Title: Chronic ethanol exposure during adolescence impairs simple spike activity of cerebellar Purkinje cells in vivo in mice

2021 ◽  
pp. 136396
Author(s):  
Guang-Hui Dong ◽  
Yin-Hua Xu ◽  
Liang-Yan Liu ◽  
Di Lu ◽  
Chun-Ping Chu ◽  
...  
PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247801
Author(s):  
Friederike Auer ◽  
Eliana Franco Taveras ◽  
Uli Klein ◽  
Céline Kesenheimer ◽  
Dana Fleischhauer ◽  
...  

Modulation of neuronal excitability is a prominent way of shaping the activity of neuronal networks. Recent studies highlight the role of calcium-activated chloride currents in this context, as they can both increase or decrease excitability. The calcium-activated chloride channel Anoctamin 2 (ANO2 alias TMEM16B) has been described in several regions of the mouse brain, including the olivo-cerebellar system. In inferior olivary neurons, ANO2 was proposed to increase excitability by facilitating the generation of high-threshold calcium spikes. An expression of ANO2 in cerebellar Purkinje cells was suggested, but its role in these neurons remains unclear. In the present study, we confirmed the expression of Ano2 mRNA in Purkinje cells and performed electrophysiological recordings to examine the influence of ANO2-chloride channels on the excitability of Purkinje cells by comparing wildtype mice to mice lacking ANO2. Recordings were performed in acute cerebellar slices of adult mice, which provided the possibility to study the role of ANO2 within the cerebellar cortex. Purkinje cells were uncoupled from climbing fiber input to assess specifically the effect of ANO2 channels on Purkinje cell activity. We identified an attenuating effect of ANO2-mediated chloride currents on the instantaneous simple spike activity both during strong current injections and during current injections close to the simple spike threshold. Moreover, we report a reduction of inhibitory currents from GABAergic interneurons upon depolarization, lasting for several seconds. Together with the role of ANO2-chloride channels in inferior olivary neurons, our data extend the evidence for a role of chloride-dependent modulation in the olivo-cerebellar system that might be important for proper cerebellum-dependent motor coordination and learning.


2021 ◽  
Vol 15 ◽  
Author(s):  
Bing-Xue Li ◽  
Guang-Hui Dong ◽  
Hao-Long Li ◽  
Jia-Song Zhang ◽  
Yan-Hua Bing ◽  
...  

Sensory information is transferred to the cerebellar cortex via the mossy fiber–granule cell (MF–GC) pathway, which participates in motor coordination and motor learning. We previously reported that chronic ethanol exposure from adolescence facilitated the sensory-evoked molecular layer interneuron–Purkinje cell synaptic transmission in adult mice in vivo. Herein, we investigated the effect of chronic ethanol exposure from adolescence on facial stimulation-evoked MF–GC synaptic transmission in the adult mouse cerebellar cortex using electrophysiological recording techniques and pharmacological methods. Chronic ethanol exposure from adolescence induced an enhancement of facial stimulation-evoked MF–GC synaptic transmission in the cerebellar cortex of adult mice. The application of an N-methyl-D-aspartate receptor (NMDAR) antagonist, D-APV (250 μM), induced stronger depression of facial stimulation-evoked MF–GC synaptic transmission in chronic ethanol-exposed mice compared with that in control mice. Chronic ethanol exposure-induced facilitation of facial stimulation evoked by MF–GC synaptic transmission was abolished by a selective GluN2A antagonist, PEAQX (10 μM), but was unaffected by the application of a selective GluN2B antagonist, TCN-237 (10 μM), or a type 1 metabotropic glutamate receptor blocker, JNJ16259685 (10 μM). These results indicate that chronic ethanol exposure from adolescence enhances facial stimulation-evoked MF–GC synaptic transmission via GluN2A, which suggests that chronic ethanol exposure from adolescence impairs the high-fidelity transmission capability of sensory information in the cerebellar cortex by enhancing the NMDAR-mediated components of MF–GC synaptic transmission in adult mice in vivo.


2015 ◽  
Vol 113 (7) ◽  
pp. 2524-2536 ◽  
Author(s):  
Haibo Zhou ◽  
Kai Voges ◽  
Zhanmin Lin ◽  
Chiheng Ju ◽  
Martijn Schonewille

The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic, inhibitory output. This implies that pauses in Purkinje cell simple spike activity are potentially instrumental in cerebellar information processing, but their occurrence and extent are still heavily debated. The cerebellar cortex, although often treated as such, is not homogeneous. Cerebellar modules with distinct anatomical connectivity and gene expression have been described, and Purkinje cells in these modules also differ in firing rate of simple and complex spikes. In this study we systematically correlate, in awake mice, the pausing in simple spike activity of Purkinje cells recorded throughout the entire cerebellum, with their location in terms of lobule, transverse zone, and zebrin-identified cerebellar module. A subset of Purkinje cells displayed long (>500-ms) pauses, but we found that their occurrence correlated with tissue damage and lower temperature. In contrast to long pauses, short pauses (<500 ms) and the shape of the interspike interval (ISI) distributions can differ between Purkinje cells of different lobules and cerebellar modules. In fact, the ISI distributions can differ both between and within populations of Purkinje cells with the same zebrin identity, and these differences are at least in part caused by differential synaptic inputs. Our results suggest that long pauses are rare but that there are differences related to shorter intersimple spike intervals between and within specific subsets of Purkinje cells, indicating a potential further segregation in the activity of cerebellar Purkinje cells.


1993 ◽  
Vol 69 (4) ◽  
pp. 1082-1090 ◽  
Author(s):  
Y. Sato ◽  
A. Miura ◽  
H. Fushiki ◽  
T. Kawasaki

1. Some scientists reported that the simple spike (SS) activity was transiently depressed after climbing fiber input, but others reported that predominant population of Purkinje cells increased their SS activity after the complex spike (CS). In the present study, SS activity after spontaneous CS was compared before and after the administration of pentobarbital sodium and of ketamine in high decerebrate cats. 2. Frequencies of spontaneous CS and SS firing were reduced (P < 0.001, t test) after pentobarbital administration of a total dose of 20-30 mg/kg. 3. In the peri-CS time histogram, the SS activity during a post-CS period of 10-110 ms with respect to that during a pre-CS period of -100-0 ms was reduced (P < 0.001) after the pentobarbital administration from, on average, 132.4 to 81.9%. In contrast, the SS activity during a post-CS period of 110-210 ms remained unchanged (P > 0.2). 4. In the pre-CS time histogram constructed after the pentobarbital administration, there were no significant differences (P > 0.01) between the SS activity during a pre-CS period of -600 to -500 ms and that during each of other pre-CS periods, suggesting that the barbiturate had little effect on the SS activity preceding the CS. 5. Analysis of raster diagrams revealed the variability of individual SS activity after the CS.(ABSTRACT TRUNCATED AT 250 WORDS)


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