traces are encoded by sparse populations of hippocampal principal neurons that are recruited based on their inhibitory-excitatory balance during memory formation. Later, the reactivation of the same principal neurons can recall the memory. The details of this mechanism are still unclear. Here, we investigated whether disinhibition could play a major role in this process. Using optogenetic behavioral experiments, we found that when fear was associated with the inhibition of mouse hippocampal somatostatin positive interneurons, the re-inhibition of the same interneurons could recall fear memory. Pontine nucleus incertus neurons selectively inhibit hippocampal somatostatin cells. We also found that when fear was associated with the activity of these incertus neurons or fibers, the reactivation of the same incertus neurons or fibers could also recall fear memory. These incertus neurons showed correlated activity with hippocampal principal neurons during memory recall and were strongly innervated by memory-related neocortical centers, from which the inputs could also control hippocampal disinhibition in vivo. Nonselective inhibition of these mouse hippocampal somatostatin or incertus neurons impaired memory recall. Our data suggest a novel disinhibition-based memory mechanism in the hippocampus that is supported by local somatostatin interneurons and their pontine brainstem inputs.
MeSH term(s)	Mice ; Animals ; Interneurons/metabolism ; Memory/physiology ; Hippocampus/metabolism ; Fear/physiology ; Somatostatin/metabolism
Chemical Substances	Somatostatin (51110-01-1)
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3002154
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Article ; Online: Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons.

Takács, Virág / Bardóczi, Zsuzsanna / Orosz, Áron / Major, Abel / Tar, Luca / Berki, Péter / Papp, Péter / Mayer, Márton I / Sebők, Hunor / Zsolt, Luca / Sos, Katalin E / Káli, Szabolcs / Freund, Tamás F / Nyiri, Gábor

PLoS biology

2024 Volume 22, Issue 3, Page(s) e3002539

Abstract: GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas ... ...

Abstract	GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo, and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed, and make available several key data sets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The data set includes detailed scanning electron microscopy (SEM)-based 3D reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core data set with other anatomical data, patch-clamp electrophysiology, and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For example, we estimated that an OLM cell receives about 8,400, whereas an HS cell about 15,600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network.
MeSH term(s)	Mice ; Animals ; Hippocampus/physiology ; Interneurons/physiology ; Neurons ; Somatostatin
Chemical Substances	Somatostatin (51110-01-1)
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3002539
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Article ; Online: Innovation in assessment of the geothermal energy potential of abandoned hydrocarbon wells in the southern and southeastern foreground of the Bükk Mountains, northeast Hungary

Szűcs, Péter / Turai, Endre / Mádai, Viktor / Vass, Peter / Miklós, Rita / Zákányi, Balázs / Ilyés, Csaba / Fekete, Zsombor / Kilik, Roland / Móricz, Ferenc / Nyiri, Gábor / Szilvási, Marcell / Szabó, Norbert Péter

Hydrogeol J. 2022 Dec., v. 30, no. 8 p.2267-2284

2022

Abstract: An innovative methodology is introduced to study abandoned oil exploration drillings for possible geothermal energy production at a test area in northeast Hungary. An evaluation method supported by robust statistical analysis was elaborated to provide ... ...

