Our overarching goal is to achieve a deeper mechanistic understanding of both functional and dysfunctional neural circuits, particularly how they emerge during development and how their disruption contributes to neurological disorders.

To this end, our research focuses on the analysis of synaptic networks in both health and disease, with particular—though not exclusive—emphasis on developing neural circuits. We investigate how neuronal connectivity is established, maintained, and altered across developmental stages and under pathological conditions.

To address these questions, we employ a broad and integrative methodological framework. This includes high-resolution light microscopy for structural and dynamic imaging, ultrastructural 3D electron microscopy for detailed subcellular architecture, and functional approaches such as patch-clamp electrophysiology combined with optogenetics and calcium imaging. By correlating structure and function across multiple scales, we interrogate the organization and activity of neural networks at high resolution.

Cajal–Retzius Cells in the Postnatal Hippocampus

We investigate the role of Cajal–Retzius cells—among the earliest-born neuronal populations—in the postnatal hippocampus. While their function during embryonic development is relatively well characterized, their persistence and influence in postnatal stages remain insufficiently understood. Our work focuses on how these cells modulate local neural networks, including their synaptic integration, signaling properties, and potential regulatory roles in circuit maturation and plasticity.

Synaptic Network Maturation in the Hippocampus

A central project in our group addresses the maturation of synaptic networks at the microcircuit level within the hippocampus. By combining structural, morphological, and computational approaches, we quantify changes in synapse formation, distribution, and functional integration over developmental time. This includes high-resolution mapping of synaptic architectures and the development of computational models to link structural parameters with emergent network behavior.

Cancer Neuroscience: Neuron–Tumor Interactions

We study the formation and function of neuron-to-cancer synapses, a rapidly emerging concept in cancer neuroscience. Our focus lies on understanding how neuronal activity influences tumor growth and progression, particularly in brain cancers. Additionally, we aim to identify strategies to disrupt these pathological synaptic interactions, thereby exploring novel avenues for therapeutic intervention.

Dysfunctional Neural Networks in Epilepsy Models

Using in vitro models of epilepsy, we analyze the structural and functional remodeling of neural networks under pathological conditions. Our work emphasizes alterations in synaptic connectivity, aberrant signaling pathways, and the identification of potential pharmacological targets. By integrating structural data with electrophysiological and molecular analyses, we aim to better understand the mechanisms underlying network hyperexcitability and seizure generation.

1. Sakthivelu V, Schmitt A, Odenthal F, Ndoci K, Touet M, Shaib AH, Chihab A, Wani GA, Nieper P, Hartmann GG, Pintelon I, Kisis I, Boecker M, Eckert NM, Iannicelli Caiaffa M, Ibruli O, Weber J, Maresch R, Bebber CM, Chitsaz A, Lütz A, Kim Alves Carpinteiro M, Morris KM, Franchino CA, Benz J, Pérez-Revuelta L, Soriano-Campos JA, Huetzen MA, Goergens J, Jevtic M, Jahn-Kelleter HM, Zempel H, Placzek A, Hennrich AA, Conzelmann KK, Tumbrink HL, Hunold P, Isensee J, Werr L, Gaedke F, Schauss A, Minère M, Müller M, Fenselau H, Liu Y, Heimsoeth A, Gülcüler Balta GS, Walczak H, Frezza C, Jachimowicz RD, George J, Schmiel M, Brägelmann J, Hucho T, von Karstedt S, Peifer M, Annibaldi A, Hänsel-Hertsch R, Persigehl T, Grüll H, Sos ML, Reifenberger G, Fischer M, Adriaensen D, Büttner R, Sage J, Brouns I, Rad R, Thomas RK, Anstötz M, Rizzoli SO, Bergami M, Motori E, Reinhardt HC, Beleggia F. Functional synapses between neurons and small cell lung cancer. Nature 2025 Oct;646(8087):1243-1253. DOI: 10.1038/s41586-025-09434-9
2. Anstötz M, Lee SK, Maccaferri G. Glutamate released by Cajal-Retzius cells impacts specific hippocampal circuits and behaviors. Cell Reports 2022 May 17;39(7):110822. DOI: 10.1016/j.celrep.2022.110822
3. Anstötz M, Fiske MP, Maccaferri G. Impaired KCC2 function triggers interictal-like activity driven by parvalbumin-expressing interneurons in the isolated subiculum in vitro. Cerebral Cortex 2021 Aug 26;31(10):4681-4698. DOI: 10.1093/cercor/bhab115
4. Fiske MP, Anstötz M, Welty LJ, Maccaferri G. The intrinsic cell type-specific excitatory connectivity of the developing mouse subiculum is sufficient to generate synchronous epileptiform activity. Journal of Physiology 2020 May;598(10):1965-1985. DOI: 10.1113/JP279561
5. Anstötz M, Huang H, Haumann I, Marchionni I, Maccaferri G, Lübke JHR. Developmental Profile, Morphology, and Synaptic Connectivity of Cajal-Retzius Cells in the Postnatal Mouse Hippocampus. Cereb Cortex. 2016 Feb;26(2):855-72. DOI: 10.1093/cercor/bhv271