Contents I. Introduction
Profound knowledge of brain function at the cellular level is important for understanding sensory systems [1] and other higher brain functions. It is also important for the development of medicines for neurological disorders such as Parkinson’s and Alzheimer’s disease [2]. The brain processes a large amount of information through billions of interconnected neurons. To understand neural processing, it is necessary to electrophysiologically measure the internal activity of individual neurons in their natural environment. This requires techniques that allow in vivo intracellular recordings [3]. Patch clamp is originally an in vitro technique developed in the late 1970s that allows simultaneous recording of neuronal input and output signals with excellent temporal and spatial resolution [4]. Since the 2000s, this technique has been adopted for in vivo measurements in living organisms [5]. During the whole-cell patch-clamping procedure, a glass micropipette filled with a conductive solution is inserted into the brain and advanced to a neuron of interest. Then, the pipette is brought into contact with the neuronal membrane after which it is locally aspirated to make electrical internal contact [6], called a “patch.” However, making an in vivo patch is a huge challenge with limited success due to the small size of neurons (~10 ) [7], the lack of visualization [8], and especially the inherent physiologically induced motion by heartbeat and breathing [9]. The latter involves the risk of an uncontrolled penetration of the neuron. If this happens the whole procedure needs to be repeated with a new micropipette [10].
