CCL

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1.

001-es BibID:BIBFORM078411
035-os BibID:(PMID)30734834 (WoS)000472512500009 (Scopus)85061242629
Első szerző:Baksa Brigitta (fogorvos)
Cím:Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus / Baksa B., Kovács A., Bayasgalan T., Szentesi P., Kőszeghy Á., Szücs P., Pál B.
Dátum:2019
ISSN:1420-682X
Megjegyzések:The pedunculopontine nucleus (PPN) is a part of the reticular activating system which is composed of cholinergic, glutamatergic and GABAergic neurons. Early electrophysiological studies characterized and grouped PPN neurons based on certain functional properties (i.e. the presence or absence of the A-current, spike latency, and low threshold spikes). Although other electrophysiological characteristics of these neurons were also described (as high threshold membrane potential oscillations, great differences in spontaneous firing rate and the presence or absence of the M-current), systematic assessment of these properties and correlation of them with morphological markers are still missing. In this work, we conducted electrophysiological experiments on brain slices of genetically identified cholinergic neurons in the PPN. Electrophysiological properties were compared with rostrocaudal location of the neuronal soma and selected morphometric features obtained with post hoc reconstruction. We found that functional subgroups had different proportions in the rostral and caudal subregions of the nucleus. Neurons with A-current can be divided to early-firing and late-firing neurons, where the latter type was found exclusively in the caudal subregion. Similar to this, different parameters of high threshold membrane potential oscillations also showed characteristic rostrocaudal distribution. Furthermore, based on our data we propose that high threshold oscillations rather emerge from neuronal somata and not from the proximal dendrites. In summary, we demonstrated the existence and spatial distribution of functional subgroups of genetically identified PPN cholinergic neurons, which are in accordance with differences found in projection and in vivo functional findings of the subregions. Being aware of functional differences of PPN subregions will help the design and analysis of experiments using genetically encoded opto- and chemogenetic markers for in vivo experiments.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
pedunculopontine nucleus
cholinergic neuron
spike delay
A-current
rostrocaudal gradient
high threshold oscillation
Megjelenés:Cellular And Molecular Life Sciences. - 76 : 14 (2019), p. 2799-2815. -
További szerzők:Kovács Adrienn (1989-) (molekuláris biológus) Bayasgalan, Tsogbadrakh (1983-) (Általános orvos) Szentesi Péter (1967-) (élettanász) Kőszeghy Áron (1983-) (Ph.D hallgató, élettanász) Szűcs Péter (1974-) (kutatóorvos) Pál Balázs (1975-) (élettanász)
Pályázati támogatás:KTIA_13_NAP-A-I/10
Egyéb
2017-1.2.1-NKP-2017-00002
Egyéb
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM070542
Első szerző:Bardóczi Zsuzsanna
Cím:Glycinergic input to the mouse basal forebrain cholinergic neurons / Bardóczi Z., Pál B., Kőszeghy Á., Wilheim T., Watanabe M., Záborszky L., Liposits Z., Kalló I.
Dátum:2017
Megjegyzések:The basal forebrain (BF) receives afferents from brain stem ascending pathways, which has been implicated first by Moruzzi and Magoun (Moruzzi and Magoun, 1949) to induce forebrain activation and cortical arousal/waking behavior; however, it is very little known about how brain stem inhibitory inputs affect cholinergic functions. In the current study, glycine, a major inhibitory neurotransmitter of brain stem neurons, and gliotransmitter of local glial cells, was tested for potential interaction with basal forebrain cholinergic (BFC) neurons in male mice. In the BF, glycine receptor ? subunit-immunoreactive (GlyR?-IR) sites were localized in choline acetyltransferase (ChAT)-IR neurons. Glycine's effect on BFC neurons was demonstrated by bicuculline-resistant, strychnine-sensitive spontaneous inhibitory postsynaptic currents (IPSCs; 0.81 ? 