Brenda Bloodgood

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Brenda Bloodgood
BrendaBloodgood.jpg
NationalityAmerican
Alma materUniversity of California San Diego, Harvard University
Known forRole of Npas4 in modulating synaptic physiology
Awards2015 NIH Director’s New Innovator Award, 2015 Pew Biomedical Scholar, 2014 Searle Scholar, 2011-2012 Charles A. King Trust Postdoctoral Fellowship, 2010-2011 L’Oreal Fellowship for Women in Science
Scientific career
FieldsNeuroscience
InstitutionsUniversity of California San Diego

Brenda Bloodgood is an American neuroscientist and associate professor of neurobiology at the University of California, San Diego. Bloodgood studies the molecular and cellular basis of brain circuitry changes in response to an animal's interactions with the environment.

Contents

Early life and education

In highschool, Bloodgood participated in Columbia University’s Science Honors Program. [1] The opportunity to asking questions and formulate scientific hypotheses in this program inspired her to pursue a career in neuroscience. [1] After highschool, Bloodgood attended a community college in California [1] and then transferred to the University of California, San Diego to complete an undergraduate degree in Animal Physiology and Neuroscience. [2] While at UCSD, Bloodgood joined the lab of Dr. Ed Callaway at the Salk Institute for Biological Studies as an undergraduate research assistant. [1] After receiving her bachelors of science degree in 2001, Bloodgood continued on a path towards academic neuroscience by completing her PhD at Harvard Medical School. [3] As a graduate student at Harvard, Bloodgood studied under the mentorship of Dr. Bernardo Sabatini. [1] Bloodgood's graduate work focusing on synaptic physiology [1] led to a first author paper in the academic journal Science regarding how neuronal activity regulates diffusion across the neck of dendritic spines. [4] After completing graduate school in 2006, Bloodgood remained Boston to complete her postdoctoral studies under the mentorship of Dr. Mike Greenberg at Harvard Medical School. [1] In the Greenberg Lab, Bloodgood studied the protein Npas4 which is known to regulate neuronal gene expression [5] specifically at inhibitory synapses. [6] In her postdoc, Bloodgood explored the underlying mechanisms governing how Npas4 regulates the number and formation of inhibitory inputs onto neurons. [6] Bloodgood discovered that upon sensory stimulation, Npas4 mediates a rearrangement of the distribution of inhibitory synapses onto hippocampal neurons restricting information output while increasing the potential for dendritic plasticity. [6] This essentially increases the ability of a neuron to gather more information before relaying it further throughout the circuit. [5]

Career and research

Bloodgood completed her postdoctoral studies in 2012 and then returned to her undergraduate alma mater, the University of California, San Diego, to start her own neurobiology lab within the Division of Biological Sciences. [7] Inspired by her postdoctoral work, Bloodgood has focused her lab's research program on probing a deeper understanding of the diverse functions of Npas4 in modulating neural computations and driving changes in animal behavior. [5] [8] Just two years after starting her lab, Bloodgood and 2 other UCSD scientists received funding from Obama’s BRAIN Initiative in 2014. [9]

In 2016, Bloodgood became the co-director of the San Diego Brain Consortium, [9] an organization which helps to coordinate collaborations, build research training programs, enhance science communication, and generally foster innovation in brain research. [10] Bloodgood also serves as an Advisory Board Member and Faculty Fellow for the Kavli Institute for Brain and Mind at UCSD. [11] [12]

Recently, the Bloodgood Lab found that there are functional differences between the NMDA receptors on spines versus dendritic synaptic inputs onto Parvalbumin interneurons in the mouse cortex. [13] Further, the Bloodgood Lab discovered that Npas4 is induced by action potentials through a completely different mechanism than when Npas4 is induced by excitatory postsynaptic potentials. [14] While both action potential induced and EPSP induced Npas4 yield Npas4 heterodimers, these heterodimers remarkably have distinct effects on gene expression and regulation. [14]

Awards

Publications

Related Research Articles

<span class="mw-page-title-main">Dendrite</span> Small projection on a neuron that receives signals

A dendrite or dendron is a branched protoplasmic extension of a nerve cell that propagates the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons via synapses which are located at various points throughout the dendritic tree.

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell found in the nervous system of animals

Within a nervous system, a neuron, neurone, or nerve cell is an electrically excitable cell that fires electric signals called action potentials across a neural network. Neurons communicate with other cells via synapses - specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. Non-animals like plants and fungi do not have nerve cells.

<span class="mw-page-title-main">Chemical synapse</span> Biological junctions through which neurons signals can be sent

Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie perception and thought. They allow the nervous system to connect to and control other systems of the body.

<span class="mw-page-title-main">Dendritic spine</span> Small protrusion on a dendrite that receives input from a single axon

A dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body. Most spines have a bulbous head, and a thin neck that connects the head of the spine to the shaft of the dendrite. The dendrites of a single neuron can contain hundreds to thousands of spines. In addition to spines providing an anatomical substrate for memory storage and synaptic transmission, they may also serve to increase the number of possible contacts between neurons. It has also been suggested that changes in the activity of neurons have a positive effect on spine morphology.

