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4106 Publications

Showing 511-520 of 4106 results
Svoboda Lab
08/24/18 | Anterolateral motor cortex connects with a medial subdivision of ventromedial thalamus through cell-type-specific circuits, forming an excitatory thalamo-cortico-thalamic loop via layer 1 apical tuft dendrites of layer 5B pyramidal tract type neurons.
Guo K, Yamawaki N, Svoboda K, Shepherd GM
The Journal of Neuroscience : the official journal of the Society for Neuroscience. 2018 Aug 24;38(41):8787-97. doi: 10.1523/JNEUROSCI.1333-18.2018

The anterolateral motor cortex (ALM) and ventromedial (VM) thalamus are functionally linked to support persistent activity during motor planning. We analyzed the underlying synaptic interconnections using optogenetics and electrophysiology in mice (♀/♂). In cortex, thalamocortical (TC) axons from VM excited VM-projecting pyramidal-tract (PT) neurons in layer 5B of ALM. These axons also strongly excited layer 2/3 neurons (which strongly excite PT neurons, as previously shown) but not VM-projecting corticothalamic (CT) neurons in layer 6. The strongest connections in the VM→PT circuit were localized to apical-tuft dendrites of PT neurons, in layer 1. These tuft inputs were selectively augmented after blocking hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In thalamus, axons from ALM PT neurons excited ALM-projecting VM neurons, located medially in VM. These axons provided weak input to neurons in mediodorsal nucleus, and little or no input either to neurons in the GABAergic reticular thalamic nucleus or to neurons in VM projecting to primary motor cortex (M1). Conversely, M1 PT axons excited M1- but not ALM-projecting VM neurons. Our findings indicate, first, a set of cell-type-specific connections forming an excitatory thalamo-cortico-thalamic (T-C-T) loop for ALM↔VM communication and a circuit-level substrate for supporting reverberant activity in this system. Second, a key feature of this loop is the prominent involvement of layer 1 synapses onto apical dendrites, a subcellular compartment with distinct signaling properties, including HCN-mediated gain control. Third, the segregation of the ALM↔VM loop from M1-related circuits of VM adds cellular-level support for the concept of parallel pathway organization in the motor system.Anterolateral motor cortex (ALM), a higher-order motor area in the mouse, and ventromedial thalamus (VM) are anatomically and functionally linked, but their synaptic interconnections at the cellular level are unknown. Our results show that ALM pyramidal tract neurons monosynaptically excite ALM-projecting thalamocortical neurons in a medial subdivision of VM, and vice versa. The thalamo-cortico-thalamic loop formed by these recurrent connections constitutes a circuit-level substrate for supporting reverberant activity in this system.

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10/29/24 | Anti-seizure effects of norepinephrine-induced free fatty acid release.
Li B, Sun Q, Ding F, Xu Q, Kang N, Xue Y, Ladron-de-Guevara A, Hirase H, Weikop P, Gong S, Nathan S, Nedergaard M
Cell Metab. 2024 Oct 29:. doi: 10.1016/j.cmet.2024.10.011

The brain's ability to rapidly transition between sleep, quiet wakefulness, and states of high vigilance is remarkable. Cerebral norepinephrine (NE) plays a key role in promoting wakefulness, but how does the brain avoid neuronal hyperexcitability upon arousal? Here, we show that NE exposure results in the generation of free fatty acids (FFAs) within the plasma membrane from both astrocytes and neurons. In turn, FFAs dampen excitability by differentially modulating the activity of astrocytic and neuronal Na, K, ATPase. Direct application of FFA to the occipital cortex in awake, behaving mice dampened visual-evoked potential (VEP). Conversely, blocking FFA production via local application of a lipase inhibitor heightened VEP and triggered seizure-like activity. These results suggest that FFA release is a crucial step in NE signaling that safeguards against hyperexcitability. Targeting lipid-signaling pathways may offer a novel therapeutic approach for seizure prevention.

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01/12/17 | Antibodies to biotin enable large-scale detection of biotinylation sites on proteins
Udeshi ND, Pedram K, Svinkina T, Fereshetian S, Myers SA, Aygun O, Krug K, Clauser K, Ryan D, Ast T, Mootha VK, Ting AY, Carr SA
Nature Methods. Jan-12-2017;14(12):1167 - 1170. doi: 10.1038/nmeth.4465

Although purification of biotinylated molecules is highly efficient, identifying specific sites of biotinylation remains challenging. We show that anti-biotin antibodies enable unprecedented enrichment of biotinylated peptides from complex peptide mixtures. Live-cell proximity labeling using APEX peroxidase followed by anti-biotin enrichment and mass spectrometry yielded over 1,600 biotinylation sites on hundreds of proteins, an increase of more than 30-fold in the number of biotinylation sites identified compared to streptavidin-based enrichment of proteins.

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01/01/05 | Antibody humanization and affinity maturation using phage display.
Marvin JS, Lowman HB
Phage Display in Biotechnology and Drug Discovery. 2005:493-528
05/01/05 | Antipsychotic drugs elevate mRNA levels of presynaptic proteins in the frontal cortex of the rat.
MacDonald ML, Eaton ME, Dudman JT, Konradi C
Biological Psychiatry. 2005 May 1;57(9):1041-51. doi: 10.3389/fnana.2010.00147

Molecular adaptations are believed to contribute to the mechanism of action of antipsychotic drugs (APDs). We attempted to establish common gene regulation patterns induced by chronic treatment with APDs.

