Biology subjects

Kapoor, I.

Publications and source records attributed to Kapoor, I..

5 recordsLinked to original sources

bioRxiv2024

A modulatory attentional gate promotes recent memory expression in Drosophila

Using short-term memory (STM) requires that animals can distinguish memories of recent experience from those learned previously. In Drosophila the neuromodulator octopamine (OA) specifically affects STM through adrenergic-like receptors within neurons in the Mushroom Body (MB) network. However, why OA preferentially impacts STM remains unclear. A fly brain connectome reveals that two OA-VPM3 neurons provide most OA input to the MB network. Artificial OA-VPM3 activation during olfactory learning enhances STM and can divert odor salience. -adrenergic-like receptor knock-down in MB {beta} and {gamma} lobe MB Output Neurons (MBONs) generally impaired STM, while {beta}-adrenergic-like receptor loss from lobe MBONs enhanced memory. The identity and connectivity of the relevant MBONs suggests OA modulates an interaction between sites of STM and long-term memory (LTM) storage. Indeed, synthetic, odor, and learning-driven, OA-VPM3 activation temporarily blocks LTM expression. Therefore, OA reconfigures the MBON network so the fly prioritizes expression of recent over remote memories.

neuroscience↗

bioRxiv2022

Single neurons and networks in the claustrum integrate input from widespread cortical sources

The claustrum is thought to be one of the most highly interconnected forebrain structures but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons to understand how the structures unique convergence of input and divergence of output support binding information streams. We found that neurons in the claustrum communicate with each other across efferent projection-defined modules which were differentially innervated by sensory and frontal cortical areas. Individual claustrum neurons were responsive to inputs from more than one cortical region in a cell-type and projection-specific manner, particularly between areas of frontal cortex. In vivo imaging of claustrum axons revealed responses to both unimodal and multimodal sensory stimuli. Finally, chronic claustrum silencing specifically reduced animals sensitivity to multimodal stimuli. These findings support the view that the claustrum is a fundamentally integrative structure, consolidating information from around the cortex and redistributing it following local computations.

neuroscience↗

bioRxiv2020

Potassium starvation induces autophagy in yeast

ABSTRACTAutophagy is a conserved process that recycles cellular contents to promote survival. Although nitrogen starvation is the canonical inducer of autophagy, recent studies have revealed several other nutrients important to this process. In this study, we used a quantitative, high-throughput assay to identify potassium starvation as a new and potent inducer of autophagy. We found that potassium-dependent autophagy requires the core pathway kinases Atg1, Atg5, Vps34, as well as other components of Phosphatidylinositol 3-kinase Complex I. Transmission electron microscopy revealed abundant autophagosome formation in response to both stimuli. RNA sequencing indicated distinct transcriptional responses – nitrogen affects transport of ions such as copper while potassium targets the organization of other cellular components. Thus, nitrogen and potassium share the ability to influence metabolic supply and demand but do so in different ways. Both inputs promote catabolism through bulk autophagy, but inhibit cellular anabolism through distinct mechanisms.Competing Interest StatementThe authors have declared no competing interest.ABBREVIATIONSPIPhosphatidylinositolATGAutophagy-related geneSCDSynthetic Complete medium with DextroseYNBYeast Nitrogen BaseTEMTransmission Electron MicroscopyMAPKMitogen-Activated Protein KinaseDEGDifferentially Expressed Gene.View Full Text

biochemistry↗

bioRxiv2020

Biochemical Basis for the Regulation of Biosynthesis of Antiparasitics by Bacterial Hormones

Diffusible small molecule microbial hormones drastically alter the expression profiles of antibiotics and other drugs in actinobacteria. For example, avenolide (a butenolide) regulates production of avermectin, derivatives of which are used in the treatment of river blindness and other parasitic diseases. Butenolides and {gamma}-butyrolactones control production of pharmaceutically important secondary metabolites by binding to TetR family transcriptional repressors. Here, we describe a concise, 22-step synthetic strategy for the production of avenolide. We present crystal structures of the butenolide receptor AvaR1 in isolation, and in complex with avenolide, as well as AvaR1 bound to an oligonucleotide derived from its operator. Biochemical studies guided by the co-crystal structures enable identification of 90 new actinobacteria that may be regulated by butenolides, two of which are experimentally verified. These studies provide a foundation for understanding regulation of microbial secondary metabolite production, which may be exploited for the discovery and production of novel medicines.

biochemistry↗

bioRxiv2020

Input connectivity reveals additional heterogeneity of dopaminergic reinforcement in Drosophila

Different types of Drosophila dopaminergic neurons (DANs) reinforce memories of unique valence and provide state-dependent motivational control [1]. Prior studies suggest that the compartment architecture of the mushroom body (MB) is the relevant resolution for distinct DAN functions [2, 3]. Here we used a recent electron microscope volume of the fly brain [4] to reconstruct the fine anatomy of individual DANs within three MB compartments. We find the 20 DANs of the {gamma}5 compartment, at least some of which provide reward teaching signals, can be clustered into 5 anatomical subtypes that innervate different regions within {gamma}5. Reconstructing 821 upstream neurons reveals input selectivity, supporting the functional relevance of DAN sub-classification. Only one PAM-{gamma}5 DAN subtype {gamma}5(fb) receives direct recurrent input from {gamma}5{beta}2a mushroom body output neurons (MBONs) and behavioral experiments distinguish a role for these DANs in memory revaluation from those reinforcing sugar memory. Other DAN subtypes receive major, and potentially reinforcing, inputs from putative gustatory interneurons or lateral horn neurons, which can also relay indirect feedback from MBONs. We similarly reconstructed the single aversively reinforcing PPL1-{gamma}1pedc DAN. The {gamma}1pedc DAN inputs mostly differ from those of {gamma}5 DANs and they cluster onto distinct dendritic branches, presumably separating its established roles in aversive reinforcement and appetitive motivation [5, 6]. Tracing also identified neurons that provide broad input to {gamma}5, {beta}2a and {gamma}1pedc DANs suggesting that distributed DAN populations can be coordinately regulated. These connectomic and behavioral analyses therefore reveal further complexity of dopaminergic reinforcement circuits between and within MB compartments. HighlightsO_LINanoscale anatomy reveals additional subtypes of rewarding dopaminergic neurons. C_LIO_LIConnectomics reveals extensive input specificity to subtypes of dopaminergic neurons. C_LIO_LIAxon morphology implies dopaminergic neurons provide subcompartment-level function. C_LIO_LIUnique dopaminergic subtypes serve aversive memory extinction and sugar learning. C_LI

neuroscience↗