By investigating the complex functions of interneurons in the DG, my team has made a far-reaching contribution to memory research. Our main findings are as follows:
Lifetime memories in the mouse DG. We provide first evidence that GC assemblies, representing virtual environments, emerge slowly across ~3 subsequent days of spatial learning and once formed, are highly stable over months (Hainmueller & Bartos, Nature 558, 2018; Cholvin et al., Neuron 109, 2021; Cholvin & Bartos, Nature Com 13, 2022). In marked contrast, spatial representations are highly dynamic in downstream hippocampal areas CA1-3. We propose that lifetime memories of the external world might act as reference frame, which can be combined with the varying details of the environment (see also Muysers et al., Nature Com 15, 2024; Cell Rep 44, 2025).
Novelty detection by mossy cells. The second major principal cell type of the DG are mossy cells. By applying data-driven machine-learning tools (e.g. decoders, generalized linear models, population geometry analysis), we showed that mossy cells rapidly reconfigure their activity in response to environmental changes indicating their role in novelty detection (Huang et al., Cell Reports 24, 2024).
Division of labor among interneuron types in shaping memories. By dissecting the role of synaptic inhibition in population dynamics of the DG, we provide first evidence that parvalbumin-expressing, perisoma-targeting interneurons (PVIs) and somatostatin-positive, dendrite-targeting interneurons (SOMIs) play key roles in shaping memory traces during learning. PVIs support spike timing and facilitate generalization across environments, whereas SOMIs limit GC activity and enhance context discrimination at the level of GC populations (Hainmueller & Cazala et al., Nature Com 15, 2024).
Interneuron plasticity supports mnemonic functions. We dissected the role of interneuron plasticity in the DG by designing a Cre-dependent shRNA to allow cell type-specific knockdown of the metabotropic glutamate receptor 1- α (mGluR1 α) selectively in SOMIs. We show that loss of mGluR1α prevents long-term plasticity at glutamatergic inputs onto SOMIs and impairs memory on object locations (Grigoryan et al., PNAS USA 120, 2023).
Interneurons predict experience-dependent goal locations. We provide key evidence that SOMI activity predicts expected reward locations in expert mice, characterized by goal-anticipatory behavior, but not in non-experts. Moreover, predictive goal coding is rapidly lost once rewards are no longer available indicating that SOMIs encode current and past experiences to bias behavioral outcomes (Yuan et al., Nature Com 16:2025).
PVIs show structural plasticity in relation to novel experiences. By applying a broad set of techniques, including electron microscopy, labeling of pre- and postsynaptic partners with eGRASP, in vitro whole-cell recordings, and behavioral analysis, we demonstrated that DG PVIs possess dendritic spines that undergo novelty-related structural dynamics. Spine growth boosts functional integration of PVIs into the DG circuitry upon novel experiences (Kaufhold et al., Cell Rep 43, 2024).
Our work was presented at several national and international conferences in the form of posters, lectures, and keynote talks. It was published in high-impact journals and communicated to the public through newspapers and participation in science outreach events. In this way, we disseminated our findings to both the scientific community and the public.
