The effects of moderate neonatal ethanol exposure on eyeblink conditioning and deep cerebellar nuclei neuron numbers in the rat

Green, John T.; Arenos, Jeremy D.; Dillon, Christopher J.

doi:10.1016/j.alcohol.2006.09.002

Cited by 18 publications

(21 citation statements)

References 86 publications

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“…Adult rats exposed to ethanol as neonates have up to 50% fewer IP neurons than controls (Green et al, 2002b;Tran et al, 2005). The degree of depletion corresponds to the peak BAC level in the neonatal rat (Green et al, 2006). EtOH rats also display reduced IP unit activity across training relative to the learning-dependent increases in unit activity observed in control rats (Green et al, 2002a).…”

Section: The Conditioned Eyeblink Responsementioning

confidence: 99%

Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities

2007

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Binge-like exposure to ethanol early in development results in neurotoxic impairments throughout the brain, including the cerebellum and brainstem. Rats exposed to ethanol, during a period of time commensurate with the human third trimester, also show deficits in classical eyeblink conditioning (EBC), a cerebellar-dependent associative learning procedure. The relationship between ethanolmediated EBC deficits and the intensity of the unconditioned stimulus (US) was explored in the current study. Neonatal rats were intubated and infused with ethanol (EtOH rats), sham-intubated and given no ethanol (SI rats), or reared as unhandled controls (UC rats). As adults, all rats underwent 10 days of 350 ms delay eyeblink conditioning with a tone conditioned stimulus (CS) and one of three co-terminating periorbital shock US. The frequency and topography of the conditioned eyeblink response (CR) were impaired in EtOH rats relative to UC rats. EtOH rats produced fewer CRs, with longer onset latencies, at all US intensities. In contrast, CR amplitude was impaired in EtOH rats at the highest US intensity only. Following conditioning, the unconditioned eyeblink response (UR) was analyzed in subsets of rats from each treatment group at five US intensities. Early ethanol exposure did not impair UR peak amplitude. The deficits in CR production are proposed to result from ethanol-mediated damage within specific regions of the EBC neural circuit.

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Section: The Conditioned Eyeblink Responsementioning

confidence: 99%

Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities

2007

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“…Although studies of the consequences of Purkinje cell loss in normal aging have not been carried out, studies of ethanol effects on the cerebellum include impaired delay and trace eyeblink classical conditioning and loss of Purkinje and interpositus neurons (Goodlett & Ellers, 1997; Green, 2004; Green et al, 2006). …”

Section: Discussionmentioning

confidence: 99%

Aging in the cerebellum and hippocampus and associated behaviors over the adult life span of CB6F1 mice

2013

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In the present study we examined the effects of normal aging in the hippocampus and cerebellum, as well as behaviors associated with these substrates. A total of 67 CB6F1 hybrid mice were tested at one of five ages (4, 8, 12, 18 or 25 months) on the context pre-exposure facilitation effect modification of fear conditioning (CPFE), rotorod, Barnes maze, acoustic startle, Morris water maze (MWM) and 500 ms trace eyeblink classical conditioning (EBCC). Behavioral tasks were chosen to increase the ability to detect age-related changes in learning, as trace EBCC is considered a more difficult paradigm (compared to delay EBCC) and the CPFE has been found to be more sensitive to hippocampus insults than standard contextual fear conditioning. To assess the effects of age on the brain, hippocampus volume was calculated and unbiased stereology was used to estimate the number of Purkinje neurons in the cerebellar cortex. A significant, age-related loss of Purkinje neurons was found—beginning at 12 months of age—and hippocampus volume remained stable over the adult life span. Age-related impairment was found, beginning at 12–18 months in the rotorod, and mice with fewer Purkinje neurons showed greater impairment in this task. CB6F1 mice retained auditory acuity across the life span and mice aged 25 months showed significant age-related impairment in the EBCC task; however, deficits were not associated with the loss of Purkinje neurons. Although the CPFE task is considered more sensitive to hippocampus insult, no age-related impairment was found. Spatial memory retention was impaired in the Barnes maze at 25 months, but no significant deficits were seen in the MWM. These results support the finding of differential aging in the hippocampus and cerebellum.

