Inhibitory Interneurons Regulate Temporal Precision and Correlations in Cortical Circuits

Abstract

GABAergic interneurons, which are highly diverse, have long been thought to contribute to the timing of neural activity as well as to the generation and shaping of brain rhythms. GABAergic activity is crucial not only for entrainment of oscillatory activity across a neural population, but also for precise regulation of the timing of action potentials and the suppression of slow-timescale correlations. The diversity of inhibition provides the potential for flexible regulation of patterned activity, but also poses a challenge to identifying the elements of excitatory-inhibitory interactions underlying network engagement. This review highlights the key roles of inhibitory interneurons in spike correlations and brain rhythms, describes several scales on which GABAergic inhibition regulates timing in neural networks, and identifies potential consequences of inhibitory dysfunction.

Keywords: VIP; interneuron; oscillation; parvalbumin; somatostatin; synchrony.

Figure 1.. Diversity in the temporal synaptic properties of GABAergic interneurons.

Inhibitory interneurons exhibit distinct temporal dynamics of both their synaptic inputs and outputs. A. Excitatory synaptic inputs to PV interneurons recruit these cells quickly but rapidly show synaptic depression. In turn, the inhibitory synapses from PV interneurons to excitatory pyramidal neurons (PN) likewise show synaptic depression. B. In contrast, excitatory inputs to SST interneurons require repeated activation and exhibit synaptic facilitation, resulting in delayed recruitment of spiking activity. However, SST synapses onto PNs show little synaptic depression. C. The short-term plasticity of excitatory synapses onto VIP interneurons and from VIP interneurons to PNs remain largely unexplored.

Figure 2.. Reciprocal connectivity between interneuron populations.

Three major subtypes of neocortical inhibitory interneurons are interconnected in a repeated motif of reciprocal inhibition. Relative strength of interactions is shown by the sizes of the circles denoting synaptic connectivity, largely based on current knowledge from in vitro electrophysiology in superficial layers of primary sensory cortex. These reciprocal interactions likely play a key role in the regulation of neural timing by inhibition. PV interneurons are unique in having both strong reciprocal synaptic connectivity with other interneurons and also robustly inhibiting other PV interneurons via chemical and electrical synapses. Strong PV-PV and PV-PN interactions promote fast oscillations and precise spike timing.

Figure 3.. Distinct interneuron populations promote different cortical rhythms.

Recent work has highlighted the respective roles of PV and SST interneurons in shaping oscillations in cortical networks. A. Reciprocal interactions between PV interneurons and PNs generate ~40Hz gamma oscillations as a result of fast firing by the PV cells and strong reciprocal connections. B. SST interneurons likewise exhibit reciprocal connectivity with PNs, and their activity may underlie the generation of rhythmic activity at slower frequencies. They may generate activity at 5–30Hz and are necessary for sensory-evoked cortical beta/low gamma oscillations in the visual cortex. C. One intriguing possibility is that the simultaneous interactions of these two circuit motifs allows for the flexible selection of neural timing in low or high frequency bands as demand changes. Such interactions may be mediated by the relative occurrence of bottom-up or top-down inputs that recruit PV and SST interneuron spiking in the active circuit in vivo.