Compartmentalization of GABAergic Inhibition by Dendritic Spines

Chiu, Chia-Yu; Lür, György; Morse, Thomas M.; Carnevale, Nicholas T.; Ellis‐Davies, Graham C. R.; Higley, Michael J.

doi:10.1126/science.1234274

Cited by 278 publications

(314 citation statements)

References 42 publications

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“…At the subcellular level, somatostatinexpressing (Sst) interneuron inhibitory synapses placed along the dendritic tree of a pyramidal neuron can veto synaptic integration (2) and Ca 2+ electrogenesis (3, 4) with fine spatiotemporal specificity (5). Recent studies in several neocortical areas have highlighted the participation of superficial layer 2/3 (L2/3) Sst interneurons in a canonical disinhibitory circuit supporting context-dependent sensory processing, in which the activity of L2/3 Sst interneurons is suppressed by the action of interneuron-selective vasoactive intestinal peptide-expressing (Vip) interneurons (6).…”

mentioning

confidence: 99%

Layer-specific modulation of neocortical dendritic inhibition during active wakefulness

Muñoz

Tremblay

Levenstein

et al. 2017

Science

290

297

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g-Aminobutyric acid (GABA)ergic inputs are strategically positioned to gate synaptic integration along the dendritic arbor of pyramidal cells. However, their spatiotemporal dynamics during behavior are poorly understood. Using an optical-tagging electrophysiological approach to record and label somatostatin-expressing (Sst) interneurons (GABAergic neurons specialized for dendritic inhibition), we discovered a layer-specific modulation of their activity in behaving mice. Sst interneuron subtypes, residing in different cortical layers and innervating complementary laminar domains, exhibited opposite activity changes during transitions to active wakefulness. The relative weight of vasoactive intestinal peptide-expressing (Vip) interneuron-mediated inhibition of distinct Sst interneurons and cholinergic modulation determined their in vivo activity. These results reveal a state-dependent laminar influence of Sst interneuronmediated inhibition, with implications for the compartmentalized regulation of dendritic signaling in the mammalian neocortex.

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mentioning

confidence: 99%

Layer-specific modulation of neocortical dendritic inhibition during active wakefulness

Muñoz

Tremblay

Levenstein

et al. 2017

Science

290

297

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“…We could therefore use a much lower concentration that has minimal inhibitory action on GABA A receptors and does not cause firing pattern change (18,48). In our experimental conditions, it was difficult to predict the exact final concentration of caged glutamate in vivo, but potential disinhibition by CDNI-Glu may have changed the magnitude of Ca 2+ rise in local dendritic spines and facilitated LTP in the network (49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

Emergence of functional subnetworks in layer 2/3 cortex induced by sequential spikes in vivo

Kim

Choi

et al. 2016

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

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During cortical circuit development in the mammalian brain, groups of excitatory neurons that receive similar sensory information form microcircuits. However, cellular mechanisms underlying cortical microcircuit development remain poorly understood. Here we implemented combined two-photon imaging and photolysis in vivo to monitor and manipulate neuronal activities to study the processes underlying activity-dependent circuit changes. We found that repeated triggering of spike trains in a randomly chosen group of layer 2/3 pyramidal neurons in the somatosensory cortex triggered long-term plasticity of circuits (LTPc), resulting in the increased probability that the selected neurons would fire when action potentials of individual neurons in the group were evoked. Significant firing pattern changes were observed more frequently in the selected group of neurons than in neighboring control neurons, and the induction was dependent on the time interval between spikes, N-methyl-D-aspartate (NMDA) receptor activation, and Calcium/calmodulin-dependent protein kinase II (CaMKII) activation. In addition, LTPc was associated with an increase of activity from a portion of neighboring neurons with different probabilities. Thus, our results demonstrate that the formation of functional microcircuits requires broad network changes and that its directionality is nonrandom, which may be a general feature of cortical circuit assembly in the mammalian cortex.spike timing-dependent plasticity | layer 2/3 cortex | neuronal connectivity

