Structured spike series specify gene expression patterns for olfactory circuit formation

Neural circuits emerge through the interplay of genetic programming and activity-dependent processes. During the development of the mouse olfactory map, axons segregate into distinct glomeruli in an olfactory receptor (OR)–dependent manner. ORs generate a combinatorial code of axon-sorting molecules whose expression is regulated by neural activity. However, it remains unclear how neural activity induces OR-specific expression patterns of axon-sorting molecules. We found that the temporal patterns of spontaneous neuronal spikes were not spatially organized but were correlated with the OR types. Receptor substitution experiments demonstrated that ORs determine spontaneous activity patterns. Moreover, optogenetically differentiated patterns of neuronal activity induced specific expression of the corresponding axon-sorting molecules and regulated axonal segregation. Thus, OR-dependent temporal patterns of spontaneous activity play instructive roles in generating the combinatorial code of axon-sorting molecules during olfactory map formation.

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Efferent feedback enforces bilateral coupling of spontaneous activity in the developing auditory system

10.1101/2020.08.12.248799 ◽

2020 ◽

Author(s):

Yixiang Wang ◽

Maya Sanghvi ◽

Alexandra Gribizis ◽

Yueyi Zhang ◽

Lei Song ◽

...

Keyword(s):

Spontaneous Activity ◽

Auditory System ◽

Activity Patterns ◽

Descending Pathways ◽

Efferent System ◽

Cholinergic Pathway ◽

The Central Nervous System ◽

Necessary And Sufficient ◽

Circuit Formation

SummaryIn the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation before hearing onset. Effects of the evolving peripheral firing pattern on spontaneous activity in the central auditory system are not well understood. Here, we describe the wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the medial olivochlear (MOC) system. Knocking out the α9/α10 nicotinic acetylcholine receptor, a requisite part of the efferent cholinergic pathway, abolishes these bilateral correlations. Pharmacological and chemogenetic experiments confirm that the MOC system is necessary and sufficient to produce the bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, our results demonstrate how ascending and descending pathways collectively shape spontaneous activity patterns in the auditory system and reveal the essential role of the MOC efferent system in linking otherwise independent streams of bilateral spontaneous activity during the prehearing period.

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Electrical activity controls area-specific expression of neuronal apoptosis in the mouse developing cerebral cortex

eLife ◽

10.7554/elife.27696 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 30

Author(s):

Oriane Blanquie ◽

Jenq-Wei Yang ◽

Werner Kilb ◽

Salim Sharopov ◽

Anne Sinning ◽

...

Keyword(s):

Cortical Neurons ◽

Primary Motor Cortex ◽

Sensory Deprivation ◽

Activity Patterns ◽

Postnatal Period ◽

Dependent Manner ◽

Specific Expression ◽

Neuronal Identity ◽

Functional Maturation ◽

Dependent Processes

Programmed cell death widely but heterogeneously affects the developing brain, causing the loss of up to 50% of neurons in rodents. However, whether this heterogeneity originates from neuronal identity and/or network-dependent processes is unknown. Here, we report that the primary motor cortex (M1) and primary somatosensory cortex (S1), two adjacent but functionally distinct areas, display striking differences in density of apoptotic neurons during the early postnatal period. These differences in rate of apoptosis negatively correlate with region-dependent levels of activity. Disrupting this activity either pharmacologically or by electrical stimulation alters the spatial pattern of apoptosis and sensory deprivation leads to exacerbated amounts of apoptotic neurons in the corresponding functional area of the neocortex. Thus, our data demonstrate that spontaneous and periphery-driven activity patterns are important for the structural and functional maturation of the neocortex by refining the final number of cortical neurons in a region-dependent manner.

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Hormonal and neural correlates of care in active versus observing poison frog parents

10.1101/765503 ◽

2019 ◽

Author(s):

Eva K Fischer ◽

Lauren A O'Connell

Keyword(s):