Title translation	Innovation dans l’évaluation du potentiel d’énergie géothermique des puits d’hydrocarbures abandonnés dans l’avant-pays du sud et du sud-est des monts Bükk, dans le nord-est de la Hongrie Innovación en la evaluación del potencial de energía geotérmica en pozos de hidrocarburos abandonados en el frente sur y sureste de los Montes Bükk, al noreste de Hungría 匈牙利东北部 Bükk 山脉南部和东南部前台废弃油气井地热能潜力评估的创新 Újítás a felhagyott szénhidrogénkutak geotermikus potenciáljának felmérésében a Bükk hegység déli és délkeleti előterében, Északkelet-Magyarországon Inovações na avaliação do potencial de energia geotérmica de poços de hidrocarbonetos abandonados no primeiro plano sul e sudeste das montanhas Bükk, nordeste da Hungria
Abstract	An innovative methodology is introduced to study abandoned oil exploration drillings for possible geothermal energy production at a test area in northeast Hungary. An evaluation method supported by robust statistical analysis was elaborated to provide the possible future investors with adequate technical and earth-science related information for their decision-making processes. All the available data of 161 abandoned hydrocarbon wells, with different physical conditions, were examined based on the proposed evaluation system to provide information about the geothermal energy potential for each well, as well as over a bigger area. The abandoned wells and their environments, the quantity of stored heat, and the fluid temperature and geothermal heat were the key parameters determined, which are critical when considering geothermal energy utilization or thermal water production. The maximum amount of stored energy was determined as the sum of the amount of energy extractable from the rock and the fluid. The heat stored in the rock was determined by basin modelling. The evaluation process, using one-dimensional (1D) basin modelling and 3D lithological-stratigraphic modelling, was successfully applied in the pilot area. The maximum amount of heat stored in the fluid can be determined by subtracting the heat stored in the rock from the total heat. Drilling and completing geothermal wells are rather expensive in Hungary, depending on the depth and the types of geological formations. The application of this research could greatly reduce the cost and risk of creating new geothermal energy systems based on production wells or abandoned wells in Hungary or elsewhere.
Keywords	basins ; decision making ; energy ; geothermal energy ; heat ; oils ; risk ; statistical analysis ; temperature ; Hungary
Language	English
Dates of publication	2022-12
Size	p. 2267-2284.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	1227482-3
ISSN	0941-2816 ; 1431-2174
ISSN	0941-2816 ; 1431-2174
DOI	10.1007/s10040-022-02560-y
Database	NAL-Catalogue (AGRICOLA)

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Article: Vascular supply of the metacarpophalangeal joint.

Baksa, Gabor / Czeibert, Kalman / Sharp, Veronika / Handschuh, Stephan / Gyebnar, Janos / Barany, Laszlo / Benis, Szabolcs / Nyiri, Gabor / Mandl, Peter / Petnehazy, Ors / Balint, Peter Vince

Frontiers in medicine

2022 Volume 9, Page(s) 1015895

Abstract: Objective: To describe in detail the arterial vasculature of metacarpophalangeal joints 2-5 on cadaver specimens and to compare it to ultrasound imaging of healthy subjects.: Methods: Eighteen hands of donated human cadavers were arterially injected ... ...

Abstract	Objective: To describe in detail the arterial vasculature of metacarpophalangeal joints 2-5 on cadaver specimens and to compare it to ultrasound imaging of healthy subjects. Methods: Eighteen hands of donated human cadavers were arterially injected and investigated with either corrosion casting or cryosectioning. Each layer of cryosectioned specimens was photographed in high-resolution. Images were then segmented for arterial vessels of the metacarpophalangeal (MCP) joints 2-5. The arterial pattern of the joints was reconstructed from the segmented images and from the corrosion cast specimens. Both hands of ten adult healthy volunteers were scanned focusing on the vasculature of the same joints with high-end ultrasound imaging, including color Doppler. Measurements were made on both cryosectioned arteries and Doppler images. Results: The arterial supply of MCP joints 2-5 divides into a metacarpal and a phalangeal territory, respectively. The metacarpal half receives arteries from the palmar metacarpal arteries or proper palmar digital arteries, while the phalangeal half is supplied by both proper and common palmar digital arteries. Comparing anatomical and ultrasonographic results, we determined the exact anatomic location of normal vessels using Doppler images acquired of healthy joints. All, except three branches, were found with less than 50% frequency using ultrasound. Doppler signals were identified significantly more frequently in MCP joints 2-3 than on 4-5 ( Conclusion: Using morphological and ultrasonographic techniques, our study provides a high-resolution anatomical maps and an essential reference data set on the entire arterial vasculature of healthy human MCP 2-5 joints. We found that Doppler signal could be detected in less than 50% of the vessels of healthy volunteers except three locations. Intraarticular branches were detected with ultrasound imaging significantly more frequently on healthy MCP 2-3 joints, which should be taken into account when inflammatory and normal Doppler signals are evaluated. Our study also provides reference data for future, higher-resolution imaging techniques.
Language	English
Publishing date	2022-10-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.1015895
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Article ; Online: Neuroligin 2 is expressed in synapses established by cholinergic cells in the mouse brain.

Takács, Virág T / Freund, Tamás F / Nyiri, Gábor

PloS one

2013 Volume 8, Issue 9, Page(s) e72450

Abstract: Neuroligin 2 is a postsynaptic protein that plays a critical role in the maturation and proper function of GABAergic synapses. Previous studies demonstrated that deletion of neuroligin 2 impaired GABAergic synaptic transmission, whereas its ... ...

