Analysis of segmentation ontology reveals the similarities and differences in connectivity onto L2/3 neurons in mouse V1

AbstractQuantitatively comparing brain-wide connectivity of different types of neuron is of vital importance in understanding the function of the mammalian cortex. Here we have designed an analytical approach to examine and compare datasets from hierarchical segmentation ontologies, and applied it to long-range presynaptic connectivity onto excitatory and inhibitory neurons, mainly located in layer 2/3 (L2/3), of mouse primary visual cortex (V1). We find that the origins of long-range connections onto these two general cell classes—as well as their proportions—are quite similar, in contrast to the inputs on to a cell type in L6. These anatomical data suggest that distal inputs received by the general excitatory and inhibitory classes of neuron in L2/3 overlap considerably.

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Excitatory and inhibitory L2/3 neurons in mouse primary visual cortex are balanced in their input connectivity

10.1101/2020.04.21.053504 ◽

2020 ◽

Author(s):

Alexander P.Y. Brown ◽

Lee Cossell ◽

Troy W. Margrie

Keyword(s):

Visual Cortex ◽

Long Range ◽

Primary Visual Cortex ◽

Analytical Approach ◽

Neural Circuits ◽

Brain Regions ◽

Inhibitory Neurons ◽

Hierarchical Segmentation ◽

Layer 2 ◽

Inhibitory Networks

AbstractQuantitatively characterising brain-wide connectivity of neural circuits is of vital importance in understanding the function of the mammalian cortex. Here we have designed an analytical approach to examine data from hierarchical segmentation ontologies, and applied it in the comparison of long-range presynaptic connectivity onto excitatory and inhibitory neurons in layer 2/3 (L2/3) of mouse primary visual cortex (V1). We find that long-range connections onto these two general cell classes in L2/3 originate from highly similar brain regions, and in similar proportions, when compared to input to layer 6. These anatomical data suggest that distal information received by excitatory and inhibitory networks is highly homogenous in L2/3.

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Behavioral-state modulation of inhibition is context-dependent and cell type specific in mouse visual cortex

eLife ◽

10.7554/elife.14985 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 107

Author(s):

Janelle MP Pakan ◽

Scott C Lowe ◽

Evelyn Dylda ◽

Sander W Keemink ◽

Stephen P Currie ◽

...

Keyword(s):

Visual Cortex ◽

Pyramidal Neurons ◽

Visual Stimulation ◽

Inhibitory Neurons ◽

Behavioral State ◽

Visual Responses ◽

Cell Type ◽

Sensory Stimuli ◽

Context Dependent

Cortical responses to sensory stimuli are modulated by behavioral state. In the primary visual cortex (V1), visual responses of pyramidal neurons increase during locomotion. This response gain was suggested to be mediated through inhibitory neurons, resulting in the disinhibition of pyramidal neurons. Using in vivo two-photon calcium imaging in layers 2/3 and 4 in mouse V1, we reveal that locomotion increases the activity of vasoactive intestinal peptide (VIP), somatostatin (SST) and parvalbumin (PV)-positive interneurons during visual stimulation, challenging the disinhibition model. In darkness, while most VIP and PV neurons remained locomotion responsive, SST and excitatory neurons were largely non-responsive. Context-dependent locomotion responses were found in each cell type, with the highest proportion among SST neurons. These findings establish that modulation of neuronal activity by locomotion is context-dependent and contest the generality of a disinhibitory circuit for gain control of sensory responses by behavioral state.

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Early role for a Na+,K+-ATPase (ATP1A3) in brain development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2023333118 ◽

2021 ◽

Vol 118 (25) ◽

pp. e2023333118

Author(s):

Richard S. Smith ◽

Marta Florio ◽

Shyam K. Akula ◽

Jennifer E. Neil ◽

Yidi Wang ◽

...

Keyword(s):

Single Cell ◽

Expression Patterns ◽

Inhibitory Neurons ◽

Cell Type ◽

Animal Cells ◽

Concentration Gradients ◽

Α Subunit ◽

Early Postnatal Development ◽

Excitatory Neurons ◽

A Cell

Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function catalyzed by the Na+,K+-ATPase α-subunit. Here, we describe ATP1A3 variants encoding dysfunctional α3-subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal ATP1A3 expression, we built an ATP1A3 transcriptional atlas of fetal cortical development using mRNA in situ hybridization and transcriptomic profiling of ∼125,000 individual cells with single-cell RNA sequencing (Drop-seq) from 11 areas of the midgestational human neocortex. We found that fetal expression of ATP1A3 is most abundant to a subset of excitatory neurons carrying transcriptional signatures of the developing subplate, yet also maintains expression in nonneuronal cell populations. Moving forward a year in human development, we profiled ∼52,000 nuclei from four areas of an infant neocortex and show that ATP1A3 expression persists throughout early postnatal development, most predominantly in inhibitory neurons, including parvalbumin interneurons in the frontal cortex. Finally, we discovered the heteromeric Na+,K+-ATPase pump complex may form nonredundant cell-type–specific α-β isoform combinations, including α3-β1 in excitatory neurons and α3-β2 in inhibitory neurons. Together, the developmental malformation phenotype of affected individuals and single-cell ATP1A3 expression patterns point to a key role for α3 in human cortex development, as well as a cell-type basis for pre- and postnatal ATP1A3-associated diseases.

