Dendritic dynamics and the perceptual threshold

• Applicant: Professor Matthew Larkum
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250048060

Experimental and psychophysical experiments have established that the process of conscious perception is correlated to the integration of top-down signals with bottom-up information in primary sensory areas. Here, top-down signals arising from other cortical areas are thought to constitute internal representations and/or predictions about sensory information that is carried by the bottom-up stream. Although, the influence of top-down information can be clearly demonstrated with recordings of the activity of neurons, per se, it is not yet known what the underlying mechanisms are nor why they are so crucial. Layer 5 pyramidal neurons have been shown to be capable of explosive firing activity when the top and the bottom of the neuron are both simultaneously activated. This is important because axons carrying top-down information arrive in layer 1 of the cortex and bottom-up signals arrive at the lower (perisomatic) regions of the pyramidal neuron. It has been suggested therefore that top-down information is linked to bottom-up information in these cells via dendritic spikes. These spikes depend on calcium channels in the apical dendrite. We therefore propose the 'Dendrite Hypothesis' for cortex-based perception: 'Perception depends on the generation of dendritic calcium spikes in pyramidal neurons by the combined inputs of bottom-up and top-down signals'. This hypothesis has the advantage that it leads to a specific prediction, i.e. that dendritic Ca2+ transients should be involved in the perceptual process. This can be tested using conventional methodologies. Here, we propose to investigate this hypothesis by examining the events that occur around the 'perceptual threshold', i.e. events occurring after a stimulus ranging in intensity from undetectable to detectable. Animals will be trained to respond to whisker stimuli with a defined response behaviour that is then used as the assay for object perception. We will measure changes in dendritic calcium activity around the perceptual threshold using state-of-the-art techniques including 2-photon imaging and a fiberoptic imaging system ('Periscope' system) developed in our laboratory. We will test the necessity for dendritic spiking in process of perception by using optogenetic approaches for preventing dendritic spikes and top-down signals.

• DFG Programme: Research Grants