Cycle 3 project 3

The neuronal code in association cortex

 

PhD student: Hemanth Mohan, India
Home Institute: Amsterdam Neuroscience; Principle Investigator: Christiaan de Kock
Host Institutes:
European Neuroscience Center Zürich; Principle Investigator: Fritjof Helmchen
Neuroscience Institute Göttingen; Principle Investigator: Jochen Staiger

Executive Summary

Background
The computational power of cortical areas is embedded in the vast copy number of the characteristic processing unit: “the cortical column”. The basic design of the cortical column shows multiple layers and each layer contains different cell types (Fig.1). These cell types are characterized by distinct dendritic branching patterns, different inputs, and precise output projections and therefore almost certainly serve specific functions.

To understand sensory guided behaviour and decision making, we need to know how sensory information is represented in higher cognitive areas; collectively called association cortices. One of these association cortices is the posterior parietal cortex (PPC) which receives dense input from primary somatosensory cortex, . From behavioral studies, it was suggested that the PPC is involved in representation of the spatial relationship among different objects in the environment although it remains on open question how this hypothesis is translated into spiking activity throughout the PPC. In our ENC proposal, we therefore aim to take a cellular and network approach to elucidate how spatiotemporal information of sensory stimuli is represented throughout the cortical column of the PPC.

Rationale:
We know extremely little about the function and anatomy of cortical associative areas at a single cell level. Since these areas are critically involved in sensory-guided decision making, it is crucial to fill this gap.

Research question:
What is the layer and cell-type specific spiking in posterior parietal cortex (PPC) during sensory processing?

Working hypothesis:
Spiking frequencies, response characteristics, temporal coding schemes and reliability of the neuronal code are highly cell-type specific and differ for excitatory and inhibitory neurons. In addition, we expect to find layer-specific rules in the transfer of the neuronal code from primary sensory cortex to PPC.

Methods:
Using local injections of retrograde tracers in PPC, we are currently characterizing the detailed architecture of projections from somatosensory cortex to PPC. This will provide a solid basis for the start of our ENC proposal.

The PhD student will start performing juxtasomal recordings in urethane anaesthetized mice to determine spiking profiles in response to single or multiple whisker deflections. Recorded neurons will be labeled with biocytin for post-hoc dendritic and axonal reconstruction to obtain the wiring diagram of the cortical column. These techniques are up and running in Amsterdam,, but have never been applied to associative areas in cortex.

Next, the PhD student will perform two-photon calcium imaging to determine network computation in response to single or multiple whisker deflections in urethane anaesthetized mice. This technique is up and running in Zurich, and we will apply it for the first time in cortical association areas, such as PPC. Using post-hoc multiple immunostaining, we will identify various cell types, in particular inhibitory interneurons.

Together, these approaches will give us a detailed understanding of 1) microcircuit anatomy, 2) neuronal code, and 3) population dynamics in PPC.

Originality
The cortical column of sensory areas (such as primary visual or somatosensory cortex) has proven invaluable in studying physiological and morphological characteristics of cortical layers and the neurons that reside in it. On the other hand, this wealth of data has not been achieved in higher cortical areas, such as association areas. C. de Kock and F. Helmchen both have strong track records in elucidating cortical coding mechanisms whereas J. Staiger is an authority on identification of cell types in vitro and ex vivo. Our team is therefore in the optimal position to push the field of cortical research in this direction and explore the microcircuit in PPC using state-of-the-art electrophysiological, imaging and immunochemical techniques.

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