On the Mechanisms Behind Hippocampal Theta Oscillations The role of OLMα2 interneurons

Mikulovic, S. 2016. On the Mechanisms Behind Hippocampal Theta Oscillations. The role of OLMα2 interneurons. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1206. 47 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9542-8. 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 anxietyand 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.