TY  - JOUR
A1  - Graf, Jürgen
A1  - Rahmati, Vahid
A1  - Majoros, Myrtill
A1  - Witte, Otto W.
A1  - Geis, Christian
A1  - Kiebel, Stefan J.
A1  - Holthoff, Knut
A1  - Kirmse, Knut
T1  - Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo
JF  - eLife
N2  - Spontaneous correlated activity is a universal hallmark of immature neural circuits. However, the cellular dynamics and intrinsic mechanisms underlying network burstiness in the intact developing brain are largely unknown. Here, we use two-photon Ca\(^{2+}\) imaging to comprehensively map the developmental trajectories of spontaneous network activity in the hippocampal area CA1 of mice in vivo. We unexpectedly find that network burstiness peaks after the developmental emergence of effective synaptic inhibition in the second postnatal week. We demonstrate that the enhanced network burstiness reflects an increased functional coupling of individual neurons to local population activity. However, pairwise neuronal correlations are low, and network bursts (NBs) recruit CA1 pyramidal cells in a virtually random manner. Using a dynamic systems modeling approach, we reconcile these experimental findings and identify network bi-stability as a potential regime underlying network burstiness at this age. Our analyses reveal an important role of synaptic input characteristics and network instability dynamics for NB generation. Collectively, our data suggest a mechanism, whereby developing CA1 performs extensive input-discrimination learning prior to the onset of environmental exploration.
KW  - hippocampus
KW  - spontaneous network activity
KW  - transient bursting
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300906
VL  - 11
ER  - 
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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170004
VL  - 6
IS  - e28685
ER  -