Shared rhythmic subcortical GABAergic input to the entorhinal cortex and presubiculum
Abstract
Rhythmic theta frequency (~5-12 Hz) oscillations coordinate neuronal synchrony and higher frequency oscillations across the cortex. Spatial navigation and context-dependent episodic memories are represented in several interconnected regions including the hippocampal and entorhinal cortices, but the cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic modulation of 'upstream' and 'downstream' cortico-cortical circuits involved in mnemonic functions.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Medical Research Council (MC_UU_12024/4)
- Tim James Viney
- Minas Salib
- Abhilasha Joshi
- Gunes Unal
- Naomi Berry
- Peter Somogyi
Wellcome (108726/Z/15/Z)
- Tim James Viney
- Minas Salib
- Abhilasha Joshi
- Gunes Unal
- Naomi Berry
- Peter Somogyi
Felix Doctoral Scholarship
- Abhilasha Joshi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures involving experimental animals were approved by the Department of Pharmacology Animal Welfare and Ethical Review Body under approved personal and project licenses (project licence number: 30/3240) in accordance with the Animals (Scientific Procedures) Act, 1986 (UK) and associated regulations. All surgery was performed under isoflurane anesthesia with a peri-operative dose of buprenorphine, and every effort was made to minimize suffering.
Copyright
© 2018, Viney 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
-
- 3,074
- views
-
- 455
- downloads
-
- 28
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Neuroscience
Damage to the synapses connecting hair cells to the auditory nerve leads to undetected hearing impairments.
-
- Neuroscience
Multisensory integration (MSI) combines information from multiple sensory modalities to create a coherent perception of the world. In contexts where sensory information is limited or equivocal, it also allows animals to integrate individually ambiguous stimuli into a clearer or more accurate percept and, thus, react with a more adaptive behavioral response. Although responses to multisensory stimuli have been described at the neuronal and behavioral levels, a causal or direct link between these two is still missing. In this study, we studied the integration of audiovisual inputs in the Mauthner cell, a command neuron necessary and sufficient to trigger a stereotypical escape response in fish. We performed intracellular recordings in adult goldfish while presenting a diverse range of stimuli to determine which stimulus properties affect their integration. Our results show that stimulus modality, intensity, temporal structure, and interstimulus delay affect input summation. Mechanistically, we found that the distinct decay dynamics of FFI triggered by auditory and visual stimuli can account for certain aspects of input integration. Altogether, this is a rare example of the characterization of MSI in a cell with clear behavioral relevance, providing both phenomenological and mechanistic insights into how MSI depends on stimulus properties.