Abstract	Neuroligin 2 is a postsynaptic protein that plays a critical role in the maturation and proper function of GABAergic synapses. Previous studies demonstrated that deletion of neuroligin 2 impaired GABAergic synaptic transmission, whereas its overexpression caused increased inhibition, which suggest that its presence strongly influences synaptic function. Interestingly, the overexpressing transgenic mouse line showed increased anxiety-like behavior and other behavioral phenotypes, not easily explained by an otherwise strengthened GABAergic transmission. This suggested that other, non-GABAergic synapses may also express neuroligin 2. Here, we tested the presence of neuroligin 2 at synapses established by cholinergic neurons in the mouse brain using serial electron microscopic sections double labeled for neuroligin 2 and choline acetyltransferase. We found that besides GABAergic synapses, neuroligin 2 is also present in the postsynaptic membrane of cholinergic synapses in all investigated brain areas (including dorsal hippocampus, somatosensory and medial prefrontal cortices, caudate putamen, basolateral amygdala, centrolateral thalamic nucleus, medial septum, vertical- and horizontal limbs of the diagonal band of Broca, substantia innominata and ventral pallidum). In the hippocampus, the density of neuroligin 2 labeling was similar in GABAergic and cholinergic synapses. Moreover, several cholinergic contact sites that were strongly labeled with neuroligin 2 did not resemble typical synapses, suggesting that cholinergic axons form more synaptic connections than it was recognized previously. We showed that cholinergic cells themselves also express neuroligin 2 in a subset of their input synapses. These data indicate that mutations in human neuroligin 2 gene and genetic manipulations of neuroligin 2 levels in rodents will potentially cause alterations in the cholinergic system as well, which may also have a profound effect on the functional properties of brain circuits and behavior.
MeSH term(s)	Animals ; Cell Adhesion Molecules, Neuronal/metabolism ; Cerebral Cortex/cytology ; Cerebral Cortex/metabolism ; Cholinergic Neurons/metabolism ; GABAergic Neurons/metabolism ; Hippocampus/cytology ; Hippocampus/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins/metabolism ; Organ Specificity ; Protein Transport ; Synapses/metabolism
Chemical Substances	Cell Adhesion Molecules, Neuronal ; Nerve Tissue Proteins ; neuroligin 2
Language	English
Publishing date	2013-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0072450
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Article ; Online: Chronic Amyloid β Oligomer Infusion Evokes Sustained Inflammation and Microglial Changes in the Rat Hippocampus via NLRP3.

Fekete, Csaba / Vastagh, Csaba / Dénes, Ádám / Hrabovszky, Erik / Nyiri, Gábor / Kalló, Imre / Liposits, Zsolt / Sárvári, Miklós

Neuroscience

2018 Volume 405, Page(s) 35–46

Abstract: Microglia are instrumental for recognition and elimination of amyloid ... ...

Abstract	Microglia are instrumental for recognition and elimination of amyloid β
MeSH term(s)	Amyloid beta-Peptides/administration & dosage ; Amyloid beta-Peptides/toxicity ; Animals ; Cell Communication/drug effects ; Cytokines/blood ; Cytokines/metabolism ; Furans ; Heterocyclic Compounds, 4 or More Rings ; Hippocampus/drug effects ; Hippocampus/metabolism ; Hippocampus/pathology ; Indenes ; Inflammasomes/drug effects ; Inflammasomes/metabolism ; Inflammation/chemically induced ; Inflammation/metabolism ; Inflammation/pathology ; Infusions, Intraventricular ; Male ; Maze Learning ; Microglia/drug effects ; Microglia/metabolism ; Microglia/pathology ; Models, Animal ; NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; Peptide Fragments/administration & dosage ; Peptide Fragments/toxicity ; Rats ; Rats, Long-Evans ; Spatial Memory/drug effects ; Sulfonamides ; Sulfones
Chemical Substances	Amyloid beta-Peptides ; Cytokines ; Furans ; Heterocyclic Compounds, 4 or More Rings ; Indenes ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, rat ; Peptide Fragments ; Sulfonamides ; Sulfones ; amyloid beta-peptide (1-24) ; N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide (6RS86E2BWQ)
Language	English
Publishing date	2018-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2018.02.046
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Article ; Online: Amyloid β induces interneuron-specific changes in the hippocampus of APPNL-F mice.

