The contribution of electrical synapses to field potential oscillations in the hippocampal formation

Abstract

Electrical synapses are a type of cellular membrane junction referred to as gap junctions (GJs). They provide a direct way to exchange ions between coupled cells and have been proposed as a structural basis for fast transmission of electrical potentials between neurons in the brain. For this reason GJs have been regarded as an important component within the neuronal networks that underlie synchronous neuronal activity and field potential oscillations. Initially, GJs appeared to play a particularly key role in the generation of high frequency oscillatory patterns in field potentials. In order to assess the scale of neuronal GJs contribution to field potential oscillations in the hippocampal formation, in vivo and in vitro studies are reviewed here. These investigations have shown that blocking the main neuronal GJs, those containing connexin 36 (Cx36-GJs), or knocking out the Cx36 gene affect field potential oscillatory patterns related to awake active behavior (gamma and theta rhythm) but have no effect on high frequency oscillations occurring during silent wake and sleep. Precisely how Cx36-GJs influence population activity of neurons is more complex than previously thought. Analysis of studies on the properties of transmission through GJ channels as well as Cx36-GJs functioning in pairs of coupled neurons provides some explanations of the specific influence of Cx36-GJs on field potential oscillations. It is proposed here that GJ transmission is strongly modulated by the level of neuronal network activity and changing behavioral states. Therefore, contribution of GJs to field potential oscillatory patterns depends on the behavioral state. I propose here a model, based on large body of experimental data gathered in this field by several authors, in which Cx36-GJ transmission especially contributes to oscillations related to active behavior, where it plays a role in filtering and enhancing coherent signals in the network under high-noise conditions. In contrast, oscillations related to silent wake or sleep, especially high frequency oscillations, do not require transmission by neuronal GJs. The reliability of neuronal discharges during those oscillations could be assured by conditions of higher signal-to-noise ratio and some synaptic changes taking place during active behavior.

Keywords: electrical synapse; fast spiking cells; field potential oscillations; gap junctions; interneurons; neuronal synchronization; parvalbumin interneurons.

FIGURE 1

The transmission of threshold excitation through a GJ containing Cx36 subunit in a pair of FS interneurons. Image based on original data from Gibson et al. (2005). In response to action potential generated in a presynaptic cell (FS 1), a biphasic potential is mediated through the GJ to a postsynaptic FS cell (FS 2). Due to low-pass filtering of Cx36-GJs, fast spike is more attenuated than slow afterhyperpolarization. The biphasic potential in a postsynaptic cell is composed of a small-amplitude short depolarizing phase and long-lasting hyperpolarization in a postsynaptic FS cell.

FIGURE 2

Mechanism of synchrony detection, as described by Galarreta and Hestrin (2001). Image based on their original data (Galarreta and Hestrin, 2001). Schemas (A) and (B) represent two FS cells (FS 1 and FS 2) connected by electrical (gap junction containing Cx36 subunit, GJ) and a GABAergic synapse (GABA syn). FS 1 and FS 2 receive afferent threshold input with a delay of 1 ms (A) or 5 ms (B). In response to the threshold input, FS 1 generates an action potential (FS 1 potential, FS 1 p). The GJ and GABAergic synapse mediate potentials (GJ p, GABA p) from FS 1 to FS 2. (A) Afferent threshold inputs to FS 1 and FS 2 succeed one another by 1 ms. FS 2 generates an action potential (FS 2 potential, FS 2 p) before inhibition mediated by the GJ and GABAergic synapse. (B) Afferent threshold inputs to FS 1 and FS 2 succeed one another by 5 ms. Excitation in FS 2 is attenuated by hyperpolarization mediated through the GJ and GABAergic synapse (FS 2 p). Scale bars: 20 mV for FS cells membrane potential, 1 mV for potentials mediated by electrical and chemical synapse, 5 ms.

FIGURE 3

Possible contribution of electrical and GABAergic synapses to FS interneuron and pyramidal cell activity during gamma oscillations. Diagrams represent connections between FS cells (FS 1, FS 2) and the pyramidal cells (black triangles), and three aspects of the electrical activity of these cells: local field potential (top), FS cell membrane potentials, and schemas of pyramidal cell discharges. The top part of the diagram is identical in (A) and (B): a portion of pyramidal cells provide coherent threshold input to FS 1. In response to this input, FS 1 generates rhythmical action potentials imposing a time-frame on pyramidal cell activity. Within this time-frame, the time-windows when pyramidal cell activity is not attenuated (white stripes) alters with the time-windows when pyramidal cell activity is attenuated (gray stripes). (A) FS 1 and FS 2 are not connected. FS 2 receives subthreshold coherent inputs from a portion of pyramidal cells and subthreshold non-coherent inputs from the other portion of pyramidal cells. It therefore generates only postsynaptic potentials. (B) FS 1 and FS 2 are connected through a gap junction containing Cx36 subunit (GJ) and a GABAergic synapse (GABA syn). FS 2 receives subthreshold coherent inputs from the same portion of pyramidal cells as in (A), but it also receives coherent inputs from FS 1 mediated by the GABAergic synapse and the GJ. Summation of those coherent inputs results in rhythmical discharges of FS 2. The activity of pyramidal cells connected with FS 2 receiving non-coherent afferent inputs is attenuated. Notice the different dynamics of potentials mediated through the GJ and GABAergic synapse. Hyperpolarizing phases of GJ potential are slow. They summate, providing a long-lasting decrease in FS 2 membrane excitability and prevent FS 2 burst firing. Contrarily, inhibition provided by the GABAergic synapse between FS cells is very fast, and it precisely harmonizes the activity of FS cells. Alternatively, GABAergic synapses can transmit depolarizing currents to the FS cell when it is activated only at the moderate level and does not discharge (so long as its membrane potential does not achieve -55 mV). The small-amplitude depolarizing phase of potential mediated by the GJ almost coincides with FS 1 spikes.