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Article ; Online: Temporal disparity of action potentials triggered in axon initial segments and distal axons in the neocortex.

Rózsa, Márton / Tóth, Martin / Oláh, Gáspár / Baka, Judith / Lákovics, Rajmund / Barzó, Pál / Tamás, Gábor

2023 Volume 9, Issue 41, Page(s) eade4511

Abstract: Neural population activity determines the timing of synaptic inputs, which arrive to dendrites, cell bodies, and axon initial segments (AISs) of cortical neurons. Action potential initiation in the AIS (AIS-APs) is driven by input integration, and the ... ...

Abstract	Neural population activity determines the timing of synaptic inputs, which arrive to dendrites, cell bodies, and axon initial segments (AISs) of cortical neurons. Action potential initiation in the AIS (AIS-APs) is driven by input integration, and the phase preference of AIS-APs during network oscillations is characteristic to cell classes. Distal regions of cortical axons do not receive synaptic inputs, yet experimental induction protocols can trigger retroaxonal action potentials (RA-APs) in axons distal from the soma. We report spontaneously occurring RA-APs in human and rodent cortical interneurons that appear uncorrelated to inputs and population activity. Network-linked triggering of AIS-APs versus input-independent timing of RA-APs of the same interneurons results in disparate temporal contribution of a single cell to in vivo network operation through perisomatic and distal axonal firing.
MeSH term(s)	Humans ; Action Potentials/physiology ; Neocortex/physiology ; Axon Initial Segment ; Dendrites/physiology ; Axons/physiology
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.ade4511
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Article ; Online: Predominantly linear summation of metabotropic postsynaptic potentials follows coactivation of neurogliaform interneurons.

Ozsvár, Attila / Komlósi, Gergely / Oláh, Gáspár / Baka, Judith / Molnár, Gábor / Tamás, Gábor

eLife

2021 Volume 10

Abstract: Summation of ionotropic receptor-mediated responses is critical in neuronal computation by shaping input-output characteristics of neurons. However, arithmetics of summation for metabotropic signals are not known. We characterized the combined ionotropic ...

Abstract	Summation of ionotropic receptor-mediated responses is critical in neuronal computation by shaping input-output characteristics of neurons. However, arithmetics of summation for metabotropic signals are not known. We characterized the combined ionotropic and metabotropic output of neocortical neurogliaform cells (NGFCs) using electrophysiological and anatomical methods in the rat cerebral cortex. These experiments revealed that GABA receptors are activated outside release sites and confirmed coactivation of putative NGFCs in superficial cortical layers in vivo. Triple recordings from presynaptic NGFCs converging to a postsynaptic neuron revealed sublinear summation of ionotropic GABA
MeSH term(s)	Action Potentials/physiology ; Animals ; Axons/physiology ; Cerebral Cortex/metabolism ; Interneurons/physiology ; Mice ; Neural Inhibition ; Neuroglia/physiology ; Neurons/physiology ; Pyramidal Cells/physiology ; Rats ; Receptors, GABA-B/metabolism ; Somatosensory Cortex/physiology ; Synapses/physiology ; Synaptic Potentials/physiology ; Synaptic Transmission/physiology
Chemical Substances	Receptors, GABA-B
Language	English
Publishing date	2021-07-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.65634
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Article ; Online: Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex.

Szegedi, Viktor / Paizs, Melinda / Baka, Judith / Barzó, Pál / Molnár, Gábor / Tamas, Gabor / Lamsa, Karri

eLife

2020 Volume 9

Abstract: Inhibitory autapses are self-innervating synaptic connections in GABAergic interneurons in the brain. Autapses in neocortical layers have not been systematically investigated, and their function in different mammalian species and specific interneuron ... ...