Sos, Katalin E / Mayer, Márton I / Takács, Virág T / Major, Abel / Bardóczi, Zsuzsanna / Beres, Barnabas M / Szeles, Tamás / Saito, Takashi / Saido, Takaomi C / Mody, István / Freund, Tamás F / Nyiri, Gábor

PloS one

2020 Volume 15, Issue 5, Page(s) e0233700

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and amyloid-beta (Aβ) depositions generated by the proteolysis of amyloid precursor protein (APP) in the brain. In APPNL-F mice, APP gene was humanized and ... ...

Abstract	Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and amyloid-beta (Aβ) depositions generated by the proteolysis of amyloid precursor protein (APP) in the brain. In APPNL-F mice, APP gene was humanized and contains two familial AD mutations, and APP-unlike other mouse models of AD-is driven by the endogenous mouse APP promoter. Similar to people without apparent cognitive dysfunction but with heavy Aβ plaque load, we found no significant decline in the working memory of adult APPNL-F mice, but these mice showed decline in the expression of normal anxiety. Using immunohistochemistry and 3D block-face scanning electron microscopy, we found no changes in GABAA receptor positivity and size of somatic and dendritic synapses of hippocampal interneurons. We did not find alterations in the level of expression of perineuronal nets around parvalbumin (PV) interneurons or in the density of PV- or somatostatin-positive hippocampal interneurons. However, in contrast to other investigated cell types, PV interneuron axons were occasionally mildly dystrophic around Aβ plaques, and the synapses of PV-positive axon initial segment (AIS)-targeting interneurons were significantly enlarged. Our results suggest that PV interneurons are highly resistant to amyloidosis in APPNL-F mice and amyloid-induced increase in hippocampal pyramidal cell excitability may be compensated by PV-positive AIS-targeting cells. Mechanisms that make PV neurons more resilient could therefore be exploited in the treatment of AD for mitigating Aβ-related inflammatory effects on neurons.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Animals ; Axons/metabolism ; Axons/pathology ; Hippocampus/metabolism ; Hippocampus/pathology ; Humans ; Interneurons/metabolism ; Interneurons/pathology ; Memory, Short-Term ; Mice ; Mice, Transgenic ; Mutation ; Nerve Net/metabolism ; Nerve Net/pathology ; Peptide Fragments/genetics ; Peptide Fragments/metabolism ; Pyramidal Cells/metabolism ; Pyramidal Cells/pathology ; Receptors, GABA-A/genetics ; Receptors, GABA-A/metabolism
Chemical Substances	Amyloid beta-Peptides ; Peptide Fragments ; Receptors, GABA-A ; amyloid beta-protein (1-40) ; amyloid beta-protein (1-42)
Language	English
Publishing date	2020-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0233700
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Article ; Online: Quantitative ultrastructural analysis of basket and axo-axonic cell terminals in the mouse hippocampus.

Takács, Virág T / Szőnyi, András / Freund, Tamás F / Nyiri, Gábor / Gulyás, Attila I

Brain structure & function

2015 Volume 220, Issue 2, Page(s) 919–940

Abstract: Three functionally different populations of perisomatic interneurons establish GABAergic synapses on hippocampal pyramidal cells: parvalbumin (PV)-containing basket cells, type 1 cannabinoid receptor (CB1)-positive basket cells both of which target ... ...

