scholarly journals Molecular and functional heterogeneity of cerebellar granule cell terminals expands temporal coding in molecular layer interneurons

2018 ◽  
Author(s):  
Kevin Dorgans ◽  
Valérie Demais ◽  
Yannick Bailly ◽  
Bernard Poulain ◽  
Philippe Isope ◽  
...  

AbstractIn the cerebellum, molecular layer interneurons (MLIs) play an essential role in motor behavior by exerting precise temporal control of Purkinje cells, the sole output of the cerebellar cortex. The recruitment of MLIs is tightly controlled by the release of glutamate from granule cells (GCs) during high-frequency activities. Here we study how single MLIs are recruited by their distinct unitary GC inputs during burst of GC stimulations. Stimulation of individual GC-MLI synapses revealed four classes of connections segregated by their profile of short-term plasticity. Each class of connection differentially drives MLI recruitment. Molecular and ultrastructural analyses revealed that GC-MLI synaptic diversity is underlain by heterogeneous expression of synapsin II at individual GC terminals. In synapsin II knock-out mice, the number of classes is reduced to profiles associated with slow MLI recruitment. Our study reveals that molecular diversity across GC terminals enables diversity in temporal coding by MLIs and thereby influences the processing of sensory information by cerebellar networks.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kevin Dorgans ◽  
Valérie Demais ◽  
Yannick Bailly ◽  
Bernard Poulain ◽  
Philippe Isope ◽  
...  

Information processing by cerebellar molecular layer interneurons (MLIs) plays a crucial role in motor behavior. MLI recruitment is tightly controlled by the profile of short-term plasticity (STP) at granule cell (GC)-MLI synapses. While GCs are the most numerous neurons in the brain, STP diversity at GC-MLI synapses is poorly documented. Here, we studied how single MLIs are recruited by their distinct GC inputs during burst firing. Using slice recordings at individual GC-MLI synapses of mice, we revealed four classes of connections segregated by their STP profile. Each class differentially drives MLI recruitment. We show that GC synaptic diversity is underlain by heterogeneous expression of synapsin II, a key actor of STP and that GC terminals devoid of synapsin II are associated with slow MLI recruitment. Our study reveals that molecular, structural and functional diversity across GC terminals provides a mechanism to expand the coding range of MLIs.


2021 ◽  
Author(s):  
Kyung-Ran Kim ◽  
Hyeon-Ju Jeong ◽  
Yoonsub Kim ◽  
Seung Yeon Lee ◽  
Yujin Kim ◽  
...  

Calbindin, a major Ca2+ buffer in dentate granule cells (GCs), plays a critical role in shaping Ca2+ signals, yet how it regulates neuronal functions remains largely unknown. Here, we found that calbindin knock-out mice (CBKO) exhibited hyperexcitability in dentate GCs and impaired pattern separation, which was concurrent with reduced K+ current due to downregulated surface expression of Kv4.1. Consistently, manipulation of the calbindin expression in HT22 led to changes in CaMKII activation and the level of surface localization of Kv4.1 through phosphorylation at serine 555, confirming the mechanism underlying neuronal hyperexcitability in CBKO. We also discovered that Ca2+ buffering capacity was significantly reduced in the GCs of Tg2576 to the level of CBKO GCs, and this reduction was restored to normal levels by antioxidants, suggesting that calbindin is a target of oxidative stress. Our data suggest that regulation of CaMKII signaling by Ca2+ buffer is crucial for neuronal excitability regulation.


Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros

Although a previous study in this laboratory determined that Purkinje cells of the rat cerebellum did not appear to be damaged following 30 min of forebrain ischemia followed by 30 min of reperfusion, it was suggested that an increase in rough endoplasmic reticulum (RER) and/or polysomes had occurred in these cells. The primary objective of the present study was to morphometrically determine whether or not this increase had occurred. In addition, since there is substantial evidence that glial cells may be affected by ischemia earlier than other cell types, glial cells also were examined. To ascertain possible effects on other cerebellar components, granule cells and neuropil near Purkinje cells as well as neuropil in the molecular layer also were evaluated in this investigation.


Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.


2013 ◽  
Vol 46 (06) ◽  
Author(s):  
LK Kollmannsberger ◽  
NC Gassen ◽  
A Bultmann ◽  
J Hartmann ◽  
P Weber ◽  
...  

2007 ◽  
Vol 45 (05) ◽  
Author(s):  
A Schnur ◽  
P Hegyi ◽  
V Venglovecz ◽  
Z Rakonczay ◽  
I Ignáth ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2040-P
Author(s):  
COURTNEY J. SMITH ◽  
KYLE B. KENER ◽  
JEFFERY S. TESSEM

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