Ann Graybiel

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Ann Martin Graybiel
Ann Graybiel 2001.jpg
Graybiel receives the Medal of Science from President Bush in 2001
Born1942
Chestnut Hill, Massachusetts
Alma mater
Occupation Neuroscientist
Known for
Awards
Website http://www.graybiel-lab.com/

Ann Martin Graybiel (born 1942) is an Institute Professor and a faculty member in the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology. She is also an investigator at the McGovern Institute for Brain Research. She is an expert on the basal ganglia and the neurophysiology of habit formation, implicit learning, and her work is relevant to Parkinson's disease, Huntington's disease, obsessive–compulsive disorder, substance abuse and other disorders that affect the basal ganglia.

Contents

Research

For much of her career, Graybiel has focused on the physiology of the striatum, a basal ganglia structure implicated in the control of movement, cognition, habit formation, and decision-making. In the late 1970s, Graybiel discovered that while striatal neurons appeared to be an amorphous mass, they were in fact organized into chemical compartments, which she termed striosomes. [1] Later research revealed links between striosomal abnormalities and neurological disorders, such as mood dysfunction in Huntington's disease [2] and depletion of dopamine in Parkinson's disease. [3]

Graybiel's subsequent research demonstrated how modular organization of the striatum relates to cognition, learning, and habit formation. She found that neurons project from areas in the sensory and motor cortices governing the same body part and cluster together in the striatum, forming matrisomes. [4] Graybiel went on to show that matrisomes exist for each body part and were organized into loops connecting the neocortex, a region responsible for cognition, perception and motor control, to the brain stem, a region coordinating movement. [5] Studies of rodents and primates revealed that matrisomes were crucial to habit formation. [6] [7]

In later work, Graybiel demonstrated, first in the striatum and later in the infralimbic cortex, that a task-bracket or "chunking" pattern of neuronal activity emerges when a habit is formed, wherein neurons activate when a habitual task is initiated, show little activity during the task, and reactivate when the task is completed. [7] [8]

In more recent work, Graybiel has focused on identifying specific pathways underlying aspects of behavior such as habit formation, learning and cognition, and decision-making, including being the first to analyze the effect of dopamine depletion on the activity of neurons affected by Parkinson's disease during behavioral tasks. [9] [10]

Career

Graybiel majored in biology and chemistry at Harvard University, receiving her bachelor's degree in 1964. [11] After receiving an MA in biology from Tufts University in 1966, she began doctoral study in psychology and brain science at MIT under the direction of Hans-Lukas Teuber and Walle Nauta. [11] She received her PhD in 1971 and joined the MIT faculty in 1973. [12]

In 1994, Graybiel was one of 16 women faculty in the School of Science at MIT who drafted and co-signed a letter to the then-Dean of Science (now Chancellor of Berkeley) Robert Birgeneau, which started a campaign to highlight and challenge gender discrimination at MIT. [13]

Also in 1994, she was named the Walter A. Rosenblith Professor Neuroscience in the Department of Brain and Cognitive Science and was named an Investigator at the MIT McGovern Institute for Brain research in 2001. [12] She was named Institute Professor in 2008. [14]

Awards and recognition

In 2001, Graybiel was awarded the President's National Medal of Science for "her pioneering contributions to the understanding of the anatomy and physiology of the brain, including the structure, chemistry, and function of the pathways subserving thought and movement." [15] In 2012, she was awarded the Kavli Prize in Neuroscience, along with Cornelia Bargmann and Winfried Denk, "for elucidating basic neuronal mechanisms underlying perception and decision." [16]

In 2018, Graybiel won the Gruber Prize in Neuroscience along with Okihide Hikosaka and Wolfram Schultz.

Their work has fundamentally transformed the study of the basal ganglia and has led to influential new ideas about how the brain learns and retains new habits and skills, manages movements and processes rewards for learning and decision-making. It has also deepened our understanding of a wide range of neurodegenerative and neuropsychiatric disorders in which the basal ganglia and behavioral control is compromised.

