Our major research interests are (1) to advance optical methods for studying neuronal network dynamics in the living brain at work ('in vivo') and thereby (2) reveal fundamental principles of neural circuit function with regard to computation and learning. th under physiological and pathological conditions. Ongoing projects include:
Developing Novel In Vivo Imaging Techniques
Two-photon calcium imaging techniques
Two-photon laser-scanning microscopy has become the method of choice for imaging nerual dynamics on the cellular level in the intact brain. The particular advantage of 2-photon microscopy is its reduced sensitivity to light scattering so that individual cells with their dendrites can be resolved several hundreds of micrometers deep in neural tissue in living animals (Helmchen and Denk, 2005). Various fluorescence labeling techniques nowadays permit staining of individual cells and neuronal populations with great detail. To read out neuronal activity we apply fluorescence calcium indicators to the mouse brain. Most recently, we have been using the genetically-encoded calcium indicator Yellow Cameleon 3.60, which can be stably expressed in the mouse brain and thus permits repeated activity measurements from the exact same cells over several months (Lütcke et al. 2010; Fig. 1 from Lütcke and Helmchen 2011).
3D and high-speed calcium imaging techniques
To enhance our capabilities to read out neuronal network dynamics using fluorescent indicators, we are working on advanced special laser-scanning modes that allow measurements in 3D (Göbel et al. 2007), at high speed (Grewe et al. 2010), or both (Grewe et al. 2011). These technological advances will help us to decipher the neural code in large, distributed networks of neurons for example in mouse neocortex.
Over the past decade we have also contributed to the development of miniaturized two-photon microscopes using fiber optics, in order to enable high-resolution imaging of neuronal activity in freely behaving rodents (Helmchen et al. 2001; Engelbrecht et al. 2008)
HelioScan: A software frame work for in vivo microscopy
Many microscopes for in vivo imaging are still custom-built microscope setups that need suitable microscope control software. We are developing a highly flexible modular software framework (written in LABView), which can run various kinds of in vivo imaging modes (intrinisc imaging, standard laser scanning, 3D scanning, random access, resonant scanning etc.) and which can be easily adapted to special needs and innovative imaging modes. For further information see HelioScan
Dissecting Neural Circuit Dynamics
Signal Processing in Cortical Microcircuits
Using the optical methods described above as well as electrophysiogical techqniues we investigate the functional organization of the mammalian neocortex. We are interested in dissecting neuronal communication within and the signal flow through local microcircuits and relate it to sensory perception and animal behaviour. Using two-photon calcium imaging we are determining activity patterns in the superficial layers of various cortex areas (e.g. primary somatosensory, visual, or auditory regions). Using transgenic mouse lines or a recently developed post hoc immunoanalysis (Langer and Helmchen 2012) we aim to discriminate various neuronal subsets, including different types of GABAergic interneurons, and characterize their functional propoerties.
Sensorimotor integration in the whisker system
In rodents, the facial whiskers ('vibrissae') are a major sensory system, which shows a large one-to-one topographic representation in the somatosensory cortex (so-called 'barrel cortex'). Using this model system have studied neuronal population responses evoked by mechanical whisker deflections (Kerr et al. 2007). Our goal is to measure the neuronal activity patterns in awkae mice during natural whisking movements and during behaviors that involve processing of whisker inputs.
Computation in neuronal dendrites
Individual neurons are sophisticated signal processing devices that integrate the myriad of synaptic inputs they receive. The dendrites of neocortical pyramidal neurons, for example, contain various voltage-dependent ion channels that produce non-linear signal integration properties (e.g. Waters et al. 2003, Larkum et al. 2007). We are interested in understanding how dendrites translate the activity in incoming input streams to streams of output action potentials. We use two-photon calcium imaging as well as electrophysiological methods to measure dendritic dynamics in the intact brain.