Lab

Günther Zeck's Lab

Institution: TU Wien

About the lab

Featured research (5)

Rod bipolar cells (rBCs) represent a promising target for vision restoration as they relay information to the major image processing pathways in the retina. However, the diversity of the retinal output and the resolution obtained by optogenetic actuation of rBCs is unclear. Herein, the photostimulation of rBCs expressing channelrhodopsin‐2 is studied in a transgenic, photoreceptor‐degeneration mouse (rd10) while simultaneously recording the retinal output using a high‐density microelectrode array. After analyzing several hundred retinal output neurons, both optogenetic ON and OFF type responses are identified at similar ratio at stimulation thresholds well below photodamage intensity. The temporal latency of both response types is in the same range (≈$\approx$ 50 ms) as reported for healthy mouse retinal ganglion cells. The spatial resolution ranges between 0.1 and 0.2 cycles deg‐1, which is close to that found in healthy mice. Photostimulation over an extended area (29 deg) but not localized stimuli induces strong bursting activity, which may originate from large‐scale activation of a coupled network of retinal cells. The distinct ON and OFF optogenetically induced activity patterns in retinal ganglion cells and the high temporal and spatial resolution demonstrate that near‐physiological vision restoration may be achieved under optimal conditions in late stage retinal degeneration.
Objective: Retinal ganglion cells (RGCs) represent an attractive target in vision restoration strategies, because they undergo little degeneration compared to other retinal neurons. Here we investigated the temporal and spatial resolution in adult photoreceptor-degenerated (rd10) mouse retinas, where RGCs have been transduced with the optogenetic actuator channelrhodopsin-2 (ChR2). Approach: The RGC spiking activity was recorded continuously with a CMOS-based microelectrode array during a variety of photostimulation protocols. The temporal resolution was assessed through Gaussian white noise stimuli and evaluated using a linear-nonlinear-Poisson model. Spatial sensitivity was assessed upon photostimulation with single rectangular pulses stepped across the retina and upon stimulation with alternating gratings of different spatial frequencies. Spatial sensitivity was estimated using logistic regression or by evaluating the spiking activity of independent RGCs. Main results: The temporal resolution after photostimulation displayed an about ten times faster kinetics as compared to physiological filters in wild-type RGCs. The optimal spatial resolution estimated using the logistic regression model was 10 µm and 87 µm based on the population response. These values correspond to an equivalent acuity of 1.7 or 0.2 cycles per degree, which is better than expected from the size of RGCs' optogenetic receptive fields. Significance: The high temporal and spatial resolution obtained by photostimulation of optogenetically transduced RGCs indicate that high acuity vision restoration may be obtained by photostimulation of appropriately modified RGCs in photoreceptor-degenerated retinas.
The mammalian retina processes sensory signals through two major pathways: a vertical excitatory pathway, which involves photoreceptors, bipolar cells, and ganglion cells, and a horizontal inhibitory pathway, which involves horizontal cells, and amacrine cells. This concept explains the generation of an excitatory center—inhibitory surround sensory receptive fields—but fails to explain the modulation of the retinal output by stimuli outside the receptive field. Electrical imaging of light-induced signal propagation at high spatial and temporal resolution across and within different retinal layers might reveal mechanisms and circuits involved in the remote modulation of the retinal output. Here we took advantage of a high-density complementary metal oxide semiconductor-based microelectrode array and investigated the light-induced propagation of local field potentials (LFPs) in vertical mouse retina slices. Surprisingly, the LFP propagation within the different retinal layers depends on stimulus duration and stimulus background. Application of the same spatially restricted light stimuli to flat-mounted retina induced ganglion cell activity at remote distances from the stimulus center. This effect disappeared if a global background was provided or if gap junctions were blocked. We hereby present a neurotechnological approach and demonstrated its application, in which electrical imaging evaluates stimulus-dependent signal processing across different neural layers.
While multicompartment models have long been used to study the biophysics of neurons, it is still challenging to infer the parameters of such models from data including uncertainty estimates. Here, we performed Bayesian inference for the parameters of detailed neuron models of a photoreceptor and an OFF- and an ON-cone bipolar cell from the mouse retina based on two-photon imaging data. We obtained multivariate posterior distributions specifying plausible parameter ranges consistent with the data and allowing to identify parameters poorly constrained by the data. To demonstrate the potential of such mechanistic data-driven neuron models, we created a simulation environment for external electrical stimulation of the retina and optimized stimulus waveforms to target OFF- and ON-cone bipolar cells, a current major problem of retinal neuroprosthetics.
Human cerebrospinal fluid (hCSF) has proven advantageous over conventional medium for culturing both rodent and human brain tissue. In addition, increased activity and synchrony, closer to the dynamic states exclusively recorded in vivo, were reported in rodent slices and cell cultures switching from artificial cerebrospinal fluid (aCSF) to hCSF. This indicates that hCSF possesses properties that are not matched by the aCSF, which is generally used for most electrophysiological recordings. To evaluate the possible significance of using hCSF as an electrophysiological recording medium, also for human brain tissue, we compared the network and single-cell firing properties of human brain slice cultures during perfusion with hCSF and aCSF. For measuring the overall activity from a majority of neurons within neocortical and hippocampal human slices, we used a microelectrode array (MEA) recording technique with 252 electrodes covering an area of 3.2 × 3.2 mm². A second CMOS-based MEA with 4225 sensors on a 2 × 2 mm² area was used for detailed mapping of action potential waveforms and cell identification. We found that hCSF increased the number of active electrodes and neurons and the firing rate of the neurons in the slices and induced an increase in the numbers of single channel and population bursts. Interestingly, not only an increase in the overall activity in the slices was observed, but a reconfiguration of the network could also be detected with specific activation and inactivation of subpopulations of neuronal ensembles. In conclusion, hCSF is an important component to consider for future human brain slice studies, especially for experiments designed to mimic parts of physiology and disease observed in vivo.

Lab head

Günther Zeck
Department
  • Biomedical Electronics and Systems
About Günther Zeck
  • Günther Zeck currently works at the Vienna Technical University (TU Wien). His research focus is Biomedical Engineering, emphasizing bioelectronic developments and applications in life science. He is member of the Faculty of Electrical Engineering and Information Technology.

Members (3)

Mai Thu Bui
Mai Thu Bui
  • Not confirmed yet
Andreea-Elena Cojocaru
Andreea-Elena Cojocaru
  • Not confirmed yet
Maximilian Ell
Maximilian Ell
  • Not confirmed yet

Alumni (12)

Max Eickenscheidt
  • University of Freiburg
Henrike Stutzki
  • University of Tuebingen
Jenny Wickham
  • Lund University
Christian Leibig
  • University of Tuebingen