scholarly journals Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type

2017 ◽  
Author(s):  
Eszter Boldog ◽  
Trygve Bakken ◽  
Rebecca D. Hodge ◽  
Mark Novotny ◽  
Brian D. Aevermann ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Cortical Layer ◽  
Molecular Signature ◽  
Gabaergic Interneuron ◽  
Cell Type ◽  
Human Cortex ◽  
Dendritic Computation ◽  
Mouse Cortex ◽  
Cortical Pyramidal Neurons ◽  
Single Nucleus

AbstractWe describe convergent evidence from transcriptomics, morphology and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a novel group of human interneurons with anatomical features never described in rodents having large, “rosehip”-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1/CCK-positive, CNR1/SST/CALB2/PVALB-negative) matching a single transcriptomically-defined cell type whose molecular signature is not seen in mouse cortex. Rosehip cells make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.

scholarly journals Cholinergic modulation of sensory processing in awake mouse cortex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Javier Jimenez-Martin ◽  
Daniil Potapov ◽  
Kay Potapov ◽  
Thomas Knöpfel ◽  
Ruth M. Empson
Keyword(s):  
Pyramidal Neurons ◽  
Brain Activity ◽  
Critical Role ◽  
Sensory Information ◽  
Sensory Stimulation ◽  
Cholinergic Modulation ◽  
Neuronal Populations ◽  
Mouse Cortex ◽  
Cortical Pyramidal Neurons ◽  
Sensory Evoked

AbstractCholinergic modulation of brain activity is fundamental for awareness and conscious sensorimotor behaviours, but deciphering the timing and significance of acetylcholine actions for these behaviours is challenging. The widespread nature of cholinergic projections to the cortex means that new insights require access to specific neuronal populations, and on a time-scale that matches behaviourally relevant cholinergic actions. Here, we use fast, voltage imaging of L2/3 cortical pyramidal neurons exclusively expressing the genetically-encoded voltage indicator Butterfly 1.2, in awake, head-fixed mice, receiving sensory stimulation, whilst manipulating the cholinergic system. Altering muscarinic acetylcholine function re-shaped sensory-evoked fast depolarisation and subsequent slow hyperpolarisation of L2/3 pyramidal neurons. A consequence of this re-shaping was disrupted adaptation of the sensory-evoked responses, suggesting a critical role for acetylcholine during sensory discrimination behaviour. Our findings provide new insights into how the cortex processes sensory information and how loss of acetylcholine, for example in Alzheimer’s Disease, disrupts sensory behaviours.

scholarly journals Comprehensive in situ mapping of human cortical transcriptomic cell types

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Christoffer Mattsson Langseth ◽  
Daniel Gyllborg ◽  
Jeremy A. Miller ◽  
Jennie L. Close ◽  
Brian Long ◽  
...  
Keyword(s):  
Brain Function ◽  
Cortical Cell ◽  
Cell Types ◽  
Cell Type ◽  
Cortical Cells ◽  
Human Cortex ◽  
Single Nucleus ◽  
Genetic Signatures ◽  
Cell Typing

AbstractThe ability to spatially resolve the cellular architecture of human cortical cell types over informative areas is essential to understanding brain function. We combined in situ sequencing gene expression data and single-nucleus RNA-sequencing cell type definitions to spatially map cells in sections of the human cortex via probabilistic cell typing. We mapped and classified a total of 59,816 cells into all 75 previously defined subtypes to create a first spatial atlas of human cortical cells in their native position, their abundances and genetic signatures. We also examined the precise within- and across-layer distributions of all the cell types and provide a resource for the cell atlas community. The abundances and locations presented here could serve as a reference for further studies, that include human brain tissues and disease applications at the cell type level.

scholarly journals The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons

2009 ◽  
Vol 106 (17) ◽  
pp. 7227-7232 ◽  
Author(s):  
Pascal Chameau ◽  
Dragos Inta ◽  
Tania Vitalis ◽  
Hannah Monyer ◽  
Wytse J. Wadman ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Signal Transduction Pathway ◽  
Cortical Layer ◽  
Postnatal Maturation ◽  
Receptor Knockout Mouse ◽  
Basal Dendrites ◽  
Excitatory Synaptic Input ◽  
Cortical Pyramidal Neurons ◽  
Layer I ◽  
Retzius Cells

Cajal-Retzius cells, located in layer I of the cortex, synthesize and secrete the glycoprotein reelin, which plays a pivotal role in neuronal migration during embryonic development. Cajal-Retzius cells persist after birth, but their postnatal role is unknown. Here we show that Cajal-Retzius cells receive a major excitatory synaptic input via serotonin 5-HT3 receptors. Blocking this input using pharmacological tools or neutralization of reelin signaling results in hypercomplexity of apical, but not basal, dendrites of cortical layer II/III pyramidal neurons. A similar hypercomplexity is observed in the cortex of the 5-HT3A receptor knockout mouse. The increased dendritic complexity can be rescued by application of recombinant full-length reelin or its N-terminal fragment, but not by the central fragment of reelin, and involves a signal transduction pathway independent of the activation of the canonical reelin receptors. Taken together, our results reveal a novel role of serotonin, Cajal-Retzius cells, and reelin in the postnatal maturation of the cortex.

Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice

2020 ◽  
Vol 12 (570) ◽  
pp. eabc1492
Author(s):  
Lawrence S. Hsieh ◽  
John H. Wen ◽  
Lena H. Nguyen ◽  
Longbo Zhang ◽  
Stephanie A. Getz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Pyramidal Neurons ◽  
Focal Cortical Dysplasia ◽  
Repetitive Firing ◽  
Intracellular Camp ◽  
Main Role ◽  
Channel Activity ◽  
Mechanistic Target Of Rapamycin ◽  
Cortical Pyramidal Neurons ◽  
Causative Link

The causative link between focal cortical malformations (FCMs) and epilepsy is well accepted, especially among patients with focal cortical dysplasia type II (FCDII) and tuberous sclerosis complex (TSC). However, the mechanisms underlying seizures remain unclear. Using a mouse model of TSC- and FCDII-associated FCM, we showed that FCM neurons were responsible for seizure activity via their unexpected abnormal expression of the hyperpolarization-activated cyclic nucleotide–gated potassium channel isoform 4 (HCN4), which is normally not present in cortical pyramidal neurons after birth. Increasing intracellular cAMP concentrations, which preferentially affects HCN4 gating relative to the other isoforms, drove repetitive firing of FCM neurons but not control pyramidal neurons. Ectopic HCN4 expression was dependent on the mechanistic target of rapamycin (mTOR), preceded the onset of seizures, and was also found in diseased neurons in tissue resected from patients with TSC and FCDII. Last, blocking HCN4 channel activity in FCM neurons prevented epilepsy in the mouse model. These findings suggest that HCN4 play a main role in seizure and identify a cAMP-dependent seizure mechanism in TSC and FCDII. Furthermore, the unique expression of HCN4 exclusively in FCM neurons suggests that gene therapy targeting HCN4 might be effective in reducing seizures in FCDII or TSC.

scholarly journals Gonadal Hormones Modulate the Dendritic Spine Densities of Primary Cortical Pyramidal Neurons in Adult Female Rat

2009 ◽  
Vol 19 (11) ◽  
pp. 2719-2727 ◽  
Author(s):  
J.-R. Chen ◽  
Y.-T. Yan ◽  
T.-J. Wang ◽  
L.-J. Chen ◽  
Y.-J. Wang ◽  
...  
Keyword(s):  
Adult Female ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Gonadal Hormones ◽  
Female Rat ◽  
Cortical Pyramidal Neurons
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