General anesthesia globally synchronizes activity selectively in layer 5 cortical pyramidal neurons

Neuron, Год журнала: 2022, Номер 110(12), С. 2024 - 2040.e10

Опубликована: Апрель 21, 2022

General anesthetics induce loss of consciousness, a global change in behavior. However, corresponding activity the context defined cortical cell types has not been identified. Here, we show that spontaneous mouse layer 5 pyramidal neurons, but no other type, becomes consistently synchronized vivo by different general anesthetics. This heightened neuronal synchrony is aperiodic, present across large distances, and absent neurons presynaptic to neurons. During transition from anesthesia, changes coincide with recovery consciousness. Activity within both apical basal dendrites synchronous, only dendrites' temporally locked somatic activity. Given major output, our results suggest brain-wide may contribute consciousness during anesthesia.

Язык: Английский

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Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

Science, Год журнала: 2023, Номер 382(6667)

Опубликована: Окт. 12, 2023

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion human neocortex marked by distinctive pyramidal neurons with extensive L1 branching, but whether interneurons are similarly diverse underexplored. Using Patch-seq recordings from neurosurgical tissue, we identified four transcriptomic subclasses mouse homologs, along distinct subtypes types unmatched in L1. Subclass subtype comparisons showed stronger differences were correlated strong morphoelectric variability dimensions variability. Accompanied greater thickness other cytoarchitecture changes, these findings suggest that has diverged evolution, reflecting the demands regulating expanded neocortical circuit.

Язык: Английский

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Video-based pooled screening yields improved far-red genetically encoded voltage indicators

Nature Methods, Год журнала: 2023, Номер 20(7), С. 1082 - 1094

Опубликована: Янв. 9, 2023

Язык: Английский

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Astrocyte-secreted neurocan controls inhibitory synapse formation and function

Neuron, Год журнала: 2024, Номер 112(10), С. 1657 - 1675.e10

Опубликована: Апрель 3, 2024

Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis remain elusive. Here, we identify neurocan as an protein. After secretion from astrocytes, is cleaved into N- C-terminal fragments. We found these fragments have distinct localizations in extracellular matrix. The fragment localizes to controls cortical function. Neurocan knockout mice lacking whole protein or only its domain reduced numbers Through super-resolution microscopy, vivo proximity labeling TurboID, astrocyte-specific rescue approaches, discovered somatostatin-positive regulates their formation. Together, our results unveil a mechanism through which astrocytes control circuit-specific mammalian brain.

Язык: Английский

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An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

Neuron, Год журнала: 2025, Номер 113(10), С. 1525 - 1547.e15

Опубликована: Май 1, 2025

Язык: Английский

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The Medial Prefrontal Cortex as a Central Hub for Mental Comorbidities Associated with Chronic Pain

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(10), С. 3440 - 3440

Опубликована: Май 13, 2020

Chronic pain patients frequently develop and suffer from mental comorbidities such as depressive mood, impaired cognition, other significant constraints of daily life, which can only insufficiently be overcome by medication. The emotional cognitive components are processed the medial prefrontal cortex, comprises anterior cingulate prelimbic, infralimbic cortex. All three subregions significantly affected chronic pain: magnetic resonance imaging has revealed gray matter loss in all these areas conditions. While cortex appears hyperactive, regions show reduced activity. receives ascending, nociceptive input, but also exerts important top-down control sensation: its projections main cortical input periaqueductal gray, is part descending inhibitory system at spinal level. A multitude neurotransmitter systems contributes to fine-tuning local circuitry, cholinergic GABAergic signaling particularly emerging relevant affective processing within Accordingly, factors distraction, positive anticipation relief placebo ameliorate affecting mPFC function, making this area a promising target region for medical well psychosocial interventions therapy.

Язык: Английский

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Mediodorsal and Ventromedial Thalamus Engage Distinct L1 Circuits in the Prefrontal Cortex

Neuron, Год журнала: 2020, Номер 109(2), С. 314 - 330.e4

Опубликована: Ноя. 13, 2020

Язык: Английский

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Pathway-, layer- and cell-type-specific thalamic input to mouse barrel cortex

eLife, Год журнала: 2019, Номер 8

Опубликована: Дек. 20, 2019

Mouse primary somatosensory barrel cortex (wS1) processes whisker sensory information, receiving input from two distinct thalamic nuclei. The first-order ventral posterior medial (VPM) nucleus most densely innervates layer 4 (L4) barrels, whereas the higher-order (medial part, POm) L1 and L5A. We optogenetically stimulated VPM or POm axons, recorded evoked excitatory postsynaptic potentials (EPSPs) in different cell-types across cortical layers wS1. found that neurons parvalbumin-expressing inhibitory received largest EPSPs, dominated by to L4 In contrast, somatostatin-expressing very little either pathway any layer. Vasoactive intestinal peptide-expressing an intermediate level of with less apparent layer-specificity. Our data help understand how wS1 neocortical microcircuits might process integrate inputs.

Язык: Английский

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Neuronal Circuits in Barrel Cortex for Whisker Sensory Perception

Physiological Reviews, Год журнала: 2020, Номер 101(1), С. 353 - 415

Опубликована: Авг. 20, 2020

The array of whiskers on the snout provides rodents with tactile sensory information relating to size, shape and texture objects in their immediate environment. Rodents can use detect stimuli, distinguish textures, locate navigate. Important aspects whisker sensation are thought result from neuronal computations somatosensory cortex (wS1). Each is individually represented somatotopic map wS1 by an anatomical unit named a ‘barrel’ (hence also called barrel cortex). This allows precise investigation processing context well-defined map. Here, we first review signaling pathways wS1, then discuss current understanding various types excitatory inhibitory neurons present within wS1. Different classes cells be defined according anatomical, electrophysiological molecular features. synaptic connectivity local microcircuits, as well long-range interactions impact neuromodulators, beginning understood. Recent technological progress has allowed cell-type-specific related activity during whisker-related behaviors. An important goal for future research obtain causal mechanistic how selected processed specific synaptically connected networks signaled downstream brain areas, thus contributing sensory-guided decision-making.

Язык: Английский

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A dopamine gradient controls access to distributed working memory in the large-scale monkey cortex

Neuron, Год журнала: 2021, Номер 109(21), С. 3500 - 3520.e13

Опубликована: Сен. 17, 2021

Dopamine is required for working memory, but how it modulates the large-scale cortex unknown. Here, we report that dopamine receptor density per neuron, measured by autoradiography, displays a macroscopic gradient along macaque cortical hierarchy. This incorporated in connectome-based model endowed with multiple neuron types. The captures an inverted U-shaped dependence of memory on and spatial patterns persistent activity observed over 90 experimental studies. Moreover, show crucial filtering out irrelevant stimuli enhancing inhibition from dendrite-targeting interneurons. Our revealed activity-silent trace can be realized facilitation inter-areal connections adjusting induces switch this internal state to distributed activity. work represents cross-level understanding molecules cell types recurrent circuit dynamics underlying core cognitive function across primate cortex.

Язык: Английский

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