Lisa Gunaydin

Last updated
Lisa Gunaydin
NationalityAmerican
Alma materB.A. Swarthmore College, Ph.D. Stanford University
Known forOptogenetics
Awards2017 Chan Zuckerberg Biohub Investigator Program Investigator, 2016 UCSF Weill Institute for Neurosciences Innovation Award, 2008 Bio-X Bowes Fellow Stanford
Scientific career
FieldsNeuroscience
InstitutionsWeill Institute for Neurosciences, University of California, San Francisco

Lisa Gunaydin is an American neuroscientist and assistant professor at the Weill Institute for Neurosciences at the University of California San Francisco. Gunaydin helped discover optogenetics in the lab of Karl Deisseroth and now uses this technique in combination with neural and behavioral recordings to probe the neural circuits underlying emotional behaviors.

Contents

Early life and education

Gunaydin completed her undergraduate education at Swarthmore College with a degree in biological sciences. [1] Gunaydin then continued on an academic path by pursuing a Ph.D. at Stanford University. Under the mentorship of Dr. Karl Deisseroth, Gunaydin helped to discover optogenetic technology and apply it to Systems Neuroscience by dissecting neural circuits that drive a variety of complex behaviors in rodents. [2] [3] Optogenetics is a tool used in Systems Neuroscience to activate or inhibit specific neural circuits using transgenically expressed light-activated opsins, originally derived from bacterial opsins. [4] Shining lasers of specific wavelengths causes the channels to open. [4] In the case of Channelrhodopsins, cations ions flow into the neuron to depolarize it, while in the case of Halorhodopsins, anions flow into the neuron to hyperpolarize it. [4] This can effectively allow a scientist to activate or inhibit specific neurons or neural circuits in an organism expressing the transgenic protein.

In 2008, Gunaydin was named the Bio-X Bowes Fellow at Stanford for her work developing new optogenetic technologies and applying them to probe dopaminergic circuitry implicated in social behaviors. [3] In 2009, Gunaydin co-first authored a paper in Nature Neuroscience where she helped to test and optimize step-function opsins which allow longer lasting membrane depolarization than regular opsins providing extended effects on neural circuits. [5] In 2010, Gunaydin published a first author paper in Nature Neuroscience highlighting her optimization of a new opsin based tool for ultrafast neural circuit control. [6] In this work Gunaydin showed that this novel opsin does not produce unwanted spikes nor persistent depolarizations like what might occur when a cell over-expresses Channelrhodopsin. [6] In 2015, Gunaydin and her colleagues in the Deisseroth Lab published a paper in the journal Cell, where they used fiber photometry to observe calcium dynamics in dopaminergic neural circuits involved in social behavior. [7] She and her colleagues also found that the neural projection from the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc) encodes and predicts social behaviors. [7] Using optogenetics, Gunaydin probed the causal effects of stimulating the dopaminergic projection from the VTA to the NAc and found that modulation of this projection bi-directionally affected social behaviors. [6]  Gunaydin went on to present this work at the Cold Spring Harbour Symposia on Quantitative Biology. [8] This was one of the first studies ever to manipulate social neural circuits in real time, using optogenetics, and observe changes in social behavior. [8] After her PhD, Gunaydin pursued her postdoctoral work with Dr. Anatol Kreitzer at the University of California San Francisco’s Gladstone Institute of Neurological Disease. [1] Under Kreitzer's mentorship, Gunaydin brought her experience and expertise with optogenetics to explore fronto-striatal circuitry and its implications in anxiety-like behavior. [9]

Career and research

Gunaydin started her lab at the University of California, San Francisco in 2016 and has since held an assistant professorship in Psychiatry as well as an appointment at the Institute for Neurodegenerative Diseases. [10] [11] In addition, Gunaydin is a member of the UCSF Neuroscience Graduate Program, the Kavli Institute for Fundamental Neuroscience, and in 2017 was named a Chan Zuckerberg Biohub Investigator. [12] Gunaydin's lab aims to investigate the neural circuits underlying motivated behaviors and further understand how they aberrantly function in disease states. [13] Gunaydin's lab is currently focusing on three main projects to address this aim. The first project involves probing the role of cortico-striatal circuitry in modulating anxiety-like behavior as well as elucidating the potential of this circuit as a target of chronic therapeutic stimulation. [11] In line with this project, the Gunaydin Lab published their first paper in 2020 highlighting their discovery of a subpopulation of striatal projecting prefrontal neurons that regulate approach-avoidance conflict in rodents. [14] The other two projects her lab is working on explore the roles of cortical neural subpopulations in obsessive-compulsive disorder behaviors as well as the mechanisms of circuit defects in genetic mouse models for obsessive-compulsive disorder and autism. [11]