Gene Expression ◽

Parental Care ◽

Neural Activity ◽

Parental Behavior ◽

Activity Patterns ◽

Expression Patterns ◽

Neural Correlates ◽

Poison Frog ◽

Hormone Levels ◽

Brain Gene Expression

The occasional reversal of sex-typical behavior suggests that many of the neural circuits underlying behavior are conserved between males and females and can be activated in response to the appropriate social condition or stimulus. Most poison frog species (Family Dendrobatidae) exhibit male uniparental care, but flexible compensation has been observed in some species, where females will take over parental care duties when males disappear. We investigated hormonal and neural correlates of sex-typical and sex-reversed parental care in a typically male uniparental species, the Dyeing Poison Frog (Dendrobates tinctorius). We first characterized hormone levels and whole brain gene expression across parental care stages during sex-typical care. Surprisingly, hormonal changes and brain gene expression differences associated with active parental behavior in males were mirrored in their non-caregiving female partners. To further explore the disconnect between neuroendocrine patterns and behavior, we characterized hormone levels and neural activity patterns in females performing sex-reversed parental care. In contrast to hormone and gene expression patterns, we found that patterns of neural activity were linked to the active performance of parental behavior, with sex-reversed tadpole transporting females exhibiting neural activity patterns more similar to those of transporting males than non-caregiving females. We suggest that parallels in hormones and brain gene expression in active and observing parents are related to females ability to flexibly take over parental care in the absence of their male partners.

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Spontaneous and evoked activity patterns diverge over development

eLife ◽

10.7554/elife.61942 ◽

2021 ◽

Vol 10 ◽

Author(s):

Lilach Avitan ◽

Zac Pujic ◽

Jan Mölter ◽

Shuyu Zhu ◽

Biao Sun ◽

...

Keyword(s):

Spontaneous Activity ◽

Neural Activity ◽

Activity Patterns ◽

Higher Dimension ◽

Immature Brain ◽

Geometric Distance ◽

Larval Zebrafish ◽

Emerging Patterns ◽

Evoked Activity ◽

Bayesian Prior

The immature brain is highly spontaneously active. Over development this activity must be integrated with emerging patterns of stimulus-evoked activity, but little is known about how this occurs. Here we investigated this question by recording spontaneous and evoked neural activity in the larval zebrafish tectum from 4 to 15 days post fertilisation. Correlations within spontaneous and evoked activity epochs were comparable over development, and their neural assemblies properties refined in similar ways. However both the similarity between evoked and spontaneous assemblies, and also the geometric distance between spontaneous and evoked patterns, decreased over development. At all stages of development evoked activity was of higher dimension than spontaneous activity. Thus spontaneous and evoked activity do not converge over development in this system, and these results do not support the hypothesis that spontaneous activity evolves to form a Bayesian prior for evoked activity.

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The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2020.609752 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ken-ichi Matsumoto ◽

Hiroki Aoki

Keyword(s):

Connective Tissue ◽

Inflammatory Diseases ◽

Expression Patterns ◽

Connective Tissue Diseases ◽

Connective Tissue Disorder ◽

Tissue Homeostasis ◽

Dependent Manner ◽

Specific Expression ◽

Ehlers Danlos Syndrome ◽

Tenascin C

Tenascins are a family of multifunctional extracellular matrix (ECM) glycoproteins with time- and tissue specific expression patterns during development, tissue homeostasis, and diseases. There are four family members (tenascin-C, -R, -X, -W) in vertebrates. Among them, tenascin-X (TNX) and tenascin-C (TNC) play important roles in human pathologies. TNX is expressed widely in loose connective tissues. TNX contributes to the stability and maintenance of the collagen network, and its absence causes classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder. In contrast, TNC is specifically and transiently expressed upon pathological conditions such as inflammation, fibrosis, and cancer. There is growing evidence that TNC is involved in inflammatory processes with proinflammatory or anti-inflammatory activity in a context-dependent manner. In this review, we summarize the roles of these two tenascins, TNX and TNC, in cardiovascular and inflammatory diseases and in clEDS, and we discuss the functional consequences of the expression of these tenascins for tissue homeostasis.

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Spontaneous activity and functional connectivity in the developing cerebellorubral system

Journal of Neurophysiology ◽

10.1152/jn.00461.2016 ◽

2016 ◽

Vol 116 (3) ◽

pp. 1316-1327 ◽

Cited By ~ 12

Author(s):

Carlos Del Rio-Bermudez ◽

Alan M. Plumeau ◽

Nicholas J. Sattler ◽

Greta Sokoloff ◽

Mark S. Blumberg

Keyword(s):

