scholarly journals Neocortical layer 4 in adult mouse differs in major cell types and circuit organization between primary sensory areas

2018 ◽  
Author(s):  
F. Scala ◽  
D. Kobak ◽  
S. Shan ◽  
Y. Bernaerts ◽  
S. Laturnus ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Building Blocks ◽  
Cell Types ◽  
Excitatory Input ◽  
Excitatory Neurons ◽  
Layer 4 ◽  
Cell Type Specific ◽  
Fast Spiking ◽  
Mouse Visual Cortex ◽  
Whole Cell Recordings

AbstractLayer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM+) non-fast-spiking neurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM+ neurons were non-Martinotti. These morphologically distinct SOM+ interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell-type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are optionally used across the cortex as building blocks to assemble cortical circuits.

scholarly journals Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Federico Scala ◽  
Dmitry Kobak ◽  
Shen Shan ◽  
Yves Bernaerts ◽  
Sophie Laturnus ◽  
...  
Keyword(s):  
Building Blocks ◽  
Cell Types ◽  
Excitatory Input ◽  
Cortical Circuits ◽  
Excitatory Neurons ◽  
Layer 4 ◽  
Cell Type Specific ◽  
Fast Spiking ◽  
Mouse Visual Cortex ◽  
Whole Cell Recordings

Abstract Layer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM+) non-fast-spiking interneurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM+ interneurons were non-Martinotti. These morphologically distinct SOM+ interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are used across the cortex as building blocks to assemble cortical circuits.

scholarly journals Cell type–specific expression of SEPT3-homology subgroup members controls the subunit number of heteromeric septin complexes

2014 ◽  
Vol 25 (10) ◽  
pp. 1594-1607 ◽  
Author(s):  
Mikael E. Sellin ◽  
Sonja Stenmark ◽  
Martin Gullberg
Keyword(s):  
Animal Cell ◽  
Building Blocks ◽  
Cell Types ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cell Type Specific Expression ◽  
A Subunit ◽  
Cell Type Specific ◽  
Genetically Manipulated ◽  
Differential Properties

Septins are filament-forming proteins important for organizing the cortex of animal and fungal cells. In mammals, 13 septin paralogues were recently shown to assemble into core heterohexamer and heterooctamer complexes, which serve as building blocks for apolar filamentous structures that differ among cell types. To determine how tissue-specific septin paralogue expression may shape core heteromer repertoires and thereby modulate properties of septin filaments, we devised protocols to analyze native septin heteromers with distinct numbers of subunits. Our evidence based on genetically manipulated human cells supports and extends recent concepts of homology subgroup–restricted assembly into distinct categories of apolar heterohexamers and heterooctamers. We also identify a category of tetramers that have a subunit composition equivalent to an octameric building block. These atypical tetramers are prevalent in lymphocytes and neural tissues, in which octamers are abundant but hexamers are rare. Our results can be explained by tissue-specific expression of SEPT3 subgroup members: SEPT3, SEPT9, and SEPT12. These serve as cognate subunits in either heterooctamers or atypical tetramers but exhibit different preferences in various tissues. The identified tissue-specific repertoires of septin heteromers provide insights into how higher-order septin structures with differential properties and stabilities may form in diverse animal cell types.

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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
B Semihcan Sermet ◽  
Pavel Truschow ◽  
Michael Feyerabend ◽  
Johannes M Mayrhofer ◽  
Tess B Oram ◽  
...  
Keyword(s):  
Thalamic Nucleus ◽  
Barrel Cortex ◽  
Sensory Information ◽  
Cell Types ◽  
Excitatory Input ◽  
Higher Order ◽  
Inhibitory Neurons ◽  
Thalamic Nuclei ◽  
Thalamic Input ◽  
Layer 4

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

scholarly journals Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex

2017 ◽  
Author(s):  
Wuqiang Guan ◽  
Jun-Wei Cao ◽  
Lin-Yun Liu ◽  
Zhi-Hao Zhao ◽  
Yinghui Fu ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Synaptic Transmission ◽  
Animal Development ◽  
Quantal Size ◽  
Excitatory Neurons ◽  
Artificial Opening ◽  
Eye Opening ◽  
Fast Spiking ◽  
And Function ◽  
Mouse Visual Cortex