Awards and honors

Select publications

Related Research Articles

<span class="mw-page-title-main">Striatum</span> Nucleus in the basal ganglia of the brain

The striatum or corpus striatum is a nucleus in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamatergic and dopaminergic inputs from different sources; and serves as the primary input to the rest of the basal ganglia.

<span class="mw-page-title-main">Nucleus accumbens</span> Region of the basal forebrain

The nucleus accumbens is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia. The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle. Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

<span class="mw-page-title-main">Nigrostriatal pathway</span> Bilateral pathway in the brain

The nigrostriatal pathway is a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum in the forebrain. It is one of the four major dopamine pathways in the brain, and is critical in the production of movement as part of a system called the basal ganglia motor loop. Dopaminergic neurons of this pathway release dopamine from axon terminals that synapse onto GABAergic medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), located in the striatum.

Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.

<span class="mw-page-title-main">Medium spiny neuron</span> Type of GABAergic neuron in the striatum

Medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), are a special type of GABAergic inhibitory cell representing 95% of neurons within the human striatum, a basal ganglia structure. Medium spiny neurons have two primary phenotypes : D1-type MSNs of the direct pathway and D2-type MSNs of the indirect pathway. Most striatal MSNs contain only D1-type or D2-type dopamine receptors, but a subpopulation of MSNs exhibit both phenotypes.

<span class="mw-page-title-main">Gero Miesenböck</span>

Gero Andreas Miesenböck is an Austrian scientist. He is currently Waynflete Professor of Physiology and Director of the Centre for Neural Circuits and Behaviour (CNCB) at the University of Oxford and a fellow of Magdalen College, Oxford.

Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient with Retinitis pigmentosa.

<span class="mw-page-title-main">Karl Deisseroth</span> American optogeneticist (born 1971)

Karl Alexander Deisseroth is an American scientist. He is the D.H. Chen Foundation Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

<span class="mw-page-title-main">Peter Hegemann</span> German biophysicist

Peter Hegemann is a Hertie Senior Research Chair for Neurosciences and a professor of Experimental Biophysics at the Department of Biology, Faculty of Life Sciences, Humboldt University of Berlin, Germany. He is known for his discovery of channelrhodopsin, a type of ion channels regulated by light, thereby serving as a light sensor. This created the field of optogenetics, a technique that controls the activities of specific neurons by applying light. He has received numerous accolades, including the Rumford Prize, the Shaw Prize in Life Science and Medicine, and the Albert Lasker Award for Basic Medical Research.

<span class="mw-page-title-main">Kay Tye</span> American neuroscientist (born c. 1981)

Kay M. Tye is an American neuroscientist and professor and Wylie Vale Chair in the Salk Institute for Biological Sciences. Her research has focused on using optogenetics to identify connections in the brain that are involved in innate emotion, motivation and social behaviors.

<span class="mw-page-title-main">Anion-conducting channelrhodopsin</span> Class of light-gated ion channels

Anion-conducting channelrhodopsins are light-gated ion channels that open in response to light and let negatively charged ions enter a cell. All channelrhodopsins use retinal as light-sensitive pigment, but they differ in their ion selectivity. Anion-conducting channelrhodopsins are used as tools to manipulate brain activity in mice, fruit flies and other model organisms (Optogenetics). Neurons expressing anion-conducting channelrhodopsins are silenced when illuminated with light, an effect that has been used to investigate information processing in the brain. For example, suppressing dendritic calcium spikes in specific neurons with light reduced the ability of mice to perceive a light touch to a whisker. Studying how the behavior of an animal changes when specific neurons are silenced allows scientists to determine the role of these neurons in the complex circuits controlling behavior.

