Cortical inhibitory interneurons control sensory processing

doi:10.1016/j.conb.2017.08.018

Current Opinion in Neurobiology

Volume 46, October 2017, Pages 200-207

https://doi.org/10.1016/j.conb.2017.08.018 Get rights and content

Highlights

•
Distinct cortical interneurons control sensory perception.
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Modulating cortical inhibition sharpens or broadens stimulus tuning in sensory cortex.
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Locomotion increases activity in visual, and suppresses activity in auditory cortex.
•
Future studies to combine targeted perturbation of activity with recurrent models.

Inhibitory and excitatory neurons form intricate interconnected circuits in the mammalian sensory cortex. Whereas the function of excitatory neurons is largely to integrate and transmit information within and between brain areas, inhibitory neurons are thought to shape the way excitatory neurons integrate information, and they exhibit context-specific and behavior-specific responses. Over the last few years, work across sensory modalities has begun unraveling the function of distinct types of cortical inhibitory neurons in sensory processing, identifying their contribution to controlling stimulus selectivity of excitatory neurons and modulating information processing based on the behavioral state of the subject. Here, we review results from recent studies and discuss the implications for the contribution of inhibition to cortical circuit activity and information processing.

Section snippets

Role of interneurons in sensory processing

A fundamental quest of sensory neuroscience is to link a specific function in sensory processing to an identified circuit within the sensory pathway. One of the most striking aspects of neuronal morphology in the sensory cortex is the astonishing diversity of inhibitory interneurons. This diversity is thought to underlie the brain's ability to process and respond to complex and varied everyday sensory environments. By exhibiting differential patterns in their connectivity to excitatory and

Role of interneurons in stimulus selectivity

Behavioral discrimination of sensory stimuli is thought to rely on sensory tuning, or selectivity, of neuronal populations. Neurons in the sensory cortex typically exhibit selectivity for specific aspects of sensory stimuli — for example, neurons in the auditory cortex exhibit frequency tuning with elevated responses to tones of particular frequency [27, 28, 29]. This stimulus selectivity arises through the combination of excitatory and inhibitory inputs to neurons (Figure 1a), which themselves

Role of interneurons in behavioral state modulation

Inhibitory interneurons are also involved in modulation of sensory responses by the behavioral state of the subject across sensory modalities. A striking example of this modulation is provided by locomotion. Locomotion has been predicted to affect sensory processing, for example by activating visual processing pathways dedicated to processing of rapidly changing stimuli; or by suppressing activity that would be due to locomotion artifact.

In visual cortex, locomotion was found to increase

Future goals for investigation of the function of inhibition in sensory processing and perception

The development of optogenetic tools led to considerable progress in understanding the role of inhibitory interneurons in sensory processing over a relatively brief period of time. However, application of optogenetics has thus far been generally coarse, targeting a broad class of interneurons over a relatively large area. Future studies need to target specific subclasses of interneurons, which will become amenable to specific targeting as genetic understanding of the classes and subclasses of

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

This work was supported by National Institutes of Health (Grant numbers NIH R03DC013660, NIH R01DC014700, NIH R01DC015527), Klingenstein Award in Neuroscience, Human Frontier in Science Foundation Young Investigator Award and the Pennsylvania Lions Club Hearing Research Fellowship to MGN. MNG is the recipient of the Burroughs Wellcome Award at the Scientific Interface. JFB is supported by National Institutes of Health (Grant number NIH NIMH T32MH017168).

References (73)

Y. Kawaguchi
Neostriatal cell subtypes and their functional roles
Neurosci Res
(1997)
R. Tremblay et al.
GABAergic interneurons in the neocortex: from cellular properties to circuits
Neuron
(2016)
R.G. Natan et al.
Complementary control of sensory adaptation by two types of cortical interneurons
eLife
(2015)
M. Aizenberg et al.
Bidirectional regulation of innate and learned behaviors that rely on frequency discrimination by cortical inhibitory neurons
PLoS Biol
(2015)
A.K. Moore et al.
Parvalbumin-expressing inhibitory interneurons in auditory cortex are well-tuned for frequency
J Neurosci
(2013)
A.M. Oswald et al.
Synaptic mechanisms underlying auditory processing
Curr Opin Neurobiol
(2006)
G.K. Wu et al.
Lateral sharpening of cortical frequency tuning by approximately balanced inhibition
Neuron
(2008)
S.H. Lee et al.
Interneuron subtypes and orientation tuning
Nature
(2014)
B.V. Atallah et al.
Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli
Neuron
(2012)
H. Adesnik et al.
A neural circuit for spatial summation in visual cortex
Nature
(2012)

S. El-Boustani et al.

Response-dependent dynamics of cell-specific inhibition in cortical networks in vivo

Nat Commun

(2014)

A. Nelson et al.

The basal forebrain and motor cortex provide convergent yet distinct movement-related inputs to the auditory cortex

Neuron

(2016)

J. Jackson et al.

VIP + interneurons control neocortical activity across brain states

J Neurophysiol

(2016)

A. Nelson et al.

A circuit for motor cortical modulation of auditory cortical activity

J Neurosci

(2013)

E. Eggermann et al.

Cholinergic signals in mouse barrel cortex during active whisker sensing

Cell Rep

(2014)

L.J. Gentet et al.

Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex

Nat Neurosci

(2012)

J.C. Cottam et al.

Target-specific effects of somatostatin-expressing interneurons on neocortical visual processing

J Neurosci

(2013)

J.H. Lee et al.

A computational analysis of the function of three inhibitory cell types in contextual visual processing

Front Comput Neurosci

(2017)

J. Dimidschstein et al.

A viral strategy for targeting and manipulating interneurons across vertebrate species

Nat Neurosci

(2016)

J. DeFelipe et al.

New insights into the classification and nomenclature of cortical GABAergic interneurons

Nat Rev Neurosci

(2013)

A. Kepecs et al.

Interneuron cell types are fit to function

Nature

(2014)

J. Urban-Ciecko et al.

Somatostatin-expressing neurons in cortical networks

Nat Rev Neurosci

(2016)

B. Rudy et al.

Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons

Dev Neurobiol

(2011)

Y. Wang et al.

Anatomical, physiological, molecular and circuit properties of nest basket cells in the developing somatosensory cortex

Cereb Cortex

(2002)

A.M. Packer et al.

Dense, unspecific connectivity of neocortical parvalbumin-positive interneurons: a canonical microcircuit for inhibition?

J Neurosci

(2011)

Y. Wang et al.

Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat

J Physiol

(2004)

E.T. Vu et al.

Evidence for a computational distinction between proximal and distal neuronal inhibition

Science

(1992)

F. Walker et al.

Parvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells

Nat Commun

(2016)

S. Lee et al.

A disinhibitory circuit mediates motor integration in the somatosensory cortex

Nat Neurosci

(2013)

C.K. Pfeffer et al.

Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons

Nat Neurosci

(2013)

H.J. Pi et al.

Cortical interneurons that specialize in disinhibitory control

Nature

(2013)

X. Jiang et al.

Principles of connectivity among morphologically defined cell types in adult neocortex

Science

(2015)

E.S. Boyden et al.

Millisecond-timescale, genetically targeted optical control of neural activity

Nat Neurosci

(2005)

V.S. Sohal et al.

Parvalbumin neurons and gamma rhythms enhance cortical circuit performance

Nature

(2009)

K. Deisseroth

Optogenetics

Nat Methods

(2011)

S.H. Lee et al.

Activation of specific interneurons improves V1 feature selectivity and visual perception

Nature

(2012)

