Ephaptic coupling in cortical neurons

The electrochemical processes that underlie neural function manifest themselves in ceaseless spatial and temporal fluctuations in the extracellular electric field. The local field potential (LFP), used to study neural interactions during various brain states, is regarded as an epiphenomenon of coordinated neural activity. Yet the extracellular field activity feeds back onto the electrical potential across the neuronal membrane via ephaptic coupling (Jefferys et al, Physiol Rev, 1995). The extent to which such ephaptic coupling alters the functioning of individual neurons and neural assemblies under physiological conditions has remained largely speculative despite recent advances (Ozen et al, JNeurosci, 2010; Fröhlich & McCormick, Neuron, 2010, Anastassiou et al, JNeurosci, 2010). To address this question we use a 12-pipette setup that allows independent positioning of each pipette under visual control with μm accuracy, with the flexibility of using an arbitrary number of these as patching, extracellularly stimulating or extracellular recording pipettes only a few μm away from the cell body of patched neurons (Anastassiou et al, Nat Neurosci, 2011). We stimulated in rat somatosensory cortical slices a variety of layer 5 neural types and recorded inside and outside their cell bodies while pharmacologically silencing synaptic transmission. Pyramidal cells couple to the extracellular field distinctly different from interneurons. Ephaptic coupling strength depends both on the field strength (as measured at the neuron soma) as well as the spike-history of neurons. In particular, we find that ephaptic coupling strength depends both on the field strength (as measured at the cell body) as well as the spike-history of neurons. How do such effects manifest themselves in vivo? We address this question through detailed large-scale simulations from thousands of biophysically realistic and interconnected neurons (Reimann, Anastassiou et al, Neuron, 2013) emulating circuit activity. The simulations allow us to examine ephaptic coupling and dissociate between the feedforward (from membrane currents to LFP) and feedback (from LFPs to membrane voltage via ephapic coupling) effect in unprecedented detail. Our results support the notion that ephaptic coupling to endogenous electric fields in the brain may crucially impact neural communication. We hypothesize the functional role of such coupling in various brain states, for example, during visual processing (Anastassiou, Encyclopedia for Computational Neuroscience, Springer, 2014).