Behaviour-dependent prefrontal-hippocampal coupling via oscillatory interference between subcortical theta oscillators

• Applicant: Dr. Hiroshi Ito
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505443461

One of the most notable features of the brain is its ability to cope with various types of computation by using the same neural-circuit architecture. Such flexible computational capability is in part derived from a strategy of labour division, whereby each brain region has a somewhat dedicated role, allowing for parallel computations to solve a complex problem. However, this feature imposes an additional requirement for the brain: the information processed in each brain region must be integrated to provide a coherent solution – known as a binding problem. For example, during spatial navigation, the brain must process and integrate two information streams; one is about the self’s position processed in the hippocampal formation, and another is on the animal’s next destination represented in the orbitofrontal cortex. While this computation requires the brain to change functional coupling between regions, its mechanism has remained poorly understood. The main objective of this project is to address this long-standing question from the perspective of oscillatory interference generated by two subcortical theta oscillators, the medial septum (MS) and the supramammillary nucleus (SUM). Our preliminary findings suggest that these two regions generate theta oscillations largely independently, and their coherence is modulated depending on behavioural demands. These two theta rhythms may thus create interference patterns in a projection-area-specific manner, which may allow for desirable coordination between regions. We will investigate this question by using high-density recordings from multiple brain areas, including MS and SUM, when an animal performs a goal-directed navigation task as well as is in the rapid-eye-movement (REM) sleep state. All these behavioural states are characterised by the prominent hippocampal theta rhythm, but we predict that these theta states are not necessarily the same but rather have a distinct role depending on interference patterns generated by MS and SUM. We will quantify the change of multiregional interactions by analysing spectral coherence, spike-phase relationships, as well as by applying a recently-developed nonlinear causality detection method - the convergent cross mapping. The causal impact of theta interference will further be tested by optogenetic manipulation of the oscillators. We foresee that the project will provide an initial key step to understand the brain’s mechanism for desirable control of regional coupling and may provide novel insights into why REM sleep is necessary for the brain.

• DFG Programme: Research Grants