A Review of Synaptic Plasticity at Purkinje Neurons with a Focus on Ethanol-Induced Cerebellar Dysfunction

Valenzuela, C. Fernando; Lindquist, Britta E.; Zamudio-Bulcock, Paula A.

doi:10.1016/s0074-7742(10)91011-8

Cited by 33 publications

(32 citation statements)

References 136 publications

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“…Our results are similar to those of Napper and West (1995), with cell death on Purkinje cells mostly. Besides this, motor incoordination and cerebellar Purkinje cell loss were also reported after long-term ethanol consumption (Belmeguenai et al, 2008;Idrus et al, 2011;Valenzuela et al, 2010). This suggests that the interactions may be much more complex than postulated here and could be related to downstream muscular activities, an effect also reported earlier by us (Sun et al, unpublished data).…”

Section: Discussionsupporting

confidence: 83%

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

Chan

Fan

et al. 2011

Microscopy Res & Technique

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To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before the test. Downregulation on the activity of cerebellum was observed and the level of activation in the cerebellum decreased dramatically in habitual ketamine users with alcohol consumption before the test. Further studies were performed by using male ICR mice receiving treatment of ketamine only [30 mg kg(-1) intraperitoneally (i.p.)] or ethanol only everyday (0.5 mL 12% orally) and those with coadministration of the above dosages of ketamine and ethanol for 3 months. Fewer Purkinje cells were observed in the cerebellar sections of ketamine treated mice under silver staining. For TUNEL test, a significant increase in the apoptotic cells were observed in the cerebella of the ketamine treated mice (P = 0.016) and of those with co-administration of ketamine and ethanol (P < 0.001), when compared with the control. A statistical significance (P < 0.001) in two-way ANOVA test indicated that there might be an interactive mechanism between ethanol and ketamine acting on the cerebellum.

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Section: Discussionsupporting

confidence: 83%

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

Chan

Fan

et al. 2011

Microscopy Res & Technique

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“…Although the precise mechanisms responsible for these effects are presently unknown, studies with rodent models suggest that ethanol disrupts neuronal migration and survival both in the developing cerebellar cortex and deep cerebellar nuclei [13, 15, 28, 30, 31]. Longer-term deficits in neuronal function, synaptic transmission, and plasticity have also been observed in Purkinje and granule cells of rodents exposed to ethanol during development [8, 19, 20, 29, 40, 43]. However, little is known regarding the impact of developmental ethanol exposure on other cerebellar neuronal populations.…”

Section: Introductionmentioning

confidence: 99%

“…The molecular layer of the cerebellar cortex contains two populations of specialized GABAergic interneurons that control the function of Purkinje cells [22, 42]. Stellate cells, located in the outer portion of the molecular layer, make synaptic connections with Purkinje cell dendrites.…”

Section: Introductionmentioning

confidence: 99%

“…This process continues during the first 2 weeks of postnatal development in rodents, which is, in part, equivalent to the 3 rd trimester of human pregnancy. Specifically, between postnatal day (P) 4 and P7, undifferentiated molecular layer interneurons migrate toward the developing molecular layer and by P12 they begin to form synaptic connections with Purkinje cells [43]. This process is generally completed by P21.…”

Section: Introductionmentioning

confidence: 99%

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Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis

Nirgudkar

Taylor

Yanagawa

et al. 2016

Neuroscience Letters

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Cerebellar alterations are a hallmark of Fetal Alcohol Spectrum Disorders and are thought to be responsible for deficits in fine motor control, motor learning, balance, and higher cognitive functions. These deficits are, in part, a consequence of dysfunction of cerebellar circuits. Although the effect of developmental ethanol exposure on Purkinje and granule cells has been previously characterized, its actions on other cerebellar neuronal populations are not fully understood. Here, we assessed the impact of repeated ethanol exposure on the number of inhibitory neurons in the cerebellar vermis. We exposed pregnant mice to ethanol in vapor inhalation chambers during gestational days 12–19 and offspring during postnatal days 2–9. We used transgenic mice expressing the fluorescent protein, Venus, in GABAergic/glycinergic neurons. Using unbiased stereology techniques, we detected a reduction in Venus positive neurons in the molecular and granule cell layers of lobule II in the ethanol exposed group at postnatal day 16. In contrast, ethanol produced a more widespread reduction in Purkinje cell numbers that involved lobules II, IV–V and IX. We also found a reduction in the volume of lobules II, IV–V, VI–VII, IX and X in ethanol-exposed pups. These findings indicate that second and third trimester ethanol exposure has a greater impact on Purkinje cells than interneurons in the developing cerebellar vermis. The decrease in the volume of most lobules could be a consequence of a reduction in cell numbers, dendritic arborizations, or axonal projections.

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“…Several laboratories, including our own, have demonstrated that the cerebellum is an important target of ethanol [5, 10, 18]. Acute ethanol exposure has been shown to have significant effects on PC synaptic transmission, including increased GABA release onto these neurons and potentiation of GABA A receptor function [7-9].…”

Section: Introductionmentioning

confidence: 99%

Characterization of activity-dependent changes in flavoprotein fluorescence in cerebellar slices from juvenile rats

Jotty

Shuttleworth

Valenzuela

2015

Neuroscience Letters

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Flavoprotein autofluorescence signals attributed to neuronal metabolism have been used to assess synaptic function. Here, we characterized flavoprotein autofluorescence responses in the molecular layer of rat cerebellar slices. High frequency stimulation elicited a transient fluorescence increase (peak phase) that was followed by a longer-lasting fluorescence decrease (valley phase). The peak phase was restricted to the molecular layer, whereas the valley phase extended into the Purkinje cell layer and a portion of the granule cell layer. Responses were abolished by either the Na+ channel antagonist, tetrodotoxin, or a combination of the AMPA receptor antagonists, NBQX and GIKI-53655, and were also reduced by a flavoprotein inhibitor (diphenyleneiodonium). These findings are consistent with responses being mediated by an increase in mitochondrial activity triggered by increased energy demands evoked by AMPA receptor-mediated synaptic transmission. The GABAA receptor antagonist picrotoxin did not significantly influence evoked responses. Likewise, exogenous application of ethanol, at concentrations known to increase GABAA receptor-mediated synaptic transmission at Purkinje cells, did not modify peak responses. These observations indicate that flavoprotein autofluorescence imaging could be useful to assess the coupling between glutamatergic synaptic transmission and neuronal metabolism in cerebellar slices.

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A Review of Synaptic Plasticity at Purkinje Neurons with a Focus on Ethanol-Induced Cerebellar Dysfunction

Cited by 33 publications

References 136 publications

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis

Characterization of activity-dependent changes in flavoprotein fluorescence in cerebellar slices from juvenile rats

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