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OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
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2012 (English)In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 15, no 11, 1524-1530 p.Article in journal (Refereed) Published
Abstract [en]

The vast diversity of GABAergic interneurons is believed to endow hippocampal microcircuits with the required flexibility for memory encoding and retrieval. However, dissection of the functional roles of defined interneuron types has been hampered by the lack of cell-specific tools. We identified a precise molecular marker for a population of hippocampal GABAergic interneurons known as oriens lacunosum-moleculare (OLM) cells. By combining transgenic mice and optogenetic tools, we found that OLM cells are important for gating the information flow in CA1, facilitating the transmission of intrahippocampal information (from CA3) while reducing the influence of extrahippocampal inputs (from the entorhinal cortex). Furthermore, we found that OLM cells were interconnected by gap junctions, received direct cholinergic inputs from subcortical afferents and accounted for the effect of nicotine on synaptic plasticity of the Schaffer collateral pathway. Our results suggest that acetylcholine acting through OLM cells can control the mnemonic processes executed by the hippocampus.

Place, publisher, year, edition, pages
2012. Vol. 15, no 11, 1524-1530 p.
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:uu:diva-184961DOI: 10.1038/nn.3235ISI: 000310424900012OAI: oai:DiVA.org:uu-184961DiVA: diva2:569954
Available from: 2012-11-15 Created: 2012-11-15 Last updated: 2017-12-07Bibliographically approved
In thesis
1. On the Mechanisms Behind Hippocampal Theta Oscillations: The role of OLMα2 interneurons
Open this publication in new window or tab >>On the Mechanisms Behind Hippocampal Theta Oscillations: The role of OLMα2 interneurons
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Theta activity is one of the most prominent rhythms in the brain and appears to be conserved among mammals.  These 4-12 Hz oscillations have been predominantly studied in the dorsal hippocampus where they are correlated with a broad range of voluntary and exploratory behaviors. Theta activity has been also implicated in a number of mnemonic processes, long-term potentiation (LTP) induction and even acting as a global synchronizing mechanism. Moving along the dorso-ventral axis theta activity is reduced in power and desynchronized from the dorsal part. However, theta activity can also be generated in the ventral hippocampus itself during anxiety- and fear-related behaviors. Until now it was unknown which hippocampal cell population was capable to generate theta activity and it was controversial if its origin was local, in the hippocampus, or driven by other brain regions. In this thesis I present compelling in vitro and in vivo  evidence that   a subpopulation of OLM interneurons (defined by the Chrna2-cre line)  distinctively enriched  in the CA1 region of  the ventral hippocampus is implicated in LTP function (paper I,II), information control (paper V) and the induction of theta activity that is under cholinergic  control (paper IV). Importantly, a concomitant effect of the optogenetically induced theta activity is reduction in anxiety (Paper IV). Another innovation of this work was the development of a methodological approach to avoid artefactual signals when combining electrophysiology with light activation during optogenetic experiments (Paper III). In summary, the work presented in this thesis elucidates the role of a morphologically and electrophysiologially identified cell population, OLMα2 interneurons, first on the cellular, then on the circuit and ultimately on the behavioral level.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1206
Keyword
hippocampus, interneuron, optogenetics, theta oscillations, anxiety
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-282144 (URN)978-91-554-9542-8 (ISBN)
Public defence
2016-05-28, A1:111a, Husargatan 3, Uppsala, 09:15 (English)
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Available from: 2016-05-04 Created: 2016-04-03 Last updated: 2016-05-12

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Leão, Richardson NavesMikulovic, SanjaLeão, Katarina E.Gezelius, HenrikEnjin, AndersPatra, KalicharanKullander, Klas

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