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Prabhu, P.

Publications and source records attributed to Prabhu, P..

4 recordsLinked to original sources

Identifying neuropeptides in Hydra: a custom pipeline reveals a non-amidated regulator of muscle contraction and other new members

Neuropeptides play a critical role in neurotransmission and organismal development. Members of phylum Cnidaria, with a diffused nervous system, are one of the earliest divergent animals and might provide insights into the fundamentals of the emergence of neuronal communications. The neuropeptide diversity in Hydra (a cnidarian model) has been extensively studied using various strategies, each with certain limitations. Here, we have developed an in silico pipeline which identified both reported peptides and many new potential candidates. A comparative analysis within Cnidaria suggests a rapid divergence of neuropeptides which might be involved in complex behaviors. We identified new Hydra neuropeptides that belong to the RFamide and PRGamide families and a novel class of peptides lacking amidation (LW-peptides). A detailed expression and functional analysis of a new LW-peptide indicates its role in the longitudinal contraction of Hydra polyps. This study provides compelling evidence for the existence of intricate peptidergic communication in early neuronal circuits. The extensive diversity of neuropeptides within this phylum underscores their rapid evolutionary adaptability. This current pipeline also proves to be simple and adaptable to perform neuropeptide identification in other multicellular organisms.

neuroscience↗

Slow and fast gamma oscillations show phase-amplitude coupling with distinct high-frequency bands in macaque primary visual cortex

Gamma oscillations (25-70 Hz) can be induced in the visual cortex by presenting stimuli like gratings. Large stimuli produce two distinct gamma oscillations in primate primary visual cortex (V1) - slow (25-40 Hz) and fast (40-70 Hz), possibly due to different interneuronal networks. While fast-gamma has been shown to strongly lock spikes, slow-gamma does not, and hence its role in cortical processing is unclear. Here, we studied potential influence of gamma rhythms on neural activity using phase-amplitude coupling (PAC). We recorded spikes, local field potential and electrocorticogram (ECoG) from V1 of two adult female monkeys while presenting stimuli that simultaneously induced both gamma rhythms, and developed a novel method that reduces the influence of spike-related-transient on PAC. Interestingly, while fast-gamma showed coupling with frequencies above 150 Hz, reflecting spike-locking, slow-gamma showed PAC in a distinct frequency range between 80-150 Hz, which was especially prominent in ECoG. PAC varied with orientation and spatial frequency in the same way as power in the respective frequency bands, confirming dissociation in the coupling of the two gamma rhythms. Thus, fast-gamma could be more involved in spike-locking, while slow-gamma could represent a modulatory signal acting by amplitude modulation between 80-150 Hz at a more global scale. Significance StatementGamma oscillations in the visual cortex can be induced by stimuli like gratings, producing two distinct gamma oscillations: slow (20-40 Hz) and fast (40-70 Hz). While fast-gamma strongly locks spikes, the role of slow gamma is unclear. Oscillations have been proposed to influence processing through phase-amplitude coupling (PAC). We recorded spikes, local field potential (LFP) and electrocorticogram (ECoG) from female monkeys and developed a new method to study PAC. While fast-gamma showed PAC with 150-500 Hz, reflecting spike-locking, we found PAC between slow-gamma and 80-150 Hz, which was especially strong in ECoG. The two PAC signatures varied differently with stimulus, reflecting distinct origins. Thus, while fast-gamma could lock spikes, slow-gamma could modulate amplitudes between 80-150 Hz at a global scale.

neuroscience↗

Role of PARP1 in oligodendrocyte differentiation during developmental myelination and remyelination after myelin damage

The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remain enigmatic. Here we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a novel PARylated target which we show controls OPC differentiation through PARylation-modulated de-repression of myelin protein expression. Furthermore, PARP1s enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.

neuroscience↗

Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways

The mechanisms by which oligodendroglia modulate CNS angiogenesis remain elusive. Previous in vitro data suggest that oligodendroglia regulate CNS endothelial cell proliferation and blood vessel formation through hypoxia inducible factor alpha (HIF)-activated Wnt (but not VEGF) signaling. Using in vivo genetic models, we show that HIF in oligodendroglia is necessary and sufficient for angiogenesis independent of CNS regions. At the molecular level, HIF stabilization in oligodendroglia does not perturb Wnt signaling but remarkably activates VEGF. At the functional level, genetically blocking oligodendroglia-derived VEGF but not Wnt significantly decreases oligodendroglial HIF-regulated CNS angiogenesis. Interestingly, blocking astroglia-derived Wnt signaling reduces astroglial HIF-regulated CNS angiogenesis. Together, our in vivo data clearly demonstrate that oligodendroglial HIF regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling. Our findings represent an alternative mechanistic understanding of CNS angiogenesis by postnatal glial cells and unveil a glial cell type-dependent HIF-Wnt axis in regulating CNS vessel formation.

neuroscience↗