Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of a number of neuropsychiatric disorders. The GABA
receptors are G-protein coupled receptors consisting of principle subunits and auxiliary potassium channel tetramerization domain (KCTD) subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that determine the kinetics of the GABA
receptor response. Previously, we demonstrated that Kctd12 null mutant mice (Kctd12
) exhibit increased auditory fear learning and that Kctd12
mice show altered circadian activity, as well as increased intrinsic excitability in hippocampal pyramidal neurons. KCTD16 has been demonstrated to influence neuronal excitability by regulating GABA
receptor-mediated gating of postsynaptic ion channels. In the present study we investigated for behavioural endophenotypes in Kctd16
and Kctd16
mice. Compared with wild-type (WT) littermates, auditory and contextual fear conditioning were normal in both Kctd16
and Kctd16
mice. When fear memory was tested on the following day, Kctd16
mice exhibited less extinction of auditory fear memory relative to WT and Kctd16
mice, as well as more contextual fear memory relative to WT and, in particular, Kctd16
mice. Relative to WT, both Kctd16
and Kctd16
mice exhibited normal circadian activity. This study adds to the evidence that auxillary KCTD subunits of GABA
receptors contribute to the regulation of behaviours that could constitute endophenotypes for hyper-reactivity to aversive stimuli in neuropsychiatric disorders.