Trends in Neurosciences

Trends in Neurosciences

Volume 41, Issue 10, October 2018, Pages 689-700
Journal home page for Trends in Neurosciences

Review
Special Issue: Time in the Brain
Inhibitory Interneurons Regulate Temporal Precision and Correlations in Cortical Circuits

https://doi.org/10.1016/j.tins.2018.07.015Get rights and content

Highlights

The intrinsic and synaptic properties of GABAergic interneurons shape their impact on temporal patterns in the local circuit.

Synaptic inhibition enhances short-timescale correlations in spiking, such as spike synchrony, but suppresses long-timescale correlations, such as noise correlations.

Different inhibitory interneuron populations, including parvalbumin and somatostatin cells, may engage distinct rhythms in the cortex.

The emergence of circuit timing characteristics is shaped on the developmental timescale by multiple interneuron populations.

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.

Section snippets

Inhibitory Effects on Multiple Timescales

Inhibitory regulation of neural activity occurs on several distinct but interacting timescales. GABAergic influences on local circuits are constrained by the intrinsic properties of interneurons, which vary across diverse populations. The postsynaptic impact of inhibitory transmission is further sculpted by short- and long-term synaptic dynamics. In particular, synaptic depression and facilitation can rapidly modulate both the excitatory synaptic recruitment of interneurons and their

Diverse Sources of GABAergic Inhibition

One major challenge to identifying the function of GABAergic inhibition is the diversity of inhibitory interneurons, which can be subdivided into distinct classes with different physiology, synaptic targets, and molecular markers 1, 2. Recent work has focused on three major classes: (i) fast-spiking basket cells that target the cell bodies of excitatory neurons and coexpress the calcium-binding protein parvalbumin (PV), (ii) low-threshold spiking cells that target the distal dendrites of

Excitation–Inhibition Interactions and Spike Timing

Locally recurrent networks in the hippocampus and neocortex show a typical pattern of synaptic recruitment, with feed-forward excitatory input (E) preceding locally recruited inhibition (I). This temporal pattern of E–I interactions allows a ‘window of opportunity’ in which spikes may be evoked by excitation before further responses are quenched by the following inhibition [8]. The influence of synaptic inhibition recruited by feed-forward inputs into a network temporally restricts

Inhibitory Control of Brain Rhythms

Inhibition plays key roles in the generation of oscillations in the neocortex and hippocampus, as well as in other brain areas. Gamma-band activity (30–80 Hz) relies on fast inhibitory synaptic transmission by GABAergic interneurons [47]. Optogenetic activation of fast-spiking basket interneurons 39, 48 or pyramidal neurons [40] in sensory cortex evokes robust gamma oscillations that depend on both GABAergic and glutamatergic synaptic transmission. Spontaneous gamma oscillations in vivo are

Inhibitory Regulation of Correlated Spiking

In addition to regulating spike timing, synaptic inhibition promotes synchrony of spiking among interneurons and between groups of excitatory neurons. Synchrony among PV interneurons is enhanced by extensive synaptic interconnectivity [86] and gap junctions [52]. Spike synchrony among interneurons can be observed in extracellular recordings of neocortical fast-spiking putative PV interneurons in vivo [29], and appears to promote millisecond-timescale synchrony in the hippocampus both between

Developmental Role of Inhibition in the Timing of Circuit Activity

The overall temporal profile of neural activity is shaped by early developmental events. In rodents, GABA is depolarizing during the first postnatal week of life, and synaptic connectivity has not yet matured, giving rise to large bouts of activity coordinated by inhibitory interneurons [106]. After the developmental shift to hyperpolarizing GABA, mediated by a change in expression of the Cl− extruder KCC2, synaptic inhibition begins to shape network activity in a more temporally constrained

Disruption of Inhibition and Abnormal Timing

Dysregulation of inhibition is linked to altered timing of neural activity on several timescales. Profound disruption of GABAergic synaptic transmission or loss of major interneuron populations have long been thought to contribute to the emergence of hypercorrelated activity and seizures 114, 115, 116. However, the specific contributions of different interneuron populations to seizure initiation and resulting pathophysiology remain unclear. Developmental loss of interneuron activity reduces

Concluding Remarks and Future Perspectives

Inhibition plays varied roles in regulating neural timing on several scales. Inhibitory cell types vary in their intrinsic and synaptic properties, and inhibitory interneuron properties, even within the same cell type, can differ depending on developmental stage, neuromodulation, and brain region. Excitatory synaptic recruitment of GABAergic interneuron activity is modulated by cell type-specific short-term synaptic plasticity, as is the impact of synaptic inhibition onto excitatory neurons. In

Acknowledgements

This work was supported by National Institutes of Health (NIH) grants R01 MH102365, R01 EY022951, and R01 MH113852, a Smith Family Award for Excellence in Biomedical Research, a Klingenstein Fellowship Award, an Alfred P. Sloan Fellowship, a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award, a McKnight Fellowship, and a grant from the Ludwig Family Foundation to J.A.C. The author thanks Drs M.J. Higley and B. Doiron for insightful discussions.

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