In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuits in the brain, synaptic plasticity is one of the important neurochemical foundations of learning and memory.

An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. IPSPs were first investigated in motorneurons by David P. C. Lloyd, John Eccles and Rodolfo Llinás in the 1950s and 1960s. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. IPSPs can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell to cell signalling. Inhibitory presynaptic neurons release neurotransmitters that then bind to the postsynaptic receptors; this induces a change in the permeability of the postsynaptic neuronal membrane to particular ions. An electric current that changes the postsynaptic membrane potential to create a more negative postsynaptic potential is generated, i.e. the postsynaptic membrane potential becomes more negative than the resting membrane potential, and this is called hyperpolarisation. To generate an action potential, the postsynaptic membrane must depolarize—the membrane potential must reach a voltage threshold more positive than the resting membrane potential. Therefore, hyperpolarisation of the postsynaptic membrane makes it less likely for depolarisation to sufficiently occur to generate an action potential in the postsynaptic neurone.

<span class="mw-page-title-main">Excitatory synapse</span> Sort of synapse

An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell.

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.

An apical dendrite is a dendrite that emerges from the apex of a pyramidal cell. Apical dendrites are one of two primary categories of dendrites, and they distinguish the pyramidal cells from spiny stellate cells in the cortices. Pyramidal cells are found in the prefrontal cortex, the hippocampus, the entorhinal cortex, the olfactory cortex, and other areas. Dendrite arbors formed by apical dendrites are the means by which synaptic inputs into a cell are integrated. The apical dendrites in these regions contribute significantly to memory, learning, and sensory associations by modulating the excitatory and inhibitory signals received by the pyramidal cells.

<span class="mw-page-title-main">Synapse</span> Structure connecting neurons in the nervous system

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to the target effector cell.

<span class="mw-page-title-main">Kalirin</span> Protein-coding gene in the species Homo sapiens

Kalirin, also known as Huntingtin-associated protein-interacting protein (HAPIP), protein duo (DUO), or serine/threonine-protein kinase with Dbl- and pleckstrin homology domain, is a protein that in humans is encoded by the KALRN gene. Kalirin was first identified in 1997 as a protein interacting with huntingtin-associated protein 1. Is also known to play an important role in nerve growth and axonal development.

<span class="mw-page-title-main">Chloride potassium symporter 5</span> Protein-coding gene in the species Homo sapiens

Potassium-chloride transporter member 5 is a neuron-specific chloride potassium symporter responsible for establishing the chloride ion gradient in neurons through the maintenance of low intracellular chloride concentrations. It is a critical mediator of synaptic inhibition, cellular protection against excitotoxicity and may also act as a modulator of neuroplasticity. Potassium-chloride transporter member 5 is also known by the names: KCC2 for its ionic substrates, and SLC12A5 for its genetic origin from the SLC12A5 gene in humans.

Michael Greenberg is an American neuroscientist who specializes in molecular neurobiology. He served as the Chair of the Department of Neurobiology at Harvard Medical School from 2008 to 2022.

Activity-dependent plasticity is a form of functional and structural neuroplasticity that arises from the use of cognitive functions and personal experience; hence, it is the biological basis for learning and the formation of new memories. Activity-dependent plasticity is a form of neuroplasticity that arises from intrinsic or endogenous activity, as opposed to forms of neuroplasticity that arise from extrinsic or exogenous factors, such as electrical brain stimulation- or drug-induced neuroplasticity. The brain's ability to remodel itself forms the basis of the brain's capacity to retain memories, improve motor function, and enhance comprehension and speech amongst other things. It is this trait to retain and form memories that is associated with neural plasticity and therefore many of the functions individuals perform on a daily basis. This plasticity occurs as a result of changes in gene expression which are triggered by signaling cascades that are activated by various signaling molecules during increased neuronal activity.

<span class="mw-page-title-main">Granule cell</span> Type of neuron with a very small cell body

The name granule cell has been used for a number of different types of neurons whose only common feature is that they all have very small cell bodies. Granule cells are found within the granular layer of the cerebellum, the dentate gyrus of the hippocampus, the superficial layer of the dorsal cochlear nucleus, the olfactory bulb, and the cerebral cortex.

Memory allocation is a process that determines which specific synapses and neurons in a neural network will store a given memory. Although multiple neurons can receive a stimulus, only a subset of the neurons will induce the necessary plasticity for memory encoding. The selection of this subset of neurons is termed neuronal allocation. Similarly, multiple synapses can be activated by a given set of inputs, but specific mechanisms determine which synapses actually go on to encode the memory, and this process is referred to as synaptic allocation. Memory allocation was first discovered in the lateral amygdala by Sheena Josselyn and colleagues in Alcino J. Silva's laboratory.

Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, which is otherwise known as operant conditioning.

