The function of neuronal circuits is flexible, and adjusted on a moment-by-moment basis to optimize information processing to the current context and the animal's behavioral demands. We investigate the mechanisms and consequences of this flexibility in sensory neocortex, using a simple set of sensory stimuli whose relevance is systematically varied in different behavioral paradigms. Using in vivo 2-photon calcium imaging, targeted electrophysiology and optogenetics in combination with transgenic and viral strategies in mice, we ask how defined types of interneurons and projection neurons in the local circuit are modulated. In parallel, we aim to identify the long-range inputs, such as for instance the cholinergic system, that convey these signals to neocortex. In a complementary approach, we use optogenetic manipulation of defined circuit elements to determine how their activity in turn affects the local computations and the animal's behavior. We expect that this combination of approaches will define principles of circuit modulation that endow neocortex with computational flexibility.
Letzkus JJ, Wolff SBE, Lüthi A (2015). Disinhibition, a circuit mechanism for associative learning and memory. Neuron 88; 264-76.
Wolff SBE, Gruendemann J, Tovote P, Krabbe S, Jacobson GA, Müller C, Herry C, Ehrlich I, Friedrich RW, Letzkus JJ*, Lüthi A* (2014) Amygdala interneuron subtypes control fear learning through disinhibition. Nature 509; 453-458. (* shared senior authorship).
Letzkus JJ, Wolff SBE, Meyer EMM, Tovote P, Courtin J, Herry C, Lüthi A (2011) A disinhibitory microcircuit for associative fear learning in auditory cortex. Nature 480; 331-335.
Kole MH*, Letzkus JJ*, Stuart GJ (2007) Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. Neuron 55; 633-647. (* shared first authorship).
Letzkus JJ, Kampa BM, Stuart GJ (2006) Learning rules for spike timing-dependent plasticity depend on dendritic synapse location. Journal of Neuroscience 26; 10420-29.