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“…Author Manuscript CDNI-GABA was, in fact, the first caged GABA probe reported to be effective for 2P optoneurobiology [15] , and is starting to be used for biological studies [21,22] , therefore we compared the 2P-evoked currents from this probe with G5-DEAC450-GABA. We have found that we can very reliably elicit GABAergic currents from 2P uncaging along he main apical dendrite of CA1 neurons [18] .…”

Section: Author Manuscript Author Manuscriptmentioning

confidence: 99%

“…Since our antagonism data suggests the cloaked caged GABA is essentially inert up to about 0.6 mM ( Figure 2) we bath applied the probe to brain slices at this concentration. We did this because we knew CDNI-Glu is best used at about 1 mM [21,[23][24][25][26] , and has an IC 50 = 0.24 mM for GABA-A receptor blockade [18] . Thus, we patch-clamped a CA1 neuron and monitored voltage changes produced by two-color, 2P uncaging.…”

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confidence: 99%

Cloaked Caged Compounds: Chemical Probes for Two‐Photon Optoneurobiology

et al. 2016

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Caged neurotransmitters, in combination with focused light beams, enable precise interrogation of neuronal function, even at the level of single synapses. However, most caged transmitters are, surprisingly, severe antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors. By conjugation of a large, neutral dendrimer to a caged GABA probe we introduce a "cloaking" technology that effectively reduces such antagonism to very low levels. Such cloaked caged compounds will enable the study of the signaling of the inhibitory neurotransmitter GABA in its natural state using two-photon uncaging microscopy for the first time. Graphical abstractCaged neurotransmitters are known to be quite antagonistic toward the GABA-A receptor. The conjugation of a polyester dendrimer "cloak" to the caged compound DEAC450-GABA significantly decreased its GABA-A receptor antagonism. The chemical probe was inert at concentrations required for effective two-photon photolysis on living cells. Keywords caged compounds; GABA-A receptors; optical methods; two-photon; biologically inert Correspondence to: Graham C. R. Ellis-Davies. b These authors contributed equally to this work.Supporting information for this article is given via a link at the end of the document. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptPhotochemical probes have revolutionized modern physiological studies. In an era initiated by Galvani, electrodes were the best technology available for real-time stimulation and measurement. However, the photon is more precise and versatile than the electron, so the former is not merely starting to "replace" the latter, but light, in combination with chemistry, is being used to open completely new avenues of physiological discovery [1] . To deliver their potential, the new chemical technologies require novel light sources and so pulsed lasers have been vital for time-resolved chemical biology [2] . Enabled by ultra-fast, pseudocontinuous Ti:sapphire lasers, neurobiology now routinely uses two-photon (2P) microscopy for live cell imaging in complex tissue such as acutely isolated brain slices and living animals. But, as noted by Denk, et al. in their seminal 1990 paper [3] , 2P excitation "also provides unprecedented capabilities for three-dimensional, spatially resolved photochemistry, particularly photolytic release of caged effector molecules." While initial reports of two-photon uncaging used probes [4,5] originally designed for linear actuation, more recently caged compounds designed for 2P excitation have been introduced for Glu, GABA, IP 3 , calcium, etc [6] . Some of these have even proved useful for independent 2P physiological studies [2] . It is striking that caged Glu probes, in particular, have proved very useful but caged GABA probes much less so. One reason for this must the inherent antagonism of all caged GABA compounds towards GABA-A receptors at concentrations required for effective 2P photolysis in brain tissue [7] . We have developed a new technology, which ...

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Compartmentalization of GABAergic Inhibition by Dendritic Spines

Cited by 278 publications

References 42 publications

Layer-specific modulation of neocortical dendritic inhibition during active wakefulness

Layer-specific modulation of neocortical dendritic inhibition during active wakefulness

Emergence of functional subnetworks in layer 2/3 cortex induced by sequential spikes in vivo

Cloaked Caged Compounds: Chemical Probes for Two‐Photon Optoneurobiology

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