Field effects in the CNS play functional roles

Abstract

An endogenous electrical field effect, i.e., ephaptic transmission, occurs when an electric field associated with activity occurring in one neuron polarizes the membrane of another neuron. It is well established that field effects occur during pathological conditions, such as epilepsy, but less clear if they play a functional role in the healthy brain. Here, we describe the principles of field effect interactions, discuss identified field effects in diverse brain structures from the teleost Mauthner cell to the mammalian cortex, and speculate on the function of these interactions. Recent evidence supports that relatively weak endogenous and exogenous field effects in laminar structures reach significance because they are amplified by network interactions. Such interactions may be important in rhythmogenesis for the cortical slow wave and hippocampal sharp wave-ripple, and also during transcranial stimulation.

Keywords: LFP; computation; ephaptic; field effect; neurotransmission; transcranial stimulation.

Figure 1

(A1, B1) An EPSP in the soma of the left neuron produces a depolarization (Vm) in the soma of the right inactive neuron (thick line). The extracellular resistance (Re) is larger in (A) than in (B). Because the resistance is higher, more current is channeled across the membrane of the cell to the right in (A) and the field effect is bigger. (A2, B2) The equivalent circuit, with the dotted line representing the membranes, demonstrates how the magnitude of the field effect depends upon the relative values of the intracellular, transmembrane, and extracellular resistances. The transmembrane potential in cell 2 (Vm) is calculated as the difference between the extracellular potential (Ve) and the intracellular potential (Vi).

Figure 2

Spatiotemporal properties of field effects. (A) Cylinders of varying electrotonic length (colors) in a uniform electric field (E). The membrane polarization along the cable depends on the cable's electrotonic length. Adapted from Chan and Nicholson (1986). (B) Extra- (red) and intracellular (black) stimulation of a passive sphere results in a different time course of membrane polarization. Adapted from Cartee and Plonsey (1992).

Figure 3

Illustration of the electrical inhibition mediated by impulses in interneurons that inhibit the M-cell. Inward currents generated at the excitable heminode, or last node of Ranvier (red) of the inhibitory interneurons cell‘s myelinated axon (black) flow passively out at the terminal and other unmyelinated portions in the cap and inward across the membrane of the axon hillock (blue) of the M-cell. A region of high extracellular resistance (gray area), the axon cap, reduces extracellular currents returning to the heminode or last node of Ranvier within the cap (arrow with dashed line) and directs the current across the membrane of the M-cell.

Figure 4

A comparison of the strength of endogenous electric fields with that of exogenous fields shown to alter spike timing in vitro. Approximate strength of endogenous electrical fields resulting from normal activity in the cortex and hippocampus (blue arrows), as well as the in the M-cell system (yellow arrow, vertical line indicates range). The approximate field strength of epileptic discharges (green arrow and vertical line). Spike timing in hippocampal slices (red arrows) is altered by exogenous fields that are considerably weaker in strength.

Figure 5

Field effects can be amplified by network interactions involving chemical synapses. (A) An illustration of pyramidal neurons arranged in a parallel laminar orientation interconnected by excitatory chemical synapses on the apical and basal dendrites. Colors indicate the extracellular potential resulting from synaptic activity in the apical and basal dendrites in this network. (B) Field effects associated with the EPSPs in the network are amplified by affecting spike timing and consequently chemical synaptic transmission. Note this amplification can theoretically occur within diverse network architectures.