A novel subtype of pineal projection neurons expressing melanopsin share a common developmental program with classical projection neurons

SummaryThe zebrafish pineal organ is a photoreceptive structure containing two main neuronal populations (photoreceptors and projections neurons). Here we describe a new pineal cell type that harbors both characteristics of projection neurons and photoreceptors. Indeed, a subpopulation of projection neurons expresses the melanopsin gene opn4xa suggesting photoreceptive properties. This population of hybrid cell fates, share a similar behaviour regarding dependency for BMP and Notch signalling pathways with classical non-photosensitive projection neurons (PNs) suggesting they are closer to the PN population. We describe two distinct types of activity within PNs: an achromatic LIGHT OFF activity in opn4xa− PNs and a LIGHT ON activity elicited by green and blue light in opn4xa+ PNs. Altogether the discovery and characterization of opn4xa+ PNs suggest a previously unanticipated heterogeneity in the projection neuron population.

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Connectivity characterization of the mouse basolateral amygdalar complex

Nature Communications ◽

10.1038/s41467-021-22915-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Houri Hintiryan ◽

Ian Bowman ◽

David L. Johnson ◽

Laura Korobkova ◽

Muye Zhu ◽

...

Keyword(s):

Granular Cell ◽

Cell Types ◽

Projection Neurons ◽

Cell Type ◽

Connectivity Map ◽

Analysis Techniques ◽

Domain Specific ◽

Cell Type Specific ◽

Unique Domain

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

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St18 specifies globus pallidus projection neuron identity in MGE lineage

10.1101/2021.08.03.454907 ◽

2021 ◽

Author(s):

Luke Nunnelly ◽

Melissa Campbell ◽

Dylan Lee ◽

Guoqiang Gu ◽

Vilas Menon ◽

...

Keyword(s):

Globus Pallidus ◽

Long Range ◽

Projection Neuron ◽

Migratory Behavior ◽

Projection Neurons ◽

Loss Of Function ◽

Downstream Target ◽

Neuronal Populations ◽

Downstream Effector ◽

Large Expansion

The medial ganglionic eminence (MGE) is a progenitor domain in the subpallium that produces both locally-projecting interneurons which undergo tangential migration in structures such as the cortex as well as long-range projection neurons that occupy subcortical nuclei. Very little is known about the transcriptional mechanisms specifying the migratory behavior and axonal projection patterns of these two broad classes of MGE-derived neurons. In this study, we identify St18 as a novel transcriptional determinant specifying projection neuron fate in the MGE lineage. St18 is transiently expressed in the MGE subventricular zone (SVZ) and mantle, and we assessed its function using an ES cell-based model of MGE development. Induction of St18 is sufficient to direct ES-derived MGE neurons to adopt a projection neuron-like identity as defined by migration and morphology. Using genetic loss-of-function in mice, we find that St18 is required for the production of globus pallidus pars externa (GPe) prototypic projection neurons. Single cell RNA sequencing revealed that St18 regulates MGE output of specific neuronal populations: in the absence of St18, we observe a large expansion of cortical interneurons at the expense of putative GPe neurons. Through gene expression analysis we identified a downstream effector of St18, Cbx7, which is a component of Polycomb repressor complex 1. We find that Cbx7 is essential for projection neuron-like migration and is not involved in St18-mediated projection neuron-like morphology. Our results characterize a novel transcriptional determinant that directs GPe prototypic projection neuron identity. Further, we identified a downstream target of St18, Cbx7, which regulates only the migratory behavior of long-range projection neurons, suggesting that specific features of MGE projection neuron identity may be governed in a compartmentalized fashion by distinct transcriptional modules downstream of St18.

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Basolateral amygdala parvalbumin neurons report aversive prediction error to constrain fear learning

10.1101/2020.09.22.307561 ◽

2020 ◽

Author(s):

Joanna Oi-Yue Yau ◽

Chanchanok Chaichim ◽

John M. Power ◽

Gavan P. McNally

Keyword(s):

Prediction Error ◽

Basolateral Amygdala ◽

Projection Neuron ◽

Fear Learning ◽

Neuron Activity ◽

Projection Neurons ◽

Cell Type ◽

Learning Mechanisms ◽

Aversive Events ◽

Cell Type Specific

AbstractAnimals, including humans, use prediction error to guide learning about danger in the environment. The basolateral amygdala (BLA) is obligatory for this learning and BLA excitatory projection neurons are instructed by aversive prediction error to form fear associations. Complex networks of inhibitory interneurons, dominated by parvalbumin (PV) expressing GABAergic neurons, form the intrinsic microcircuitry of the BLA to control projection neuron activity. Whether BLA PV interneurons are also sensitive to prediction error and how they use this error to control fear learning remains unknown. We used PV cell-type specific recording and manipulation approaches in male transgenic PV-Cre rats to address these issues. We show that BLA PV neurons control fear learning about aversive events but not learning about their omission. Furthermore, during fear learning BLA PV neurons express the activity signatures of aversive prediction error: greater activity to unexpected than expected aversive events and greater activity to better rather than poorer predictors of these events. Crucially, we show that BLA PV neurons act to limit fear learning across these variations in prediction error. Together, this demonstrates that prediction error instructs and regulates BLA fear association formation in a cell-type specific manner. Whereas BLA projection neurons use prediction error signals to form and store fear associations, BLA PV interneurons use prediction error signals to constrain fear association formation.Significance StatementThe capacity to predict sources of danger in the environment is essential for survival. This capacity is supported by associative learning mechanisms that are triggered when the danger experienced is greater than the danger expected. Here we show that the activity of parvalbumin positive GABAergic interneurons in the rat basolateral amygdala neurons report this difference between the danger expected and the danger experienced and that they use this difference to limit the amount of fear which is learned.

