Event

 

Name: Nathaniel Renegar

 

Committee:

Professor Timothy Horiuchi (Chair)

Professor Behtash Babadi

Professor Sahil Shah

 

Date/time: Thursday, September 10 at 10:00 AM

 

Location: AVW1146

 

Title: Connection Mapping, Synaptic Plasticity, and Dendritic Computation in Dissociated Cortical Cultures

 

Abstract: In recent decades, there has been increasing interest in using dissociated cortical cultures as computational devices. The energy efficiency, adaptability, and robustness of in-tact nervous systems make the possibility of harnessing in vitro neuronal systems appealing. The most used tool for interfacing with cortical cultures is the microelectrode array (MEA). While MEAs can record the spikes of many neurons simultaneously, their electrodes are extracellular. This creates two issues: (1) extracellular stimulation tends to be broad and unspecific, and (2) all plastic changes must be inferred from observed spike trains. These properties make the induction and observation of plasticity with MEAs a major challenge in the field, slowing efforts to find effective learning protocols. The patch clamp technique circumvents these issues by directly controlling and observing a neuron’s membrane potential, but it is extremely invasive and therefore incompatible with long term learning. Recently, genetically encoded fluorescent voltage indicators (GEVIs) have become sensitive enough to feasibly observe post synaptic potentials (PSPs) within a few trials given a suitable imaging setup. This is a promising alternative to patch clamp when the neuron of interest must survive after the experiment. In this thesis, I propose a solution to the non-invasive observation of plasticity in dissociated cortical networks by combining voltage imaging with high-density microelectrode arrays. With this combination of techniques, I plan to make two main contributions. First, I will attempt to induce and observe synaptic plasticity using MEAs and voltage imaging and investigate any relationship between the plasticity outcome and the ongoing network spiking. Second, I will build a ground truth dataset for connection detection by stimulating presynaptic neurons with the MEA and imaging PSPs in a postsynaptic cell. In addition, this combination of techniques can be used to investigate dendritic integration by voltage imaging dendrites and simultaneously stimulating presynaptic neurons in defined spatiotemporal patterns.