Abstract	Inhibitory autapses are self-innervating synaptic connections in GABAergic interneurons in the brain. Autapses in neocortical layers have not been systematically investigated, and their function in different mammalian species and specific interneuron types is poorly known. We investigated GABAergic parvalbumin-expressing basket cells (pvBCs) in layer 2/3 (L2/3) in human neocortical tissue resected in deep-brain surgery, and in mice as control. Most pvBCs showed robust GABA
MeSH term(s)	Animals ; Axons/physiology ; Brain/physiology ; Carisoprodol ; Dendrites/physiology ; Electrophysiology ; Female ; GABA Agents/metabolism ; Humans ; Interneurons/physiology ; Male ; Mice ; Microscopy, Electron ; Neocortex/cytology ; Neocortex/physiology ; Parvalbumins ; Patch-Clamp Techniques
Chemical Substances	GABA Agents ; Parvalbumins ; Carisoprodol (21925K482H)
Language	English
Publishing date	2020-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.51691
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Article ; Online: Stress Resilience is Associated with Hippocampal Synaptoprotection in the Female Rat Learned Helplessness Paradigm.

Huzian, Orsolya / Baka, Judith / Csakvari, Eszter / Dobos, Nikoletta / Leranth, Csaba / Siklos, Laszlo / Duman, Ronald S / Farkas, Tamas / Hajszan, Tibor

Neuroscience

2021 Volume 459, Page(s) 85–103

Abstract: The synaptogenic hypothesis of major depressive disorder implies that preventing the onset of depressive-like behavior also prevents the loss of hippocampal spine synapses. By applying the psychoactive drugs, diazepam and fluoxetine, we investigated ... ...

Abstract	The synaptogenic hypothesis of major depressive disorder implies that preventing the onset of depressive-like behavior also prevents the loss of hippocampal spine synapses. By applying the psychoactive drugs, diazepam and fluoxetine, we investigated whether blocking the development of helpless behavior by promoting stress resilience in the rat learned helplessness paradigm is associated with a synaptoprotective action in the hippocampus. Adult ovariectomized and intact female Sprague-Dawley rats (n = 297) were treated with either diazepam, fluoxetine, or vehicle, exposed to inescapable footshocks or sham stress, and tested in an active escape task to assess helpless behavior. Escape-evoked corticosterone secretion, as well as remodeling of hippocampal spine synapses at a timepoint representing the onset of escape testing were also analyzed. In ovariectomized females, treatment with diazepam prior to stress exposure prevented helpless behavior, blocked the loss of hippocampal spine synapses, and muted the corticosterone surge evoked by escape testing. Although fluoxetine stimulated escape performance and hippocampal synaptogenesis under non-stressed conditions, almost all responses to fluoxetine were abolished following exposure to inescapable stress. Only a much higher dose of fluoxetine was capable of partly reproducing the strong protective actions of diazepam. Importantly, these protective actions were retained in the presence of ovarian hormones. Our findings indicate that stress resilience is associated with the preservation of spine synapses in the hippocampus, raising the possibility that, besides synaptogenesis, hippocampal synaptoprotection is also implicated in antidepressant therapy.
MeSH term(s)	Animals ; Depressive Disorder, Major ; Disease Models, Animal ; Female ; Fluoxetine/pharmacology ; Helplessness, Learned ; Hippocampus ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Fluoxetine (01K63SUP8D)
Language	English
Publishing date	2021-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.2021.01.029
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Article ; Online: Quantitative analysis of lipid debris accumulation caused by cuprizone induced myelin degradation in different CNS areas.

Ozsvár, Attila / Szipőcs, Róbert / Ozsvár, Zoltán / Baka, Judith / Barzó, Pál / Tamás, Gábor / Molnár, Gábor

Brain research bulletin

2018 Volume 137, Page(s) 277–284

Abstract: Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on the mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently ... ...