<span class="mw-page-title-main">Herwig Baier</span> German neurobiologist

Herwig Baier is a German neurobiologist with dual German and US-American citizenship. He is Director at the Max Planck Institute for Biological Intelligence and head of the department Genes – Circuits – Behavior. Herwig Baier's research aims to understand how animal brains convert sensory inputs into behavioral responses.

D. James "Jim" Surmeier, an American neuroscientist and physiologist of note, is the Nathan Smith Davis Professor and Chair in the Department of Neuroscience at Northwestern University Feinberg School of Medicine. His research is focused on the cellular physiology and circuit properties of the basal ganglia in health and disease, primarily Parkinson's and Huntington's disease as well as pain.

<span class="mw-page-title-main">Georg Nagel</span>

Georg Nagel is a biophysicist and professor at the Department for Neurophysiology at the University of Würzburg in Germany. His research is focused on microbial photoreceptors and the development of optogenetic tools.

Camilla Bellone is an Italian neuroscientist and assistant professor in the Department of Basic Neuroscience at the University of Geneva, in Switzerland. Bellone's laboratory explores the molecular mechanisms and neural circuits underlying social behavior and probes how defects at the molecular and circuit level give rise to psychiatric disease states such as Autism Spectrum Disorders.

Ilana B. Witten is an American neuroscientist and professor of psychology and neuroscience at Princeton University. Witten studies the mesolimbic pathway, with a focus on the striatal neural circuit mechanisms driving reward learning and decision making.

Jessica Cardin is an American neuroscientist who is an associate professor of neuroscience at Yale University School of Medicine. Cardin's lab studies local circuits within the primary visual cortex to understand how cellular and synaptic interactions flexibly adapt to different behavioral states and contexts to give rise to visual perceptions and drive motivated behaviors. Cardin's lab applies their knowledge of adaptive cortical circuit regulation to probe how circuit dysfunction manifests in disease models.

Dayu Lin is a neuroscientist and Professor of Psychiatry, Neuroscience and Physiology at the New York University Grossman School of Medicine in New York City. Lin discovered the neural circuits in the hypothalamus that give rise to aggression in mice. Her lab at NYU now probes the neural circuits underlying innate social behaviors, with a focus on aggressive and defensive behaviors.

<span class="mw-page-title-main">Polina Anikeeva</span> Russian-American materials scientist

Polina Olegovna Anikeeva is a Russian-born American materials scientist who is a Professor of Material Science & Engineering as well as Brain & Cognitive Sciences at the Massachusetts Institute of Technology (MIT). She also holds faculty appointments in the McGovern Institute for Brain Research and Research Laboratory of Electronics at MIT. Her research is centered on developing tools for studying the underlying molecular and cellular bases of behavior and neurological diseases. She was awarded the 2018 Vilcek Foundation Prize for Creative Promise in Biomedical Science, the 2020 MacVicar Faculty Fellowship at MIT, and in 2015 was named a MIT Technology Review Innovator Under 35.

Fiber photometry is a calcium imaging technique that captures 'bulk' or population-level calcium (Ca2+) activity from specific cell-types within a brain region or functional network in order to study neural circuits Population-level calcium activity can be correlated with behavioral tasks, such as spatial learning, memory recall and goal-directed behaviors. The technique involves the surgical implantation of fiber optics into the brains of living animals. The benefits to researchers are that optical fibers are simpler to implant, less invasive and less expensive than other calcium methods, and there is less weight and stress on the animal, as compared to miniscopes. It also allows for imaging of multiple interacting brain regions and integration with other neuroscience techniques. The limitations of fiber photometry are low cellular and spatial resolution, and the fact that animals must be securely tethered to a rigid fiber bundle, which may impact the naturalistic behavior of smaller mammals such as mice.

