2-Photon Imaging and Optogenetics
We utilize 2-photon imaging to record neural activity from genetically-defined cell populations. In a separate channel, we can simultaneously monitor an additional genetically-encoded sensor, such as the endocannabinoid biosensor (e.g. see Farrell et al., Neuron 2021).
We also have the ability to optogenetically manipulate individual neurons at the single cell level with 2-photon activation of an opsin. This gives us the ability to study local microcircuit dynamics in vivo.
Experiments are performed on awake, behaving mice, often in combination with high density electrophysiological recordings (see below).
High Density Electrophysiology
Silicon probes offer the opportunity to study large populations of neurons at a fast time scale. Moreover, the local field potential dynamics provide critical insights into distinct brain states, which can be used to ground our calcium imaging recordings to to known memory processes such as memory replay during sharp-wave ripples.
Cell Type-Guided Focused Ultrasound Neuromodulation
Using an ultrasound transducer that is coupled to a fiber optic cannula, we can monitor the activity of genetically defined cell populations at the site of sonication. Importantly, different parameters can have profoundly different effects on the local circuit and can bias the network towards inhibitory or excitatory states. In many cases, fUS parameters can be optimized to have a desired effect on the network to counteract pathophysiology, which we showed was possible for rodent models of temporal lobe epilepsy (see Murphy et al., PNAS 2022). We will move towards studying the neuromodulatory effects of ultrasound in vivo at sub-cellular resolution to better understand which cells, including where (dendrites vs. axons?) and when (rapid onset vs. delayed?), are most affected.