Neurons are the small processing units that make up our brain, and collectively enable the enormous computational power of the brain. Computations performed by individual neurons rarely consist of a simple summation of inputs. Input integration is a rather complex, highly dynamic process that often involves nonlinear processes such as NMDA receptor activation and dendritic Ca²⁺ spikes. I am interested in how the integrative properties of neurons are regulated by the diverse interneuron subtypes that target distinct neuronal compartments. A detailed knowledge of their cellular computations and inhibitory regulation mechanisms are essential to gain a better understanding of the interneurons’ contribution to the functioning of the whole network.

The first project focuses on the role of dendritic inhibition mediated by GABA_A receptor (α5-GABARs) activation in pyramidal neurons of the hippocampus. We have recently shown that α5-GABARs mediate a slow voltage-dependent conductance that powerfully regulates NMDA receptor activation (Schulz et al., Nature Communications 2018). Therefore, α5-GABARs are in an ideal position to regulate synaptic plasticity. In turn, pharmacological modulation may be a strategy for treatments of cognitive deficits caused by imbalances in dendritic inhibition in various neurological disorders such as Down Syndrome and Autism Spectrum Disorder.

A second project investigates the cellular basis of increased inhibition in Down Syndrome. For this, we systematically explore the physiological properties of different classes of interneurons that are defined by molecular markers (e.g. parvalbumin) and anatomy in a mouse model of Down Syndrome.

Previously, I studied GABA_B-mediated regulation of dendritic integration in layer 5 pyramidal neurons of the somatosensory cortex in Matthew Larkum’s lab. We could show that this form of inhibition, which is primarily mediated by neurogliaform interneurons, is important for the communication between cerebral hemispheres and may underlie a phenomenon called interhemispheric inhibition that is particularly prominent in unilateral stroke patients.

Techniques

Whole-cell patch-clamp recording from somata and dendrites in vitro. Extra- and intracellular recording in vivo. Local field potential recording in vivo and in vitro. Calcium imaging in single neurons in vitro. Confocal microscopy. Animal surgery for in vivo experiments. Stereotaxic injection of drugs and viruses. Light stimulation of Channel rhodopsin. Data analyses with customized scripts in stimfit, python and Matlab. Simulations in Matlab and Neuron.