"When these three extraordinary scientists began their careers, few people were paying much attention to the basal ganglia," says Dr. Robert Wurtz, NIH Distinguished Investigator and chair of the Selection Advisory Board to the Prize. "Today, thanks to their pioneering research, we now recognize the central role that this area of the brain plays in normal brain function and behavior. The significance of their work cannot be [over]stated, as it has also transformed our understanding of the neurobiology behind some of our most devastating brain disorders, including Parkinson's disease, Huntington's disease, and drug addiction."

Graybiel discovered that the striatum, the largest nucleus within the basal ganglia, has a complex, modular structure. She then followed this transformative discovery with studies describing the functionally of that architecture, including the finding that changes in striatal neural activity during the learning process lead to the formation of pathological habits, such as those that characterize obsessive compulsive disorder. [17]

She is a member of the US National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, the National Academy of Medicine (formerly Institute of Medicine), [12] and the Norwegian Academy of Science and Letters. [18]

Related Research Articles

<span class="mw-page-title-main">Putamen</span> Round structure at the base of the forebrain

The putamen is a round structure located at the base of the forebrain (telencephalon). The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that compose the basal nuclei. Through various pathways, the putamen is connected to the substantia nigra, the globus pallidus, the claustrum, and the thalamus, in addition to many regions of the cerebral cortex. A primary function of the putamen is to regulate movements at various stages and influence various types of learning. It employs GABA, acetylcholine, and enkephalin to perform its functions. The putamen also plays a role in degenerative neurological disorders, such as Parkinson's disease.

<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">Substantia nigra</span> Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

<span class="mw-page-title-main">Dopamine</span> Organic chemical that functions both as a hormone and a neurotransmitter

Dopamine is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.

<span class="mw-page-title-main">Basal ganglia</span> Group of subcortical nuclei involved in the motor and reward systems

The basal ganglia (BG) or basal nuclei are a group of subcortical nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into external and internal regions, and in the division of the striatum. Positioned at the base of the forebrain and the top of the midbrain, they have strong connections with the cerebral cortex, thalamus, brainstem and other brain areas. The basal ganglia are associated with a variety of functions, including regulating voluntary motor movements, procedural learning, habit formation, conditional learning, eye movements, cognition, and emotion.

<span class="mw-page-title-main">Dopaminergic pathways</span> Projection neurons in the brain that synthesize and release dopamine

Dopaminergic pathways in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons.

<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.

The pars reticulata (SNpr) is a portion of the substantia nigra and is located lateral to the pars compacta. Most of the neurons that project out of the pars reticulata are inhibitory GABAergic neurons.

<span class="mw-page-title-main">Primate basal ganglia</span>

The basal ganglia form a major brain system in all species of vertebrates, but in primates there are special features that justify a separate consideration. As in other vertebrates, the primate basal ganglia can be divided into striatal, pallidal, nigral, and subthalamic components. In primates, however, there are two pallidal subdivisions called the external globus pallidus (GPe) and internal globus pallidus (GPi). Also in primates, the dorsal striatum is divided by a large tract called the internal capsule into two masses named the caudate nucleus and the putamen—in most other species no such division exists, and only the striatum as a whole is recognized. Beyond this, there is a complex circuitry of connections between the striatum and cortex that is specific to primates. This complexity reflects the difference in functioning of different cortical areas in the primate brain.

The pars compacta (SNpc) is one of two subdivisions of the substantia nigra of the midbrain ; it is situated medial to the pars reticulata. It is formed by dopaminergic neurons. It projects to the striatum and portions of the cerebral cortex. It is functionally involved in fine motor control.

<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">Reward system</span> Group of neural structures responsible for motivation and desire

The reward system is a group of neural structures responsible for incentive salience, associative learning, and positively-valenced emotions, particularly ones involving pleasure as a core component. Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding.

