Variability, compensation, and modulation in neurons and circuits.

Abstract:

:I summarize recent computational and experimental work that addresses the inherent variability in the synaptic and intrinsic conductances in normal healthy brains and shows that multiple solutions (sets of parameters) can produce similar circuit performance. I then discuss a number of issues raised by this observation, such as which parameter variations arise from compensatory mechanisms and which reflect insensitivity to those particular parameters. I ask whether networks with different sets of underlying parameters can nonetheless respond reliably to neuromodulation and other global perturbations. At the computational level, I describe a paradigm shift in which it is becoming increasingly common to develop families of models that reflect the variance in the biological data that the models are intended to illuminate rather than single, highly tuned models. On the experimental side, I discuss the inherent limitations of overreliance on mean data and suggest that it is important to look for compensations and correlations among as many system parameters as possible, and between each system parameter and circuit performance. This second paradigm shift will require moving away from measurements of each system component in isolation but should reveal important previously undescribed principles in the organization of complex systems such as brains.

authors

Marder E

doi

10.1073/pnas.1010674108

subject

Has Abstract

pub_date

2011-09-13 00:00:00

pages

15542-8

eissn

0027-8424

issn

1091-6490

pii

1010674108

journal_volume

108 Suppl 3

pub_type

杂志文章,评审
  • Adaptive integration of habits into depth-limited planning defines a habitual-goal-directed spectrum.

    abstract::Behavioral and neural evidence reveal a prospective goal-directed decision process that relies on mental simulation of the environment, and a retrospective habitual process that caches returns previously garnered from available choices. Artificial systems combine the two by simulating the environment up to some depth ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1609094113

    authors: Keramati M,Smittenaar P,Dolan RJ,Dayan P

    更新日期:2016-11-08 00:00:00

  • Evidence for adaptive radiation from a phylogenetic study of plant defenses.

    abstract::One signature of adaptive radiation is a high level of trait change early during the diversification process and a plateau toward the end of the radiation. Although the study of the tempo of evolution has historically been the domain of paleontologists, recently developed phylogenetic tools allow for the rigorous exam...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0904862106

    authors: Agrawal AA,Fishbein M,Halitschke R,Hastings AP,Rabosky DL,Rasmann S

    更新日期:2009-10-27 00:00:00

  • Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in alpha -gustducin.

    abstract::Biochemical and genetic studies have implicated alpha-gustducin as a key component in the transduction of both bitter or sweet taste. Yet, alpha-gustducin-null mice are not completely unresponsive to bitter or sweet compounds. To gain insights into how gustducin mediates responses to bitter and sweet compounds, and to...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.151235798

    authors: Ruiz-Avila L,Wong GT,Damak S,Margolskee RF

    更新日期:2001-07-17 00:00:00

  • Specific phospholipids are required to reconstitute adenylate cyclase solubilized from rat brain.

    abstract::Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] was solubilized from a rat brain homogenate with sodium deoxycholate. This solubilized preparation had no detectable enzymic activity with either Mg-ATP or Mn-ATP as substrate. The activity could be restored by addition of either nonionic detergent or...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.1.120

    authors: Hebdon GM,LeVine H 3rd,Sahyoun NE,Schmitges CJ,Cuatrecasas P

    更新日期:1981-01-01 00:00:00

  • Inhibition of triple-negative breast cancer models by combinations of antibodies to EGFR.

    abstract::Breast tumors lacking expression of human epidermal growth factor receptor 2 (HER2) and the estrogen and the progesterone receptors (triple negative; TNBC) are more aggressive than other disease subtypes, and no molecular targeted agents are currently available for their treatment. Because TNBC commonly displays EGF r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1220763110

    authors: Ferraro DA,Gaborit N,Maron R,Cohen-Dvashi H,Porat Z,Pareja F,Lavi S,Lindzen M,Ben-Chetrit N,Sela M,Yarden Y

    更新日期:2013-01-29 00:00:00

  • A thermodynamic framework for Mg2+ binding to RNA.