Abstract	Three functionally different populations of perisomatic interneurons establish GABAergic synapses on hippocampal pyramidal cells: parvalbumin (PV)-containing basket cells, type 1 cannabinoid receptor (CB1)-positive basket cells both of which target somata, and PV-positive axo-axonic cells that innervate axon initial segments. Using electron microscopic reconstructions, we estimated that a pyramidal cell body receives synapses from about 60 and 140 synaptic terminals in the CA1 and CA3 area, respectively. About 60 % of these terminals were PV positive, whereas 35-40 % of them were CB1 positive. Only about 1 % (CA1) and 4 % (CA3) of the somatic boutons were negative for both markers. Using fluorescent labeling, we showed that most of the CB1-positive terminals expressed vesicular glutamate transporter 3. Reconstruction of somatic boutons revealed that although their volumes are similar, CB1-positive boutons are more flat and the total volume of their mitochondria was smaller than that of PV-positive boutons. Both types of boutons contain dense-core vesicles and frequently formed multiple release sites on their targets and innervated an additional soma or dendrite as well. PV-positive boutons possessed small, macular synapses; whereas the total synaptic area of CB1-positive boutons was larger and formed multiple irregular-shaped synapses. Axo-axonic boutons were smaller than somatic boutons, had only one synapse and their ultrastructural parameters were closer to those of PV-positive somatic boutons. Our results represent the first quantitative measurement-using a highly reliable method-of the contribution of different cell types to the perisomatic innervation of pyramidal neurons, and may help to explain functional differences in their output properties.
MeSH term(s)	Amino Acid Transport Systems, Acidic ; Animals ; Hippocampus/metabolism ; Hippocampus/ultrastructure ; Interneurons/metabolism ; Interneurons/ultrastructure ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/ultrastructure ; Parvalbumins/analysis ; Presynaptic Terminals/metabolism ; Presynaptic Terminals/ultrastructure ; Pyramidal Cells/metabolism ; Pyramidal Cells/ultrastructure ; Receptor, Cannabinoid, CB1/analysis
Chemical Substances	Amino Acid Transport Systems, Acidic ; Parvalbumins ; Receptor, Cannabinoid, CB1 ; vesicular glutamate transporter 3, mouse
Language	English
Publishing date	2015-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-013-0692-6
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Article ; Online: Cellular architecture and transmitter phenotypes of neurons of the mouse median raphe region.

Sos, Katalin E / Mayer, Márton I / Cserép, Csaba / Takács, Flóra S / Szőnyi, András / Freund, Tamás F / Nyiri, Gábor

Brain structure & function

2016 Volume 222, Issue 1, Page(s) 287–299

Abstract: The median raphe region (MRR, which consist of MR and paramedian raphe regions) plays a crucial role in regulating cortical as well as subcortical network activity and behavior, while its malfunctioning may lead to disorders, such as schizophrenia, major ...

Abstract	The median raphe region (MRR, which consist of MR and paramedian raphe regions) plays a crucial role in regulating cortical as well as subcortical network activity and behavior, while its malfunctioning may lead to disorders, such as schizophrenia, major depression, or anxiety. Mouse MRR neurons are classically identified on the basis of their serotonin (5-HT), vesicular glutamate transporter type 3 (VGLUT3), and gamma-aminobutyric acid (GABA) contents; however, the exact cellular composition of MRR regarding transmitter phenotypes is still unknown. Using an unbiased stereological method, we found that in the MR, 8.5 % of the neurons were 5-HT, 26 % were VGLUT3, and 12.8 % were 5-HT and VGLUT3 positive; whereas 37.2 % of the neurons were GABAergic, and 14.4 % were triple negative. In the whole MRR, 2.1 % of the neurons were 5-HT, 7 % were VGLUT3, and 3.6 % were 5-HT and VGLUT3 positive; whereas 61 % of the neurons were GABAergic. Surprisingly, 25.4 % of the neurons were triple negative and were only positive for the neuronal marker NeuN. PET-1/ePET-Cre transgenic mouse lines are widely used to specifically manipulate only 5-HT containing neurons. Interestingly, however, using the ePET-Cre transgenic mice, we found that far more VGLUT3 positive cells expressed ePET than 5-HT positive cells, and about 38 % of the ePET cells contained only VGLUT3, while more than 30 % of 5-HT cells were ePET negative. These data should facilitate the reinterpretation of PET-1/ePET related data in the literature and the identification of the functional role of a putatively new type of triple-negative neuron in the MRR.
MeSH term(s)	Amino Acid Transport Systems, Acidic/metabolism ; Animals ; Cell Count ; Dorsal Raphe Nucleus/chemistry ; Dorsal Raphe Nucleus/cytology ; Dorsal Raphe Nucleus/physiology ; GABAergic Neurons/cytology ; GABAergic Neurons/metabolism ; GABAergic Neurons/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/cytology ; Neurons/metabolism ; Neurons/physiology ; Phenotype ; Serotonergic Neurons/cytology ; Serotonergic Neurons/metabolism ; Serotonergic Neurons/physiology ; Serotonin/metabolism ; Transcription Factors/metabolism ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Amino Acid Transport Systems, Acidic ; Transcription Factors ; vesicular glutamate transporter 3, mouse ; Serotonin (333DO1RDJY) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2016-04-04
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-016-1217-x
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Article ; Online: Divergent in vivo activity of non-serotonergic and serotonergic VGluT3-neurones in the median raphe region.