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

The striosomes are one of two complementary chemical compartments within the striatum that can be visualized by staining for immunocytochemical markers such as mu opioid receptors, acetylcholinesterase, enkephalin, substance P, limbic system-associated membrane protein (LAMP), AMPA receptor subunit 1 (GluR1), dopamine receptor subunits, and calcium binding proteins. Striosomal abnormalities have been associated with neurological disorders, such as mood dysfunction in Huntington's disease, though their precise function remains unknown. Recently studies have identified the presence of "exo-patch" neurons that are biochemically and genetically the same as striosomal neurons, but reside in the matrix compartment. This study also characterized the different input and output connections of the striosome and matrix compartments, revealing that both regions have direct inputs to dopamine neurons. The authors also revealed unique inputs to the striosome from subcortical limbic structures like the amygdala and bed nucleus of the stria terminalis.

<span class="mw-page-title-main">Basal ganglia disease</span> Group of physical problems resulting from basal ganglia dysfunction

Basal ganglia disease is a group of physical problems that occur when the group of nuclei in the brain known as the basal ganglia fail to properly suppress unwanted movements or to properly prime upper motor neuron circuits to initiate motor function. Research indicates that increased output of the basal ganglia inhibits thalamocortical projection neurons. Proper activation or deactivation of these neurons is an integral component for proper movement. If something causes too much basal ganglia output, then the ventral anterior (VA) and ventral lateral (VL) thalamocortical projection neurons become too inhibited, and one cannot initiate voluntary movement. These disorders are known as hypokinetic disorders. However, a disorder leading to abnormally low output of the basal ganglia leads to reduced inhibition, and thus excitation, of the thalamocortical projection neurons which synapse onto the cortex. This situation leads to an inability to suppress unwanted movements. These disorders are known as hyperkinetic disorders.

<span class="mw-page-title-main">Blocq's disease</span> Loss of memory of specialized movements causing the inability to maintain an upright posture

Blocq's disease was first considered by Paul Blocq (1860–1896), who described this phenomenon as the loss of memory of specialized movements causing the inability to maintain an upright posture, despite normal function of the legs in the bed. The patient is able to stand up, but as soon as the feet are on the ground, the patient cannot hold himself upright nor walk; however when lying down, the subject conserved the integrity of muscular force and the precision of movements of the lower limbs. The motivation of this study came when a fellow student Georges Marinesco (1864) and Paul published a case of parkinsonian tremor (1893) due to a tumor located in the substantia nigra.

<span class="mw-page-title-main">Anne B. Young</span> American neuroscientist

Anne Buckingham Young is an American physician and neuroscientist who has made major contributions to the study of neurodegenerative diseases, with a focus on movement disorders like Huntington's disease and Parkinson's disease. Young completed her undergraduate studies at Vassar College and earned a dual MD/PhD from Johns Hopkins Medical School. She has held faculty positions at University of Michigan and Harvard University. She became the first female chief of service at Massachusetts General Hospital when she was appointed Chief of Neurology in 1991. She retired from this role and from clinical service in 2012. She is a member of many academic societies and has won numerous awards. Young is also the only person to have been president of both the international Society for Neuroscience and the American Neurological Association.

<span class="mw-page-title-main">Cortico-basal ganglia-thalamo-cortical loop</span> System of neural circuits in the brain

The cortico-basal ganglia-thalamo-cortical loop is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease, as well as to mental disorders of control, such as attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and Tourette syndrome.

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">Anders Björklund</span> Swedish histologist (born 1945)

Anders Björklund' is a Swedish neuroscientist and pioneer in the study of cell- and gene-based reparative and neuroprotective mechanisms in the brain. He has spent his academic career at Lund University in Sweden, as professor since 1983 and as senior professor at the Wallenberg Neuroscience Center since his formal retirement in 2012.

Stephanie J. Cragg is a full Professor of Neuroscience at the University of Oxford. She holds a joint appointment as Professor in the University Department of Physiology, Anatomy and Genetics and as a Fellow, Director of Studies and Tutor for Medicine at the college Christ Church, Oxford.

