Propagation of postsynaptic currents and potentials via gap junctions in GABAergic networks of the rat hippocampus

Abstract

The integration of synaptic signalling in the mammalian hippocampus underlies higher cognitive functions such as learning and memory. We have studied the gap junction-mediated cell-to-cell and network propagation of GABA A receptor-mediated events in stratum lacunosum moleculare interneurons of the rat hippocampus. Propagated events were identified both in voltage-and current-clamp configurations. After blockade of ionotropic excitatory synaptic transmission, voltage-clamp recordings with chloride-loaded electrodes (predicted GABA A receptor reversal potential: 0 mV) at −15 mV revealed the unexpected presence of spontaneous events of opposite polarities. Inward events were larger and kinetically faster when compared to outward currents. Both types of events were blocked by gabazine, but only outward currents were significantly affected by the gap junction blocker carbenoxolone, indicating that outward events originated in electrically coupled neurons. These results were in agreement with computational modelling showing that propagated events were modulated in size and shape by their relative distance to the gap junction site. Paired recordings from electrically coupled interneurons performed with highand low-chloride pipettes (predicted GABA A receptor reversal potentials: 0 mV and −80 mV, respectively) directly demonstrated that depolarizing postsynaptic events could propagate to the cell recorded with the low-chloride solution. Cell-to-cell propagation was abolished by carbenoxolone, and was not observed in uncoupled pairs. Application of 4-aminopyridine on slices resulted in spontaneous network activation of interneurons, which was driven by excitatory GABA A receptor-mediated input. Population activity was greatly depressed by carbenoxolone, suggesting that propagation of depolarizing synaptic GABAergic potentials may be a critical determinant of interneuronal synchronous bursting in the hippocampus.

Noradrenergic Modulation of Electrical Coupling in GABAergic Networks of the Hippocampus

“…Events were first collected using the template-based analysis feature of Clampfit, and then reviewed by visual inspection. As extensively discussed in a previous publication (Zsiros et al, 2007), voltage clamp in an interneuron may propagate across electrical synapses, and help discriminate between direct-versus gap junctionpropagated synaptic input. Although the propagation of voltage clamp may be strongly attenuated in the coupled cells, this attenuation may be much less at membrane domains close to the site of the electrical connection.…”

“…Although the propagation of voltage clamp may be strongly attenuated in the coupled cells, this attenuation may be much less at membrane domains close to the site of the electrical connection. Therefore, synaptic input impinging close to site of the gap junctions may be recorded (Zsiros et al, 2007). Coupled cells that are not subjected to the chloride loading of the recorded electrode have an estimated reversal potential for GABA A receptor-mediated events (E GABA-A ) of approximately Ϫ70 mV (Zsiros et al, 2007).…”

“…As for the Csmethylsulfate, QX-314-based solution described above, external ZD7288 (100 M) was constantly present in the bath. Liquid junction potential was experimentally determined and subtracted off-line (Zsiros et al, 2007).…”

“…A dense plexus of noradrenergic fibers runs through stratum lacunosum-moleculare (Oleskevich et al, 1989) and colocalizes with a network of local interneurons connected via gap junctions (Price et al, 2005;Zsiros and Maccaferri, 2005;Zsiros et al, 2007), thus suggesting the possibility of noradrenergic control of electrical coupling. Electrical coupling in stratum lacunosummoleculare interneurons has been shown to occur frequently [values ranging between 33 and 83% of tested pairs were reported coupled (Price et al, 2005;Zsiros and Maccaferri, 2005)], to be important for oscillatory and firing synchronization (Price et al, 2005), and to enhance network synaptic divergence by propagating mixed polysynaptic events (Zsiros et al, 2007).…”

“…Electrical coupling in stratum lacunosummoleculare interneurons has been shown to occur frequently [values ranging between 33 and 83% of tested pairs were reported coupled (Price et al, 2005;Zsiros and Maccaferri, 2005)], to be important for oscillatory and firing synchronization (Price et al, 2005), and to enhance network synaptic divergence by propagating mixed polysynaptic events (Zsiros et al, 2007). Therefore, modulation of coupling could endow a local source of GABA release with additional flexibility in the spatiotemporal domain.…”