Research Group Cognition & Emotion
Humans are - just like mice and rats - social creatures. We learn and understand our environment not only cognitively but also emotionally, for example through interactions with others.
That is why we store emotional memories in addition to purely cognitive memory content and often both types of memory are linked.
How exactly do cognition and emotion interact in the brain? How does information about rational connections and about feelings reach the memory structures of the brain? Our research group is dedicated to these questions.
- Cellular substrates of hippocampal oscillations in cognitive and emotional learning and memory
In this project, we aim to understand how different hippocampal cell types along the dorsoventral axis are recruited and contribute to theta and gamma oscillations during cognitive and emotional memory formation, with a specific focus on the ventral hippocampus. While cellular properties in the dorsal hippocampus have been extensively studied, ventral hippocampal networks are significantly less understood. How the molecular diversity of interneurons subtypes in the dorsal and ventral hippocampus relates to their function is one of our key questions. To address this it, our group will perform a combination of calcium imaging in the dorsal and ventral hippocampus, whilst high-density silicone probes will be implanted contralaterally along the dorsoventral hippocampal axis. To reveal the molecular identity of the imaged cell bodies in relation to oscillatory activity and behavior, we will perform expansion microscopy of the imaged tissue and use machine learning algorithms to match molecular identity with the imaged cell bodies. The molecular identity will be ultimately related to the cognitive and emotional memory-guided behaviors of interest.
- Memory-related input-output clusters of subcortical and hippocampal neurons
Dorsal and ventral hippocampus receive different subcortical inputs from the regions such as medial septum and ventral tegmental area, but the functional role of these inputs is incompletely understood. We became fascinated by the question how gradients in subcortical axon and hippocampal target cell distributions contribute to mnemonic functions. To investigate this, we are using a state-of-the art methodological repertoire to directly monitor the activity of axons and target cell populations in combination with field potential oscillations along the dorsoventral hippocampal axis. This will allow us to directly address our key question: Are subcortical inputs differentially recruited during cognitive and emotional types of memory?
- Mechanisms of social learning and memory
In order to understand naturalistic behaviours, we must provide laboratory conditions that are as similar as possible to those observed in nature. Mice and rats are, as humans, social animals and their learning processes are significantly influenced by their interactions with peers. The aim of this project is to detect complex social behaviours such as parental behaviour, play, sexual interaction, aggression, and communication of fear in a group. In particular, I hypothesize that specific sub-circuits within the ventral hippocampus regulate different types of social behaviours and interact with the circuits underlying memory formation. We will build “mice and rats cities” in which animals will be housed in larger groups and their behavior will be continuously monitored. Novel, wire-free models of 1 Photon UCLA miniscopes will be implanted in the dorsal and ventral hippocampus, combined with silicone probe recordings. This project will be conducted in close collaboration with the Neural Data Science group led by Pavol Bauer (CNeu).
Sanja Bauer Mikulovic studied biomedical engineering at the Technical University of Vienna and received her doctorate in neuroscience from the University of Uppsala in Sweden. Subsequently, she conducted research in Sweden in the Department of Neuroscience as a postdoc on the role of specific types of interneurons in the hippocampus and their importance for oscillations underlying cognitive and emotional behaviour. In 2018 she received an international postdoc grant, which enabled her to conduct her research in parallel at the Karolinska Institute in Stockholm and at the German Center for Neurodegenerative Diseases (DZNE) in Bonn. From January 2021, Sanja Bauer Mikulovic will head the Cognition & Emotion research group.
Hilscher MM, Nogueira I, Mikulovic S, Kullander K, Leao RN, Leao KE. „Chrna2-OLM interneurons display different membrane properties and h-current magnitude depending on dorsoventral location” Hippocampus. 2019. 10.1002/hipo.23134
Mikulovic S, Restrepo CE, Siwani S, Bauer P, Pupe S, Tort AB, Kullander K, Leao RN. “Ventral hippocampal OLM cells control type 2 theta oscillations and response to predator odor.” Nature Communications. 2018; 9(1):3638.
Siwani S, Franca ASC, Mikulovic S, Reis A, Hilscher MM, Edwards SJ, Leao RN, Tort AB, Kullander K, Leao RN. “OLMα2 Cells Bidirectionally Modulate Learning.” Neuron. 2018; 99(2):404-412.e3.
Winne J, Franzon R, De Miranda A, Malfatti T, Patriota J, Mikulovic S, Leao KE, Leao RN. “Salicylate induces anxiety-like behavior and slow theta oscillation and abolishes the relationship between running speed and fast theta oscillation frequency”. Hippocampus. 2018; 0.1002/hipo.23021.
Bauer P, Engblom S, Mikulovic S, Senek A. “Multiscale modelling via split-step methods in neural firing”. Mathematical and Computer Modelling of Dynamical Systems. 2018; 10.1080/13873954.2018.1488740.
Mikulovic S, Pupe S, Maia Peixoto H, Nascimiento G, Kullander K, Tort AB, Leao RN. “On the photovoltaic effect in local field potential recordings.” Journal of Neurophotonics. 2016; 3(1):015002.
Mikulovic S, Restrepo CE, Hilscher MM, Kullander K, Leao RN. “Novel markers for OLM interneurons in the hippocampus.” Frontiers in Cellular Neuroscience. 2015; 2;9:201.
Arvidsson E, Viereckel T, Mikulovic S, Wallén-Mackenzie Å. “Age- and sex-dependence of dopamine release and capacity for recovery identified in the dorsal striatum of C57/Bl6J mice.” PLoS One. 2014; 9(6):e99592.
Zelano J, Mikulovic S, Patra K, Kuehnemund M, Larhammar M, Emilsson L, Leao RN, Kullander K. ”The synaptic protein encoded by the gene Slc10A4 suppresses epileptiform activity and regulates sensitivity to cholinergic chemoconvulsants.” Journal of ExperimentalNeurology. 2013; 239:73-81
Leao RN, Mikulovic S, Leao KE, Munguba H, Gezelius H, Enjin A,Patra K, Eriksson A, Loew LM, Tort AB, Kullander K. “OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons.” Nature Neuroscience. 2012; 15(11):1524-30.
Enjin A, Leao KE, Mikulovic S, Le Merre P, Tourtellotte WG, Kullander K. “Sensorimotor function is modulated by the serotonin receptor 1d, a novel marker for gamma motoneurons.” Journal of Molecular and Cellular neuroscience. 2012; 49(3):322-32.