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“…In the only experimental studies performed on ethanol-induced structural alterations in the cerebellar nuclei of mature animals, young adult rats displayed a loss of cerebellar nuclei neurons and a disruption of cerebellar-dependent learning (eyeblink conditioning) after a neonatal, moderate to heavy ethanol exposure (28,29). To our knowledge, there are no data available on the effects of chronic ethanol exposure of adult rats on the structure and function of the cerebellar nuclei.…”

Section: Introductionmentioning

confidence: 88%

“…Remarkable losses (around 30250%) of cerebellar nuclei cells have been reported in rats after a heavy, binge-like ethanol exposure on PD 4-9 (28,59). Neuron numbers in the interpositus and lateral nuclei also decreased due to a more moderate neonatal ethanol exposure, i.e., 3 g/kg/day of ethanol on PD 2-11 (29). A concomitant impairment in eyeblink conditioning was observed both after the moderate and the heavy neonatal ethanol exposure, as well as a highly significant correlation between the number of cerebellar nuclear cells and the learning rate in eyeblink conditioning (28,29).…”

Section: Ethanol-induced Structural Alterations In the Developing Cermentioning

confidence: 93%

“…Neuron numbers in the interpositus and lateral nuclei also decreased due to a more moderate neonatal ethanol exposure, i.e., 3 g/kg/day of ethanol on PD 2-11 (29). A concomitant impairment in eyeblink conditioning was observed both after the moderate and the heavy neonatal ethanol exposure, as well as a highly significant correlation between the number of cerebellar nuclear cells and the learning rate in eyeblink conditioning (28,29). Based on the time course of ethanol-induced neuronal degeneration in the cerebellar nuclei vs. that of Purkinje and granule cells, Dikranian and co-workers, (60) suggested that cerebellar nuclei neurons, as well as granule cells, are lost by both a direct toxic effect of ethanol and a secondary degeneration due to a loss of Purkinje cells in the ethanol-exposed developing cerebellum.…”

Section: Ethanol-induced Structural Alterations In the Developing Cermentioning

confidence: 95%

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Mechanisms of ethanol-induced degeneration in the developing, mature, and aging cerebellum

Jaatinen

Rintala

2008

Cerebellum

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The adverse effects of acute and chronic ethanol exposure on cerebellar functions have been acknowledged for decades, in terms of impaired control of movement and balance. In addition to the motor impairment, cerebellar degeneration has recently been shown to contribute to distinct neuropsychological deficits in chronic alcoholics, as well as in children with prenatal ethanol exposure. The basic mechanisms underlying these ethanol-induced functional alterations and the related neuropathology in the cerebellum have mostly been clarified only recently. These mechanisms include: (i) excitotoxicity; (ii) dietary factors, especially thiamine depletion; (iii) glial abnormalities; (iv) changes in growth factors; (v) apoptotic mechanisms; (vi) oxidative stress; and (vii) compromised energy production. Although these mechanisms widely apply not only to the mature cerebellum, but also to the developing and the aging cerebella, the developing and the aged cerebellum have some special characteristics, which may make them even more vulnerable to ethanol-induced degeneration. These special instances will be discussed along with the general mechanisms of ethanol-induced cerebellar degeneration.

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The effects of moderate neonatal ethanol exposure on eyeblink conditioning and deep cerebellar nuclei neuron numbers in the rat

Cited by 18 publications

References 86 publications

Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities

Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities

Aging in the cerebellum and hippocampus and associated behaviors over the adult life span of CB6F1 mice

Mechanisms of ethanol-induced degeneration in the developing, mature, and aging cerebellum

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