Co-transmission of acetylcholine and GABA regulates hippocampal states

Virág T. Takács, Csaba Cserép, Dániel Schlingloff, Balázs Pósfai, András Szőnyi, Katalin E. Sos, Zsuzsanna Környei, Ádám Dénes, Attila I. Gulyás, T. Freund, G. Nyíri

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter. Yet, we find that mouse hippocampal cholinergic terminals invariably establish GABAergic synapses, and their cholinergic vesicles dock at those synapses only. We demonstrate that these synapses do not co-release but co-transmit GABA and acetylcholine via different vesicles, whose release is triggered by distinct calcium channels. This co-transmission evokes composite postsynaptic potentials, which are mutually cross-regulated by presynaptic autoreceptors. Although postsynaptic cholinergic receptor distribution cannot be investigated, their response latencies suggest a focal, intra- and/or peri-synaptic localisation, while GABAA receptors are detected intra-synaptically. The GABAergic component alone effectively suppresses hippocampal sharp wave-ripples and epileptiform activity. Therefore, the differentially regulated GABAergic and cholinergic co-transmission suggests a hitherto unrecognised level of control over cortical states. This novel model of hippocampal cholinergic neurotransmission may lead to alternative pharmacotherapies after cholinergic deinnervation seen in neurodegenerative disorders.

Original languageEnglish
Article number2848
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

cholinergics
acetylcholine
gamma-Aminobutyric Acid
Cholinergic Agents
Acetylcholine
synapses
Synapses
Drug therapy
Autoreceptors
Synaptic Potentials
Docks
neurotransmitters
Cholinergic Receptors
GABA-A Receptors
Calcium Channels
Synaptic Transmission
Neurodegenerative Diseases
Reaction Time
Neurotransmitter Agents
ripples

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Takács, V. T., Cserép, C., Schlingloff, D., Pósfai, B., Szőnyi, A., Sos, K. E., ... Nyíri, G. (2018). Co-transmission of acetylcholine and GABA regulates hippocampal states. Nature Communications, 9(1), [2848]. https://doi.org/10.1038/s41467-018-05136-1

Co-transmission of acetylcholine and GABA regulates hippocampal states. / Takács, Virág T.; Cserép, Csaba; Schlingloff, Dániel; Pósfai, Balázs; Szőnyi, András; Sos, Katalin E.; Környei, Zsuzsanna; Dénes, Ádám; Gulyás, Attila I.; Freund, T.; Nyíri, G.

In: Nature Communications, Vol. 9, No. 1, 2848, 01.12.2018.

Research output: Contribution to journalArticle

Takács, VT, Cserép, C, Schlingloff, D, Pósfai, B, Szőnyi, A, Sos, KE, Környei, Z, Dénes, Á, Gulyás, AI, Freund, T & Nyíri, G 2018, 'Co-transmission of acetylcholine and GABA regulates hippocampal states', Nature Communications, vol. 9, no. 1, 2848. https://doi.org/10.1038/s41467-018-05136-1
Takács VT, Cserép C, Schlingloff D, Pósfai B, Szőnyi A, Sos KE et al. Co-transmission of acetylcholine and GABA regulates hippocampal states. Nature Communications. 2018 Dec 1;9(1). 2848. https://doi.org/10.1038/s41467-018-05136-1
Takács, Virág T. ; Cserép, Csaba ; Schlingloff, Dániel ; Pósfai, Balázs ; Szőnyi, András ; Sos, Katalin E. ; Környei, Zsuzsanna ; Dénes, Ádám ; Gulyás, Attila I. ; Freund, T. ; Nyíri, G. / Co-transmission of acetylcholine and GABA regulates hippocampal states. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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