0.25 *10-1 Hz) recorded in whole cell conditions. Potential neuronal, as well as glial sources of glycine were indicated in the extracellular space of cholinergic neurons by glycine transporter 1 and 2 (GLYT1 and 2)-IR processes found in apposition to ChAT-IR cells. Ultrastructural analyses identified synapses of GLYT2-positive axon terminals on ChAT-IR neurons, as well as GLYT1-positive astroglial processes, which were localized in the vicinity of synapses of ChAT-IR neurons. The brain stem raphe magnus was determined to be a major source of glycinergic axons traced retrogradely from the BF. Our results indicate a direct effect of glycine on BFC neurons. Furthermore, the presence of high levels of plasma membrane glycine transporters in the vicinity of cholinergic neurons suggests a tight control of extracellular glycine in the BF.SIGNIFICANCE STATEMENTBFC neurons receive various activating inputs from specific brain stem areas, and channel this information to the cortex via multiple projections. So far very little is known about inhibitory brain stem afferents to the BF. The current study established glycine as a major regulator of BFC neurons by (1) identifying glycinergic neurons in the brain stem projecting to the BF, (2) showing GlyR?-IR sites in ChAT-IR neurons, (3) demonstrating GLYT2-positive axon terminals synapsing on ChAT-IR neurons, and (4) localizing GLYT1-positive astroglial processes in the vicinity of synapses of ChAT-IR neurons. Glycine's effect on BFC neurons was demonstrated by bicuculline-resistant, strychnine-sensitive spontaneous IPSCs recorded in whole cell conditions.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
basal forebrain
glycinergic
Megjelenés:The Journal of Neuroscience 37 : 39 (2017), p. 9534-9549. -
További szerzők:Pál Balázs (1975-) (élettanász) Kőszeghy Áron (1983-) (Ph.D hallgató, élettanász) Wilheim Tamás Watanabe, Masahiko Záborszky László Liposits Zsolt Kalló Imre
Pályázati támogatás:KTIA_13_NAP-A-I/10
Egyéb
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM079005
035-os BibID:(cikkazonosító)10562 (WOS)000438343600072 (Scopus)85049897404 (PubMed)30002493
Első szerző:Hegyi Zoltán (molekuláris biológus)
Cím:CB1 receptor activation induces intracellular Ca2+ mobilization and 2-arachidonoylglycerol release in rodent spinal cord astrocytes / Zoltán Hegyi, Tamás Oláh, Áron Kőszeghy, Fabiana Piscitelli, Krisztina Holló, Balázs Pál, László Csernoch, Vincenzo Di Marzo, Miklós Antal
Dátum:2018
ISSN:2045-2322
Megjegyzések:Accumulating evidence supports the role of astrocytes in endocannabinoid mediated modulation of neural activity. It has been reported that some astrocytes express the cannabinoid type 1 receptor (CB1-R), the activation of which is leading to Ca2+ mobilization from internal stores and a consecutive release of glutamate. It has also been documented that astrocytes have the potential to produce the endocannabinoid 2-arachidonoylglycerol, one of the best known CB1-R agonist. However, no relationship between CB1-R activation and 2-arachidonoylglycerol production has ever been demonstrated. Here we show that rat spinal astrocytes co-express CB1-Rs and the 2-arachidonoylglycerol synthesizing enzyme, diacylglycerol lipase-alpha in close vicinity to each other. We also demonstrate that activation of CB1-Rs induces a substantial elevation of intracellular Ca2+ concentration in astrocytes. Finally, we provide evidence that the evoked Ca2+ transients lead to the production of 2-arachidonoylglycerol in cultured astrocytes. The results provide evidence for a novel cannabinoid induced endocannabinoid release mechanism in astrocytes which broadens the bidirectional signaling repertoire between astrocytes and neurons.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 8 (2018), p. 10562. -
További szerzők:Oláh Tamás (1983-) (élettanász) Kőszeghy Áron (1983-) (Ph.D hallgató, élettanász) Piscitelli, Fabiana Holló Krisztina (1967-) (vegyész) Pál Balázs (1975-) (élettanász) Csernoch László (1961-) (élettanász) Di Marzo, Vincenzo Antal Miklós (1951-) (orvos, anatómus)
Pályázati támogatás:TKI 242
MTA
KTIA_NAP_13-1-2013-0001
Egyéb
KTIA_NAP_13-1-2013-0010
Egyéb
NN-107765
OTKA
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM074377
035-os BibID:(cikkazonosító)13715 (WOS)000444026700001 (Scopus)85053012698 (PubMed)30194313
Első szerző:Hegyi Zoltán (molekuláris biológus)
Cím:Author correction : CB1 receptor activation induces intracellular Ca2+ mobilization and 2-arachidonoylglycerol release in rodent spinal cord astrocytes / Hegyi Z., Oláh T., Kőszeghy Á., Pisticelli F., Holló K., Pál B., Csernoch L., Di Marzo V., Antal M.
