Altered emotionality and neuronal excitability in mice lacking KCTD12, an auxiliary subunit of GABAB receptors associated with mood disorders
| Autor: | Erich Seifritz, Bernhard Bettler, L Schmid, Max Gassmann, Flurin Cathomas, Hannes Sigrist, M Stegen, Christopher R. Pryce |
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| Přispěvatelé: | University of Zurich, Pryce, C R |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Heterozygote
Protein subunit Emotions 2804 Cellular and Molecular Neuroscience 610 Medicine & health GABAB receptor Hippocampal formation Motor Activity Hippocampus 03 medical and health sciences Cellular and Molecular Neuroscience 2738 Psychiatry and Mental Health Mice 0302 clinical medicine Receptors GABA Memory medicine Animals Learning Bipolar disorder Circadian rhythm Biological Psychiatry 030304 developmental biology Mice Knockout 0303 health sciences Behavior Animal Fear medicine.disease Circadian Rhythm Psychiatry and Mental health Electrophysiology Mood disorders 10054 Clinic for Psychiatry Psychotherapy and Psychosomatics Major depressive disorder Original Article Psychology Neuroscience 2803 Biological Psychiatry 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry Translational psychiatry Translational Psychiatry, 5 |
| ISSN: | 2158-3188 |
| Popis: | Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, is fundamental to brain function andimplicated in the pathophysiology of several neuropsychiatric disorders. GABA activates G-protein-coupled GABABreceptorscomprising principal GABAB1and GABAB2subunits as well as auxiliary KCTD8, 12, 12b and 16 subunits. TheKCTD12gene has beenassociated with bipolar disorder, major depressive disorder and schizophrenia. Here we compareKctd12null mutant (Kctd12−/−)and heterozygous (Kctd12+/−) with wild-type (WT) littermate mice to determine whether lack of or reduced KCTD12 expressionleads to phenotypes that, extrapolating to human, could constitute endophenotypes for neuropsychiatric disorders with whichKCTD12is associated.Kctd12−/−mice exhibited increased fear learning but not increased memory of a discrete auditory-conditioned stimulus.Kctd12+/−mice showed increased activity during the inactive (light) phase of the circadian cycle relative toWT andKctd12−/−mice. Electrophysiological recordings from hippocampal slices, a region of highKctd12expression, revealed anincreased intrinsic excitability of pyramidal neurons inKctd12−/−andKctd12+/−mice. This is thefirst direct evidence forinvolvement of KCTD12 in determining phenotypes of emotionality, behavioral activity and neuronal excitability. This studyprovides empirical support for the polymorphism and expression evidence thatKCTD12confers risk for and is associated withneuropsychiatric disorders. Translational Psychiatry, 5 ISSN:2158-3188 |
| Databáze: | OpenAIRE |
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