Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex

Abstract

Networks of ␥-aminobutyric acid (GABA)ergic interneurons connected via electrical and chemical synapses are thought to play an important role in detecting and promoting synchronous activity in the cerebral cortex. Although the properties of electrical and chemical synaptic interactions among inhibitory interneurons are critical for their function as a network, they have only been studied systematically in juvenile animals. Here, we have used transgenic mice expressing the enhanced green fluorescent protein in cells containing parvalbumin (PV) to study the synaptic connectivity among fast-spiking (FS) cells in slices from adult animals (2-7 months old). We have recorded from pairs of PV-FS cells and found that the majority of them were electrically coupled (61%, 14 of 23 pairs). In addition, 78% of the pairs were connected via GABAergic chemical synapses, often reciprocally. The average coupling coefficient for step injections was 1.5% (n ‫؍‬ 14), a smaller value than that reported in juvenile animals. GABA-mediated inhibitory postsynaptic currents and potentials decayed with exponential time constants of 2.6 and 5.9 ms, respectively, and exhibited paired-pulse depression (50-ms interval). The inhibitory synaptic responses in the adult were faster than those observed in young animals. Our results indicate that PV-FS cells are highly interconnected in the adult cerebral cortex by both electrical and chemical synapses, establishing networks that can have important implications for coordinating activity in cortical circuits.

Cerebral Energy Metabolism and the Brain’s Functional Network Architecture: An Integrative Review

“…18 The excitatory drive to interneurons required to sustain g-frequency oscillations is commonly thought to arise from pyramidal cells 27,28 but evidence for gap junction-mediated excitation across interneurons also exists. 29 In agreement with this view, AMPA-mediated principal neuron-to-interneuron excitatory synapses have been identified in the neocortex and hippocampus, and the associated postsynaptic currents have a particularly rapid time course 30 indicative of functional specialization to facilitate rapid oscillations. Moreover, N-methyl-D-aspartate (NMDA) R1 receptor deletion in GABAergic interneurons results in a loss of neuronal synchronization in slices, 31 and glutamatergic synapses on interneurons are stronger than those on principal neurons, 19 also consistent with a directional role in providing tonic excitatory inputs to PV cells.…”

Signaling between periglomerular cells reveals a bimodal role for GABA in modulating glomerular microcircuitry in the olfactory bulb

“…inhibition (22,23). In the OB, the existence of PG-PG synapses has been demonstrated (8, 9) although whether, or how, they might participate in altering input-output functions of the glomerular microcircuit is not known.…”

Gap junctions promote synchronous activities in a network of inhibitory interneurons

“…): FS interneurons have high firing rates (up to ∼210 Hz), average resting membrane potential of (−72 ± 1) mV and input resistance of (89.2 ± 2.9) M ; their action potential has a mean half-width of (0.35 ± 0.01) ms, average amplitude of (61 ± 2) mV and afterhyperpolarization of (25.4 ± 0.6) mV (Galarreta and Hestrin, 2002). The mean value of the electrical conductance between two FS cells is <G El > ± G El = (0.203 ± 0.044) nS, the maximal conductance of unitary GABAergic synapses is <G GABA > ± G GABA = (0.8 ± 0.26) nS with a reversal potential of −80 mV, the mean value of the decay time constant of the inhibitory postsynaptic current (IPSC) is <τ Exp > ± τ = (2.6 ± 0.2) ms (Galarreta and Hestrin, 2002). We used the experimental time course of the average (50 trials) IPSC to determine, by standard fitting method, the simplest mathematical form capable to capture the rising and decay kinetics of the IPSC.…”

“…For the discharges recorded from neocortical FS cell in in vitro experiments, a very low value of the coefficient of variation (CV) of the interspike intervals (ISIs) has been measured: CV = 0.086 (Galarreta and Hestrin, 2002). Thus, the amplitude of the EPSC for our computer experiments was fixed in order to yield for the uncoupled FS cell a CV value of the same magnitude as the experimental one.…”

“…electrical synapses too (Galarreta and Hestrin, 1999;Gibson et al, 1999;Galarreta and Hestrin, 2002). The relevance of the electrical synapses for the generation of the synchronous neural activity comes from the experimental finding that impairing the electrical synapses between cortical interneurons disrupts synchronous oscillations in the gamma frequency band (Deans et al, 2001;Hormuzdi et al, 2001).…”