Dátum:2018
ISSN:2045-2322
Tárgyszavak:Orvostudományok Elméleti orvostudományok hozzászólás
folyóiratcikk
Megjelenés:Scientific Reports. - 8 (2018), p. 13715. -
További szerzők:Oláh Tamás (1983-) (élettanász) Kőszeghy Áron (1983-) (Ph.D hallgató, élettanász) Pisticelli, Fabiana Holló Krisztina (1967-) (vegyész) Pál Balázs (1975-) (élettanász) Csernoch László (1961-) (élettanász) Di Marzo, Vincenzo Antal Miklós (1951-) (orvos, anatómus)
Pályázati támogatás:MTA-TKI 242
MTA
Nemzeti Agykutatási Program
Egyéb
OTKA-107765
OTKA
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM060025
Első szerző:Kőszeghy Áron (Ph.D hallgató, élettanász)
Cím:Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes. / Áron Kőszeghy, Adrienn Kovács, Tamás Bíró, Péter Szűcs, János Vincze, Zoltán Hegyi, Miklós Antal, Balázs Pál
Dátum:2015
Megjegyzések:The pedunculopontine nucleus (PPN) is known as the cholinergic part of the reticular activating system (RAS) and it plays an important role in transitions of slow-wave sleep to REM sleep and wakefulness. Although both exogenous and endocannabinoids affect sleep, the mechanism of endocannabinoid neuromodulation has not been characterized at cellular level in the PPN. In this paper, we demonstrate that both neurons and glial cells from the PPN respond to cannabinoid type 1 (CB1) receptor agonists. The neuronal response can be depolarization or hyperpolarization, while astrocytes exhibit more frequent calcium waves. All these effects are absent in CB1 gene-deficient mice. Blockade of the fast synaptic neurotransmission or neuronal action potential firing does not change the effect on the neuronal membrane potential significantly, while inhibition of astrocytic calcium waves by thapsigargin diminishes the response. Inhibition of group I metabotropic glutamate receptors (mGluRs) abolishes hyperpolarization, whereas blockade of group II mGluRs prevents depolarization. Initially active neurons and glial cells display weaker responses partially due to the increased endocannabinoid tone in their environment. Taken together, we propose that cannabinoid receptor stimulation modulates PPN neuronal activity in the following manner: active neurons may elicit calcium waves in astrocytes via endogenous CB1 receptor agonists. Astrocytes in turn release glutamate that activates different metabotropic glutamate receptors of neurons and modulate PPN neuronal activity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Endocannabinoid
Pedunculopontine nucleus
CB1 receptor
Neuromodulation
Astrocyte
Metabotropic glutamate receptor
Megjelenés:Brain structure and function 220 : 5 (2015), p. 3023-3041. -
További szerzők:Kovács Adrienn (1989-) (molekuláris biológus) Bíró Tamás (1968-) (élettanász) Szűcs Péter (1974-) (kutatóorvos) Vincze János (1988-) (orvos) Hegyi Zoltán (1983-) (molekuláris biológus) Antal Miklós (1951-) (orvos, anatómus) Pál Balázs (1975-) (élettanász)
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Intézményi repozitóriumban (DEA) tárolt változat
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6.

001-es BibID:BIBFORM037815
Első szerző:Kőszeghy Áron (Ph.D hallgató, élettanász)
Cím:Purkinje-like cells of the rat cochlear nucleus : a combined functional and morphological study / Kőszeghy, Á., Pál, B., Pap, P., Pocsai, K., Nagy, Zs., Szücs, G., Rusznák, Z.
Dátum:2009
ISSN:0006-8993
Megjegyzések:Purkinje-like cells (PLCs) of the cochlear nucleus (CN) are strongly calbindin positive neurones with unknown function. In the present work functional and morphological methods have been employed to provide data about PLCs in general, and about their possible involvement in the synaptic organisation of the CN in particular. PLCs had slightly elongated soma, from which a complex dendritic arborisation extended with highly variable dimensions. On the basis of their morphology, three classes of PLCs were identified. Positively identified PLCs fired a train of action potentials on sustained depolarization. When hyperpolarizing stimuli were applied, the presence of a slowly activating, ZD7288-sensitive inward current was noted that corresponded to the h-current. PLCs received both excitatory and inhibitory synaptic inputs. Functional experiments revealed that 76% and 14% of the spontaneous inhibitory postsynaptic currents recorded from the cell bodies of the PLCs were mediated via glycinergic and GABAergic synapses, respectively. PLCs presented strong cerebellin1-like immunoreactivity, but its distribution differed from that seen in cerebellar Purkinje cells. Our results indicate that PLCs are parts of the synaptic circuitry of the CN, thus they may be actively involved in the processing and analysis of auditory information.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Brain Research. - 1297 (2009), p. 57-69. -
További szerzők:Pál Balázs (1975-) (élettanász) Pap Pál (1981-) (élettanász) Pocsai Krisztina (1978-) (élettanász) Nagy Zsuzsanna (1986-) (élettanász) Szűcs Géza (1948-) (élettanász) Rusznák Zoltán (1965-) (élettanász)
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Intézményi repozitóriumban (DEA) tárolt változat
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7.

