TY  - JOUR
A1  - Waider, Jonas
A1  - Popp, Sandy
A1  - Mlinar, Boris
A1  - Montalbano, Alberto
A1  - Bonfiglio, Francesco
A1  - Aboagye, Benjamin
A1  - Thuy, Elisabeth
A1  - Kern, Raphael
A1  - Thiel, Christopher
A1  - Araragi, Naozumi
A1  - Svirin, Evgeniy
A1  - Schmitt-Böhrer, Angelika G.
A1  - Corradetti, Renato
A1  - Lowry, Christopher A.
A1  - Lesch, Klaus-Peter
T1  - Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity
JF  - Frontiers in Neuroscience
N2  - Brain serotonin (5-hydroxytryptamine, 5-HT) system dysfunction is implicated in exaggerated fear responses triggering various anxiety-, stress-, and trauma-related disorders. However, the underlying mechanisms are not well understood. Here, we investigated the impact of constitutively inactivated 5-HT synthesis on context-dependent fear learning and extinction using tryptophan hydroxylase 2 (Tph2) knockout mice. Fear conditioning and context-dependent fear memory extinction paradigms were combined with c-Fos imaging and electrophysiological recordings in the dorsal hippocampus (dHip). Tph2 mutant mice, completely devoid of 5-HT synthesis in brain, displayed accelerated fear memory formation and increased locomotor responses to foot shock. Furthermore, recall of context-dependent fear memory was increased. The behavioral responses were associated with increased c-Fos expression in the dHip and resistance to foot shock-induced impairment of hippocampal long-term potentiation (LTP). In conclusion, increased context-dependent fear memory resulting from brain 5-HT deficiency involves dysfunction of the hippocampal circuitry controlling contextual representation of fear-related behavioral responses.
KW  - tryptophan hydroxylase 2
KW  - knockout
KW  - fear learning
KW  - extinction
KW  - long-term potentiation
KW  - hippocampus
KW  - immediate-early gene
KW  - serotonin deficiency
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196077
SN  - 1662-453X
VL  - 13
IS  - 245
ER  - 
TY  - JOUR
A1  - Liu, Ruiqi
A1  - Kinoshita, Masato
A1  - Adolfi, Mateus C.
A1  - Schartl, Manfred
T1  - Analysis of the role of the Mc4r system in development, growth, and puberty of medaka
JF  - Frontiers in Endocrinology
N2  - In mammals the melanocortin 4 receptor (Mc4r) signaling system has been mainly associated with the regulation of appetite and energy homeostasis. In fish of the genus Xiphophorus (platyfish and swordtails) puberty onset is genetically determined by a single locus, which encodes the mc4r. Wild populations of Xiphophorus are polymorphic for early and late-maturing individuals. Copy number variation of different mc4r alleles is responsible for the difference in puberty onset. To answer whether this is a special adaptation of the Mc4r signaling system in the lineage of Xiphophorus or a more widely conserved mechanism in teleosts, we studied the role of Mc4r in reproductive biology of medaka (Oryzias latipes), a close relative to Xiphophorus and a well-established model to study gonadal development. To understand the potential role of Mc4r in medaka, we characterized the major features of the Mc4r signaling system (mc4r, mrap2, pomc, agrp1). In medaka, all these genes are expressed before hatching. In adults, they are mainly expressed in the brain. The transcript of the receptor accessory protein mrap2 co-localizes with mc4r in the hypothalamus in adult brains indicating a conserved function of modulating Mc4r signaling. Comparing growth and puberty between wild-type and mc4r knockout medaka revealed that absence of Mc4r does not change puberty timing but significantly delays hatching. Embryonic development of knockout animals is retarded compared to wild-types. In conclusion, the Mc4r system in medaka is involved in regulation of growth rather than puberty.
KW  - medaka
KW  - Mc4r
KW  - knockout
KW  - puberty
KW  - growth
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201472
VL  - 10
ER  -