Thalamocortical modulation of intracortical computation (TIC)

• Applicant: Dr. Yangfan Peng
• Subject Area: Experimental and Theoretical Network Neuroscience ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 451242556

The computational capacity of neural networks is constrained by the underlying network architecture. However, the function of local connections among the main group of cortical neurons, pyramidal cells, is not well understood. Previously, I have established multi-neuron patch-clamp recordings in human cortical tissue allowing detection of monosynaptic connections between neighbouring neurons. This methodological advance revealed a remarkable feedforward structure of the human cortical microcircuit, similar to structures found in rodents. I believe that this feedforward architecture could support sequential activation of cortical neurons and result in specific spatiotemporal spiking patterns.To test these functional hypotheses, I plan to study the emergence of cortical spiking patterns in an in vivo mouse model. The temporal structure of cortical activity will be greatly influenced by external inputs to this circuit, the most prominent of which are the thalamocortical projections. The motor system represents an ideal system to study this interaction as it contains well characterised thalamocortical pathways. Consequently, I have identified the group of Prof. Andrew Sharott to be the ideal place for this project. They have established multiple viral strategies to specifically express channelrhodopsin in the first order cerebellum-recipient and in the higher order basal ganglia-recipient motor thalamus. This allows pathway-specific stimulation of these cortical inputs combined with simultaneous Neuropixel recordings, which are novel high-density silicon probes with 960 electrodes. The host lab could also show that layer 1 NDNF interneurons in motor cortex are recruited by higher order thalamus and established optogenetic modulations of these interneurons. The overall aim of my proposed project is to define the temporal structure of cortical activity evoked by first order thalamic input in vivo and examine how it is modulated by a higher order thalamocortical pathway. First, I will establish a framework to measure the spatiotemporal structure of evoked cortical activity. I will perform Neuropixel recordings in head-fixed mice, optimise a protocol for optogenetic stimulation of the first order thalamus and develop analytical methods to extract the spatiotemporal structure of spiking activity. Next, I will determine the capacity of layer 1 NDNF interneurons to modulate this cortical activity. As these interneurons can inhibit dendritic spikes of pyramidal cells, they can precisely control the driving and modulating inputs onto cortical pyramidal cells. After establishing optogenetic stimulation and inhibition of these interneurons, I will combine them with optogenetic first order thalamic stimulation to study the influence of higher order thalamic input onto the spatiotemporal structure of cortical activity. In conclusion, I am convinced that this project represents a unique opportunity to uncover fundamental principles on thalamocortical computation.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Dr. Andrew Sharott