Domonkos, Andor / Nikitidou Ledri, Litsa / Laszlovszky, Tamás / Cserép, Csaba / Borhegyi, Zsolt / Papp, Edit / Nyiri, Gábor / Freund, Tamás F / Varga, Viktor

The Journal of physiology

2016 Volume 594, Issue 13, Page(s) 3775–3790

Abstract: Key points: The median raphe is a key subcortical modulatory centre involved in several brain functions, such as regulation of the sleep-wake cycle, emotions and memory storage. A large proportion of median raphe neurones are glutamatergic and implement ...

Abstract	Key points: The median raphe is a key subcortical modulatory centre involved in several brain functions, such as regulation of the sleep-wake cycle, emotions and memory storage. A large proportion of median raphe neurones are glutamatergic and implement a radically different mode of communication compared to serotonergic cells, although their in vivo activity is unknown. We provide the first description of the in vivo, brain state-dependent firing properties of median raphe glutamatergic neurones identified by immunopositivity for the vesicular glutamate transporter type 3 (VGluT3) and serotonin (5-HT). Glutamatergic populations (VGluT3+/5-HT- and VGluT3+/5-HT+) were compared with the purely serotonergic (VGluT3-/5-HT+ and VGluT3-/5-HT-) neurones. VGluT3+/5-HT+ neurones fired similar to VGluT3-/5-HT+ cells, whereas they significantly diverged from the VGluT3+/5-HT- population. Activity of the latter subgroup resembled the spiking of VGluT3-/5-HT- cells, except for their diverging response to sensory stimulation. The VGluT3+ population of the median raphe may broadcast rapidly varying signals on top of a state-dependent, tonic modulation. Abstract: Subcortical modulation is crucial for information processing in the cerebral cortex. Besides the canonical neuromodulators, glutamate has recently been identified as a key cotransmitter of numerous monoaminergic projections. In the median raphe, a pure glutamatergic neurone population projecting to limbic areas was also discovered with a possibly novel, yet undetermined function. In the present study, we report the first functional description of the vesicular glutamate transporter type 3 (VGluT3)-expressing median raphe neurones. Because there is no appropriate genetic marker for the separation of serotonergic (5-HT+) and non-serotonergic (5-HT-) VGluT3+ neurones, we utilized immunohistochemistry after recording and juxtacellular labelling in anaesthetized rats. VGluT3+/5-HT- neurones fired faster, more variably and were permanently activated during sensory stimulation, as opposed to the transient response of the slow firing VGluT3-/5-HT+ subgroup. VGluT3+/5-HT- cells were also more active during hippocampal theta. In addition, the VGluT3-/5-HT- population, comprising putative GABAergic cells, resembled the firing of VGluT3+/5-HT- neurones but without any significant reaction to the sensory stimulus. Interestingly, the VGluT3+/5-HT+ group, spiking slower than the VGluT3+/5-HT- population, exhibited a mixed response (i.e. the initial transient activation was followed by a sustained elevation of firing). Phase coupling to hippocampal and prefrontal slow oscillations was found in VGluT3+/5-HT- neurones, also differentiating them from the VGluT3+/5-HT+ subpopulation. Taken together, glutamatergic neurones in the median raphe may implement multiple, highly divergent forms of modulation in parallel: a slow, tonic mode interrupted by sensory-evoked rapid transients, as well as a fast one capable of conveying complex patterns influenced by sensory inputs.
MeSH term(s)	Animals ; Hippocampus/physiology ; Male ; Neurons/physiology ; Prefrontal Cortex/physiology ; Raphe Nuclei/physiology ; Rats, Wistar ; Serotonin/physiology ; Vesicular Glutamate Transport Proteins/physiology
Chemical Substances	Slc17a8 protein, rat ; Vesicular Glutamate Transport Proteins ; Serotonin (333DO1RDJY)
Language	English
Publishing date	2016-04-28
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP272036
Database	MEDical Literature Analysis and Retrieval System OnLINE

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