Abstract	Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on the mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to image lipid structures in living tissue. We confirmed earlier results showing a brain region dependent myelin destructive effect of cuprizone. In addition, high resolution in situ CARS imaging revealed myelin debris forming lipid droplets alongwith myelinated axon fibers. Quantification of lipid debris with custom-made software for segmentation and three dimensional reconstruction revealed brain region dependent accumulation of lipid drops inversely correlated with the thickness of myelin sheaths. Finally, we confirmed that in situ CARS imaging is applicable to living human brain tissue in brain slices derived from a patient. Thus, CARS microscopy is potent tool for quantitative monitoring of myelin degradation in unprecedented spatiotemporal resolution during oligodendrocyte damage. We think that the accumulation of lipid drops around degrading myelin might be instrumental in triggering subsequent inflammatory processes.
MeSH term(s)	Aged ; Animals ; Axons/drug effects ; Axons/metabolism ; Axons/pathology ; Brain/drug effects ; Brain/metabolism ; Brain/pathology ; Brain/surgery ; Brain Neoplasms/pathology ; Brain Neoplasms/surgery ; Cuprizone/toxicity ; Demyelinating Diseases/metabolism ; Demyelinating Diseases/pathology ; Female ; Humans ; Lipid Droplets/drug effects ; Lipid Droplets/pathology ; Lipid Metabolism ; Male ; Mice, Inbred C57BL ; Myelin Sheath/drug effects ; Myelin Sheath/metabolism ; Myelin Sheath/pathology ; Tissue Culture Techniques
Chemical Substances	Cuprizone (5N16U7E0AO)
Language	English
Publishing date	2018-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2018.01.003
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Article ; Online: Unitary GABAergic volume transmission from individual interneurons to astrocytes in the cerebral cortex.

Rózsa, Márton / Baka, Judith / Bordé, Sándor / Rózsa, Balázs / Katona, Gergely / Tamás, Gábor

Brain structure & function

2017 Volume 222, Issue 1, Page(s) 651–659

Abstract: Communication between individual GABAergic cells and their target neurons is mediated by synapses and, in the case of neurogliaform cells (NGFCs), by unitary volume transmission. Effects of non-synaptic volume transmission might involve non-neuronal ... ...

Abstract	Communication between individual GABAergic cells and their target neurons is mediated by synapses and, in the case of neurogliaform cells (NGFCs), by unitary volume transmission. Effects of non-synaptic volume transmission might involve non-neuronal targets, and astrocytes not receiving GABAergic synapses but expressing GABA receptors are suitable for evaluating this hypothesis. Testing several cortical interneuron types in slices of the rat cerebral cortex, we show selective unitary transmission from NGFCs to astrocytes with an early, GABA
MeSH term(s)	Action Potentials ; Animals ; Astrocytes/cytology ; Astrocytes/physiology ; Calcium Signaling ; Cerebral Cortex/cytology ; Cerebral Cortex/physiology ; GABAergic Neurons/cytology ; GABAergic Neurons/physiology ; Interneurons/cytology ; Interneurons/physiology ; Male ; Rats ; Rats, Wistar ; Receptors, GABA-A/physiology ; Receptors, GABA-B/physiology
Chemical Substances	Receptors, GABA-A ; Receptors, GABA-B
Language	English
Publishing date	2017-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-015-1166-9
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Article ; Online: Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles.

Molnár, Gábor / Rózsa, Márton / Baka, Judith / Holderith, Noémi / Barzó, Pál / Nusser, Zoltan / Tamás, Gábor

eLife

2016 Volume 5

Abstract: Classic theories link cognitive abilities to synaptic properties and human-specific biophysical features of synapses might contribute to the unparalleled performance of the human cerebral cortex. Paired recordings and multiple probability fluctuation ... ...

