Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network
- University of Edinburgh, United Kingdom
- University of Freiburg, Germany
- Charité - Universitätsmedizin Berlin, Germany
Abstract
Information processing in cortical neuronal networks relies on properly balanced excitatory and inhibitory neurotransmission. A ubiquitous motif for maintaining this balance is the somatostatin interneuron (SOM-IN) feedback microcircuit. Here, we investigate the modulation of this microcircuit by presynaptic GABAB receptors (GABABRs) in the rodent hippocampus. Whole-cell recordings from SOM-INs revealed that both excitatory and inhibitory synaptic inputs are strongly inhibited by GABABRs, while optogenetic activation of the interneurons shows that their inhibitory output is also strongly suppressed. Electron microscopic analysis of immunogold-labelled freeze-fracture replicas confirms that GABABRs are highly expressed presynaptically at both input and output synapses of SOM-INs. Activation of GABABRs selectively suppresses the recruitment of SOM-INs during gamma oscillations induced in vitro. Thus, axonal GABABRs are positioned to efficiently control the input and output synapses of SOM-INs and can functionally uncouple them from local network with implications for rhythmogenesis and the balance of entorhinal versus intrahippocampal afferents.
Data availability
Quantitative electrophysiological, optogenetic and immuno-electron microscopic data presented in the figures and text has been deposited to Dryad (doi:10.5061/dryad.gt160v2).
-
Presynaptic GABAB Receptors Functionally Uncouple Somatostatin Interneurons from the Active Hippocampal NetworkDryad Digital Repository, doi:10.5061/dryad.gt160v2.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (FOR 2134)
- Marlene Bartos
- Akos Kulik
- Imre Vida
Deutsche Forschungsgemeinschaft (BIOSS-2)
- Akos Kulik
Tenovus
- Imre Vida
McNaught Bequest, University of Glasgow
- Sam A Booker
- Imre Vida
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- John Huguenard, Stanford University School of Medicine, United States
Ethics
Animal experimentation: Care and handling of the animals prior to and during the experimental procedures followed European Union and national regulations (German Animal Welfare Act; ASPA, United Kingdom Home Office) and all experiments were performed in accordance with institutional guidelines (Charité - Universitätmedizin Berlin; University of Freiburg, Freiburg, Germany), with permissions from local authorities (LaGeSo, Berlin, T-0215/11 LaGeSo; Freiburg, X14/11H and 35-9185.81/G-19/59).
Version history
- Received: August 16, 2019
- Accepted: February 18, 2020
- Accepted Manuscript published: February 19, 2020 (version 1)
- Version of Record published: March 6, 2020 (version 2)
Copyright
© 2020, Booker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,574
- Page views
-
- 391
- Downloads
-
- 20
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network
eLife 9:e51156.
https://doi.org/10.7554/eLife.51156
Further reading
-
- Neuroscience
Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.
-
- Neuroscience
Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.
