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| Key Developmental Mechanisms Of Amygdala Found |
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| SciMed - Neuroscience | |||||
| TS-Si News Service | |||||
| Tuesday, 13 January 2009 10:00 | |||||
 Washington, DC, USA. Scientists have successfully identified a key developmental step for the
 amygdala, a part of the human limbic system that creates emotional memories and responses. Enhanced understanding of the structure's origins have implications for charting the brain's developmental history and addressing neurodevelopmental disorders.The amydala is subject to heightened activity durng periods of intense introspection and stress. The structure has been implicated in the normal processing, albeit at a higher rate, when a human sorts out a variety of life's conundrums (such as the mismatch of brain structure and body plan).
Even though the amygdala plays a central role in normal brain function and behavior, little has been known about how neuronal cell diversity is generated during its development. The new findings, published in the journal Nature Neuroscience, identify a pool (i.e., group) of precursor cells of neurons that are earmarked specifically for the amygdala and comprise part of a unique system of growth and development for this portion of the brain.
 The amygdala (Gr. almond) is a small structure in the medial
temporal lobe of the brain, a few inches from either ear. The left and right amygdalae are not physically identical. Neuroimaging studies suggest that the right amygdala has a larger volume than the left. Additionally, the two are functionally asymmetrical as well.
Recent research points to the circuits, not just the structure. The nerves coursing through the amygdala connect it to a number of important brain centers, including the
neocortex and visual cortex. Specifically, the left amygdala appears to be consistently activated in response to negative, withdrawal-related stimuli. The right amygdala seems to be involved in autonomic responses (heart rate, skin responses, blood pressure, etc.).
Amygdala activation can be driven by one's own emotional experiences. It has long been linked with a person's mental and emotional state, playing a critical role in several emotional behaviors.
These include the evaluation of and response to emotionally salient information, anxiety disorders, depression, and the arousal-related components of drug abuse.
The fact that the amygdala influences diverse emotional responses suggests that it serves an important emotional function. It likely influences perception and arousal responses before higher-level, cognitive analysis of the stimuli.
"It was thought that development of this region occurred similarly to other brain structures like the
cerebral cortex, but our findings indicate that a specific precursor pool exists that is pre-assigned exclusively to the limbic system. It is a breakthrough to our understanding of this little studied region of the brain."Using studies of embryonic mice, Corbin and his team located two specific pools of precursor cells marked by a specific
transcription factor (sometimes called a sequence-specific DNA binding factor). A transcription factor is a protein that binds to specific sequences of DNA and thereby controls the transfer (or transcription) of genetic information from DNA to RNA. Such factors contain one or more DNA binding domains (DBDs) which attach to specific sequences of DNA adjacent to the genes that they regulate.
Scientists have suspected the Dbx1 transcription factor of a role in patterning the central
nervous system during embryogenesis. In this case, the precuror cells migrate from both the ventral pallium and the preoptic area — a previously undiscovered pool of migratory cells — to create the requisite mix of excitatory and inhibitory neurons that ultimately comprise the amygdala. Remarkably, the preoptic area precursor cells are exclusive contributors to the development of the limbic system, and no other portion of the brain.
Because of its importance in normal brain functioning, the amygdala has been a focus of investigations into altered brain development that leads to neurodevelopmental disorders (suuch as autism). "A more clear understanding of the normal development of this important brain structure provides a roadmap to understand the consequences of altered brain development in neurodevelopmental disorders," says Dr. Corbin.
This new knowledge could help scientists to better understand autism and similar disorders in which altered function of this region is known to occur. "Altered function of the amygdala is a hallmark characteristic of disorders such as autism," said Dr. Corbin.
The Corbin LabJoshua Corbin, Ph.D, has provided the following mission statement for his laboratory.
My lab is interested in the genetic and cellular basis of the development of the mammalian amygdala. The amygdala is a major component of the brain's limbic system, a functionally interconnected set of forebrain structures that also includes the hippocampus, prefrontal and cingulate cortices, hypothalamus, and nucleus accumbens. Despite an extensive understanding of amygdala function and anatomy, currently little is known regarding the embryonic development of this complex structure. Using the mouse as an experimental model, we are examining how migrating neural progenitor cells in the developing telencephalon contribute to neuronal cell diversity in the mature amygdala and how these cells become wired together to form mature brain circuits.The ultimate goal of our studies is to understand the link between developmental events and the assembly of the mature amygdala at a genetic, cellular, structural and functional level. To investigate these questions we employ a variety of tools including generation and analysis of conditional knockout mice, cell specific lineage tracing using recombination-mediated lineage marking in transgenic animals and ultrasound guided imaging which allows us to deliver labeled cells or retroviruses to the early developing embryonic telencephalon at developmental times that were previously inaccessible. From these studies, we hope to elucidate not only the normal mechanisms of brain development, but also gain a greater understanding of the etiology of developmental disorders in which development of the amygdala is affected. FundingThe current study was funded by the National Institute of Drug Abuse (NIDA) at the U. S. National Institutes of Health (NIH).
CitationIdentification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala. Tsutomu Hirata, Peijun Li, Guillermo M Lanuza, Laura A Cocas, Molly M Huntsman & Joshua G Corbin. Nature Neuroscience (11 January 2009). doi: 10.1038 / nn.2241
Abstract The development of the amygdala, a central structure of the limbic system, remains poorly understood. We found that two spatially distinct and early-specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature mouse amygdala. We found that Dbx1-positive cells of the ventral pallium generate the excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a previously unknown migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1-positive, POA-derived population migrated specifically to the amygdala and, as defined by both immunochemical and electrophysiological criteria, generated a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a previously unknown progenitor pool dedicated to the limbic system.  The TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. Sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.TS-Si is dedicated to the acceptance, medical treatment, and legal protection of individuals correcting the misalignment of their brains and their anatomical sex, while supporting their transition into society as hormonally reconstituted and surgically corrected citizens.
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