TY  - JOUR
A1  - Grünewald, Benedikt
A1  - Lange, Maren D
A1  - Werner, Christian
A1  - O'Leary, Aet
A1  - Weishaupt, Andreas
A1  - Popp, Sandy
A1  - Pearce, David A
A1  - Wiendl, Heinz
A1  - Reif, Andreas
A1  - Pape, Hans C
A1  - Toyka, Klaus V
A1  - Sommer, Claudia
A1  - Geis, Christian
T1  - Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis
T2  - eLife
N2  - Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3\(^{Δex1-6}\)) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.
KW  - CLN3
KW  - mutation
KW  - mouse model
KW  - synaptic transmission
KW  - amygdala
KW  - hippocampus
Y1  - 2017
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/17000
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-170004
VL  - 6
IS  - e28685
ER  -