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Sacha B. Nelson

Bio: Sacha B. Nelson is an academic researcher from Brandeis University. The author has contributed to research in topics: Visual cortex & Excitatory postsynaptic potential. The author has an hindex of 68, co-authored 134 publications receiving 27897 citations. Previous affiliations of Sacha B. Nelson include Salk Institute for Biological Studies & Center for Neural Science.


Papers
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Journal ArticleDOI
TL;DR: Evidence is discussed from a number of systems that homeostatic synaptic plasticity is crucial for processes ranging from memory storage to activity-dependent development, and how these processes maintain stable activity states in the face of destabilizing forces is discussed.
Abstract: Activity has an important role in refining synaptic connectivity during development, in part through 'Hebbian' mechanisms such as long-term potentiation and long-term depression. However, Hebbian plasticity is probably insufficient to explain activity-dependent development because it tends to destabilize the activity of neural circuits. How can complex circuits maintain stable activity states in the face of such destabilizing forces? An idea that is emerging from recent work is that average neuronal activity levels are maintained by a set of homeostatic plasticity mechanisms that dynamically adjust synaptic strengths in the correct direction to promote stability. Here we discuss evidence from a number of systems that homeostatic synaptic plasticity is crucial for processes ranging from memory storage to activity-dependent development.

2,315 citations

Journal ArticleDOI
26 Feb 1998-Nature
TL;DR: A new form of synaptic plasticity is described that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity, and may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs.
Abstract: Information is stored in neural circuits through long-lasting changes in synaptic strengths. Most studies of information storage have focused on mechanisms such as long-term potentiation and depression (LTP and LTD), in which synaptic strengths change in a synapse-specific manner. In contrast, little attention has been paid to mechanisms that regulate the total synaptic strength of a neuron. Here we describe a new form of synaptic plasticity that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity. Chronic blockade of cortical culture activity increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) without changing their kinetics. Conversely, blocking GABA (gamma-aminobutyric acid)-mediated inhibition initially raised firing rates, but over a 48-hour period mESPC amplitudes decreased and firing rates returned to close to control values. These changes were at least partly due to postsynaptic alterations in the response to glutamate, and apparently affected each synapse in proportion to its initial strength. Such 'synaptic scaling' may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs, as well as stabilizing synaptic strengths during Hebbian modification and facilitating competition between synapses.

2,197 citations

Journal ArticleDOI
TL;DR: This work reviews three Hebbian forms of plasticity—synaptic scaling, spike-timing dependent plasticity and synaptic redistribution—and discusses their functional implications.
Abstract: Synaptic plasticity provides the basis for most models of learning, memory and development in neural circuits. To generate realistic results, synapse-specific Hebbian forms of plasticity, such as long-term potentiation and depression, must be augmented by global processes that regulate overall levels of neuronal and network activity. Regulatory processes are often as important as the more intensively studied Hebbian processes in determining the consequences of synaptic plasticity for network function. Recent experimental results suggest several novel mechanisms for regulating levels of activity in conjunction with Hebbian synaptic modification. We review three of them-synaptic scaling, spike-timing dependent plasticity and synaptic redistribution-and discuss their functional implications.

2,118 citations

Journal ArticleDOI
10 Jan 1997-Science
TL;DR: Modeling work based on experimental measurements indicates that short-term depression of intracortical synapses provides a dynamic gain-control mechanism that allows equal percentage rate changes on rapidly and slowly firing afferents to produce equal postsynaptic responses.
Abstract: Cortical neurons receive synaptic inputs from thousands of afferents that fire action potentials at rates ranging from less than 1 hertz to more than 200 hertz. Both the number of afferents and their large dynamic range can mask changes in the spatial and temporal pattern of synaptic activity, limiting the ability of a cortical neuron to respond to its inputs. Modeling work based on experimental measurements indicates that short-term depression of intracortical synapses provides a dynamic gain-control mechanism that allows equal percentage rate changes on rapidly and slowly firing afferents to produce equal postsynaptic responses. Unlike inhibitory and adaptive mechanisms that reduce responsiveness to all inputs, synaptic depression is input-specific, leading to a dramatic increase in the sensitivity of a neuron to subtle changes in the firing patterns of its afferents.

1,724 citations

Journal ArticleDOI
22 Sep 2011-Neuron
TL;DR: Using genetic engineering in mice, approximately 20 Cre and inducible CreER knockin driver lines that reliably target major classes and lineages of GABAergic neurons are generated, thereby enabling a systematic and comprehensive analysis from cell fate specification, migration, and connectivity, to their functions in network dynamics and behavior.

1,655 citations


Cited by
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Journal ArticleDOI
TL;DR: This article reviews studies investigating complex brain networks in diverse experimental modalities and provides an accessible introduction to the basic principles of graph theory and highlights the technical challenges and key questions to be addressed by future developments in this rapidly moving field.
Abstract: Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks--such as small-world topology, highly connected hubs and modularity--both at the whole-brain scale of human neuroimaging and at a cellular scale in non-human animals. In this article, we review studies investigating complex brain networks in diverse experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans) and provide an accessible introduction to the basic principles of graph theory. We also highlight some of the technical challenges and key questions to be addressed by future developments in this rapidly moving field.