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11/30/91 | Aphid soldiers discriminate between soldiers and non-soldiers, rather than between kin and non-kin, in Ceratoglyphina bambusae
Shigeyuki Aoki , Utako Kurosu , David L Stern
Animal behaviour;42(5):865-866. doi: 10.1016/S0003-3472(05)80135-6

Examined kin discrimination and colony defense in soldier-producing aphids from the surface of 3 galls. Soldiers always attacked conspecific nonsoldiers, regardless of origin, and never attacked conspecific soldiers. Soldier attacks of nonsoldiers may exclude unrelated nonsoldier aphids from the gall where they would propagate and compete with resident aphids. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

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12/16/14 | Aphids evolved novel secreted proteins for symbiosis with bacterial endosymbiont.
Shigenobu S, Stern DL
Proc Biol Sci. 2013 Jan 7;280(1750):20121952. doi: 10.1098/rspb.2012.1952

Aphids evolved novel cells, called bacteriocytes, that differentiate specifically to harbour the obligatory mutualistic endosymbiotic bacteria Buchnera aphidicola. The genome of the host aphid Acyrthosiphon pisum contains many orphan genes that display no similarity with genes found in other sequenced organisms, prompting us to hypothesize that some of these orphan genes are related to lineage-specific traits, such as symbiosis. We conducted deep sequencing of bacteriocytes mRNA followed by whole mount in situ hybridizations of over-represented transcripts encoding aphid-specific orphan proteins. We identified a novel class of genes that encode small proteins with signal peptides, which are often cysteine-rich, that are over-represented in bacteriocytes. These genes are first expressed at a developmental time point coincident with the incorporation of symbionts strictly in the cells that contribute to the bacteriocyte and this bacteriocyte-specific expression is maintained throughout the aphid's life. The expression pattern suggests that recently evolved secretion proteins act within bacteriocytes, perhaps to mediate the symbiosis with beneficial bacterial partners, which is reminiscent of the evolution of novel cysteine-rich secreted proteins of leguminous plants that regulate nitrogen-fixing endosymbionts.

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06/24/08 | Aphids.
Stern DL
Curr Biol. 2008 Jun 24;18(12):R504-5. doi: 10.1016/j.cub.2008.03.034

Mammalian herbivores profoundly influence plant-dwelling insects [1]. Most studies have focused on the indirect effect of herbivory on insect populations via damage to the host plant [2,3]. Many insects, however, are in danger of being inadvertently ingested during herbivore feeding. Here, we report that pea aphids (Acyrthosiphon pisum) are able to sense the elevated heat and humidity of the breath of an approaching herbivore and thus salvage most of the colony by simultaneously dropping off the plant in large numbers immediately before the plant is eaten. Dropping entails the risk of losing the host plant and becoming desiccated or preyed upon on the ground [4,5], yet pea aphids may sporadically drop when threatened by insect enemies [6]. The immediate mass dropping, however, is an adaptation to the potential destructive impact of mammalian herbivory on the entire aphid colony. The combination of heat and humidity serves as a reliable cue to impending mammalian herbivory, enabling the aphids to avoid unnecessary dropping. No defensive behavior against incidental predation by herbivores has ever been demonstrated. The pea aphids' highly adaptive escape behavior uniquely demonstrates the strength of the selective pressure large mammalian herbivores impose on insect herbivores.

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07/02/18 | Apical and basal matrix remodeling control epithelial morphogenesis.
Diaz-de-la-Loza M, Ray RP, Ganguly PS, Alt S, Davis JR, Hoppe A, Tapon N, Salbreux G, Thompson BJ
Developmental Cell. 2018 Jul 02;46(1):23-39.e5. doi: 10.1016/j.devcel.2018.06.006

Epithelial tissues can elongate in two dimensions by polarized cell intercalation, oriented cell division, or cell shape change, owing to local or global actomyosin contractile forces acting in the plane of the tissue. In addition, epithelia can undergo morphogenetic change in three dimensions. We show that elongation of the wings and legs of Drosophila involves a columnar-to-cuboidal cell shape change that reduces cell height and expands cell width. Remodeling of the apical extracellular matrix by the Stubble protease and basal matrix by MMP1/2 proteases induces wing and leg elongation. Matrix remodeling does not occur in the haltere, a limb that fails to elongate. Limb elongation is made anisotropic by planar polarized Myosin-II, which drives convergent extension along the proximal-distal axis. Subsequently, Myosin-II relocalizes to lateral membranes to accelerate columnar-to-cuboidal transition and isotropic tissue expansion. Thus, matrix remodeling induces dynamic changes in actomyosin contractility to drive epithelial morphogenesis in three dimensions.

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06/01/13 | APP2: automatic tracing of 3D neuron morphology based on hierarchical pruning of a gray-weighted image distance-tree.
Xiao H, Peng H
Bioinformatics (Oxford, England). 2013 Jun 1;29:1448-54. doi: 10.1093/bioinformatics/btt170

Tracing of neuron morphology is an essential technique in computational neuroscience. However, despite a number of existing methods, few open-source techniques are completely or sufficiently automated and at the same time are able to generate robust results for real 3D microscopy images.

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