    abstract::We present a model describing how Mg(2+) binds and stabilizes specific RNA structures. In this model, RNA stabilization arises from two energetically distinct modes of Mg(2+) binding: diffuse- and site-binding. Diffusely bound Mg(2+) are electrostatically attracted to the strong anionic field around the RNA and are ac...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.221234598

    authors: Misra VK,Draper DE

    更新日期:2001-10-23 00:00:00

  • Clustering of solitons in weakly correlated wavefronts.

    abstract::We demonstrate theoretically and experimentally the spontaneous clustering of solitons in partially coherent wavefronts during the final stages of pattern formation initiated by modulation instability and noise. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.072287299

    authors: Chen Z,Sears SM,Martin H,Christodoulides DN,Segev M

    更新日期:2002-04-16 00:00:00

  • Different rat-derived transforming retroviruses code for an immunologically related intracellular phosphoprotein.

    abstract::Kirsten sarcoma virus (Ki-MSV) and Harvey sarcoma virus (Ha-MSV) are mouse-rat recombinant viruses that were originally isolated by experimental inoculation of rats with helper-independent mouse type C viruses. We have recently identified in cells transformed by Ki-MSV or Ha-MSV, a phosphoprotein, p21, coded for by Ki...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.7.3523

    authors: Young HA,Shih TY,Scolnick EM,Rasheed S,Gardner MB

    更新日期:1979-07-01 00:00:00

  • Beliefs about willpower determine the impact of glucose on self-control.

    abstract::Past research found that the ingestion of glucose can enhance self-control. It has been widely assumed that basic physiological processes underlie this effect. We hypothesized that the effect of glucose also depends on people's theories about willpower. Three experiments, both measuring (experiment 1) and manipulating...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1313475110

    authors: Job V,Walton GM,Bernecker K,Dweck CS

    更新日期:2013-09-10 00:00:00

  • Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea.

    abstract::Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus "Nitrosopumilus maritimus" strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0913533107

    authors: Walker CB,de la Torre JR,Klotz MG,Urakawa H,Pinel N,Arp DJ,Brochier-Armanet C,Chain PS,Chan PP,Gollabgir A,Hemp J,Hügler M,Karr EA,Könneke M,Shin M,Lawton TJ,Lowe T,Martens-Habbena W,Sayavedra-Soto LA,Lang D,Sieve

    更新日期:2010-05-11 00:00:00

  • Oxygen intermediates and mixed valence states of cytochrome oxidase: infrared absorption difference spectra of compounds A, B, and C of cytochrome oxidase and oxygen.

    abstract::A study of the near-infrared absorption spectra of three oxygen compounds of membrane-bound cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) shows that the formation of compound A (oxycytochrome oxidase) causes no significant infrared absorbance changes at -103 degrees. At -64 degrees, the form...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.11.4777

    authors: Chance B,Leigh JS Jr

    更新日期:1977-11-01 00:00:00

  • Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins.

    abstract::The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falciparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.10.4017

    authors: Herrera S,Herrera MA,Perlaza BL,Burki Y,Caspers P,Döbeli H,Rotmann D,Certa U

    更新日期:1990-05-01 00:00:00

  • Protein 4.1R-dependent multiprotein complex: new insights into the structural organization of the red blood cell membrane.

    abstract::Protein 4.1R (4.1R) is a multifunctional component of the red cell membrane. It forms a ternary complex with actin and spectrin, which defines the nodal junctions of the membrane-skeletal network, and its attachment to the transmembrane protein glycophorin C creates a bridge between the protein network and the membran...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0803225105

    authors: Salomao M,Zhang X,Yang Y,Lee S,Hartwig JH,Chasis JA,Mohandas N,An X

    更新日期:2008-06-10 00:00:00

  • Strong balancing selection at HLA loci: evidence from segregation in South Amerindian families.

