Holographic Induction of Neural Circuit Plasticity (360G-Wellcome-201964_Z_16_Z)

Key words: Plasticity, Optogenetics, Neocortex, Neural Microcircuits, Functional Connectomics, Computer-generated Holography, Two-photon Microscopy Neocortical circuits modify both structure and function in order to learn, remember, refine task performance, and recover from injury. Electrical patch-clamp methods have identified several plasticity mechanisms on the single-cell level. The number of cells that can be simultaneously patched is however limited, hindering efforts to connect single-cell plasticity with circuit- and system-scale learning and memory. Computer-generated holography (CGH), combined with genetically encoded light-sensitive actuators ("optogenetics"), holds immense promise to overcome this limitation by targeting light to rapidly activate one or several neurons without physical electrode penetration. I will adapt two-photon CGH to: 1) rapidly map local inputs to a neuron in depth of neocortical brain slices; and, 2) manipulate the connection strengths between the neuron and its presynaptic inputs by holographically actuating spikes in the presynaptic neurons at short delays with respect to electically actuated post-synaptic spikes. CGH’s ability to rapidly solicited spikes in hundreds neurons will enable, for the first time, single-cell resolution plasticity interrogation in whole functioning microcircuits. The Wellcome Seed award will enable these critical first steps toward connecting synaptic plasticity with neural circuit emergent properties, learning, memory, and injury recovery.