Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo Journal Article

Author(s): Gan, Jian; Weng, Shih-Ming; Pernía-Andrade, Alejandro J; Csicsvári, József; Jonas, Peter
Article Title: Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo
Affiliation IST Austria
Abstract: Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo.
Keywords: Hippocampus; GABAergic synapses; sharp wave-ripples; in vivo recording; in vivo voltage clamp; EPSCs; IPSCs; CA1 region; network oscillations; PV+ interneurons
Journal Title: Neuron
Volume: 93
Issue 2
ISSN: 0896-6273
Publisher: Elsevier  
Date Published: 2017-01-18
Start Page: 308
End Page: 314
Copyright Statement: CC-BY 4.0
DOI: 10.1016/j.neuron.2016.12.018
Notes: We thank Hua Hu and Xiaomin Zhang for critically reading the manuscript, Jose Guzman for help with neuron reconstruction, Pradeep Bhandari for support with perfusion, and Gyorgy Buzsaki for sharing unpublished material. We thank Edward Boyden, Karl Deisseroth, James Wilson,University of North Carolina Vector Core, and University of Pennsylvania Vector Core for providing viral vectors. We are extremely grateful to A. Schlögl for programming, F. Marr for technical assistance, E. Kramberger for manuscript editing, and T. Asenov(Machine Shop) for device construction. We also thank the Scientific Service Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclin- ical Facility) for help. This project has received funding from the Fond zur Förderung der Wissenschaftlichen Forschung (P 24909-B24) and the European Research Council (ERC) under the European Union’s seventh framework programme with grant agreement number 268548 (both to P.J.).
Open access: yes (OA journal)