    abstract::The genotypic proportions for major histocompatibility complex loci, HLA-A and HLA-B, of progeny in families in 23 South Amerindian tribes in which segregation for homozygotes and heterozygotes could occur are examined. Overall, there is a large deficiency of homozygotes compared with Mendelian expectations (for HLA-A...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.23.12452

    authors: Black FL,Hedrick PW

    更新日期:1997-11-11 00:00:00

  • Development of auditory neuronal responses in avian embryos.

    abstract::Neurons in the cochlear nuclei of duck embryos become responsive to tonal stimuli in an orderly spatial and temporal sequence. Cells responding to lower frequencies are recorded before those responding to higher frequencies. Auditory neurons are spatially arranged according to their characteristic frequencies, indicat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.6.1795

    authors: Konishi M

    更新日期:1973-06-01 00:00:00

  • Repression of the overproduction of porphyrin precursors in acute intermittent porphyria by intravenous infusions of hematin.

    abstract::In a patient with a severe attack of acute intermittent porphyria, hematin given intravenously caused marked diminution of serum delta-aminolevulinic acid and porphobilinogen. The decline of aminolevulinate was more rapid than that of porphobilinoge. After 2 days of hematin administration, about 5 days were required f...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.11.2725

    authors: Bonkowsky HL,Tschudy DP,Collins A,Doherty J,Bossenmaier I,Cardinal R,Watson CJ

    更新日期:1971-11-01 00:00:00

  • Mechanism of action of nerve growth factor and cyclic AMP on neurite outgrowth in embryonic chick sensory ganglia: demonstration of independent pathways of stimulation.

    abstract::The suggested role of adenosine 3':5'-cyclic monophosphate as the "second messenger" in the neurite outgrowth from chick embryonic sensory ganglia mediated by nerve growth factor was examined. Although N(6),O(2)-dibutyryl adenosine 3':5'-cyclic monophosphate induces fiber outgrowth at concentrations of 1-5 mM, this re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.8.2448

    authors: Frazier WA,Ohlendorf CE,Boyd LF,Aloe L,Johnson EM,Ferrendelli JA,Bradshaw RA

    更新日期:1973-08-01 00:00:00

  • Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP.

    abstract::In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. The crystal structure of the stimulatory complex reveals that the GTPCHI decame...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.022646999

    authors: Maita N,Okada K,Hatakeyama K,Hakoshima T

    更新日期:2002-02-05 00:00:00

  • Vitamin D deficiency in rats with normal serum calcium concentrations.

    abstract::Rats were raised after weaning on a vitamin D-deficient diet which used whole wheat and casein as the major protein source. For at least the first year of life, plasma calcium concentrations of these rats were the same as those of vitamin D-replete rats, and the rate of growth was normal for at least 6 months. The fol...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.15.4791

    authors: Lester GE,VanderWiel CJ,Gray TK,Talmage RV

    更新日期:1982-08-01 00:00:00

  • Synthesis of Rauscher murine leukemia virus-specific polypeptides in vitro.

    abstract::The biosynthesis of specific polypeptides directed by purified viral messenger RNA from JLS-V9 cells infected with Rauscher leukemia virus has been studied in a rabbit reticulocyte lysate. The 35S viral mRNA gives rise to two major products of 65,000 and 72,000 molecular weight. The synthesis of specific polypeptides ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.2.356

    authors: Gielkens AL,Van Zaane D,Bloemers HP,Bloemendal H

    更新日期:1976-02-01 00:00:00

  • Architected cellular ceramics with tailored stiffness via direct foam writing.

    abstract::Hierarchical cellular structures are ubiquitous in nature because of their low-density, high-specific properties, and multifunctionality. Inspired by these systems, we created lightweight ceramic architectures composed of closed-cell porous struts patterned in the form of hexagonal and triangular honeycombs by direct ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1616769114

    authors: Muth JT,Dixon PG,Woish L,Gibson LJ,Lewis JA

    更新日期:2017-02-21 00:00:00

  • Remote sensing of future competitors: impacts on plant defenses.

