Interaction of acetylcholine and oxytocin neuromodulation in the hippocampus

Yiyao Zhang; Mursel Karadas; JingJing Liu; Xinyi Gu; Mihály Vöröslakos; Yulong Li; Richard W Tsien; György Buzsáki

doi:10.1016/j.neuron.2024.02.021

Interaction of acetylcholine and oxytocin neuromodulation in the hippocampus

Neuron. 2024 Mar 18:S0896-6273(24)00154-5. doi: 10.1016/j.neuron.2024.02.021. Online ahead of print.

Authors

Yiyao Zhang¹, Mursel Karadas¹, JingJing Liu¹, Xinyi Gu¹, Mihály Vöröslakos¹, Yulong Li², Richard W Tsien³, György Buzsáki⁴

Affiliations

¹ Neuroscience Institute, New York, NY, USA.
² School of Life Science, Peking University, Beijing, China.
³ Neuroscience Institute, New York, NY, USA; Department of Neurology, Langone Medical Center, New York University, New York, NY 10016, USA; Center for Neural Science, New York University, New York, NY 10003, USA.
⁴ Neuroscience Institute, New York, NY, USA; Department of Neurology, Langone Medical Center, New York University, New York, NY 10016, USA; Center for Neural Science, New York University, New York, NY 10003, USA. Electronic address: gyorgy.buzsaki@nyumc.org.

PMID: 38537642
DOI: 10.1016/j.neuron.2024.02.021

Abstract

A postulated role of subcortical neuromodulators is to control brain states. Mechanisms by which different neuromodulators compete or cooperate at various temporal scales remain an open question. We investigated the interaction of acetylcholine (ACh) and oxytocin (OXT) at slow and fast timescales during various brain states. Although these neuromodulators fluctuated in parallel during NREM packets, transitions from NREM to REM were characterized by a surge of ACh but a continued decrease of OXT. OXT signaling lagged behind ACh. High ACh was correlated with population synchrony and gamma oscillations during active waking, whereas minimum ACh predicts sharp-wave ripples (SPW-Rs). Optogenetic control of ACh and OXT neurons confirmed the active role of these neuromodulators in the observed correlations. Synchronous hippocampal activity consistently reduced OXT activity, whereas inactivation of the lateral septum-hypothalamus path attenuated this effect. Our findings demonstrate how cooperative actions of these neuromodulators allow target circuits to perform specific functions.

Keywords: cholinergic system; hippocampus; hypothalamus; lateral septum; medial septum; neuromodulation; optogenetics; oxytocin; pharmacogenetics; sharp-wave ripples.