Dendrodendritic synapses are connections between the dendrites of two different neurons. This is in contrast to the more common axodendritic synapse (chemical synapse) where the axon sends signals and the dendrite receives them. Dendrodendritic synapses are activated in a similar fashion to axodendritic synapses in respects to using a chemical synapse. An incoming action potential permits the release of neurotransmitters to propagate the signal to the post synaptic cell. There is evidence that these synapses are bi-directional, in that either dendrite can signal at that synapse. Ordinarily, one of the dendrites will display inhibitory effects while the other will display excitatory effects. The actual signaling mechanism utilizes Na+ and Ca2+ pumps in a similar manner to those found in axodendritic synapses.

<span class="mw-page-title-main">Neuronal PAS domain protein 4</span> Protein-coding gene in the species Homo sapiens

Neuronal PAS domain protein 4 is a protein that in humans is encoded by the NPAS4 gene. The NPAS4 gene is a neuronal activity-dependent immediate early gene that has been identified as a transcription factor. The protein regulates the transcription of genes that control inhibitory synapse development, synaptic plasticity and most recently reported also behavior.

<span class="mw-page-title-main">Synaptic stabilization</span> Modifying synaptic strength via cell adhesion molecules

Synaptic stabilization is crucial in the developing and adult nervous systems and is considered a result of the late phase of long-term potentiation (LTP). The mechanism involves strengthening and maintaining active synapses through increased expression of cytoskeletal and extracellular matrix elements and postsynaptic scaffold proteins, while pruning less active ones. For example, cell adhesion molecules (CAMs) play a large role in synaptic maintenance and stabilization. Gerald Edelman discovered CAMs and studied their function during development, which showed CAMs are required for cell migration and the formation of the entire nervous system. In the adult nervous system, CAMs play an integral role in synaptic plasticity relating to learning and memory.

References

  1. 1 2 3 4 5 6 7 "Dr. Brenda Bloodgood". Stories of WiN. Retrieved 2020-03-27.
  2. "Brenda Bloodgood – 2018-Sept Kavli Institute Community Symposium: Cutting-edge science from around the world". oslo2018.kavlimeetings.org. Retrieved 2020-03-27.
  3. 1 2 3 4 5 6 7 "Brenda Bloodgood - Faculty - Neurograd Program". UC San Diego Health Sciences. Retrieved 2020-03-27.
  4. Bloodgood, Brenda L.; Sabatini, Bernardo L. (2005-11-04). "Neuronal activity regulates diffusion across the neck of dendritic spines". Science. 310 (5749): 866–869. Bibcode:2005Sci...310..866B. doi:10.1126/science.1114816. ISSN   1095-9203. PMID   16272125. S2CID   16886082.
  5. 1 2 3 4 "Brenda L. Bloodgood, Ph.D." Archived from the original on 2015-09-15. Retrieved 2020-03-27.
  6. 1 2 3 Bloodgood, Brenda L.; Sharma, Nikhil; Browne, Heidi Adlman; Trepman, Alissa Z.; Greenberg, Michael E. (2013-11-07). "The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition". Nature. 503 (7474): 121–125. Bibcode:2013Natur.503..121B. doi:10.1038/nature12743. ISSN   1476-4687. PMC   4169177 . PMID   24201284.
  7. "Brenda Bloodgood". www-biology.ucsd.edu. Retrieved 2020-03-27.
  8. "Brenda Bloodgood – 2018-Sept Kavli Institute Community Symposium: Cutting-edge science from around the world". oslo2018.kavlimeetings.org. Retrieved 2020-03-27.
  9. 1 2 McAllister, Toni (2016-10-14). "NIH Awards UCSD Brain Researchers $2.27 Million". Times of San Diego. Retrieved 2020-03-27.
  10. "The San Diego BRAIN Consortium". sdbrain.org. Retrieved 2020-03-27.
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  12. "People | Kavli Institute for Brain & Mind". kibm.ucsd.edu. Retrieved 2020-03-27.
  13. 1 2 Sancho, Laura; Bloodgood, Brenda L. (2018-08-21). "Functional Distinctions between Spine and Dendritic Synapses Made onto Parvalbumin-Positive Interneurons in Mouse Cortex". Cell Reports. 24 (8): 2075–2087. doi: 10.1016/j.celrep.2018.07.070 . ISSN   2211-1247. PMID   30134169.
  14. 1 2 3 Brigidi, G. Stefano; Hayes, Michael G. B.; Delos Santos, Nathaniel P.; Hartzell, Andrea L.; Texari, Lorane; Lin, Pei-Ann; Bartlett, Anna; Ecker, Joseph R.; Benner, Christopher; Heinz, Sven; Bloodgood, Brenda L. (2019-10-03). "Genomic Decoding of Neuronal Depolarization by Stimulus-Specific NPAS4 Heterodimers". Cell. 179 (2): 373–391.e27. doi:10.1016/j.cell.2019.09.004. ISSN   0092-8674. PMC   6800120 . PMID   31585079.
  15. "NIH Director's New Innovator Award Program - 2015 Award Recipients | NIH Common Fund". commonfund.nih.gov. 18 September 2018. Retrieved 2020-03-27.
  16. "Searle Scholars Program". Scholar Profile Brenda L. Bloodgood. Archived from the original on September 5, 2015. Retrieved 2 June 2023.