References

  1. ↑ Graybiel, AM; Ragsdale, Jr., CW (November 1978). "Histochemically distinct compartments in the striatum of human, monkey, and cat demonstrated by acetylthiocholinesterase staining". Proc Natl Acad Sci U S A. 75 (11) (published 1978): 5723–26. Bibcode:1978PNAS...75.5723G. doi: 10.1073/pnas.75.11.5723 . PMC   393041 . PMID   103101.
  2. ↑ Tippet, LJ; Waldvogel, HJ; Thomas, SJ; Hogg, VM; van Roon-Mom, W; Synek, BJ; Graybiel, AM; Faull, RL (Jan 2007). "Striosomes and mood dysfunction in Huntington's disease". Brain. 130 (1): 206–21. doi: 10.1093/brain/awl243 . PMID   17040921.
  3. ↑ Roffler-Tarlov, S; Graybiel, AM (5 Jan 1984). "Weaver mutation has differential effects on the dopamine-containing innervation of the limbic and nonlimbic striatum". Nature. 307 (5946): 62–66. Bibcode:1984Natur.307...62R. doi:10.1038/307062a0. PMID   6690983. S2CID   4235703.
  4. ↑ Flaherty, AW; Graybiel, AM (1991). "Corticostriatal transformations in the primate somatosensory system. Projections from physiologically mapped body-part representations". J Neurophysiol. 66 (4): 1249–63. doi:10.1152/jn.1991.66.4.1249. PMID   1722244.
  5. ↑ Graybiel, AM; Toshihiko, A; Flaherty, AW; Kimura, M (1994). "The basal ganglia and adaptive motor control". Science. 265 (5180): 1826–31. Bibcode:1994Sci...265.1826G. doi:10.1126/science.8091209. JSTOR   2884650. PMID   8091209.
  6. ↑ Illing, R.-B.; Graybiel, AM (1994). "Pattern formation in the developing superior colliculus: Ontogeny of the periodic architecture in the intermediate layers". Journal of Comparative Neurology. 340 (3): 311–27. doi:10.1002/cne.903400303. PMID   8188853. S2CID   37267745.
  7. 1 2 Graybiel, AM (1998). "The Basal Gangila and Chunking of Action Repertoires". Neurobiology of Learning and Memory. 70 (3): 119–36. doi:10.1006/nlme.1998.3843. PMID   9753592. S2CID   16824424.
  8. ↑ Smith, KS; Graybiel, AM (July 2013). "A dual operator view of habitual behavior reflecting cortical and striatal dynamics". Neuron. 79 (2): 361–74. doi:10.1016/j.neuron.2013.05.038. PMC   3951965 . PMID   23810540.
  9. ↑ Hernandez, LF; Kubota, Y; Hu, D; Howe, MW; Lemaire, N; Graybiel, AM (2013). "Selective effects of dopamine depletion and L-DOPA therapy on learning-related firing dynamics of striatal neurons". Journal of Neuroscience. 33 (11): 4782–95. doi:10.1523/JNEUROSCI.3746-12.2013. PMC   3655722 . PMID   23486949.
  10. ↑ Trafton, Anne (12 March 2013). "MIT News". Breaking down the Parkinson’s pathway. Retrieved 23 October 2014.
  11. 1 2 "Neuroscience Laureate Biographies". The Kavli Foundation. Archived from the original on 23 October 2014. Retrieved 23 October 2014.
  12. 1 2 3 "Ann Graybiel". McGovern Institute for Brain Research at MIT. Retrieved 23 October 2014.
  13. ↑ Zernike, Kate (2023). The Exceptions: Nancy Hopkins, MIT, and the Fight for Women in Science. New York, NY: Scribner. ISBN   978-1-9821-3183-8.
  14. ↑ Ann Graybiel named Institute Professor – MIT News Office. Web.mit.edu (2008-11-03). Retrieved on 2012-06-25.
  15. ↑ US NSF – The President's National Medal of Science: Recipient Details. Nsf.gov. Retrieved on 2012-06-25.
  16. ↑ The Kavli Prize. Kavliprize.no. Retrieved on 2012-06-25.
  17. ↑ "3 Pre-Eminent Neuroscientists Share 2018 Gruber Award For Pioneering Work on the Basal Ganglia". Neuroscience from Technology Networks. Retrieved 2020-09-20.
  18. ↑ "Medlemmer - Utenlandske medlemmer - Den matematisk-naturvitenskapelige klasse". Norwegian Academy of Science and Letters. Retrieved 13 December 2023.
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