Cycle 5 project 2

Bridging the anatomy and physiology of neocortical circuits


P02-AzhikkattuparambilPhD student: Arjun Bashkaran, India
Home Institute: Bordeaux Neuroscampus; Principle Investigator: Andreas Frick
Host Institute: Neuroscience Center Zürich; Principle Investigator: Fritjof Helmchen
2nd Host Institute: European Neuroscience Institute Göttingen; Principle Investigator: Jochen Staiger

Executive Summary

In the mammalian neocortex, a quantitative knowledge of the brain-wide distribution of neurons that are presynaptically connected to a specific neuron type is completely lacking. Furthermore, it is unknown how activity in these presynaptic neurons contributes to the activity of the postsynaptic neuron. Recent studies are beginning to elucidate how neocortical neurons that are projecting to different target brain regions are differentially engaged by behavioral tasks (e.g. Chen et al., 2013 Nature). We are now in the position to bring these different aspects – the detailed wide-spread input connectivity on one hand and the functional activation patterns of presynaptic neuron pools on the other – together, to shed light on how the structure of the neocortex relates to its function.

In the proposed project, we will measure the biophysical profiles and physiological, whisker-driven responses of specific neocortical pyramidal neurons of the barrel cortex and combine this knowledge with that of their anatomical large-scale input connectivity. To this end, we will characterize in a quantitative manner the distribution and cell-type composition of the neurons that are directly presynaptic to the recorded neuron. In a third step, we will measure the calcium transients (as a readout for action potential firing) in these presynaptic neuronal populations (within the barrel cortex and in other neocortical regions) to better understand how they contribute to the response of the postsynaptic neuron. This will be achieved by genetically expressing a calcium indicator in both the presynaptic neurons and the postsynaptic neuron using a rabies virus based mono-trans-synaptic tracing approach.

Techniques: In vivo whole-cell recording of single neocortical pyramidal neurons; mono-trans-synaptic tracing based on modified rabies virus; calcium imaging at cellular resolution from neuronal populations; visualization, and brain-wide quantification and identification of neurons presynaptic to the recorded neuron.

Originality: The quantitative, brain-wide analysis of all mono-synaptically connected presynaptic neurons to any neuron type is so far completely lacking. We have now successfully established this method for neocortical pyramidal neurons. This enables us to correlate the resulting ‘anatomical receptive field’ of a postsynaptic neuron with its biophysical profile and ‘synaptive receptive field’. In this project we will use this approach, and take it even one step further by recording the population activity of both pre- and postsynaptic neurons following the genetic expression of a calcium indicator exclusively in these neurons. These approaches are highly novel and promise to provide crucial knowledge regarding the structure-function relationship of neocortical circuits.

Rationale for collaboration: The consortium provides the necessary expertise for this ambitious project. The Frick lab now routinely uses the novel methodological approach of combining measurements of the physiology of individual neurons in vivo with the quantitative mono-trans-synaptic tracing of their presynaptic neurons (Rancz et al, 2011). Furthermore, the production of novel rabies virus variants (in collaboration with Dr. K.-K. Conzelmann, Gene Center Munich, Germany) is established. The Helmchen lab has long-standing expertise in the measurement of the physiology of single neurons in vivo, as well as of calcium signals from neuronal populations at cellular resolution during behavioral tasks. Dr. Staiger is a leading expert in neuroanatomy and in the characterization of neuronal cell types including the large arsenal of GABAergic interneurons. This combined expertise is fundamental to the success of the project.

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