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Ventral hippocampus OLMα2 interneurons control type 2 theta oscillations and anxiety responses to predator odor
Neuroscience.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The 4-12 Hz oscillations have been predominantly studied in the dorsal hippocampus where they appear to be strongly correlated with movements and explorative behavior. However, moving along the septotemporal axis theta activity during movements is reduced in power and desynchronized from the dorsal part. In fact, theta activity can also be generated in the ventral hippocampus itself in anxiety, stress and fear-related behaviors. These functional differences are similarly reflected in local hippocampal circuit properties and anatomy. We found a specific subpopulation of oriens-lacunosum moleculare (OLM) interneurons expressing nicotinic acetylcholine receptor α2 subunit (Chrna2) differentially distributed along the dorso-ventral hippocampal axis, OLMα2 cells. The activation of OLMα2 cells is sufficient to induce theta activity in anesthetized mice and it is abolished by the application of atropine. While the induced theta rhythm did not affect frequency ranges related to animals movements (8-10 Hz), it significantly influenced lower frequency range, 6-8 Hz. It has been suggested that the low range theta activity corresponds to type 2 theta and is associated with innate responses to the predator smell. We conducted this test and observed that OLMα2 cells stimulation leads to a significant increase of mice risk-taking behavior. In summary, our data suggest that vHipp OLMα2 cells control hippocampal type 2 theta activity and innate anxiety responses to predator odor. 

National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-282141OAI: oai:DiVA.org:uu-282141DiVA: diva2:916515
Available from: 2016-04-03 Created: 2016-04-03 Last updated: 2016-05-12
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)
Opponent
Supervisors
Available from: 2016-05-04 Created: 2016-04-03 Last updated: 2016-05-12

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