AbstractEye opening, a natural and timed event during animal development, influences cortical circuit assembly and maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here we show that coinciding with eye opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (SST-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to excitatory neurons significantly increases during eye opening. More importantly, these developmental changes can be prevented by dark rearing or binocular lid suture, and reproduced by artificial opening of sutured lids. Mechanistically, this differential maturation of synaptic transmission is accompanied by a significant change in the postsynaptic quantal size. Together, our study reveals a differential regulation in GABAergic circuits in the cortex driven by eye opening likely crucial for cortical maturation and function.

scholarly journals Sharp tuning of head direction by somatosensory fast-spiking interneurons

2020 ◽  
Author(s):  
Xiaoyang Long ◽  
Calvin K. Young ◽  
Sheng-Jia Zhang
Keyword(s):  
Cell Types ◽  
Inhibitory Neurons ◽  
Local Network ◽  
Head Direction ◽  
Layer 4 ◽  
Fast Spiking ◽  
External Stimuli ◽  
The Brain ◽  
Spatial Cell

AbstractHead direction (HD) information is intricately linked to spatial navigation and cognition. We recently reported the co-existence of all currently recognized spatial cell types can be found in the hindlimb primary somatosensory cortex (S1HL). In this study, we carried out an in-depth characterization of HD cells in S1HL. We show fast-spiking (FS), putative inhibitory neurons are over-represented in and sharply tuned to HD compared to regular-spiking (RS), putative excitatory neurons. These FS HD cells are non-conjunctive, rarely theta modulated, not locally connected and are enriched in layer 4/5a. Their co-existence with RS HD cells and angular head velocity (AHV) cells in a layer-specific fashion through the S1HL presents a previously unreported organization of spatial circuits. These findings challenge the notion that FS, putative inhibitory interneurons are weakly tuned to external stimuli in general and present a novel local network configuration not reported in other parts of the brain.

scholarly journals A unique role for DNA (hydroxy)methylation in epigenetic regulation of human inhibitory neurons

2018 ◽  
Vol 4 (9) ◽  
pp. eaau6190 ◽  
Author(s):  
Alexey Kozlenkov ◽  
Junhao Li ◽  
Pasha Apontes ◽  
Yasmin L. Hurd ◽  
William M. Byne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Brain Cell ◽  
Inhibitory Neurons ◽  
Brain Diseases ◽  
Unique Role ◽  
Neuropsychiatric Diseases ◽  
Excitatory Neurons ◽  
Cell Type Specific

Brain function depends on interaction of diverse cell types whose gene expression and identity are defined, in part, by epigenetic mechanisms. Neuronal DNA contains two major epigenetic modifications, methylcytosine (mC) and hydroxymethylcytosine (hmC), yet their cell type–specific landscapes and relationship with gene expression are poorly understood. We report high-resolution (h)mC analyses, together with transcriptome and histone modification profiling, in three major cell types in human prefrontal cortex: glutamatergic excitatory neurons, medial ganglionic eminence–derived γ-aminobutyric acid (GABA)ergic inhibitory neurons, and oligodendrocytes. We detected a unique association between hmC and gene expression in inhibitory neurons that differed significantly from the pattern in excitatory neurons and oligodendrocytes. We also found that risk loci associated with neuropsychiatric diseases were enriched near regions of reduced hmC in excitatory neurons and reduced mC in inhibitory neurons. Our findings indicate differential roles for mC and hmC in regulation of gene expression in different brain cell types, with implications for the etiology of human brain diseases.

Sensory Learning Differentially Affects GABAergic Tonic Currents in Excitatory Neurons and Fast Spiking Interneurons in Layer 4 of Mouse Barrel Cortex

2010 ◽  
Vol 104 (2) ◽  
pp. 746-754 ◽  
Author(s):  
Joanna Urban-Ciecko ◽  
Małgorzata Kossut ◽  
Jerzy W. Mozrzymas
Keyword(s):  
Barrel Cortex ◽  
Spiking Neurons ◽  
Gaba Uptake ◽  
Cortical Representation ◽  
Regulation Of Expression ◽  
Sensory Learning ◽  
Excitatory Neurons ◽  
Layer 4 ◽  
Fast Spiking ◽  
The Impact