Abstract	Classic theories link cognitive abilities to synaptic properties and human-specific biophysical features of synapses might contribute to the unparalleled performance of the human cerebral cortex. Paired recordings and multiple probability fluctuation analysis revealed similar quantal sizes, but 4-times more functional release sites in human pyramidal cell to fast-spiking interneuron connections compared to rats. These connections were mediated on average by three synaptic contacts in both species. Each presynaptic active zone (AZ) contains 6.2 release sites in human, but only 1.6 in rats. Electron microscopy (EM) and EM tomography showed that an AZ harbors 4 docked vesicles in human, but only a single one in rats. Consequently, a Katz's functional release site occupies ~0.012 μm(2) in the human presynaptic AZ and ~0.025 μm(2) in the rat. Our results reveal a robust difference in the biophysical properties of a well-defined synaptic connection of the cortical microcircuit of human and rodents.
MeSH term(s)	Animals ; Biophysical Phenomena ; Electron Microscope Tomography ; Humans ; Interneurons/physiology ; Microscopy, Electron, Transmission ; Presynaptic Terminals/metabolism ; Presynaptic Terminals/ultrastructure ; Pyramidal Cells/physiology ; Rats ; Synaptic Vesicles/metabolism ; Synaptic Vesicles/ultrastructure
Language	English
Publishing date	2016-08-18
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.18167
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Article: Expansion-assisted selective plane illumination microscopy for nanoscale imaging of centimeter-scale tissues.

Glaser, Adam / Chandrashekar, Jayaram / Vasquez, Joshua / Arshadi, Cameron / Ouellette, Naveen / Jiang, Xiaoyun / Baka, Judith / Kovacs, Gabor / Woodard, Micah / Seshamani, Sharmishtaa / Cao, Kevin / Clack, Nathan / Recknagel, Andrew / Grim, Anna / Balaram, Pooja / Turschak, Emily / Liddell, Alan / Rohde, John / Hellevik, Ayana /

Takasaki, Kevin / Barner, Lindsey Erion / Logsdon, Molly / Chronopoulos, Chris / de Vries, Saskia / Ting, Jonathan / Perlmutter, Steve / Kalmbach, Brian / Dembrow, Nikolai / Reid, R Clay / Feng, David / Svoboda, Karel

bioRxiv : the preprint server for biology

2023

Abstract: Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure of cells and tissues at sub-diffraction resolutions and near single molecule sensitivity, driving discoveries in diverse fields ...

Abstract	Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure of cells and tissues at sub-diffraction resolutions and near single molecule sensitivity, driving discoveries in diverse fields of biology, including neuroscience. Biological tissue is organized over scales of nanometers to centimeters. Harnessing molecular imaging across three-dimensional samples on this scale requires new types of microscopes with larger fields of view and working distance, as well as higher imaging throughput. We present a new expansion-assisted selective plane illumination microscope (ExA-SPIM) with diffraction-limited and aberration-free performance over a large field of view (85 mm
Language	English
Publishing date	2023-06-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.08.544277
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Article ; Online: Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression.

Baka, Judith / Csakvari, Eszter / Huzian, Orsolya / Dobos, Nikoletta / Siklos, Laszlo / Leranth, Csaba / MacLusky, Neil J / Duman, Ronald S / Hajszan, Tibor

Neuroscience

2016 Volume 343, Page(s) 384–397

Abstract: Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of ... ...

Abstract	Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague-Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn 'postpartum', simulated proestrus, and hormone-treated 'postpartum' animals. After 'postpartum' withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn 'postpartum' females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during 'postpartum' stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during 'postpartum' stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated 'postpartum' females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging 'synaptogenic hypothesis' of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness.
MeSH term(s)	Animals ; Corticosterone/blood ; Depression, Postpartum/metabolism ; Depression, Postpartum/pathology ; Depressive Disorder, Major/metabolism ; Depressive Disorder, Major/pathology ; Disease Models, Animal ; Estradiol/administration & dosage ; Estradiol/metabolism ; Female ; Hippocampus/metabolism ; Hippocampus/pathology ; Neuronal Plasticity/physiology ; Ovariectomy ; Postpartum Period ; Proestrus/physiology ; Progesterone/administration & dosage ; Progesterone/metabolism ; Rats, Sprague-Dawley ; Synapses/metabolism ; Synapses/pathology
Chemical Substances	Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E) ; Corticosterone (W980KJ009P)
Language	English
Publishing date	2016-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.2016.12.021
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Article ; Online: Human neuronal changes in brain edema and increased intracranial pressure.