9,700 citations

Journal ArticleDOI
TL;DR: A set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra is generated and enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo.
Abstract: The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universally responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in several Cre-driver lines, including new Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.

5,365 citations

Journal ArticleDOI
Ed S. Lein1, Michael Hawrylycz1, Nancy Ao2, Mikael Ayres1, Amy Bensinger1, Amy Bernard1, Andrew F. Boe1, Mark S. Boguski1, Mark S. Boguski3, Kevin S. Brockway1, Emi J. Byrnes1, Lin Chen1, Li Chen2, Tsuey-Ming Chen2, Mei Chi Chin1, Jimmy Chong1, Brian E. Crook1, Aneta Czaplinska2, Chinh Dang1, Suvro Datta1, Nick Dee1, Aimee L. Desaki1, Tsega Desta1, Ellen Diep1, Tim A. Dolbeare1, Matthew J. Donelan1, Hong-Wei Dong1, Jennifer G. Dougherty1, Ben J. Duncan1, Amanda Ebbert1, Gregor Eichele4, Lili K. Estin1, Casey Faber1, Benjamin A.C. Facer1, Rick Fields2, Shanna R. Fischer1, Tim P. Fliss1, Cliff Frensley1, Sabrina N. Gates1, Katie J. Glattfelder1, Kevin R. Halverson1, Matthew R. Hart1, John G. Hohmann1, Maureen P. Howell1, Darren P. Jeung1, Rebecca A. Johnson1, Patrick T. Karr1, Reena Kawal1, Jolene Kidney1, Rachel H. Knapik1, Chihchau L. Kuan1, James H. Lake1, Annabel R. Laramee1, Kirk D. Larsen1, Christopher Lau1, Tracy Lemon1, Agnes J. Liang2, Ying Liu2, Lon T. Luong1, Jesse Michaels1, Judith J. Morgan1, Rebecca J. Morgan1, Marty Mortrud1, Nerick Mosqueda1, Lydia Ng1, Randy Ng1, Geralyn J. Orta1, Caroline C. Overly1, Tu H. Pak1, Sheana Parry1, Sayan Dev Pathak1, Owen C. Pearson1, Ralph B. Puchalski1, Zackery L. Riley1, Hannah R. Rockett1, Stephen A. Rowland1, Joshua J. Royall1, Marcos J. Ruiz2, Nadia R. Sarno1, Katherine Schaffnit1, Nadiya V. Shapovalova1, Taz Sivisay1, Clifford R. Slaughterbeck1, Simon Smith1, Kimberly A. Smith1, Bryan I. Smith1, Andy J. Sodt1, Nick N. Stewart1, Kenda-Ruth Stumpf1, Susan M. Sunkin1, Madhavi Sutram1, Angelene Tam2, Carey D. Teemer1, Christina Thaller2, Carol L. Thompson1, Lee R. Varnam1, Axel Visel5, Axel Visel4, Ray M. Whitlock1, Paul Wohnoutka1, Crissa K. Wolkey1, Victoria Y. Wong1, Matthew J.A. Wood2, Murat B. Yaylaoglu2, Rob Young1, Brian L. Youngstrom1, Xu Feng Yuan1, Bin Zhang2, Theresa A. Zwingman1, Allan R. Jones1 
11 Jan 2007-Nature
TL;DR: An anatomically comprehensive digital atlas containing the expression patterns of ∼20,000 genes in the adult mouse brain is described, providing an open, primary data resource for a wide variety of further studies concerning brain organization and function.
Abstract: Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

4,944 citations

Journal ArticleDOI
TL;DR: This Review looks at some key brain theories in the biological and physical sciences from the free-energy perspective, suggesting that several global brain theories might be unified within a free- energy framework.
Abstract: A free-energy principle has been proposed recently that accounts for action, perception and learning. This Review looks at some key brain theories in the biological (for example, neural Darwinism) and physical (for example, information theory and optimal control theory) sciences from the free-energy perspective. Crucially, one key theme runs through each of these theories — optimization. Furthermore, if we look closely at what is optimized, the same quantity keeps emerging, namely value (expected reward, expected utility) or its complement, surprise (prediction error, expected cost). This is the quantity that is optimized under the free-energy principle, which suggests that several global brain theories might be unified within a free-energy framework.

4,866 citations

Journal ArticleDOI
TL;DR: The evidence for this hypothesis, and the origins of the different kinetic phases of synaptic enhancement, as well as the interpretation of statistical changes in transmitter release and roles played by other factors such as alterations in presynaptic Ca(2+) influx or postsynaptic levels of [Ca(2+)]i are discussed.
Abstract: ▪ Abstract Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca2+]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases...

4,687 citations