title: Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials.
abstract: A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.
authors: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Milos
authors: M
authors: Radivojevic
authors: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: David
authors: D
authors: Jäckel
authors: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Michael
authors: M
authors: Altermatt
authors: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Jan
authors: J
authors: Müller
authors: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Vijay
authors: V
authors: Viswam
authors: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Andreas
authors: A
authors: Hierlemann
authors: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
authors: Douglas J
authors: DJ
authors: Bakkum
mesh_terms: D000200:Action Potentials; D000818:Animals; D001369:Axons / Q000502:physiology; D008564:Membrane Potentials; D008839:Microelectrodes; D019579:Neocortex / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D061848:Optical Imaging; D018408:Patch-Clamp Techniques