Patch-walking electrophysiology recordings

Significant technical challenges exist when measuring synaptic connections
between neurons in living brain tissue. The patch clamping technique, when
used to probe for synaptic connections, is manually laborious and
time-consuming. To improve its efficiency, we pursued another approach:
instead of retracting all patch clamping electrodes after each recording
attempt, we cleaned just one of them and reused it to obtain another
recording while maintaining the others. With one new patch clamp recording
attempt, many new connections can be probed. By placing one pipette in
front of the others in this way, one can “walk” across the mouse brain
slice, termed “patch-walking.” We performed 136 patch clamp attempts for
two pipettes, achieving 71 successful whole cell recordings (52.2%). Of
these, we probed 29 pairs (i.e., 58 bidirectional probed connections)
averaging 91 μm intersomatic distance, finding 3 connections.
Patch-walking yields 80-92% more probed connections, for experiments with
10-100 cells than the traditional synaptic connection searching method.