PHYSIOLOGY SHORTS: Seeing beyond the spikes: spatiotemporal membrane potential distribution

In this Physiology Shorts, Dr Zoltán Somogyvári of HUN-REN WIGNER Research Centre for Physics, Hungary discusses their recent paper: Seeing beyond the spikes: reconstructing the complete spatiotemporal membrane potential distribution from paired intra- and extracellular recordings.

Read more in The Journal of Physiology: Seeing beyond the spikes: reconstructing the complete spatiotemporal membrane potential distribution from paired intra- and extracellular recordings. Domokos Meszéna, Anna Barlay, Péter Boldog, Kristóf Furuglyás, Dorottya Cserpán, Lucia Wittner, István Ulbert, and Zoltán Somogyvári. 601 (15), pp. 3351-3376

Transcript:
The aim of our research was to infer the full spatial temporal resolution of the membrane potential and the synaptic currents on single neurons with the spatial and temporary resolution of an action potential.

An average neuron receives inputs from approximately 15,000 synapses. Detecting the output spikes of the neurons is relatively straightforward using an extracellular probe. However a significant challenge remains: we lack techniques to precisely infer the synaptic inputs that trigger these neuronal firings.

These inputs are essentially the cumulative spatial temporal patterns of synaptic currents on the neuron's membrane converging at the soma to elicit an action potential. Despite the rapid development of optical techniques they are unable to resolve the membrane potential on a single neuron along its entire dendritic tree on the time scale of an action potential.

Moreover in a simulated experiment we showed that exciting the soma can lead to the same extracellular potential as inhibiting the dendrites.

Therefore determining input currents or membrane potential changes solely based on extracellular measurements is not possible. In contrast we have taken a novel approach by integrating multi - channel extracellular recordings with single - channel intracellular recordings. Our research builds on the foundational Hodgkin - Huxley equations and cable theory.

This fusion complemented by the calculation of current source density across dendritic branches allows for the reconstruction of the neuron's full spatial temporal membrane potential distribution. This process requires a challenging experiment we need to patch and record the neuron that is located less than 100 microns from the multi-channel silicon probe and perform intracellular and extracellular colocalized and simultaneous recordings.

Additionally, since the calculations are based on the detailed morphology of the neuron, cells need to be filled by anatomical tracer dies and their shape should be reconstructed.

The reconstructed membrane potential allowed us to differentiate between two key current components: capacitive membrane currents which predominantly comprise passive return currents and resistive or transmembrane currents encompassing all synaptic, voltage dependent, and leakage channel currents.

We validated this methodology on simulated data and demonstrated the application to a real neuron with concurrent intracellular and extracellular recordings.

From left to right the figure shows the measured intracellular and extracellular potentials, the colour coded current source density, the calculated membrane potential, the inferred resistive membrane currents on the neuron, and the reconstructed extracellular potential field around the neuron during an action potential.

It is visible that the peak of the extracellular potential precedes the peak of the membrane potential while the resistive current calculations revealed dendritic currents that were invisible on the current source density map.

Now let's see our method in action! We are privileged that our work has been recognised as an editor's choice in the anniversary issue of Journal of physiology to honour Hodgkin and Huxley's groundbreaking discovery.