From circuit motifs to computations: mapping the behavioral repertoire of cortical interneurons

Hangya, Balázs; Pi, Hyun Jae; Kvitsiani, Duda; Ranade, Sachin; Kepecs, Ádám

doi:10.1016/j.conb.2014.01.007

Cited by 83 publications

(78 citation statements)

References 86 publications

(99 reference statements)

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“…20). SOM + cells, on the other hand, may function as integrators of top-down inputs that modulate visual processing (11). Our finding that OD plasticity extends into adulthood is consistent with a reduction in inhibition received by pyramidal neurons, and with a recent report that OD plasticity after PV-specific MeCP2 deletion can be initiated by enhancing inhibition via intracerebral infusion of the GABA A receptor agonist diazepam (81).…”

Section: Discussionsupporting

confidence: 91%

“…Anatomically diverse inhibitory interneuron subtypes with distinct physiological signatures influence different aspects of neocortical function and behavior (11,12). Soma-targeting parvalbumin-expressing (PV + ) and dendritetargeting somatostatin-expressing (SOM + ) interneurons are the two major nonoverlapping populations of interneurons in mice that target cortical pyramidal neurons (13).…”

mentioning

confidence: 99%

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Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Banerjee

Rikhye

Breton-Provencher

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

154

202

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Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging. and increases KCC2 expression to normalize the KCC2/NKCC1 ratio. Thus, loss of MeCP2 in the brain alters both excitation and inhibition in brain circuits via multiple mechanisms. Loss of MeCP2 from a specific interneuron subtype contributes crucially to the cell-specific and circuit-wide deficits of RTT. The joint restoration of inhibition and excitation in cortical circuits is pivotal for functionally correcting the disorder.MeCP2 | E/I balance | parvalbumin neurons | IGF1 | chloride transporters S ynaptic excitation (E) and inhibition (I), along with the neuronal balance of excitation and inhibition (E/I), is key to the function of brain circuits, and is often disrupted in neurodevelopmental disorders, including autism spectrum disorders (ASDs) (1-3). Rett syndrome (RTT) is a severe neurodevelopmental and adult disorder that arises from sporadic loss-of-function mutations in the X-linked (Xq28) methyl-CpG binding protein 2 gene (Mecp2) encoding the protein MeCP2 (4-7). MeCP2 is a critical regulator of brain development and adult neural function (8), and arrested brain maturation due to synaptic dysfunction is one of the hallmarks of RTT (3). However, the effects of MeCP2 on excitatory and inhibitory synaptic mechanisms in vivo, and on neuronal and circuit function underlying RTT pathophysiology, are unknown.MeCP2 is ubiquitously expressed in multiple cell types and subregions of the brain (4, 6, 9), including inhibitory interneurons, and has cell-autonomous as well as non-cell-autonomous effects (10); thus, it has been particularly challenging to identify its role in cell-specific brain circuits. Anatomically diverse inhibitory interneuron subtypes with distinct physiological signatures influence different aspects of neocortical function and behavior (11,12). Soma-targeting parvalbumin-expressing (PV + ) and dendritetargeting somatostatin-expressing (SOM + ) interneurons are the two major nonoverlapping populations of interneurons in mice that target cortical pyramidal neurons (13). Inhibition by PV + and SOM + neurons powerfully influences neuronal responses and circuit computations in visual cortex (14-17). Deletion of MeCP2 from all forebrain GABAergic interneurons recapitulates key aspects of RTT (18), demonstrating that altered inhibitory function is an important facet of RTT pathophysiology. Indeed, a major phenotype of MeCP2 reduction in individuals with RTT and in mouse models is ...

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Banerjee

Rikhye

Breton-Provencher

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

154

202

View full text Add to dashboard Cite

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“…A growing body of evidence suggests that the interactions of distinct types of neuron within highly organized neuronal circuits are critical for any higher brain function [47][48][49] , and that circuit dysregulation contributes to psychiatric conditions, among which fear …”

Section: Discussionmentioning

confidence: 99%

Midbrain circuits for defensive behaviour

Tovote

Esposito

Botta

et al. 2016

Nature

594

627

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Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.

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“…8D). These cells may regulate the excitatory-inhibitory balance at different timescales (frequency bands) and, together with B1 and B4 cells, are expected to be directly implicated in information transfer (Constantinidis et al, 2002;Hangya et al, 2014;Kepecs and Fishell, 2014), gating the firing of pyramidal cells at distinct rhythms, specifically at theta versus beta bands (Figs. 8D, 11B).…”

Section: Division Of Labor In the Primate Prefrontal Microcircuit In mentioning

confidence: 99%

Mapping of Functionally Characterized Cell Classes onto Canonical Circuit Operations in Primate Prefrontal Cortex

et al. 2015

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Microcircuits are composed of multiple cell classes that likely serve unique circuit operations. But how cell classes map onto circuit functions is largely unknown, particularly for primate prefrontal cortex during actual goal-directed behavior. One difficulty in this quest is to reliably distinguish cell classes in extracellular recordings of action potentials. Here we surmount this issue and report that spike shape and neural firing variability provide reliable markers to segregate seven functional classes of prefrontal cells in macaques engaged in an attention task. We delineate an unbiased clustering protocol that identifies four broad spiking (BS) putative pyramidal cell classes and three narrow spiking (NS) putative inhibitory cell classes dissociated by how sparse, bursty, or regular they fire. We speculate that these functional classes map onto canonical circuit functions. First, two BS classes show sparse, bursty firing, and phase synchronize their spiking to 3-7 Hz (theta) and 12-20 Hz (beta) frequency bands of the local field potential (LFP). These properties make cells flexibly responsive to network activation at varying frequencies. Second, one NS and two BS cell classes show regular firing and higher rate with only marginal synchronization preference. These properties are akin to setting tonically the excitation and inhibition balance. Finally, two NS classes fired irregularly and synchronized to either theta or beta LFP fluctuations, tuning them potentially to frequency-specific subnetworks. These results suggest that a limited set of functional cell classes emerges in macaque prefrontal cortex (PFC) during attentional engagement to not only represent information, but to subserve basic circuit operations.

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From circuit motifs to computations: mapping the behavioral repertoire of cortical interneurons

Cited by 83 publications

References 86 publications

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Midbrain circuits for defensive behaviour

Mapping of Functionally Characterized Cell Classes onto Canonical Circuit Operations in Primate Prefrontal Cortex

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