001-es BibID:BIBFORM038850
Első szerző:Lontay Beáta (biokémikus)
Cím:Protein phosphatase-1M and Rho-kinase affect exocytosis from cortical synaptosomes and influence neurotransmission at a glutamatergic giant synapse of the rat auditory system / Lontay Beáta, Pál Balázs, Serfőző Zoltán, Kőszeghy Áron, Szücs Géza, Rusznák Zoltán, Erdődi Ferenc
Dátum:2012
ISSN:0022-3042
Megjegyzések:Protein phosphatase-1M (PP1M, myosin phosphatase) consists of a PP1 catalytic subunit (PP1c) and the myosin phosphatase target subunit-1 (MYPT1). RhoA-activated kinase (ROK) regulates PP1M via inhibitory phosphorylation of MYPT1. Using multidisciplinary approaches, we have studied the roles of PP1M and ROK in neurotransmission. Electron microscopy demonstrated the presence of MYPT1 and ROK in both pre- and post-synaptic terminals. Tautomycetin (TMC), a PP1-specific inhibitor, decreased the depolarization-induced exocytosis from cortical synaptosomes. trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride, a ROK-specific inhibitor, had the opposite effect. Mass spectrometry analysis identified several MYPT1-bound synaptosomal proteins, of which interactions of synapsin-I, syntaxin-1, calcineurin-A subunit, and Ca(2+) /calmodulin-dependent kinase II with MYPT1 were confirmed. In intact synaptosomes, TMC increased, whereas Y27632 decreased the phosphorylation levels of MYPT1(Thr696) , myosin-II light chain(Ser19) , synapsin-I(Ser9) , and syntaxin-1(Ser14) , indicating that PP1M and ROK influence their phosphorylation status. Confocal microscopy indicated that MYPT1 and ROK are present in the rat ventral cochlear nucleus both pre- and post-synaptically. Analysis of the neurotransmission in an auditory glutamatergic giant synapse demonstrated that PP1M and ROK affect neurotransmission via both pre- and post-synaptic mechanisms. Our data suggest that both PP1M and ROK influence synaptic transmission, but further studies are needed to give a full account of their mechanism of action.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Molekuláris Medicina
Megjelenés:Journal of Neurochemistry. - 123 : 1 (2012), p. 84-99. -
További szerzők:Pál Balázs (1975-) (élettanász) Serfőző Zoltán Kőszeghy Áron (1983-) (Ph.D hallgató, élettanász) Szűcs Géza (1948-) (élettanász) Rusznák Zoltán (1965-) (élettanász) Erdődi Ferenc (1953-) (biokémikus)
Pályázati támogatás:TÁMOP-4.2.2-08/1-2008-0019
TÁMOP
TÁMOP-4.2.2/B-10/1-2010-0024
TÁMOP
TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Biomolekuláris interakciók jellemzőinek kvantitatív meghatározása
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Intézményi repozitóriumban (DEA) tárolt változat
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8.

001-es BibID:BIBFORM009112
Első szerző:Pál Balázs (élettanász)
Cím:Targets, receptors and effects of muscarinic neuromodulation on giant neurones of the rat dorsal cochlear nucleus / Pal, B., Koszeghy, A., Pap, P., Bakondi, G., Pocsai, K., Szucs, G., Rusznak, Z.
