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Altering the hippocampal code by rapid modulation of inhibition

In 2009 we described a novel form of modulation in the median raphe – hippocampus connection capable of selectively and rapidly recruiting a subset of inhibitory neurons. The function of this highly efficient form of modulation in shaping hippocampal representations is still unknown. In this project, we aim to unravel how the emergence and reorganization of hippocampal coding patterns linked to salient event is influenced by raphe-hippocampal rapid modulation.

Population coding of behavioral events in the median raphe circuit

Coding by transiently emerging co-active ensembles of neurons has long been a central tenet of neuroscience formulated in the influential assembly hypothesis. Accordingly, the animal’s actions can be predicted much more efficiently from the coordinated activity pattern of neurons than from the stimulus or event-locked spiking of single units. In contrast to cortical and hippocampal networks, assembly coding in subcortical modulatory circuits is almost fully unexplored. In this project, we aim to reveal and characterize the assembly code in the median raphe (MR), the source of ascending serotonergic neuromodulation of the limbic system. We expect to identify a fundamentally novel mode of neuromodulation whereby adaptive behavioral responses are controlled by the correlated activity of modulatory neuronal assemblies.

Cortical control of subcortical modulation

Subcortical modulation is an indispensable component of cortical function, and ultimately, is key for adaptive behavioral responses. Therefore, disruption of subcortical modulation leads to debilitating psychiatric conditions. A key but largely ignored area of research concerns the control of subcortical modulation by cortical feedback. In this project we explore how the top-down control of the median raphe by the prefrontal cortex controls memory-guided behaviors. Our hope is to identify a missing link in the process that leads from normal subcortical function to pathological cortical operation.

Representation of fearful information in the hippocampus

Throughout life animals inevitably encounter unforeseen threatening events. Activity of principal cells in the hippocampus is tuned for locations and for salient stimuli in the animals’ environment thus, forming a map known to be pivotal for guiding behavior. Here, we investigate if a code corresponding to threatening stimuli exists in the CA1 region of the dorsal hippocampus.