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Connectivity characterization of the mouse basolateral amygdalar complex

10.1101/807743 ◽

2019 ◽

Cited By ~ 1

Author(s):

Houri Hintiryan ◽

Ian Bowman ◽

David L. Johnson ◽

Laura Korobkova ◽

Muye Zhu ◽

...

Keyword(s):

Cell Body ◽

Computational Analysis ◽

Functional Characterization ◽

Granular Cell ◽

Cell Types ◽

Projection Neurons ◽

Cell Type ◽

Analysis Techniques ◽

Cell Type Specific

ABSTRACTThe basolateral amygdalar complex (BLA) is implicated in behavioral processing ranging from fear acquisition to addiction. Newer methods like optogenetics have enabled the association of circuit-specific functionality to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. In this work, we applied computational analysis techniques to the results of our circuit-tracing experiments to create a foundational, comprehensive, multiscale connectivity atlas of the mouse BLA. The analyses identified three domains within the classically defined anterior BLA (BLAa) that house target-specific projection neurons with distinguishable cell body and dendritic morphologies. Further, we identify brain-wide targets of projection neurons located in the three BLAa domains as well as in the posterior BLA (BLAp), ventral BLA (BLAv), lateral (LA), and posterior basomedial (BMAp) nuclei. Projection neurons that provide input to each nucleus are also identifed. Functional characterization of some projection-defined BLA neurons were demonstrated via optogenetic and recording experiments. Hypotheses relating function to connection-defined BLA cell types are proposed.

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Faculty Opinions recommendation of Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1002127.211470 ◽

2004 ◽

Author(s):

Mark Fortini

Keyword(s):

Cell Type ◽

Sensory Organs ◽

Cell Fates

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Faculty Opinions recommendation of Identification and characterization of a Y-like primate retinal ganglion cell type.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091526.547827 ◽

2007 ◽

Author(s):

Matteo Carandini

Keyword(s):

Ganglion Cell ◽

Retinal Ganglion Cell ◽

Retinal Ganglion ◽

Cell Type ◽

Identification And Characterization

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Characterization of the cell type-specific determinant in the genome of minute virus of mice.

Journal of Virology ◽

10.1128/jvi.62.2.552-557.1988 ◽

1988 ◽

Vol 62 (2) ◽

pp. 552-557 ◽

Cited By ~ 28

Author(s):

J P Antonietti ◽

R Sahli ◽

P Beard ◽

B Hirt

Keyword(s):

Cell Type ◽

Minute Virus Of Mice ◽

Cell Type Specific ◽

Minute Virus ◽

Specific Determinant

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Cytometric Profiling of CD133+ Cells in Human Colon Carcinoma Cell Lines Identifies a Common core Phenotype and Cell Type-specific Mosaics

The International Journal of Biological Markers ◽

10.5301/jbm.5000020 ◽

2013 ◽

Vol 28 (3) ◽

pp. 267-273 ◽

Cited By ~ 11

Author(s):

Marica Gemei ◽

Rosa Di Noto ◽

Peppino Mirabelli ◽

Luigi Del Vecchio

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Colon Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Cell Type ◽

Carcinoma Cell Lines ◽

Cell Type Specific

In colorectal cancer, CD133+ cells from fresh biopsies proved to be more tumorigenic than their CD133– counterparts. Nevertheless, the function of CD133 protein in tumorigenic cells seems only marginal. Moreover, CD133 expression alone is insufficient to isolate true cancer stem cells, since only 1 out of 262 CD133+ cells actually displays stem-cell capacity. Thus, new markers for colorectal cancer stem cells are needed. Here, we show the extensive characterization of CD133+ cells in 5 different colon carcinoma continuous cell lines (HT29, HCT116, Caco2, GEO and LS174T), each representing a different maturation level of colorectal cancer cells. Markers associated with stemness, tumorigenesis and metastatic potential were selected. We identified 6 molecules consistently present on CD133+ cells: CD9, CD29, CD49b, CD59, CD151, and CD326. By contrast, CD24, CD26, CD54, CD66c, CD81, CD90, CD99, CD112, CD164, CD166, and CD200 showed a discontinuous behavior, which led us to identify cell type-specific surface antigen mosaics. Finally, some antigens, e.g. CD227, indicated the possibility of classifying the CD133+ cells into 2 subsets likely exhibiting specific features. This study reports, for the first time, an extended characterization of the CD133+ cells in colon carcinoma cell lines and provides a “dictionary” of antigens to be used in colorectal cancer research.

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