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  1. Artikel: Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.

    Dwivedi, Deepanjali / Bhalla, Upinder S

    Frontiers in molecular neuroscience

    2021  Band 14, Seite(n) 658435

    Abstract: SK, HCN, and M channels are medium afterhyperpolarization (mAHP)-mediating ion channels. The three channels co-express in various brain regions, and their collective action strongly influences cellular excitability. However, significant diversity exists ... ...

    Abstract SK, HCN, and M channels are medium afterhyperpolarization (mAHP)-mediating ion channels. The three channels co-express in various brain regions, and their collective action strongly influences cellular excitability. However, significant diversity exists in the expression of channel isoforms in distinct brain regions and various subcellular compartments, which contributes to an equally diverse set of specific neuronal functions. The current review emphasizes the collective behavior of the three classes of mAHP channels and discusses how these channels function together although they play specialized roles. We discuss the biophysical properties of these channels, signaling pathways that influence the activity of the three mAHP channels, various chemical modulators that alter channel activity and their therapeutic potential in treating various neurological anomalies. Additionally, we discuss the role of mAHP channels in the pathophysiology of various neurological diseases and how their modulation can alleviate some of the symptoms.
    Sprache Englisch
    Erscheinungsdatum 2021-06-03
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2021.658435
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Impaired Reliability and Precision of Spiking in Adults But Not Juveniles in a Mouse Model of Fragile X Syndrome.

    Dwivedi, Deepanjali / Chattarji, Sumantra / Bhalla, Upinder S

    eNeuro

    2019  Band 6, Heft 6

    Abstract: Fragile X syndrome (FXS) is the most common source of intellectual disability and autism. Extensive studies have been performed on the network and behavioral correlates of the syndrome, but our knowledge about intrinsic conductance changes is still ... ...

    Abstract Fragile X syndrome (FXS) is the most common source of intellectual disability and autism. Extensive studies have been performed on the network and behavioral correlates of the syndrome, but our knowledge about intrinsic conductance changes is still limited. In this study, we show a differential effect of FMRP knockout in different subsections of hippocampus using whole-cell patch clamp in mouse hippocampal slices. We observed no significant change in spike numbers in the CA1 region of hippocampus, but a significant increase in CA3, in juvenile mice. However, in adult mice we see a reduction in spike number in the CA1 with no significant difference in CA3. In addition, we see increased variability in spike numbers in CA1 cells following a variety of steady and modulated current step protocols. This effect emerges in adult mice (8 weeks) but not juvenile mice (4 weeks). This increased spiking variability was correlated with reduced spike number and with elevated AHP. The increased AHP arose from elevated SK currents (small conductance calcium-activated potassium channels), but other currents involved in medium AHP, such as
    Mesh-Begriff(e) Action Potentials/drug effects ; Action Potentials/physiology ; Age Factors ; Animals ; Apamin/pharmacology ; CA1 Region, Hippocampal/drug effects ; CA1 Region, Hippocampal/physiopathology ; CA3 Region, Hippocampal/drug effects ; CA3 Region, Hippocampal/physiopathology ; Disease Models, Animal ; Fragile X Mental Retardation Protein/genetics ; Fragile X Syndrome/genetics ; Fragile X Syndrome/physiopathology ; Male ; Mice ; Mice, Knockout ; Neurons/drug effects ; Neurons/physiology ; Patch-Clamp Techniques ; Potassium Channel Blockers/pharmacology ; Reproducibility of Results ; Small-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors
    Chemische Substanzen Fmr1 protein, mouse ; Potassium Channel Blockers ; Small-Conductance Calcium-Activated Potassium Channels ; Fragile X Mental Retardation Protein (139135-51-6) ; Apamin (24345-16-2)
    Sprache Englisch
    Erscheinungsdatum 2019-12-03
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0217-19.2019
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development.

    Dwivedi, Deepanjali / Dumontier, Dimitri / Sherer, Mia / Lin, Sherry / Mirow, Andrea Mc / Qiu, Yanjie / Xu, Qing / Liebman, Samuel A / Joseph, Djeckby / Datta, Sandeep R / Fishell, Gord / Pouchelon, Gabrielle

    bioRxiv : the preprint server for biology

    2024  

    Abstract: During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian "fire together, wire together" precept. However, select connections, essential for ...

    Abstract During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian "fire together, wire together" precept. However, select connections, essential for circuit development, are transient. They are effectively connected early in development, but strongly diminish during maturation. The mechanisms by which transient connectivity recedes are unknown. To investigate this process, we characterize transient thalamocortical inputs, which depress onto somatostatin inhibitory interneurons during development, by employing optogenetics, chemogenetics, transcriptomics and CRISPR-based strategies. We demonstrate that in contrast to typical activity-dependent mechanisms, transient thalamocortical connectivity onto somatostatin interneurons is non-canonical and involves metabotropic signaling. Specifically, metabotropic-mediated transcription, of guidance molecules in particular, supports the elimination of this connectivity. Remarkably, we found that this developmental process impacts the development of normal exploratory behaviors of adult mice.
    Sprache Englisch
    Erscheinungsdatum 2024-04-03
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.09.21.558862
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Disruption of Cholinergic Retinal Waves Alters Visual Cortex Development and Function.

