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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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001-es BibID:	BIBFORM113771
035-os BibID:	(cikkazonosító)e13939 (WOS)001035767500001 (Scopus)85165549817
Első szerző:	Csemer Andrea (molekuláris biológus)
Cím:	Astrocyte- and NMDA receptor-dependent slow inward currents differently contribute to synaptic plasticity in an age-dependent manner in mouse and human neocortex / Csemer Andrea, Kovács Adrienn, Maamrah Baneen, Pocsai Krisztina, Korpás Kristóf, Klekner Álmos, Szücs Péter, Nánási Péter P., Pál Balázs
Dátum:	2023
ISSN:	1474-9718 1474-9726
Megjegyzések:	Slow inward currents (SICs) are known as excitatory events of neurons elicited by astrocytic glutamate via activation of extrasynaptic NMDA receptors. By using slice electrophysiology, we tried to provide evidence that SICs can elicit synaptic plasticity. Age dependence of SICs and their impact on synaptic plasticity was also investigated in both on murine and human cortical slices. It was found that SICs can induce a moderate synaptic plasticity, with features similar to spike timing-dependent plasticity. Overall SIC activity showed a clear decline with aging in humans and completely disappeared above a cutoff age. In conclusion, while SICs contribute to a form of astrocyte-dependent synaptic plasticity both in mice and humans, this plasticity is differentially affected by aging. Thus, SICs are likely to play an important role in age-dependent physiological and pathological alterations of synaptic plasticity.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk NMDA receptor aging astrocyte human brain neocortex pyramidal cell slow inward current synaptic plasticity
Megjelenés:	Aging Cell. - 22 : 9 (2023), p. e13939. -
További szerzők:	Kovács Adrienn (1989-) (molekuláris biológus) Maamrah, Baneen (1994-) (molekuláris biológus) Pocsai Krisztina (1978-) (élettanász) Korpás Kristóf Levente (1998-) (orvostanhallgató) Klekner Álmos (1970-) (idegsebész) Szűcs Péter (1974-) (kutatóorvos) Nánási Péter Pál (1956-) (élettanász) Pál Balázs (1975-) (élettanász)
Pályázati támogatás:	138090 OTKA 2020-4.1.1-TKP2020 Egyéb 2017-1.2.1-NKP-2017-00002 Egyéb KTIA_NAP_13-2-2014-0005 Egyéb KTIA_13_NAP-A-I/10 Egyéb Stipendium Hungaricum PhD program Egyéb NKFIH-K138090 Egyéb
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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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001-es BibID:	BIBFORM062728
Első szerző:	Kovács Adrienn (molekuláris biológus)
Cím:	Direct presynaptic and indirect astrocyte-mediated mechanisms both contribute to endocannabinoid signaling in the pedunculopontine nucleus of mice / Kovács A., Bordás Cs., Bíró T., Hegyi Z., Antal M., Szücs P., Pál B.
Dátum:	2017
ISSN:	1863-2653 1863-2661
Megjegyzések:	The pedunculopontine nucleus (PPN), a cholinergic nucleus of the reticular activating system, is known to be involved in the regulation of sleep and wakefulness. Endogenous and exogenous cannabinoids, either by systemic or local administration to the pedunculopontine nucleus can both influence sleep. We previously demonstrated that activation of astrocytes by cannabinoid type 1 (CB1) receptor agonists was able to modulate the membrane potential of PPN neurons, even in the presence of blockers of fast synaptic neurotransmission. In the present work we provide evidence that synaptic inputs of PPN neurons are also affected by activation of presynaptic and astrocytic CB1 receptors.Using slice electrophysiology combined with calcium imaging, optogenetics and immunohistochemistry, we revealed a direct presynaptic inhibitory action on inhibitory postsynaptic currents, along with a mild increase of excitatory postsynaptic currents during CB1 receptor stimulation. Besides inhibition of excitatory and inhibitory neurotransmission through stimulation of presynaptic CB1 receptors, astrocyte- and mGluR-dependent tonic inhibition and excitation also developed. The mild stimulatory action of CB1 receptor activation on excitatory neurotransmission is the combination of astrocyte-dependent tonic excitation on excitatory neurons and the canonical presynaptic CB1 receptor activation and consequential inhibition of excitatory synaptic neurotransmission, whereas the astrocyte-dependent stimulatory action was not observed on inhibitory neurotransmission within the PPN.Our findings demonstrate that endocannabinoids act in the PPN via a dual pathway, consisting of a direct presynaptic and an indirect, astrocyte-mediated component, regulating synaptic strength and neuronal activity via independent mechanisms.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban pedunculopontine nucleus CB1 receptor optogenetics astrocyte neuromodulation
Megjelenés:	Brain Structure & Function 222 : 1 (2017), p. 247-266. -
További szerzők:	Bordás Csilla Bíró Tamás (1968-) (élettanász) Hegyi Zoltán (1983-) (molekuláris biológus) Antal Miklós (1951-) (orvos, anatómus) Szűcs Péter (1974-) (kutatóorvos) Pál Balázs (1975-) (élettanász)
Pályázati támogatás:	Nemzeti Agykutatási Program KTIA_13_NAP-A-I/10 Egyéb Nemzeti Agykutatási Program KTIA_NAP_13-1-2013-0001 Egyéb Nemzeti Agykutatási Program KTIA_NAP_13-2-2014-0005 Egyéb MTA-TKI 242 MTA TÁMOP-4.2.2.B-15/1/KONV-2015-0001 TÁMOP
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