Cycle 3 project 1

Activity Contrast Imaging in dendritic networks in the brain


PhD student: Camille Okom, France
Home Institute: European Neuroscience Institute Göttingen; Principle Investigator: Detlev Schild
Host Institute: Amsterdam Neuroscience; Principle Investigator: Huib Mansvelder

Executive Summary

Neurons operate within highly ordered structural networks in the brain using precisely-timed patterns of activity. These activity patterns are mediated by synapses made across the dendrites of each neuron. Synaptic activity is integrated in the dendrites and if strong enough, induces a neuron to fire action potentials and activate its neuronal neighbours in the network. Morphological abnormalities of dendritic synapses are observed throughout the brain in specific cognitive disorders of mental retardation. Structural impairments in the dendrites can significantly alter the function of the neuronal network and are proposed to underlie cognitive deficits seen in these cognitive disorders.

The last two decades of imaging technology have seen rapid progress to visualise the neuronal activity either at high resolution on a single dendrite or at lower resolution across an intact network of hundreds of neurons in the brain. Relating the function of a neuronal network and mapping it to the synaptic activity in the individual dendrites is a challenging task. However, it is essential if we wish to understand the integration of synaptic activity in an intact circuit in the brain during both normal and impaired information processing.

Our lab at the University of Göttingen has recently developed the novel methodology called “activity correlation imaging” in order to image the activities of entire neuronal populations while simultaneously visualising activity in their dendritic structures. Membrane permeable calcium indicator dyes e.g. Fluo4, are loaded into neuronal networks to provide a read-out signal of neuronal activity. Each neuron in the ensemble can be identified by its specific temporal activity pattern and colour-coded. To visualise activity in the small dendritic structures, our novel computational methods use the recorded temporal activity patterns of all the individual neurons as a means of intrinsic contrast using a cross-correlation algorithm. The result is a multi-colour visualisation of neurons and their dendritic trees in the entire circuit.

To date, we have developed this innovative method in an invertebrate neuronal preparation. In the present project we plan to take the method to the observation of synaptic interactions in functional neuronal networks in the mammalian brain. Furthermore, we wish to exploit this technology to study the effects of dendritic abnormalities across a neuronal circuit in an established mammalian model of mental retardation. This project fulfills the remit of the ENC network to focus on the development of a technological advancement and furthermore, to elucidate mechanisms underlying impaired information processing in the brain.

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