    abstract::Far-red radiation (FR) reflected by green tissues is a key signal that plants use to detect the proximity of future competitors. Perception of increased levels of FR elicits a suite of responses collectively known as the shade-avoidance syndrome, which includes increased stem elongation, production of erect leaves, an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0509805103

    authors: Izaguirre MM,Mazza CA,Biondini M,Baldwin IT,Ballaré CL

    更新日期:2006-05-02 00:00:00

  • A pex1 missense mutation improves peroxisome function in a subset of Arabidopsis pex6 mutants without restoring PEX5 recycling.

    abstract::Peroxisomes are eukaryotic organelles critical for plant and human development because they house essential metabolic functions, such as fatty acid β-oxidation. The interacting ATPases PEX1 and PEX6 contribute to peroxisome function by recycling PEX5, a cytosolic receptor needed to import proteins targeted to the pero...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1721279115

    authors: Gonzalez KL,Ratzel SE,Burks KH,Danan CH,Wages JM,Zolman BK,Bartel B

    更新日期:2018-04-03 00:00:00

  • Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells.

    abstract::Nonsteroidal antiinflammatory drugs reduce the risk of colon cancer, possibly via cyclooxygenase (COX) inhibition. The growth factor-inducible COX-2, which is overexpressed in neoplastic colonic tissue, is an attractive target to mediate this effect. Herein we have exploited the ability of a human colon cancer cell li...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.2.657

    authors: Coffey RJ,Hawkey CJ,Damstrup L,Graves-Deal R,Daniel VC,Dempsey PJ,Chinery R,Kirkland SC,DuBois RN,Jetton TL,Morrow JD

    更新日期:1997-01-21 00:00:00

  • Casimir light: photon pairs.

    abstract::Expressions are developed for weak single pair emission probability and strong emission average number of pairs. The water transparency cutoff is closely realized, showing that the fundamental time scale is even shorter. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.10.4505

    authors: Schwinger J

    更新日期:1993-05-15 00:00:00

  • Cell-surface heparan sulfate: an intercalated membrane proteoglycan.

    abstract::Two pools of heparan sulfate proteoglycans have been selectively solubilized from rat liver plasma membranes by successive incubations with heparin and detergent. The two populations of proteoglycans have similar polyanionic properties as indicated by identical elution positions on ion-exchange chromatography on DEAE-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.9.5371

    authors: Kjellén L,Pettersson I,Höök M

    更新日期:1981-09-01 00:00:00

  • On the strength of glasses.

    abstract::The remarkable strength of glasses is examined using the random first order transition theory of the glass transition. The theory predicts that strength depends on elastic modulus but also on the configurational energy frozen in when the glass is prepared. The stress catalysis of cooperative rearrangements of the type...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1214130109

    authors: Wisitsorasak A,Wolynes PG

    更新日期:2012-10-02 00:00:00

  • Activation of purified calcium channels by stoichiometric protein phosphorylation.

    abstract::Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of 45Ca2+ uptake into vesicles containing reconstitute...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.17.6816

    authors: Nunoki K,Florio V,Catterall WA

    更新日期:1989-09-01 00:00:00

  • Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis.

    abstract::The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. During neuronal differentiation, the Ryk intracellular domain (ICD) is cleaved. Cleavage of Ryk and nuclear translocation of Ryk-ICD are required for neuronal differentiation. However, the mechanism...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1715772114

    authors: Chang WH,Choi SH,Moon BS,Cai M,Lyu J,Bai J,Gao F,Hajjali I,Zhao Z,Campbell DB,Weiner LP,Lu W

    更新日期:2017-12-12 00:00:00

  • Lines that do not increase their width under a magnifying glass.

    abstract::A light beam hitting the retina produces an excitatory process; however, around the edge of the light beam, sensory cells are inhibited and lose their sensitivity. This combination of stimulation and inhibition produces a discrepancy between the luminance pattern presented to the eye and the brightness pattern that is...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.4.885

    authors: Von Békésy G

    更新日期:1972-04-01 00:00:00