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In the primary visual cortex (V1) inhibitory interneurons form a local circuit with excitatory pyramidal cells to produce distinct receptive field properties. Parvalbumin-expressing interneurons (Pvalb+) are the most common subclass of V1 interneurons, and studies of orientation tuning indicate they shape pyramidal stimulus selectivity by balancing excitation with inhibition relative to the spike threshold. The iceberg effect, where subthreshold responses have broader tuning than spiking responses, predicts that other receptive field properties besides orientation tuning should also be affected by this balance mediated by Pvalb+ cells. To test this, we measured receptive field size and visual latency of pyramidal cells while Pvalb+ activity was optogenetically increased. We found that amplifying Pvalb+ input to pyramidal cells significantly increased their latency and decreased their receptive field size, which corroborates the proposed role of Pvalb+ interneurons in sculpting pyramidal tuning by controlling cortical gain.
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Citation Excerpt :
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The auditory system provides us with extremely rich and precise information about the outside world. Once a sound reaches our ears, the acoustic information it carries travels from the cochlea all the way to the auditory cortex, where its complexity and nuances are integrated. In the auditory cortex, functional circuits are formed by subpopulations of intermingled excitatory and inhibitory cells. In this review, we discuss recent evidence of the specific contributions of inhibitory neurons in sound processing and integration. We first examine intrinsic properties of three main classes of inhibitory interneurons in the auditory cortex. Then, we describe how inhibition shapes the responsiveness of the auditory cortex to sound. Finally, we discuss how inhibitory interneurons contribute to the sensation and perception of sounds. Altogether, this review points out the crucial role of cortical inhibitory interneurons in integrating information about the context, history, or meaning of a sound. It also highlights open questions to be addressed for increasing our understanding of the staggering complexity leading to the subtlest auditory perception.
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Disruptions to the central excitatory-inhibitory (E/I) balance are thought to be related to aging and underlie a host of neural pathologies, including Alzheimer's disease. Aging may induce an increase in excitatory signaling, causing an E/I imbalance, which has been linked to shorter lifespans in mice, flies, and worms. In humans, extended longevity correlates to greater repression of genes involved in excitatory neurotransmission. The repressor element-1 silencing transcription factor (REST) is a master regulator in neural cells and is believed to be upregulated with senescent stimuli, whereupon it counters hyperexcitability, insulin/insulin-like signaling pathway activity, oxidative stress, and neurodegeneration. This review examines the putative mechanisms that distort the E/I balance with aging and neurodegeneration, and the putative roles of REST in maintaining neuronal homeostasis.
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Sensory responses typically vary depending on the recent history of sensory experience. This is essential for processes, including adaptation, efficient coding, and change detection. In the auditory cortex (AC), the short-term history dependence of sound-evoked (onset) responses has been well characterized. Yet many AC neurons also respond to sound terminations, and little is known about the history dependence of these “offset” responses, whether the short-term dynamics of onset and offset responses are correlated, or how these properties are distributed among cell types. Here we presented awake male and female mice with repeating noise burst stimuli while recording single-unit activity from primary AC. We identified parvalbumin and somatostatin interneurons through optotagging, and also separated narrow-spiking from broad-spiking units. We found that offset responses are typically less depressive than onset responses, and this result was robust to a variety of stimulus parameters, controls, measurement types, and selection criteria. Whether a cell's onset response facilitates or depresses does not predict whether its offset response facilitates or depresses. Cell types differed in the dynamics of their onset responses, and in the prevalence, but not the dynamics, of their offset responses. Finally, we clustered cells according to spiking responses and found that response clusters were associated with cell type. Each cluster contained cells of several types, but even within a cluster, cells often showed cell type-specific response dynamics. We conclude that onset and offset responses are differentially influenced by recent sound history, and discuss the implications of this for the encoding of ongoing sound stimuli.
SIGNIFICANCE STATEMENT Sensory neuron responses depend on stimulus history. This history dependence is crucial for sensory processing, is precisely controlled at individual synapses and circuits, and is adaptive to the specific requirements of different sensory systems. In the auditory cortex, neurons respond to sound cessation as well as to sound itself, but how history dependence is used along this separate, “offset” information stream is unknown. We show that offset responses are more facilitatory than sound responses, even in neurons where sound responses depress. In contrast to sound onset responses, offset responses are absent in many cells, are relatively homogeneous, and show no cell type-specific differences in history dependence. Offset responses thus show unique response dynamics, suggesting their unique functions.

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View full text

Cortical inhibitory interneurons control sensory processing

Highlights

Section snippets

Role of interneurons in sensory processing

Role of interneurons in stimulus selectivity

Role of interneurons in behavioral state modulation

Future goals for investigation of the function of inhibition in sensory processing and perception

Conflict of interest statement

References and recommended reading

Acknowledgements

Neurosci Res

Neuron

eLife

PLoS Biol

J Neurosci

Curr Opin Neurobiol

Neuron

Nature

Neuron

Nature

Nat Commun

Neuron

J Neurophysiol

J Neurosci

Cell Rep

Nat Neurosci

J Neurosci

Front Comput Neurosci

Nat Neurosci

New insights into the classification and nomenclature of cortical GABAergic interneurons

Nat Rev Neurosci

Interneuron cell types are fit to function

Nature

Somatostatin-expressing neurons in cortical networks

Nat Rev Neurosci

Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons

Dev Neurobiol

Anatomical, physiological, molecular and circuit properties of nest basket cells in the developing somatosensory cortex

Cereb Cortex

Dense, unspecific connectivity of neocortical parvalbumin-positive interneurons: a canonical microcircuit for inhibition?

J Neurosci

Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat

J Physiol

Evidence for a computational distinction between proximal and distal neuronal inhibition

Science

Parvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells

Nat Commun

A disinhibitory circuit mediates motor integration in the somatosensory cortex

Nat Neurosci

Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons

Nat Neurosci

Cortical interneurons that specialize in disinhibitory control

Nature

Principles of connectivity among morphologically defined cell types in adult neocortex

Science

Millisecond-timescale, genetically targeted optical control of neural activity

Nat Neurosci

Parvalbumin neurons and gamma rhythms enhance cortical circuit performance

Nature

Optogenetics

Nat Methods

Activation of specific interneurons improves V1 feature selectivity and visual perception

Nature