Chronic Ethanol Consumption Impairs the Tactile-Evoked Long-Term Depression at Cerebellar Molecular Layer Interneuron-Purkinje Cell Synapses in vivo in Mice

Abstract

The cerebellum is sensitive to ethanol (EtOH) consumption. Chronic EtOH consumption impairs motor learning by modulating the cerebellar circuitry synaptic transmission and long-term plasticity. Under in vitro conditions, acute EtOH inhibits both parallel fiber (PF) and climbing fiber (CF) long-term depression (LTD). However, thus far it has not been investigated how chronic EtOH consumption affects sensory stimulation-evoked LTD at the molecular layer interneurons (MLIs) to the Purkinje cell (PC) synapses (MLI-PC LTD) in the cerebellar cortex of living animals. In this study, we investigated the effect of chronic EtOH consumption on facial stimulation-evoked MLI-PC LTD, using an electrophysiological technique as well as pharmacological methods, in urethane-anesthetized mice. Our results showed that facial stimulation induced MLI–PC LTD in the control mice, but it could not be induced in mice with chronic EtOH consumption (0.8 g/kg; 28 days). Blocking the cannabinoid type 1 (CB1) receptor activity with AM-251, prevented MLI-PC LTD in the control mice, but revealed a nitric oxide (NO)-dependent long-term potentiation (LTP) of MLI–PC synaptic transmission (MLI-PC LTP) in the EtOH consumption mice. Notably, with the application of a NO donor, S-nitroso-N-Acetyl-D, L-penicillamine (SNAP) alone prevented the induction of MLI–PC LTD, but a mixture of SNAP and AM-251 revealed an MLI-PC LTP in control mice. In contrast, inhibiting NO synthase (NOS) revealed the facial stimulation-induced MLI-PC LTD in EtOH consumption mice. These results indicate that long-term EtOH consumption can impair the sensory stimulation-induced MLI–PC LTD via the activation of a NO signaling pathway in the cerebellar cortex in vivo in mice. Our results suggest that the chronic EtOH exposure causes a deficit in the cerebellar motor learning function and may be involved in the impaired MLI–PC GABAergic synaptic plasticity.

Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2

“…This finding may be significant as acute alcohol consumption has been shown to suppress parallel fiber long-term depression in the cerebellum, which may contribute to alcohol-induced deficits in motor coordination in rats [54, 55]. Furthermore, in mice, chronic alcohol consumption has been shown to impair the sensory stimulation-induced molecular layer interneurons (MLIs) to the Purkinje cell (PC) synapses through the activation of a nitric oxide signaling pathway in the cerebellar cortex, which could lead to a deficit in cerebellar motor learning [56]. Taken together, our findings suggest that chronic alcohol abuse in AUD individuals may impact cerebellar long-term depression, which could have pleiotropic effects leading to accelerated biological aging.…”

Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

“…Chronic intermittent ethanol exposure significantly reduces the abundance of myelin sheath proteins and enzymes in the cerebellum, the corpus callosum, and the spinal cord ( Samantaray et al, 2015 ). Chronic ethanol exposure also impairs sensory stimulation-induced molecular layer interneuron–PC long-term depression via the activation of the nitric oxide signaling pathway ( Li et al, 2019 ) and significantly facilitates sensory stimulation-evoked molecular layer interneuron–PC synaptic transmission via the nitric oxide signaling pathway in the mouse cerebellar cortex ( Sun et al, 2020 ).…”

Investigação dos níveis de etanol em ar exalado, fluido oral e sangue capilar e correlação com efeitos cognitivos e psicomotores em indivíduos após o consumo de bebidas alcoólicas

“…Após o álcool alcançar a corrente sanguínea e ser distribuído, ele atravessa a membrana que separa o sangue dos alvéolos pulmonares formando um equilíbrio entre a concentração sanguínea com o volume de ar presente no pulmão. Durante a respiração, ao expelir o conteúdo gasoso do pulmão, este ar contendo o álcool pode ser empregado para verificação do consumo de etanol (LINDBERG et al, 2007).…”

“…A relação entre a quantidade de álcool detectado no ar exalado em relação ao sangue é de 2.100:1, isto é, para cada 2,1L de ar exalado pelo pulmão é equivalente a mesma quantidade de etanol presente em 1mL de sangue (LINDBERG et al, 2007).…”

“…A principal vantagem do uso do etilômetro para dosagem de etanol está no fato deste método fornece resultados simples e robustos, com resultados obtidos no campo de forma imediata, tornandose fundamental para a rotina policial (LINDBERG et al, 2007).…”