The function and connectivity of neocortical layer 7 and long-range inputs to somatosensory cortex.

• Applicant: Professor Matthew Larkum
• Subject Area: Experimental and Theoretical Network Neuroscience ; Cognitive, Systems and Behavioural Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387158597

Neocortical layer 1 and layer 6b (or layer 7), which reside on opposite sides of the cortical mantle and emerge from the first circuits during neocortical ontogeny, remain the most mysterious lamina in the neocortex. Layer 1 contains a sprinkle of locally-connected interneurons, and stands out among cortical layers for its rich array of long-range axons and terminals that carry high-order processed information that influences apical tuft dendrites of pyramidal neurons in layer 2/3 and layer 5. The influence of long-range inputs onto local interneurons and underlying pyramidal neuron somata in layer 2/3 and layer 5 are largely unknown. Layer 7 has a diverse array of excitatory and inhibitory neurons, including a prominent axonal projection into layer 1 and is also noteworthy as the only cortical layer that responds to the wakefulness promoting neuropeptide orexin. The physiology of layer 7 inputs and outputs remain entirely unexplored. Here we examine the synaptic physiology of local and long-range inputs to layer 1 and layer 7. We will employ both a novel circuit mapping strategy developed in our laboratory using the calcium integrator CaMPARI, as well as targeted patch clamp recordings to fully elucidate the connectivity and physiology of inputs and outputs to layer 7 and targeted patching of neurons influenced by layer 1. To further characterize the function of layer 7 we will perform in vivo measurements of sleep-wake behavior while influencing layer 7-specific neurons both optogenetically and pharmacologically with orexin. The data acquired from these experiments will provide a large inroad into the functional connectivity and potential functions of layer 1 and 7 and the behavioral influence of layer 7 during wakefulness and sleep.

• DFG Programme: Research Grants