Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks

Abstract

Networks of GABAergic interneurons are of critical importance for the generation of gamma frequency oscillations in the brain. To examine the underlying synaptic mechanisms, we made paired recordings from ''basket cells'' (BCs) in different subfields of hippocampal slices, using transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the parvalbumin promoter. Unitary inhibitory postsynaptic currents (IPSCs) showed large amplitude and fast time course with mean amplitudeweighted decay time constants of 2.5, 1.2, and 1.8 ms in the dentate gyrus, and the cornu ammonis area 3 (CA3) and 1 (CA1), respectively (33-34°C). The decay of unitary IPSCs at BC-BC synapses was significantly faster than that at BC-principal cell synapses, indicating target cell-specific differences in IPSC kinetics. In addition, electrical coupling was found in a subset of BC-BC pairs. To examine whether an interneuron network with fast inhibitory synapses can act as a gamma frequency oscillator, we developed an interneuron network model based on experimentally determined properties. In comparison to previous interneuron network models, our model was able to generate oscillatory activity with higher coherence over a broad range of frequencies (20 -110 Hz). In this model, high coherence and flexibility in frequency control emerge from the combination of synaptic properties, network structure, and electrical coupling.G amma frequency oscillations are thought to be of key importance for higher brain functions, such as feature binding and temporal encoding of information (1-5). Experimental and theoretical evidence suggests that local networks of synaptically connected GABAergic interneurons are critically involved in the generation of these oscillations (6-19). First, perisomatic inhibitory interneurons (basket cells) fire action potentials at high frequency during gamma activity in vivo, with single spikes phase-locked to the oscillations of the field potential (6, 7). Second, pharmacologically isolated networks of inhibitory interneurons in vitro can oscillate at gamma frequency in response to metabotropic glutamate receptor activation (8). Finally, models of mutually connected interneurons generate coherent action potential activity in the gamma frequency range in the presence of a tonic excitatory drive (9-19).The mechanisms leading to the generation of coherent gamma oscillations in interneuron networks, however, have remained unclear. Although gamma frequency oscillations can be generated in interneuron network models, coherence is fragile against variation in amplitude and time course of the inhibitory postsynaptic conductance, against heterogeneity of the tonic excitatory drive, and against sparseness of connectivity (11-14). The mechanisms contributing to the control of network frequency are also poorly understood. It is thought that the time course of the inhibitory synaptic conductance change is a major factor (8-14), but the significance of other parameters remains undetermined. Some models suggest t...

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

“…These findings showed a deficit in gamma band activity in the MAM-treated rats in both the mPFC and vHipp, the same regions that show significant reductions in PV neuron staining (Lodge et al, 2009). Fastspiking PV interneurons have been shown to be necessary for the generation of gamma band activity (Bartos et al, 2002(Bartos et al, , 2007Buzsáki et al, 1983;Lewis et al, 2011;Whittington et al, 1995), which is also disrupted in schizophrenia (Lewis et al, 2011. Our results showed that stimulation of the BLA induced an inhibition of vHippevoked firing in mPFC neurons at short latencies.…”

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

“…Networks of fast-spiking interneurons co-expressing GABA and parvalbumine have been shown to promote synchronization via perisomatic interneuron-interneuron interaction in the hippocampus, in the entorhinal cortex, and in the neocortex (Gulyás et al, 1996;Tamás et al, 1998;Galarreta and Hestrin, 1999;Gibson et al, 1999;Bartos et al, 2002Bartos et al, , 2007Hájos et al, 2004). In addition, non-synaptic interactions through gap junctions may represent an additional mechanism for interneurons synchronization during gamma oscillations (Bartos et al, 2002;Tamás et al, 2000).…”

“…In addition, non-synaptic interactions through gap junctions may represent an additional mechanism for interneurons synchronization during gamma oscillations (Bartos et al, 2002;Tamás et al, 2000). In vitro studies have also demonstrated that fast oscillations in the gamma range occur spontaneously in isolated cortical networks during up-down states usually associated to both sleep and anesthesia (Sanchez-Vives et al, 2000;Dickson et al, 2003).…”

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

“…The IPSPs at basket cellto-basket cell synapses are approximately twice as fast as IPSPs at basket cell-to-pyramidal neuron synapses. The IPSPs rise almost instantly and decay with a time constant of B2 ms. 19,26 As such, rapid inhibition at postsynaptic GABA interneurons is instrumental to the generation of high-frequency oscillations. 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.…”