    Burbridge, Timothy J / Ratliff, Jacob M / Dwivedi, Deepanjali / Vrudhula, Uma / Alvarado-Huerta, Francisco / Sjulson, Lucas / Ibrahim, Leena Ali / Cheadle, Lucas / Fishell, Gordon / Batista-Brito, Renata

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Retinal waves represent an early form of patterned spontaneous neural activity in the visual system. These waves originate in the retina before eye-opening and propagate throughout the visual system, influencing the assembly and maturation of subcortical ...

    Abstract Retinal waves represent an early form of patterned spontaneous neural activity in the visual system. These waves originate in the retina before eye-opening and propagate throughout the visual system, influencing the assembly and maturation of subcortical visual brain regions. However, because it is technically challenging to ablate retina-derived cortical waves without inducing compensatory activity, the role these waves play in the development of the visual cortex remains unclear. To address this question, we used targeted conditional genetics to disrupt cholinergic retinal waves and their propagation to select regions of primary visual cortex, which largely prevented compensatory patterned activity. We find that loss of cholinergic retinal waves without compensation impaired the molecular and synaptic maturation of excitatory neurons located in the input layers of visual cortex, as well as layer 1 interneurons. These perinatal molecular and synaptic deficits also relate to functional changes observed at later ages. We find that the loss of perinatal cholinergic retinal waves causes abnormal visual cortex retinotopy, mirroring changes in the retinotopic organization of gene expression, and additionally impairs the processing of visual information. We further show that retinal waves are necessary for higher order processing of sensory information by impacting the state-dependent activity of layer 1 interneurons, a neuronal type that shapes neocortical state-modulation, as well as for state-dependent gain modulation of visual responses of excitatory neurons. Together, these results demonstrate that a brief targeted perinatal disruption of patterned spontaneous activity alters early cortical gene expression as well as synaptic and physiological development, and compromises both fundamental and, notably, higher-order functions of visual cortex after eye-opening.
    Sprache Englisch
    Erscheinungsdatum 2024-04-15
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2024.04.05.588143
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Reciprocal regulation of spontaneous synaptic vesicle fusion by Fragile X mental retardation protein and group I metabotropic glutamate receptors.

    Subrahmanyam, Rohini / Dwivedi, Deepanjali / Rashid, Zubin / Bonnycastle, Katherine / Cousin, Michael A / Chattarji, Sumantra

    Journal of neurochemistry

    2021  Band 158, Heft 5, Seite(n) 1094–1109

    Abstract: Fragile X mental retardation protein (FMRP) is a neuronal protein mediating multiple functions, with its absence resulting in one of the most common monogenic causes of autism, Fragile X syndrome (FXS). Analyses of FXS pathophysiology have identified a ... ...

    Abstract Fragile X mental retardation protein (FMRP) is a neuronal protein mediating multiple functions, with its absence resulting in one of the most common monogenic causes of autism, Fragile X syndrome (FXS). Analyses of FXS pathophysiology have identified a range of aberrations in synaptic signaling pathways and plasticity associated with group I metabotropic glutamate (mGlu) receptors. These studies, however, have mostly focused on the post-synaptic functions of FMRP and mGlu receptor activation, and relatively little is known about their presynaptic effects. Neurotransmitter release is mediated via multiple forms of synaptic vesicle (SV) fusion, each of which contributes to specific neuronal functions. The impacts of mGlu receptor activation and loss of FMRP on these SV fusion events remain unexplored. Here we combined electrophysiological and fluorescence imaging analyses on primary hippocampal cultures prepared from an Fmr1 knockout (KO) rat model. Compared to wild-type (WT) hippocampal neurons, KO neurons displayed an increase in the frequency of spontaneous excitatory post-synaptic currents (sEPSCs), as well as spontaneous SV fusion events. Pharmacological activation of mGlu receptors in WT neurons caused a similar increase in spontaneous SV fusion and sEPSC frequency. Notably, this increase in SV fusion was not observed when spontaneous activity was blocked using the sodium channel antagonist tetrodotoxin. Importantly, the effect of mGlu receptor activation on spontaneous SV fusion was occluded in Fmr1 KO neurons. Together, our results reveal that FMRP represses spontaneous presynaptic SV fusion, whereas mGlu receptor activation increases this event. This reciprocal control appears to be mediated via their regulation of intrinsic neuronal excitability.
    Mesh-Begriff(e) Animals ; Cells, Cultured ; Excitatory Postsynaptic Potentials/physiology ; Fragile X Mental Retardation Protein/antagonists & inhibitors ; Fragile X Mental Retardation Protein/genetics ; Fragile X Mental Retardation Protein/metabolism ; Male ; Membrane Fusion/physiology ; Neurons/metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Transgenic ; Receptors, Metabotropic Glutamate/genetics ; Receptors, Metabotropic Glutamate/metabolism ; Synaptic Vesicles/genetics ; Synaptic Vesicles/metabolism
    Chemische Substanzen Fmr1 protein, rat ; Receptors, Metabotropic Glutamate ; metabotropic glutamate receptor type 1 ; Fragile X Mental Retardation Protein (139135-51-6)
    Sprache Englisch
    Erscheinungsdatum 2021-08-13
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.15484
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Adult brain neurons require continual expression of the schizophrenia-risk gene Tcf4 for structural and functional integrity.

