SUMMARY

Whole-cell patch clamp electrophysiology of neurons in vivo enables the recording of electrical events in cells with great precision, and supports a wide diversity of cellular morphological and molecular analysis experiments. It is one of the best methods of measurement of subthreshold synaptic events, as well as intrinsic channel activities, in neurons in the brain of the behaving animal. Furthermore, whole cell patch clamping can also be used to isolate mRNA from individual cells for molecular analysis, and can be used to for cell filling with dyesassessment of morphology and connectivity. Thus, in vivo patch clamping fulfills a critical niche in cellular, network, and systems neuroscience. However, a critical issue is that this technique remains an extremely difficult technique for experimenters to use and this has precluded the widespread utilization of this technique for high-throughput single cell studies. This thesis work aims to (a) develop a robotic system for automated whole cell patch clamping, (b) utilize such an automated system for high throughput cell phenotyping in the intact mammalian brain, and (c) develop the principles for scaling up the automated single cell patch clamping system for patch clamping of neuronal networks in vivo.