Faragó, Nóra / Kocsis, Ágnes Katalin / Braskó, Csilla / Lovas, Sándor / Rózsa, Márton / Baka, Judith / Kovács, Balázs / Mikite, Katalin / Szemenyei, Viktor / Molnár, Gábor / Ozsvár, Attila / Oláh, Gáspár / Piszár, Ildikó / Zvara, Ágnes / Patócs, Attila / Barzó, Pál / Puskás, László G / Tamás, Gábor

Acta neuropathologica communications

2016 Volume 4, Issue 1, Page(s) 78

Abstract: Functional and molecular changes associated with pathophysiological conditions are relatively easily detected based on tissue samples collected from patients. Population specific cellular responses to disease might remain undiscovered in samples taken ... ...

Abstract	Functional and molecular changes associated with pathophysiological conditions are relatively easily detected based on tissue samples collected from patients. Population specific cellular responses to disease might remain undiscovered in samples taken from organs formed by a multitude of cell types. This is particularly apparent in the human cerebral cortex composed of a yet undefined number of neuron types with a potentially different involvement in disease processes. We combined cellular electrophysiology, anatomy and single cell digital PCR in human neurons identified in situ for the first time to assess mRNA expression and corresponding functional changes in response to edema and increased intracranial pressure. In single pyramidal cells, mRNA copy numbers of AQP1, AQP3, HMOX1, KCNN4, SCN3B and SOD2 increased, while CACNA1B, CRH decreased in edema. In addition, single pyramidal cells increased the copy number of AQP1, HTR5A and KCNS1 mRNAs in response to increased intracranial pressure. In contrast to pyramidal cells, AQP1, HMOX1and KCNN4 remained unchanged in single cell digital PCR performed on fast spiking cells in edema. Corroborating single cell digital PCR results, pharmacological and immunohistochemical results also suggested the presence of KCNN4 encoding the α-subunit of KCa3.1 channels in edema on pyramidal cells, but not on interneurons. We measured the frequency of spontaneous EPSPs on pyramidal cells in both pathophysiological conditions and on fast spiking interneurons in edema and found a significant decrease in each case, which was accompanied by an increase in input resistances on both cell types and by a drop in dendritic spine density on pyramidal cells consistent with a loss of excitatory synapses. Our results identify anatomical and/or physiological changes in human pyramidal and fast spiking cells in edema and increased intracranial pressure revealing cell type specific quantitative changes in gene expression. Some of the edema/increased intracranial pressure modulated and single human pyramidal cell verified gene products identified here might be considered as novel pharmacological targets in cell type specific neuroprotection.
MeSH term(s)	Adult ; Brain Edema/metabolism ; Brain Edema/pathology ; Brain Edema/surgery ; Female ; Gene Expression Regulation ; Gray Matter/metabolism ; Gray Matter/pathology ; Gray Matter/surgery ; Humans ; Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism ; Intracranial Hypertension/metabolism ; Intracranial Hypertension/pathology ; Intracranial Hypertension/surgery ; Intracranial Pressure/physiology ; Male ; Membrane Potentials/physiology ; Middle Aged ; Neocortex/metabolism ; Neocortex/pathology ; Neocortex/surgery ; Neurons/metabolism ; Neurons/pathology ; RNA, Messenger/metabolism ; Tissue Culture Techniques
Chemical Substances	Intermediate-Conductance Calcium-Activated Potassium Channels ; KCNN4 protein, human ; RNA, Messenger
Language	English
Publishing date	2016-08-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-016-0356-x
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