    Sarkar, Dipannita / Shariq, Mohammad / Dwivedi, Deepanjali / Krishnan, Nirmal / Naumann, Ronald / Bhalla, Upinder Singh / Ghosh, Hiyaa Singhee

    Translational psychiatry

    2021  Band 11, Heft 1, Seite(n) 494

    Abstract: The schizophrenia-risk gene Tcf4 has been widely studied in the context of brain development using mouse models of haploinsufficiency, in utero knockdown and embryonic deletion. However, Tcf4 continues to be abundantly expressed in adult brain neurons ... ...

    Abstract The schizophrenia-risk gene Tcf4 has been widely studied in the context of brain development using mouse models of haploinsufficiency, in utero knockdown and embryonic deletion. However, Tcf4 continues to be abundantly expressed in adult brain neurons where its functions remain unknown. Given the importance of Tcf4 in psychiatric diseases, we investigated its role in adult neurons using cell-specific deletion and genetic tracing in adult animals. Acute loss of Tcf4 in adult excitatory neurons in vivo caused hyperexcitability and increased dendritic complexity of neurons, effects that were distinct from previously observed effects in embryonic-deficiency models. Interestingly, transcriptomic analysis of genetically traced adult-deleted FACS-sorted Tcf4-knockout neurons revealed that Tcf4 targets in adult neurons are distinct from those in the embryonic brain. Meta-analysis of the adult-deleted neuronal transcriptome from our study with the existing datasets of embryonic Tcf4 deficiencies revealed plasma membrane and ciliary genes to underlie Tcf4-mediated structure-function regulation specifically in adult neurons. The profound changes both in the structure and excitability of adult neurons upon acute loss of Tcf4 indicates that proactive regulation of membrane-related processes underlies the functional and structural integrity of adult neurons. These findings not only provide insights for the functional relevance of continual expression of a psychiatric disease-risk gene in the adult brain but also identify previously unappreciated gene networks underpinning mature neuronal regulation during the adult lifespan.
    Mesh-Begriff(e) Animals ; Brain ; Disease Models, Animal ; Haploinsufficiency ; Mice ; Neurons ; Schizophrenia/genetics
    Sprache Englisch
    Erscheinungsdatum 2021-09-25
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
    ZDB-ID 2609311-X
    ISSN 2158-3188 ; 2158-3188
    ISSN (online) 2158-3188
    ISSN 2158-3188
    DOI 10.1038/s41398-021-01618-x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: An Early Cortical Progenitor-Specific Mechanism Regulates Thalamocortical Innervation.

    Pal, Suranjana / Dwivedi, Deepanjali / Pramanik, Tuli / Godbole, Geeta / Iwasato, Takuji / Jabaudon, Denis / Bhalla, Upinder S / Tole, Shubha

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2021  Band 41, Heft 32, Seite(n) 6822–6835

    Abstract: The cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but "wait" for several days, entering the cortical plate postnatally. ...

    Abstract The cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but "wait" for several days, entering the cortical plate postnatally. We report that when transcription factor LHX2 is lost in E11.5 cortical progenitors, which give rise to subplate neurons, thalamocortical afferents display premature, exuberant ingrowth into the E15.5 cortex. Embryonic mutant subplate neurons are correctly positioned below the cortical plate, but they display an altered transcriptome and immature electrophysiological properties during the waiting period. The sensory thalamus in these cortex-specific
    Mesh-Begriff(e) Animals ; Brain/embryology ; Cell Movement/physiology ; Female ; LIM-Homeodomain Proteins/metabolism ; Male ; Mice ; Neural Pathways/embryology ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Neurogenesis/physiology ; Neurons, Afferent/cytology ; Neurons, Afferent/metabolism ; Transcription Factors/metabolism
    Chemische Substanzen LIM-Homeodomain Proteins ; Lhx2 protein, mouse ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2021-06-30
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.0226-21.2021
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1668: Hefte anzeigen Standort:
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  8. Artikel ; Online: The organization and development of cortical interneuron presynaptic circuits are area specific.

