Rapid Signaling at Inhibitory Synapses in a Dentate Gyrus Interneuron Network

Abstract

Mutual synaptic interactions between GABAergic interneurons are thought to be of critical importance for the generation of network oscillations and for temporal encoding of information in the hippocampus. However, the functional properties of synaptic transmission between hippocampal interneurons are largely unknown. We have made paired recordings from basket cells (BCs) in the dentate gyrus of rat hippocampal slices, followed by correlated light and electron microscopical analysis. Unitary GABA A receptor-mediated IPSCs at BC-BC synapses recorded at the soma showed a fast rise and decay, with a mean decay time constant of 2.5 Ϯ 0.2 msec (32°C). Synaptic transmission at BC-BC synapses showed paired-pulse depression (PPD) (32 Ϯ 5% for 10 msec interpulse intervals) and multiple-pulse depression during repetitive stimulation. Detailed passive cable model simulations based on somatodendritic morphology and localization of synaptic contacts further indicated that the conductance change at the postsynaptic site was even faster, decaying with a mean time constant of 1.8 Ϯ 0.6 msec. Sequential triple recordings revealed that the decay time course of IPSCs at BC-BC synapses was approximately twofold faster than that at BC-granule cell synapses, whereas the extent of PPD was comparable. To examine the consequences of the fast postsynaptic conductance change for the generation of oscillatory activity, we developed a computational model of an interneuron network. The model showed robust oscillations at frequencies Ͼ60 Hz if the excitatory drive was sufficiently large. Thus the fast conductance change at interneuron-interneuron synapses may promote the generation of high-frequency oscillations observed in the dentate gyrus in vivo.

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…Moreover, one component of the oscillation cycle shows a reversal potential close to the GABA A -mediated reversal (around −60 mV). In keeping with this evidence, computer modeling supports the hypothesis that gamma oscillations reflect the interactions within interneuron networks (Wang and Buzsáki, 1996;White et al, 1998;Traub, 2000;Bartos et al, 2001). …”

Long-term sensory deprivation selectively rearranges functional inhibitory circuits in mouse barrel cortex

“…Even though LTS neurons are only a fraction of the overall inhibitory neuronal population, the output of inhibition from this particular type of neuron may yield wide reaching effects at the network level. Changes in decay kinetics, even on the millisecond timescale, can alter the synchronization of large populations of neurons (53,54), particularly if fast decay from ␣1 subunits is involved (55). Thus, as our result of increased firing frequency in LTS cells shows, even subtle changes in recurrent inhibition onto LTS cells may result in significant consequences such as observed in basket cell development (56).…”

Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells

“…interneurons | synaptic transmission | dentate gyrus | basket cell | gamma oscillations G ABAergic parvalbumin (PV)-expressing fast-spiking perisoma-inhibiting interneurons (PIIs) provide powerful synaptic inhibition to large numbers of target cells distributed over several hundred micrometers of cortical space (1)(2)(3)(4)(5). Extent and density of their axonal projection together with the perisomatic location of their output synapses close to the site of postsynaptic action potential generation are thought to provide tight control over the activity of target cells.…”

“…Extent and density of their axonal projection together with the perisomatic location of their output synapses close to the site of postsynaptic action potential generation are thought to provide tight control over the activity of target cells. Moreover, PIIs usually interact with other PIIs by reciprocal chemical and electrical synapses, thereby forming interneuron (IN) networks (4,6,7), which have been proposed to orchestrate the activity of cortical circuits. PIIs have been shown to receive rapid synaptic excitation (8) and to provide fast, strong, and faithful inhibitory signals to their postsynaptic partners (3,5,6).…”