References

  1. 1 2 "Lisa Gunaydin, PhD | Institute for Neurodegenerative Diseases". ind.ucsf.edu. Retrieved 2020-03-31.
  2. ↑ "Breakthrough Prize – Life Sciences Breakthrough Prize Laureates – Karl Deisseroth". breakthroughprize.org. Retrieved 2020-03-31.
  3. 1 2 3 University, © Stanford; Stanford; California 94305 (2014-03-05). "Lisa Gunaydin - Bio-X Bowes Fellow". Welcome to Bio-X. Retrieved 2020-03-31.{{cite web}}: CS1 maint: numeric names: authors list (link)
  4. 1 2 3 Deisseroth, Karl (January 2011). "Optogenetics". Nature Methods. 8 (1): 26–29. doi:10.1038/nmeth.f.324. ISSN   1548-7105. PMC   6814250 . PMID   21191368.
  5. ↑ Berndt, André; Yizhar, Ofer; Gunaydin, Lisa A.; Hegemann, Peter; Deisseroth, Karl (February 2009). "Bi-stable neural state switches". Nature Neuroscience. 12 (2): 229–234. doi:10.1038/nn.2247. ISSN   1546-1726. PMID   19079251. S2CID   15125498.
  6. 1 2 3 Gunaydin, Lisa A.; Yizhar, Ofer; Berndt, André; Sohal, Vikaas S.; Deisseroth, Karl; Hegemann, Peter (March 2010). "Ultrafast optogenetic control". Nature Neuroscience. 13 (3): 387–392. doi:10.1038/nn.2495. ISSN   1546-1726. PMID   20081849. S2CID   7457755.
  7. 1 2 Gunaydin, Lisa A.; Grosenick, Logan; Finkelstein, Joel C.; Kauvar, Isaac V.; Fenno, Lief E.; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J.; Airan, Raag D.; Zalocusky, Kelly A.; Tye, Kay M. (2014-06-19). "Natural Neural Projection Dynamics Underlying Social Behavior". Cell. 157 (7): 1535–1551. doi: 10.1016/j.cell.2014.05.017 . ISSN   0092-8674. PMC   4123133 . PMID   24949967.
  8. 1 2 Gunaydin, Lisa A.; Deisseroth, Karl (2014-01-01). "Dopaminergic Dynamics Contributing to Social Behavior". Cold Spring Harbor Symposia on Quantitative Biology. 79: 221–227. doi: 10.1101/sqb.2014.79.024711 . ISSN   0091-7451. PMID   25943769.
  9. ↑ Gunaydin, Lisa; Nelson, Alexandra; Kreitzer, Anatol (2017-05-15). "500. Fronto-Striatal Modulation of Anxiety-Like Behaviors". Biological Psychiatry. 81 (10): 203–210. doi:10.1016/j.biopsych.2017.02.1108. ISSN   0006-3223. PMC   4909599 . PMID   26853120.
  10. ↑ "People". Gunaydin Lab. Retrieved 2020-03-31.
  11. 1 2 3 "Lisa Gunaydin, PhD". Neuroscience Graduate Program. Retrieved 2020-03-31.
  12. ↑ "15 UCSF Researchers Named to First Cohort of Chan Zuckerberg Biohub Investigators". 15 UCSF Researchers Named to First Cohort of Chan Zuckerberg Biohub Investigators | UC San Francisco. 8 February 2017. Retrieved 2020-03-31.
  13. ↑ "Research". Gunaydin Lab. Retrieved 2020-03-31.
  14. 1 2 Loewke, Adrienne C.; Minerva, Adelaide R.; Nelson, Alexandra B.; Kreitzer, Anatol C.; Gunaydin, Lisa A. (2020-03-06). "Fronto-striatal projections regulate approach-avoidance conflict". bioRxiv: 2020.03.05.979708. doi: 10.1101/2020.03.05.979708 .
  15. ↑ Gorrell, Sasha; Collins, Anne G.E.; Daniel, Le Grange; Yang, Tony T. (2020-03-23). "Dopaminergic Activity and Exercise Behavior in Anorexia Nervosa". OBM Neurobiology. 4 (1): 1–19. doi: 10.21926/obm.neurobiol.2001053 . PMC   7872149 . PMID   33569542.
  16. ↑ "UCSF Weill Institute for Neurosciences Announces Innovation, Scholar Awards". UCSF Neurosciences. Retrieved 2020-03-31.
  17. 1 2 3 4 5 6 7 8 9 10 11 "Publications". Gunaydin Lab. Retrieved 2020-03-31.
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