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Restricted cortical...
Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function.
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- Wallén-Mackenzie, Åsa (author)
- Uppsala universitet,Genetisk utvecklingsbiologi
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- Nordenankar, Karin (author)
- Uppsala universitet,Genetisk utvecklingsbiologi
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- Fejgin, Kim, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Lagerström, Malin C (author)
- Uppsala universitet,Genetisk utvecklingsbiologi
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- Emilsson, Lina (author)
- Uppsala universitet,Genetisk utvecklingsbiologi
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- Fredriksson, Robert (author)
- Uppsala universitet,Funktionell farmakologi,Farmakologi 3
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- Wass, Caroline, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Andersson, Daniel (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Egecioglu, Emil, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Andersson, My, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Strandberg, Joakim, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Lindhe, Örjan (author)
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- Schiöth, Helgi B (author)
- Uppsala universitet,Funktionell farmakologi,Farmakologi 3
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- Chergui, Karima (author)
- Karolinska Institutet
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- Hanse, Eric, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Långström, Bengt (author)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
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- Fredriksson, Anders (author)
- Uppsala universitet,Psykiatri, Akademiska sjukhuset
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- Svensson, Lennart, 1952 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Roman, Erika (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Neuropharmacology, Addiction and Behaviour
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- Kullander, Klas (author)
- Uppsala universitet,Genetisk utvecklingsbiologi
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 29:7, s. 2238-51
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https://doi.org/10.1...
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Abstract
Subject headings
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- A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glutamatergic neurons within the forebrain, the Vglut2-expressing neurons, in neuronal circuitry of higher brain function. Vglut2 expression was selectively deleted in the cortex, hippocampus, and amygdala of preadolescent mice, which resulted in increased locomotor activity, altered social dominance and risk assessment, decreased sensorimotor gating, and impaired long-term spatial memory. Presynaptic VGLUT2-positive terminals were lost in the cortex, striatum, nucleus accumbens, and hippocampus, and a downstream effect on dopamine binding site availability in the striatum was evident. A connection between the induced late-onset, chronic reduction of glutamatergic neurotransmission and dopamine signaling within the circuitry was further substantiated by a partial attenuation of the deficits in sensorimotor gating by the dopamine-stabilizing antipsychotic drug aripiprazole and an increased sensitivity to amphetamine. Somewhat surprisingly, given the restricted expression of Vglut2 in regions responsible for higher brain function, our analyses show that VGLUT2-mediated neurotransmission is required for certain aspects of cognitive, emotional, and social behavior. The present study provides support for the existence of a neurocircuitry that connects changes in VGLUT2-mediated neurotransmission to alterations in the dopaminergic system with schizophrenia-like behavioral deficits as a major outcome.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Aging
- metabolism
- Amygdala
- growth & development
- metabolism
- physiopathology
- Animals
- Antipsychotic Agents
- pharmacology
- Behavior
- Animal
- physiology
- Cell Differentiation
- genetics
- Cerebral Cortex
- growth & development
- metabolism
- physiopathology
- Corpus Striatum
- growth & development
- metabolism
- physiopathology
- Dopamine
- metabolism
- Glutamic Acid
- metabolism
- Hippocampus
- growth & development
- metabolism
- physiopathology
- Male
- Mice
- Mice
- Knockout
- Neural Pathways
- growth & development
- metabolism
- physiopathology
- Neuronal Plasticity
- genetics
- Nucleus Accumbens
- growth & development
- metabolism
- physiopathology
- Schizophrenia
- genetics
- metabolism
- physiopathology
- Sensory Gating
- genetics
- Synaptic Transmission
- genetics
- Vesicular Glutamate Transport Protein 2
- genetics
- neuronal network
- PHARMACY
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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Wallén-Mackenzie ...
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Nordenankar, Kar ...
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Fejgin, Kim, 197 ...
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Lagerström, Mali ...
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Emilsson, Lina
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Fredriksson, Rob ...
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Wass, Caroline, ...
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Andersson, Danie ...
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Egecioglu, Emil, ...
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Andersson, My, 1 ...
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Strandberg, Joak ...
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Lindhe, Örjan
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Schiöth, Helgi B
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Chergui, Karima
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Hanse, Eric, 196 ...
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Långström, Bengt
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Fredriksson, And ...
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Svensson, Lennar ...
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Roman, Erika
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Kullander, Klas
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MEDICAL AND HEAL ...
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and Basic Medicine
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MEDICAL AND HEAL ...
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MEDICAL AND HEAL ...
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University of Gothenburg
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Uppsala University
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Karolinska Institutet