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Opposing influence of top-down and bottom-up input on different types of excitatory layer 2/3 neurons in mouse visual cortex

10.1242/prelights.18184 ◽

2020 ◽

Author(s):

Mahesh Karnani

Keyword(s):

Visual Cortex ◽

Top Down ◽

Bottom Up ◽

Layer 2 ◽

Different Types ◽

Mouse Visual Cortex

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Tightly-coupled inhibitory and excitatory functional networks in the early visual cortex

10.1101/2021.08.27.457908 ◽

2021 ◽

Author(s):

Haleigh N. Mulholland ◽

Bettina Hein ◽

Matthias Kaschube ◽

Gordon B. Smith

Keyword(s):

Visual Cortex ◽

Spontaneous Activity ◽

Long Range ◽

Computational Models ◽

Activity Patterns ◽

Critical Role ◽

Inhibitory Neurons ◽

Functional Networks ◽

Long Range Correlations ◽

Inhibitory Networks

AbstractIntracortical inhibition plays a critical role in shaping activity patterns in the mature cortex. However, little is known about the structure of inhibition in early development prior to the onset of sensory experience, a time when spontaneous activity exhibits long-range correlations predictive of mature functional networks. Here, using calcium imaging of GABAergic neurons in the early ferret visual cortex, we show that spontaneous activity in inhibitory neurons is already highly organized into distributed modular networks before visual experience. Inhibitory neurons exhibit spatially modular activity with long-range correlations and precise local organization that is in quantitative agreement with excitatory networks. Furthermore, excitatory and inhibitory networks are strongly co-aligned at both millimeter and cellular scales. These results demonstrate a remarkable degree of organization in inhibitory networks early in the developing cortex, providing support for computational models of self-organizing networks and suggesting a mechanism for the emergence of distributed functional networks during development.

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A cell-type-specific dynamic Bayesian network model for spontaneous and optogenetically evoked activity in the primary visual cortex

BMC Neuroscience ◽

10.1186/1471-2202-12-s1-o5 ◽

2011 ◽

Vol 12 (Suppl 1) ◽

pp. O5

Author(s):

Ali Mohebi ◽

Jessica A Cardin ◽

Karim G Oweiss

Keyword(s):

Visual Cortex ◽

Bayesian Network ◽

Primary Visual Cortex ◽

Network Model ◽

Dynamic Bayesian Network ◽

Cell Type ◽

Bayesian Network Model ◽

A Cell ◽

Cell Type Specific ◽

Evoked Activity

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Cell-type–specific sub- and suprathreshold receptive fields of layer 4 and layer 2/3 pyramids in rat primary visual cortex

Neuroscience ◽

10.1016/j.neuroscience.2011.05.026 ◽

2011 ◽

Vol 190 ◽

pp. 112-126 ◽

Cited By ~ 7

Author(s):

P. Medini

Keyword(s):

Visual Cortex ◽

Primary Visual Cortex ◽

Receptive Fields ◽

Cell Type ◽

Layer 2 ◽

Layer 4 ◽

Cell Type Specific

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Tightly coupled inhibitory and excitatory functional networks in the developing primary visual cortex

eLife ◽

10.7554/elife.72456 ◽

2021 ◽

Vol 10 ◽

Author(s):

Haleigh N Mulholland ◽

Bettina Hein ◽

Matthias Kaschube ◽

Gordon B Smith

Keyword(s):

Visual Cortex ◽

Spontaneous Activity ◽

Long Range ◽

Computational Models ◽

Activity Patterns ◽

Critical Role ◽

Inhibitory Neurons ◽

Functional Networks ◽

Long Range Correlations ◽

Inhibitory Networks

Intracortical inhibition plays a critical role in shaping activity patterns in the mature cortex. However, little is known about the structure of inhibition in early development prior to the onset of sensory experience, a time when spontaneous activity exhibits long-range correlations predictive of mature functional networks. Here, using calcium imaging of GABAergic neurons in the ferret visual cortex, we show that spontaneous activity in inhibitory neurons is already highly organized into distributed modular networks before visual experience. Inhibitory neurons exhibit spatially modular activity with long-range correlations and precise local organization that is in quantitative agreement with excitatory networks. Furthermore, excitatory and inhibitory networks are strongly co-aligned at both millimeter and cellular scales. These results demonstrate a remarkable degree of organization in inhibitory networks early in the developing cortex, providing support for computational models of self-organizing networks and suggesting a mechanism for the emergence of distributed functional networks during development.

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Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084090 ◽

1978 ◽

Vol 36 (2) ◽

pp. 644-645

Author(s):

G. Rowden ◽

M. G. Lewis ◽

T. M. Phillips

Keyword(s):

Dendritic Cells ◽

Langerhans Cells ◽

Cell Types ◽

Cell Type ◽

Electron Microscopic ◽

La Antigen ◽

Microscopic Studies ◽

A Cell ◽

C3 Receptors ◽

Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

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