Dr. David Margolis

 

Main Goals, Keywords

Our percepts, thoughts, and actions are encoded by the spiking activity of large neuronal populations. In vivo imaging techniques have begun to illuminate the ensemble nature of activity within neural circuits of the neocortex. We are interested in how cortical networks process sensory information, and especially how changes in sensory experience or behavioral state alter sensory and sensorimotor processing.

Keywords: neocortex, plasticity, two-photon imaging, neural circuit activity, behavior

Group Members

1 Junior Group Leader, 2 PhD students, 1 Technician

Previous and Current Research

How does neural circuit activity change when its normal input is altered? In my previous work, I used patch clamp recordings and two-photon calcium imaging to study the activity of ganglion cells, the output cells of the retina, in a light-sensitive ex vivo preparation. I investigated the synaptic and intrinsic biophysical mechanisms that control spiking activity, both under normal conditions and after sensory input from photoreceptors was destroyed by degenerative disease.

Currently, my research focuses on plasticity of the mouse “barrel cortex”, a structure involved in sensation from the facial whiskers and in the control of whisking behavior. The barrel cortex contains a precisely organized map of the whiskers, whose topography can be changed by sensory experience. One aspect of the work investigates changes in activity of individual neurons during cortical map plasticity. These experiments are done in anesthetized mice, where sensory stimulation can be easily controlled. Another set of experiments involves imaging of cellular activity in awake head-fixed mice to understand aspects of active sensory-motor integration that cannot be studied under anesthesia.

We use new methods of chronic in vivo imaging to record activity from the same individual neurons in the mouse brain over long periods of time in different imaging sessions. This approach allows new insight into the stability and plasticity of cellular activity that so far has not been possible to investigate.

Future Projects

We plan to study the effects of sensory experience on signal transmission between sensory and motor cortex in anesthetized mice using wide-field voltage-sensitive dye imaging. Complementarily, we want to study the effects of sensory deprivation on whisking behavior and whisking-modulated network activity using chronic imaging in awake mice.

Techniques and Equipment

In vivo imaging and electrophysiology, two-photon laser-scanning microscopy, chronic imaging using genetically-encoded calcium indicators, wide-field voltage-sensitive dye imaging.

Selected Publications

• Margolis DJ¹⁼, Lütcke H¹⁼, Haiss F, Weber B, Kügler S, Hasan MT, Helmchen F, Reorganization of cortical population activity imaged throughout long-term sensory deprivation, under review.

• Minderer M¹⁼, Lui W¹⁼, Sumanovski LT, Kügler S, Helmchen F, Margolis DJ (2011), Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator, Journal of Physiology, accepted.
• Lütcke H¹⁼, Murayama M¹⁼, Hahn T, Margolis DJ, Astori S, Zum Alten Borgloh SM, Göbel W, Yang Y, Tang W, Kügler S, Sprengel R, Nagai T, Miyawaki A, Larkum ME, Helmchen F, Hasan MT (2010), Optical recording of neuronal activity with a genetically-encoded calcium indicator in anesthetized and freely moving mice, Frontiers in Neural Circuits 4:9.
• Margolis DJ, Gartland AJ, Euler T, Detwiler PB (2010), Dendritic calcium signaling in ON and OFF mouse retinal ganglion cells, Journal of Neuroscience 30(21):7127-38.
• Margolis DJ, Newkirk G, Euler T, Detwiler PB (2008), Functional stability of retinal ganglion cells after degeneration-induced changes in synaptic input, Journal of Neuroscience 28(25):6526-36.
• Margolis DJ, Detwiler PB (2007), Different mechanisms generate maintained activity in ON and OFF retinal ganglion cells, Journal of Neuroscience 27(22):5994-6005.

Funding

Ambizione grant from Swiss National Science Foundation.