Altered organization of cortical interneurons in rats exposed to ethanol during neonatal life

Granato, Alberto

doi:10.1016/j.brainres.2005.11.024

Cited by 41 publications

(42 citation statements)

References 47 publications

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“…Early alcohol exposure leads to several alterations of cortical microcircuits involving the corticocortical associative connections (Granato et al, 2003), as well as the number, distribution, and molecular properties of GABAergic interneurons (Granato, 2006;Tavian et al, 2011). As a consequence, the cortical network activity could display striking alterations, which could in turn influence the expression, targeting, or modulation of ion channels.…”

Section: Discussionmentioning

confidence: 99%

“…A small fan circulated the air inside the cage, where the temperature was kept at 22-24°C. This method of ethanol administration yields peak blood alcohol concentration ranging from 150 to 300 mg/dl (Granato et al, 2003;Granato, 2006). Control animals of matched age (Co group, three litters) were separated from the mothers for 3 h a day, omitting the ethanol inhalation procedure.…”

Section: Methodsmentioning

confidence: 99%

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Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons

Granato

Palmer²,

Giorgio³

et al. 2012

J. Neurosci.

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Exposure to alcohol in utero is a well known cause of mental retardation in humans. Using experimental models of fetal alcohol spectrum disorder, it has been demonstrated that cortical pyramidal neurons and their projections are profoundly and permanently impaired. Yet, how the functional features of these cells are modified and how such modifications impact cognitive processes is still unknown. To address this, we studied the intrinsic electrophysiological properties of pyramidal neurons in young adult rats (P30 -P60) exposed to ethanol inhalation during the first week of postnatal life (P2-P6). Dual whole-cell recordings from the soma and distal apical dendrites were performed and, following the injection of depolarizing current into the dendrites, layer 5 neurons from ethanol-treated (Et) animals displayed a lower number and a shorter duration of dendritic spikes, attributable to a downregulation of calcium electrogenesis. As a consequence, the mean number of action potentials recorded at the soma after dendritic current injection was also lower in Et animals. No significant differences between Et and controls were observed in the firing pattern elicited in layer 5 neurons by steps of depolarizing somatic current, even though the firing rate was significantly lower in Et animals. The firing pattern and the firing rate of layer 2/3 neurons were not affected by alcohol exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons

Granato

Palmer²,

Giorgio³

et al. 2012

J. Neurosci.

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“…Another model in which calretinin-immunoreactive neurons are overexpressed is in animals under early ethanol exposure (Granato 2006). This early exposure to ethanol may prevent the reduction of calretinin elements.…”

Section: Discussionmentioning

confidence: 99%

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

et al. 2010

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Down's syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4-5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients.

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“…An aberrant number and/or distribution of specific subsets of cortical interneurons have been linked to several major neurological disorders, including epilepsy (Powell et al, 2003;Garbelli et al, 2006), schizophrenia (Reynolds et al, 2002;Lewis et al, 2005;Daskalakis et al, 2007), and depression (Rajkowska et al, 2007). In a rat model of fetal alcohol syndrome, one outcome of ethanol exposure during the first postnatal week is an increase in the number of cortical calretinin-IR neurons in the adult (Granato, 2006). Furthermore, loss of TH-IR neurons in the human cortex was noted in dementia (Marui et al, 2003) and Parkinson's disease (Fukuda et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

et al. 2008

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Understanding the development of cortical interneuron phenotypic diversity is critical because interneuron dysfunction has been implicated in several neurodevelopmental disorders. Here, tyrosine hydroxylase (TH)-immunoreactive neurons in the developing and adult rat cortex were characterized in light of findings regarding interneuron neurochemistry and development. Cortical THimmunoreactive neurons were first observed two weeks postnatally and peaked in number three weeks after birth. At subsequent ages, the number of these cell profiles was gradually reduced, and they were seen less frequently in adults. No DNA fragmentation or active caspase 3 was observed in cortical TH cells at any age examined, eliminating cell death as an explanation for the decrease in cell number. Although cortical TH cells reportedly fail to produce subsequent catecholaminergic enzymes, we found that the majority of these cells at all ages contained phosphorylated TH, suggesting that the enzyme may be active and producing L-DOPA as an end-product. Morphological criteria and colocalization of some TH cells with glutamic acid decarboxylase suggests that these cells are interneurons. Previously, parvalbumin, somatostatin, and calretinin were demonstrated in nonoverlapping subsets of interneurons. Cortical TH neurons colocalized with calretinin but not with parvalbumin or somatostatin. These findings suggest that the transitory increase in TH cell number is not due to cell death but possibly due to alterations in the amount of detectable TH present in these cells, and that at least some cortical TH-producing interneurons belong to the calretinin-containing subset of interneurons that originate developmentally in the caudal ganglionic eminence.

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Altered organization of cortical interneurons in rats exposed to ethanol during neonatal life

Cited by 41 publications

References 47 publications

Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons

Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down’s syndrome

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

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