Integrated Multi-photon Microscopy and High-density Electrophysiology for Study of Hippocampus-Cortex Interaction During Learning
Abstract
In this proposal, we request funding to purchase a state-of-the-art multi-photon microscopy system with a tunable IR laser output. Multi-photon microscope will be integrated with our 256 channel electrical recording system, providing us with the ability to monitor a diverse range of brain oscillations across large areas in in vivo experiments along with high-resolution calcium imaging of neural activity. Our current ONR grant on developing computational models of hippocampus microcircuits based on experimental findings has led to exciting results. Ourtransparent graphene electrode technology have received a lot of interest because it enables seamless and crosstalk free integration of optical imaging and optogenetic stimulation with electrical recording of neural activity to probe brain circuits with high spatiotemporal resolution. We demonstrated that transparent graphene electrode technology can be used to exactly pinpointthe source of neural oscillations with cellular resolution and quantify the participation of neurons to population activity. This technology can be customized to investigate various problems related to diverse set of computations performed by the brain. New findings on mechanisms of biological intelligence may find applications in next generation artificial intelligence (AI) systems, possibly advancing current AI algorithms towards human-like cognitive skills.In our ONR project we employ this unique technology to investigate hippocampal sharp waveripples. Hippocampal sharp wave-ripples (SPW-Rs) are the most synchronous population pattern recorded in the mammalian brain, essential for information transfer from the hippocampus to the down-stream cortical structures during learning and memory consolidation. To date, most of the knowledge about SPW-Rs comes from experimental studies averagingresponses from a small number of neurons monitored by conventional microelectrodes with limited number of channels. Transparent graphene electrode technology developed by our lab enables investigation of SPW-Rs by performing multi-modal experiments combining electrophysiology and multi-photon microscopy. SPW-Rs can be recorded from hippocampus while we image whole cortex and study activation of different regions in multiple spatial scales to investigate information transfer from hippocampus to cortex during SPW-Rs.To-date, collaborations with other groups have allowed us to perform several multimodal experiments in transgenic mice models towards the goals of our ONR project. However, lack of a multi-photon microscope in our own lab significantly limits the number of experiments we can perform each month. In addition, technical challenges related to assembling our electrical recording platform to different microscopy setups every time makes repeatable progressextremely difficult. The requested funds in this DURIP proposal will provide the complete system necessary to systematically and continuously investigate the neural mechanisms proposed in the ONR grant in well-controlled experimental settings.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 30, 2019
- Source ID
- N000141912545
Entities
People
- Duygu Kuzum
Organizations
- Office of Naval Research
- United States Navy
- University of California, San Diego