    Pouchelon, Gabrielle / Dwivedi, Deepanjali / Bollmann, Yannick / Agba, Chimuanya K / Xu, Qing / Mirow, Andrea M C / Kim, Sehyun / Qiu, Yanjie / Sevier, Elaine / Ritola, Kimberly D / Cossart, Rosa / Fishell, Gord

    Cell reports

    2021  Band 37, Heft 6, Seite(n) 109993

    Abstract: Parvalbumin and somatostatin inhibitory interneurons gate information flow in discrete cortical areas that compute sensory and cognitive functions. Despite the considerable differences between areas, individual interneuron subtypes are genetically ... ...

    Abstract Parvalbumin and somatostatin inhibitory interneurons gate information flow in discrete cortical areas that compute sensory and cognitive functions. Despite the considerable differences between areas, individual interneuron subtypes are genetically invariant and are thought to form canonical circuits regardless of which area they are embedded in. Here, we investigate whether this is achieved through selective and systematic variations in their afferent connectivity during development. To this end, we examined the development of their inputs within distinct cortical areas. We find that interneuron afferents show little evidence of being globally stereotyped. Rather, each subtype displays characteristic regional connectivity and distinct developmental dynamics by which this connectivity is achieved. Moreover, afferents dynamically regulated during development are disrupted by early sensory deprivation and in a model of fragile X syndrome. These data provide a comprehensive map of interneuron afferents across cortical areas and reveal the logic by which these circuits are established during development.
    Mesh-Begriff(e) Animals ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Female ; Fragile X Mental Retardation Protein/physiology ; Fragile X Syndrome/genetics ; Fragile X Syndrome/metabolism ; Fragile X Syndrome/pathology ; Interneurons/metabolism ; Interneurons/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neural Pathways ; Presynaptic Terminals/metabolism ; Presynaptic Terminals/pathology ; Rabies virus/genetics ; Sense Organs/metabolism ; Sense Organs/pathology ; Synapses/metabolism ; Synapses/pathology
    Chemische Substanzen Fmr1 protein, mouse ; Fragile X Mental Retardation Protein (139135-51-6)
    Sprache Englisch
    Erscheinungsdatum 2021-11-10
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.109993
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Cortical somatostatin interneuron subtypes form cell-type-specific circuits.

    Wu, Sherry Jingjing / Sevier, Elaine / Dwivedi, Deepanjali / Saldi, Giuseppe-Antonio / Hairston, Ariel / Yu, Sabrina / Abbott, Lydia / Choi, Da Hae / Sherer, Mia / Qiu, Yanjie / Shinde, Ashwini / Lenahan, Mackenzie / Rizzo, Daniella / Xu, Qing / Barrera, Irving / Kumar, Vipin / Marrero, Giovanni / Prönneke, Alvar / Huang, Shuhan /
    Kullander, Klas / Stafford, David A / Macosko, Evan / Chen, Fei / Rudy, Bernardo / Fishell, Gord

    Neuron

    2023  Band 111, Heft 17, Seite(n) 2675–2692.e9

    Abstract: The cardinal classes are a useful simplification of cortical interneuron diversity, but such broad subgroupings gloss over the molecular, morphological, and circuit specificity of interneuron subtypes, most notably among the somatostatin interneuron ... ...

    Abstract The cardinal classes are a useful simplification of cortical interneuron diversity, but such broad subgroupings gloss over the molecular, morphological, and circuit specificity of interneuron subtypes, most notably among the somatostatin interneuron class. Although there is evidence that this diversity is functionally relevant, the circuit implications of this diversity are unknown. To address this knowledge gap, we designed a series of genetic strategies to target the breadth of somatostatin interneuron subtypes and found that each subtype possesses a unique laminar organization and stereotyped axonal projection pattern. Using these strategies, we examined the afferent and efferent connectivity of three subtypes (two Martinotti and one non-Martinotti) and demonstrated that they possess selective connectivity with intratelecephalic or pyramidal tract neurons. Even when two subtypes targeted the same pyramidal cell type, their synaptic targeting proved selective for particular dendritic compartments. We thus provide evidence that subtypes of somatostatin interneurons form cell-type-specific cortical circuits.
    Mesh-Begriff(e) Interneurons/physiology ; Neurons/physiology ; Pyramidal Cells/physiology ; Axons/metabolism ; Somatostatin/metabolism ; Parvalbumins/metabolism
    Chemische Substanzen Somatostatin (51110-01-1) ; Parvalbumins
    Sprache Englisch
    Erscheinungsdatum 2023-06-29
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2023.05.032
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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