Researchers develop nanopipette scanning probe method to record electrical activity at individual synapses
A team led by a researcher at Queen Mary University of London has developed a precise new method that makes it possible to measure electrical activity directly at the tiny communication junctions between neurons—synapses. Synapses in the central nervous system are extremely small, typically one micrometre or less in size, and their minute dimensions have long made it difficult to target them for physiological recordings. This advance combines high-resolution scanning probe microscopy with nanoscale electrophysiology to visualise and record current flow from individual presynaptic terminals.
The technique replaces conventional low-resolution optical approaches with a nanopipette-based microscope capable of three-dimensional topographical mapping at the nanoscale. The nanopipette scans just above the sample surface to build a 3D map of the neuronal structure, then makes targeted contact with specific points on the membrane to record electrical signals. By repeating the scan-and-record procedure across multiple locations, the researchers can produce a three-dimensional map of both structure and electrical activity across a neuronal network.
“We replaced the conventional low-resolution optical system with a high-resolution microscope based on a nanopipette,” explained Dr Pavel Novak, a bioengineering specialist in Queen Mary’s School of Engineering and Materials Science. “The nanopipette hovers above the surface of the sample and scans the structure to reveal its three-dimensional topography. The same nanopipette then attaches to the surface at selected locations on the structure to record electrical activity. By repeating the same procedure for different locations of the neuronal network we can obtain a three-dimensional map of its electrical properties and activity.”
This nanoscale-targeted patch-clamp approach enables direct measurement of presynaptic ion channel function and current flow in synaptic terminals that are otherwise inaccessible with standard electrodes. The method therefore opens a new window onto the electrical behaviour of synapses and offers a level of spatial resolution and targeting previously unavailable for functional studies of neuronal microcircuits.
Published in the journal Neuron, the study demonstrates feasibility and provides initial recordings from small presynaptic sites. Because it combines high-resolution topographical imaging with electrophysiological readout, the approach can link ultrastructure to function at the nanometre scale. That capability is important for improving our mechanistic understanding of synaptic transmission, synaptic plasticity and the molecular machinery that controls neurotransmitter release.
Beyond basic research, nanoscale recordings from individual synapses could help inform studies of neurological disorders in which synaptic function is disrupted, guide drug discovery by providing a platform for testing compound effects at the level of single terminals, and contribute to larger efforts to map brain activity with cellular precision. The authors note that their work aligns with broader initiatives, such as the BRAIN Initiative (Brain Activity Map Project), which seek to chart neuronal function at high resolution across circuits.
Notes about this neuroscience research
The research team included collaborators from University College London and Imperial College London in addition to Queen Mary University of London. The published paper is titled “Nanoscale-Targeted Patch-Clamp Recordings of Functional Presynaptic Ion Channels” and appears in Neuron.
Contact: Neha Okhandiar – Queen Mary, University of London
Source: Queen Mary, University of London press release
Image Source: The 3D representation of synaptic transmission image is adapted from the Queen Mary, University of London press release.
Original Research: “Nanoscale-Targeted Patch-Clamp Recordings of Functional Presynaptic Ion Channels,” Neuron. DOI: 10.1016/j.neuron.2013.07.012