Research
2-Photon population imaging of the dentate gyrus – from microcircuit function to control of behavior
The dentate gyrus (DG) is the entrance gate of the hippocampus and translates the rich input stream from the entorhinal cortex into sparse non-overlapping memories. The network mechanisms underlying sparse coding are however largely unknown. To study the emergence and activity of hippocampal memory engrams in awake, behaving animals, we use two-photon calcium imaging in the dentate gyrus and the hippocampal subfields CA1-3 of head-fixed mice. During the imaging sessions, the mice perform a contextual discrimination task in a virtual environment displayed on screens around them (Hainmueller and Bartos, 2018). We investigate, how principal neurons in different hippocampal subfields represent the space of the virtual sceneries and how these representations develop with increasing familiarity of the environment to the animal. We further study the local microcircuit mechanisms underlying the establishment of memory-bearing neuronal ensembles (Sheffield and Dombeck, 2017). Currently, we investigate how the activity of local inhibitory circuits is modulated by sensory experience as well as behavioral novelty detection. By these means, we are trying to decipher how neuronal circuits in the hippocampal formation store and retrieve the contents of complex episodic memories.
Interneuron diversity
During the course of the last ~25 years, there was an explosion of studies on the neurochemical, morphological, physiological and pharmacological properties of interneurons, which gave rise to the identity of a multitude of anatomically and functionally distinct GABAergic interneuron types. These studies revealed that the cell body, axon-initial segment and dendritic domains of pyramidal cells and interneurons are targeted by distinct interneuron types (Markram et al., 2004; Bartos et al., 2014), indicating that compartment-specific computational operations on the level of individual cells are controlled by specialized inhibitory cells. Interneuron diversity was largely investigated in the hippocampal CA1-3 and neocortical areas. We focus our work on the dentate gyrus, the input gate of the hippocampus using intracellular labelling of cells in slice preparations with subsequent antibody labelling, confocal and electron microscopy. Moreover, by using transgenic mice with viral expression we labell local and long-range projecting interneuron types.
