TY  - JOUR
A1  - Jansch, Charline
A1  - Ziegler, Georg C.
A1  - Forero, Andrea
A1  - Gredy, Sina
A1  - Wäldchen, Sina
A1  - Vitale, Maria Rosaria
A1  - Svirin, Evgeniy
A1  - Zöller, Johanna E. M.
A1  - Waider, Jonas
A1  - Günther, Katharina
A1  - Edenhofer, Frank
A1  - Sauer, Markus
A1  - Wischmeyer, Erhard
A1  - Lesch, Klaus-Peter
T1  - Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly
JF  - Journal of Neural Transmission
N2  - Human induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation of functionally active neurons from hiPSCs displaying 5-HT specification by modification of a previously reported protocol. Furthermore, 5-HT specific neurons were characterized using high-end fluorescence imaging including super-resolution microscopy in combination with electrophysiological techniques. Differentiated hiPSCs synthesize 5-HT, express specific markers, such as tryptophan hydroxylase 2 and 5-HT transporter, and exhibit an electrophysiological signature characteristic of serotonergic neurons, with spontaneous rhythmic activities, broad action potentials and large afterhyperpolarization potentials. 5-HT specific neurons form synapses reflected by the expression of pre- and postsynaptic proteins, such as Bassoon and Homer. The distribution pattern of Bassoon, a marker of the active zone along the soma and extensions of neurons, indicates functionality via volume transmission. Among the high percentage of 5-HT specific neurons (~ 42%), a subpopulation of CDH13 + cells presumably designates dorsal raphe neurons. hiPSC-derived 5-HT specific neuronal cell cultures reflect the heterogeneous nature of dorsal and median raphe nuclei and may facilitate examining the association of serotonergic neuron subpopulations with neuropsychiatric disorders.
KW  - neuropsychiatric disorders
KW  - human induced pluripotent stem cell (hiPSC)
KW  - serotonin-specific neurons
KW  - median and dorsal raphe
KW  - synapse formation
KW  - Cadherin-13 (CDH13)
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268519
SN  - 1435-1463
VL  - 128
IS  - 2
ER  - 
TY  - JOUR
A1  - Hepbasli, Denis
A1  - Gredy, Sina
A1  - Ullrich, Melanie
A1  - Reigl, Amelie
A1  - Abeßer, Marco
A1  - Raabe, Thomas
A1  - Schuh, Kai
T1  - Genotype- and Age-Dependent Differences in Ultrasound Vocalizations of SPRED2 Mutant Mice Revealed by Machine Deep Learning
JF  - Brain Sciences
N2  - Vocalization is an important part of social communication, not only for humans but also for mice. Here, we show in a mouse model that functional deficiency of Sprouty-related EVH1 domain-containing 2 (SPRED2), a protein ubiquitously expressed in the brain, causes differences in social ultrasound vocalizations (USVs), using an uncomplicated and reliable experimental setting of a short meeting of two individuals. SPRED2 mutant mice show an OCD-like behaviour, accompanied by an increased release of stress hormones from the hypothalamic–pituitary–adrenal axis, both factors probably influencing USV usage. To determine genotype-related differences in USV usage, we analyzed call rate, subtype profile, and acoustic parameters (i.e., duration, bandwidth, and mean peak frequency) in young and old SPRED2-KO mice. We recorded USVs of interacting male and female mice, and analyzed the calls with the deep-learning DeepSqueak software, which was trained to recognize and categorize the emitted USVs. Our findings provide the first classification of SPRED2-KO vs. wild-type mouse USVs using neural networks and reveal significant differences in their development and use of calls. Our results show, first, that simple experimental settings in combination with deep learning are successful at identifying genotype-dependent USV usage and, second, that SPRED2 deficiency negatively affects the vocalization usage and social communication of mice.
KW  - SPRED
KW  - SPRED2
KW  - mice
KW  - neural networks
KW  - ultrasound vocalizations
KW  - DeepSqueak
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248525
SN  - 2076-3425
VL  - 11
IS  - 10
ER  -