Neuronal circuits of cognition - Marie Carlén
The overall purpose of our research is to map the structure and function of circuitry underlying cognition, and provide causal evidence for how specific neuronal cell types contribute to network processes and computations underlying cognition. Our research has a strong focus on the prefrontal cortex (PFC) and we are particularly interested in cognitive functions known to be changed in psychiatric disorders such as schizophrenia or autism spectrum disorder.
The prefrontal cortex (PFC) is pivotal to the integration and coordination of internally generated information and information received from the external world. The PFC is most important when behaviour must be guided by internal intentions (often referred to as goal-directed behaviour), and in line with this the PFC is required for cognitive processes such as attention, working memory, planning and decision-making. Disturbed prefrontal function underlies many cognitive and behavioural deficits associated with neuropsychiatric disorders such as schizophrenia, ADHD, autism and drug-addiction.
The structure and composition of neuronal networks are integral to their functions. Tracing and mapping of neuronal circuits can therefore inform of function. In line with this, we have developed tools enabling whole-brain tracing of circuits. The efferent and afferent connectivity of genetically defined cell types can be mapped, identifying both local and long-range synaptic partners. These neuronal circuit building blocks can be identified, and manipulated, using electrophysiology and optogenetic tools in behaving mice and rats, providing a means for causal demonstration of the role of specific circuit motifs in cognition and behaviour.
Large-scale electrophysiological recordings of neuronal activity in behaving animals
In order to elucidate how complex computations are implemented in neuronal networks, we perform large-scale recordings of neuronal activity (action potential (AP) and local field potential (LFP)) using high-density silicon probes (Neuropixels) or tetrodes in freely moving or head-restrained behaving rodents.
Real-time imaging of neuronal activity in behaving animals
Transiently co-active assemblies of neurons, known as neuronal ensembles, are hypothesised to serve a crucial role in neuronal computation. However, the mechanisms guiding ensemble formation or the dynamic inclusion of single neurons into different ensembles still remain elusive. In order to gain insight into these processes, we perform real-time calcium imaging of large, genetically-defined populations of neurons (>500) using 2-photon microscopy in head-restrained behaving mice.
Mechanisms underlying psychiatric disorders
Ongoing research in the lab aims to understand how brain activity and neuronal networks are affected or altered in psychiatric disorders characterised by changed cognition. We use transgenic animals modelling aspects of mental disorders, as well as pharmacology and optogenetics to decipher how changed brain activity relates to changes in behaviour. This line of research aims to identify novel cellular and molecular targets for pharmacological interventions in psychiatric disorders.
A whole-brain atlas of monosynaptic input targeting four different cell types in the medial prefrontal cortex of the mouse.
Ährlund-Richter S, Xuan Y, van Lunteren JA, Kim H, Ortiz C, Pollak Dorocic I, et al
Nat. Neurosci. 2019 04;22(4):657-668
A hypothalamus-habenula circuit controls aversion.
Lazaridis I, Tzortzi O, Weglage M, Märtin A, Xuan Y, Parent M, et al
Mol. Psychiatry 2019 09;24(9):1351-1368
What constitutes the prefrontal cortex?
Science 2017 10;358(6362):478-482
Prefrontal Parvalbumin Neurons in Control of Attention.
Kim H, Ährlund-Richter S, Wang X, Deisseroth K, Carlén M
Cell 2016 Jan;164(1-2):208-218
- Wallenberg Scholar (medicine). 2019 (5 yrs)
- Karolinska Institutet Senior Researcher. 2017 (5 yrs)
- Wallenberg Academy Fellow (medicine) Prolongation. 2017 (6 yrs)
- Consolidation grant from Swedish Research Council. 2016 (6 yrs)
- CIMED Junior Investigator. 2016 (5 yrs)
NARSAD Young Investigator Award 2019 (to Pierre Le Merre)