Dátum:2009
ISSN:0953-816X
Megjegyzések:Although cholinergic modulation of the cochlear nucleus (CN) is functionally important, neither its cellular consequences nor the types of receptors conveying it are precisely known. The aim of this work was to characterise the cholinergic effects on giant cells of the CN, using electrophysiology and quantitative polymerase chain reaction. Application of the cholinergic agonist carbachol increased the spontaneous activity of the giant cells; which was partly the consequence of the reduction in a K(+) conductance. This effect was mediated via M4 and M3 receptors. Cholinergic modulation also affected the synaptic transmission targeting the giant cells. Excitatory synaptic currents evoked by the stimulation of the superficial and deep regions of the CN were sensitive to cholinergic modulation: the amplitude of the first postsynaptic current was reduced, and the short-term depression was also altered. These changes were mediated via M3 receptors alone and via the combination of M4, M2 and M3 receptors, when the superficial and deep layers, respectively, were activated. Inhibitory synaptic currents evoked from the superficial layer showed short-term depression, but they were unaffected by carbachol. In contrast, inhibitory currents triggered by the activation of the deep parts exhibited no significant short-term depression, but they were highly sensitive to cholinergic activation, which was mediated via M3 receptors. Our results indicate that pre- and postsynaptic muscarinic receptors mediate cholinergic modulation on giant cells. The present findings shed light on the cellular mechanisms of a tonic cholinergic modulation in the CN, which may become particularly important in evoking contralateral excitatory responses under certain pathological conditions
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
agonist
Carbachol
CN
Cochlear Nucleus
dorsal cochlear nucleus
Electrophysiology
giant
Health
neurone
physiology
Polymerase Chain Reaction
rat
receptor
Synaptic Transmission
Megjelenés:The European Journal of Neuroscience. - 30 : 5 (2009), p. 769-782. -
További szerzők:Kőszeghy Áron (1983-) (Ph.D hallgató, élettanász) Pap Pál (1981-) (élettanász) Bakondi Gábor (1980-) (élettanász) Pocsai Krisztina (1978-) (élettanász) Szűcs Géza (1948-) (élettanász) Rusznák Zoltán (1965-) (élettanász)
Internet cím:elektronikus változat
DOI
Borító:

9.

001-es BibID:BIBFORM040376
Első szerző:Rusznák Zoltán (élettanász)
Cím:The hyperpolarization-activated non-specific cation current (Ih) adjusts the membrane properties, excitability, and activity pattern of the giant cells in the rat dorsal cochlear nucleus / Rusznák Zoltán, Pál Balázs, Kőszeghy Áron, Fu YuHong, Szücs Géza, Paxinos George
Dátum:2013
ISSN:0953-816X
Megjegyzések:Giant cells of the cochlear nucleus are thought to integrate multimodal sensory inputs and participate in monaural sound source localization. Our aim was to explore the significance of a hyperpolarization-activated current in determining the activity of giant neurones in slices prepared from 10 to 14-day-old rats. When subjected to hyperpolarizing stimuli, giant cells produced a 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288)-sensitive inward current with a reversal potential and half-activation voltage of ?36 and ?88 mV, respectively. Consequently, the current was identified as the hyperpolarization-activated non-specific cationic current (Ih). At the resting membrane potential, 3.5% of the maximum Ih conductance was available. Immunohistochemistry experiments suggested that hyperpolarization-activated, cyclic nucleotide-gated, cation non-selective (HCN)1, HCN2, and HCN4 subunits contribute to the assembly of the functional channels. Inhibition of Ih hyperpolarized the membrane by 6 mV and impeded spontaneous firing. The frequencies of spontaneous inhibitory and excitatory postsynaptic currents reaching the giant cell bodies were reduced but no significant change was observed when evoked postsynaptic currents were recorded. Giant cells are affected by biphasic postsynaptic currents consisting of an excitatory and a subsequent inhibitory component. Inhibition of Ih reduced the frequency of these biphasic events by 65% and increased the decay time constants of the inhibitory component. We conclude that Ih adjusts the resting membrane potential, contributes to spontaneous action potential firing, and may participate in the dendritic integration of the synaptic inputs of the giant neurones. Because its amplitude was higher in young than in adult rats, Ih of the giant cells may be especially important during the postnatal maturation of the auditory system.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
developing auditory system
h-current
spontaneous activity
synaptic transmission
ZD7288
Megjelenés:European Journal Of Neuroscience. - 37 : 6 (2013), p. 876-890. -
További szerzők:Pál Balázs (1975-) (élettanász) Kőszeghy Áron (1983-) (Ph.D hallgató, élettanász) Fu, YuHong Szűcs Géza (1948-) (élettanász) Paxinos, George
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Intézményi repozitóriumban (DEA) tárolt változat
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