Functional Connectivity ◽

Spontaneous Activity ◽

Neural Activity ◽

Activity Patterns ◽

Red Nucleus ◽

Downstream Target ◽

State Dependent ◽

Age Related ◽

Extracellular Activity

The development of the cerebellar system depends in part on the emergence of functional connectivity in its input and output pathways. Characterization of spontaneous activity within these pathways provides insight into their functional status in early development. In the present study we recorded extracellular activity from the interpositus nucleus (IP) and its primary downstream target, the red nucleus (RN), in unanesthetized rats at postnatal days 8 (P8) and P12, a period of dramatic change in cerebellar circuitry. The two structures exhibited state-dependent activity patterns and age-related changes in rhythmicity and overall firing rate. Importantly, sensory feedback (i.e., reafference) from myoclonic twitches (spontaneous, self-generated movements that are produced exclusively during active sleep) drove neural activity in the IP and RN at both ages. Additionally, anatomic tracing confirmed the presence of cerebellorubral connections as early as P8. Finally, inactivation of the IP and adjacent nuclei using the GABAA receptor agonist muscimol caused a substantial decrease in neural activity in the contralateral RN at both ages, as well as the disappearance of rhythmicity; twitch-related activity in the RN, however, was preserved after IP inactivation, indicating that twitch-related reafference activates the two structures in parallel. Overall, the present findings point to the contributions of sleep-related spontaneous activity to the development of cerebellar networks.

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Spatial and temporal targeting of gene expression in Drosophila by means of a tetracycline-dependent transactivator system

Development ◽

10.1242/dev.125.12.2193 ◽

1998 ◽

Vol 125 (12) ◽

pp. 2193-2202 ◽

Cited By ~ 13

Author(s):

B. Bello ◽

D. Resendez-Perez ◽

W.J. Gehring

Keyword(s):

Gene Expression ◽

Expression System ◽

Expression Patterns ◽

Ectopic Expression ◽

Regulatory Sequences ◽

Dependent Manner ◽

Coding Region ◽

Specific Expression ◽

Regulated Gene Expression ◽

Beta Galactosidase

In order to evaluate the efficiency of the tetracycline-regulated gene expression system in Drosophila, we have generated transgenic lines expressing a tetracycline-controlled transactivator protein (tTA), with specific expression patterns during embryonic and larval development. These lines were used to direct expression of a tTA-responsive promoter fused to the coding region of either the beta-galactosidase or the homeotic protein Antennapedia (ANTP), under various conditions of tetracycline treatment. We found that expression of beta-galactosidase can be efficiently inhibited in embryos and larvae with tetracycline provided in the food, and that a simple removal of the larvae from tetracycline exposure results in the induction of the enzyme in a time- and concentration-dependent manner. Similar treatments can be used to prevent the lethality associated with the ectopic expression of ANTP in embryos and, subsequently, to control the timing of expression of the homeoprotein ANTP specifically in the antennal imaginal disc. Our results show that the expression of a gene placed under the control of a tetracycline-responsive promoter can be tightly controlled, both spatially by the regulatory sequences driving the expression of tTA and temporally by tetracycline. This provides the basis of a versatile binary system for controlling gene expression in Drosophila, with an additional level of regulation as compared to the general method using the yeast transcription factor GAL4.

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A Family of Human Zinc Finger Proteins That Bind Methylated DNA and Repress Transcription

Molecular and Cellular Biology ◽

10.1128/mcb.26.1.169-181.2006 ◽

2006 ◽

Vol 26 (1) ◽

pp. 169-181 ◽

Cited By ~ 195

Author(s):

Guillaume J. P. Filion ◽

Svetlana Zhenilo ◽

Sergey Salozhin ◽

Daisuke Yamada ◽

Egor Prokhortchouk ◽

...

Keyword(s):

Zinc Fingers ◽

Expression Patterns ◽

Differentially Methylated Region ◽

Dependent Manner ◽

Specific Expression ◽

Tissue Specific ◽

Tissue Specific Expression ◽

Methylated Dna

ABSTRACT In vertebrates, densely methylated DNA is associated with inactive transcription. Actors in this process include proteins of the MBD family that can recognize methylated CpGs and repress transcription. Kaiso, a structurally unrelated protein, has also been shown to bind methylated CGCGs through its three Krüppel-like C2H2 zinc fingers. The human genome contains two uncharacterized proteins, ZBTB4 and ZBTB38, that contain Kaiso-like zinc fingers. We report that ZBTB4 and ZBTB38 bind methylated DNA in vitro and in vivo. Unlike Kaiso, they can bind single methylated CpGs. When transfected in mouse cells, the proteins colocalize with foci of heavily methylated satellite DNA and become delocalized upon loss of DNA methylation. Chromatin immunoprecipitation suggests that both of these proteins specifically bind to the methylated allele of the H19/Igf2 differentially methylated region. ZBTB4 and ZBTB38 repress the transcription of methylated templates in transfection assays. The two genes have distinct tissue-specific expression patterns, but both are highly expressed in the brain. Our results reveal the existence of a family of Kaiso-like proteins that bind methylated CpGs. Like proteins of the MBD family, they are able to repress transcription in a methyl-dependent manner, yet their tissue-specific expression pattern suggests nonoverlapping functions.

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