Pairing tactile stimulation of whiskers with a tail shock is known to result in expansion of cortical representation of stimulated vibrissae and in the increase in synaptic GABAergic transmission. However, the impact of such sensory learning in classical conditioning paradigm on GABAergic tonic currents has not been addressed. To this end, we performed whole cell patch-clamp slice recordings of tonic currents from neurons (excitatory regular spiking, regular spiking nonpyramidal, and fast spiking interneurons) of layer 4 of the barrel cortex from naive and trained mice. Interestingly, endogenous tonic GABAergic currents measured from the excitatory neurons in the cortical representation of “trained” vibrissae were larger than in the “naïve” or pseudoconditioned ones. On the contrary, sensory learning markedly reduced tonic currents in the fast spiking interneurons but not in regular spiking nonpyramidal neurons. Changes of tonic currents were accompanied by changes in the input resistances—decrease in regular spiking and increase in fast spiking neurons, respectively. Applications of nipecotic acid, a GABA uptake blocker, enhanced the tonic currents, but the impact of the sensory learning remained qualitatively the same as in the case of the tonic currents. Similar to endogenous tonic currents, sensory learning enhanced currents induced by THIP (superagonist for δ subunit–containing GABAA receptors) in regular spiking neurons, whereas the opposite was observed for the fast spiking interneurons. In conclusion, our data show that the sensory learning strongly affects the GABAergic tonic currents in a cell-specific manner and suggest that the underlying mechanism involves regulation of expression of δ subunit–containing GABAA receptors.

scholarly journals Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lucas T Gray ◽  
Zizhen Yao ◽  
Thuc Nghi Nguyen ◽  
Tae Kyung Kim ◽  
Hongkui Zeng ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Regulatory Networks ◽  
High Throughput Sequencing ◽  
Adult Mouse ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Mouse Cortex ◽  
Mouse Visual Cortex

Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including Cux1/2, Foxp2, Nfia, Pou3f2, and Rorb. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex.

scholarly journals Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn

2019 ◽  
Author(s):  
Kwan Yeop Lee ◽  
Stéphanie Ratté ◽  
Steven A. Prescott
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Receptive Fields ◽  
Cell Types ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
Somatosensory Processing ◽  
Spinal Dorsal ◽  
Excitatory Neurons ◽  
Strong Excitation

ABSTRACTNeuropathic pain is a debilitating condition caused by the abnormal processing of somatosensory input. Synaptic inhibition in the spinal dorsal horn plays a key role in that processing. Mechanical allodynia – the misperception of light touch as painful – occurs when inhibition is compromised. Disinhibition is due primarily to chloride dysregulation caused by hypofunction of the potassium-chloride co-transporter KCC2. Here we show, in rats, that excitatory neurons are disproportionately affected. This is not because chloride is differentially dysregulated in excitatory and inhibitory neurons, but, rather, because excitatory neurons rely more heavily on inhibition to counterbalance strong excitation. Receptive fields in both cell types have a center-surround organization but disinhibition unmasks more excitatory input to excitatory neurons. Differences in intrinsic excitability also affect how chloride dysregulation affects spiking. These results deepen understanding of how excitation and inhibition are normally balanced in the spinal dorsal horn, and how their imbalance disrupts somatosensory processing.

scholarly journals Neuronal identity is maintained in the adult brain through KAT3-dependent enhancer acetylation

2019 ◽  
Author(s):  
Michal Lipinski ◽  
Rafael Muñoz-Viana ◽  
Beatriz del Blanco ◽  
Juan Medrano-Relinque ◽  
Angel Marquez-Galera ◽  
...  
Keyword(s):  
Cell Types ◽  
Adult Brain ◽  
Differentiated Cells ◽  
Excitatory Neurons ◽  
Neurological Phenotype ◽  
Neuronal Genes ◽  
Cell Type Specific ◽  
Chromatin Acetylation ◽  
Type 3 ◽  
Dendritic Complexity

ABSTRACTVery little is known about the mechanisms responsible for maintaining cell identity in mature tissues. The paralogous type 3 lysine acetyltransferases (KAT3) CBP and p300 are both essential during development, but their specific functions in nondividing differentiated cells remains unclear. Here, we show that when both proteins are simultaneously knocked-out in excitatory neurons of the adult brain, the mice express a rapidly progressing neurological phenotype associated with reduced dendritic complexity and electrical activity, the transcriptional shutdown of neuronal genes, and a dramatic loss of H3K27 acetylation and pro-neural transcription factor binding at neuronal enhancers. The neurons lacking both KAT3 rapidly acquire a molecularly undefined fate with no sign of dedifferentiation, transdifferentiation or death. Restoring CBP expression or lysine acetylation reestablished neuronal-specific transcription. Our experiments demonstrate that KAT3 proteins act as fate-keepers in excitatory neurons and other cell types by jointly safeguarding chromatin acetylation levels at cell type-specific enhancers throughout life.

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