Telencephalic cytoarchitectonics in the brains of rats with graded degrees of micrencephaly

Dambska, M; Haddad, R.; Kozlowski, Piotr B.; Lee, M. H.; Shek, J.W.

doi:10.1007/bf00690802

Cited by 59 publications

(14 citation statements)

References 15 publications

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“…In agreement with previous reports (12)(13)(14), we observed that prenatal treatment with MAM induces a diffuse cortical malformations in all of the offsets of a litter. MAM rats exhibit cortical thinning mainly affecting the supragranular layers and heterotopias in and below the white matter (WM) as well as in the CA1 region of the hippocampus (Fig.…”

Section: Resultssupporting

confidence: 93%

“…In the present study, we have used the prenatal methylazoxymethanol (MAM) model that is associated with microcephaly (9,10) and cortical disorganization with periventricular and intrahippocampal heterotopias (11)(12)(13). We report that intrahippocampal neocortical heterotopic neurons have bi-directional monosynaptic connections with the neocortex and are integrated in the hippocampal circuitry.…”

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confidence: 99%

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Neuronal migration disorders: Heterotopic neocortical neurons in CA1 provide a bridge between the hippocampus and the neocortex

Chevassus-au-Louis

Congar

Represa

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Neuronal migration disorders have been involved in various pathologies, including epilepsy, but the properties of the neural networks underlying disorders have not been determined. In the present study, patch clamp recordings were made from intrahippocampal heterotopic as well as from neocortical and hippocampal neurons from brain slices of rats with prenatally methylazoxymethanol-induced cortical malformation. We report that heterotopic neurons have morphometrical parameters and cellular properties of neocortical supragranular neurons and are integrated in both neocortical and hippocampal networks. Thus, stimulation of the white matter induces both antidromic and orthodromic response in heterotopic and neocortical neurons. Stimulation of hippocampal afferents evokes a monosynaptic response in the majority of heterotopic neurons and a polysynaptic allor-none epileptiform burst in the presence of bicuculline to block ␥-aminobutyric acid type A inhibition. Furthermore, hippocampal paroxysmal activity generated by bath application of bicuculline can spread directly to the neocortex via the heterotopia in methylazoxymethanol-treated but not in naive rats. We conclude that heterotopias form a functional bridge between the limbic system and the neocortex, providing a substrate for pathological conditions. Migration of young postmitotic neurons from the ventricular zone to the cortical plate where they differentiate is a key event in cortical development. Neuronal migration disorders lead neurons to differentiate in an abnormal or heterotopic position (1). Periventricular and subcortical heterotopias long have been described in the brain of patients suffering from epilepsy (2-6). Moreover, discrete intracortical heterotopias also have been described in the brains of patients suffering from dyslexia (7) and schizophrenia (8). Together, these data suggest that neuronal migration disorders may constitute a morphological basis for these pathologies.Despite their importance for the understanding of the physiopathological mechanisms of these disorders, the cellular properties and connections of heterotopic neurons are known poorly. In the present study, we have used the prenatal methylazoxymethanol (MAM) model that is associated with microcephaly (9, 10) and cortical disorganization with periventricular and intrahippocampal heterotopias (11-13). We report that intrahippocampal neocortical heterotopic neurons have bi-directional monosynaptic connections with the neocortex and are integrated in the hippocampal circuitry. They therefore provide a direct aberrant link between the hippocampus and the neocortex and a basis for disorders associated with cortical malformation. As an example for this, we report that paroxysmal activity generated in the hippocampus can directly propagate to the neocortex via the heterotopia. MATERIALS AND METHODSAnimals. Pregnant Wistar rats were injected i.p. with 25 mg͞kg of MAM (Sigma) dissolved in saline at embryonic day 14 (first gestation day as embryonic day 0). After normal delivery, r...

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Section: Resultssupporting

confidence: 93%

mentioning

confidence: 99%

Neuronal migration disorders: Heterotopic neocortical neurons in CA1 provide a bridge between the hippocampus and the neocortex

Chevassus-au-Louis

Congar

Represa

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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“…Exposure to MAM on or prior to E15 leads to abnormalities in corticocortical synaptic transmission (Chevassus-Au-Louis et al 1998), striatal hyperdopaminergia with increased responsiveness to psychostimulants (Archer et al 1988;Watanabe et al 1995), and cognitive and sensorimotor gating deficits (Mohammed et al 1986;Talamini et al 2000). While these abnormalities are relevant to a number of developmental brain disorders (Cattabeni and Di Luca 1997;Chevassus-Au-Louis et al 1998;Coyle et al 1984), their validity for modeling schizophrenia is limited due to the microcephaly produced by MAM exposure on or before E15 (Dambska et al 1982;Jongen-Relo et al 2004;Kabat et al 1985;Singh 1980). To address this limitation, we administered MAM on E17 (Grace and Moore 1998;Moore et al 2001).…”

Section: Introductionmentioning

confidence: 99%

A Neurobehavioral Systems Analysis of Adult Rats Exposed to Methylazoxymethanol Acetate on E17: Implications for the Neuropathology of Schizophrenia

Moore

Jentsch

Ghajarnia

et al. 2006

Biological Psychiatry

324

405

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Background-As a test of plausibility for the hypothesis that schizophrenia can result from abnormal brain, especially cerebral cortical, development, these studies examined whether, in the rat, disruption of brain development initiated on embryonic day (E) 17, using the methylating agent methylazoxymethanol acetate (MAM), leads to a schizophrenia-relevant pattern of neural and behavioral pathology. Specifically, we tested whether this manipulation leads to disruptions of frontal and limbic corticostriatal circuit function, while producing schizophrenia-like, regiondependent reductions in gray matter in cortex and thalamus.

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“…When administered at embryonic day 14 (E14) in rats, MAM causes cell death in the proliferative neuro-epithelium and secondary disorganisation of radial glial cells [Ashwell, 1992;Zhang et al, 1995] that guide neuroblast migration to the cortical plate. Consequently, the so-called MAM rats are microcephalic, with a particular reduction of the external cortical layers [Dambska et al, 1982;Yurkewicz et al, 1984], and exhibit a variety of migration disorders such as subcortical, subpial and deep cortical layers and intrahippocampal neocortical heterotopias [Singh, 1977;Collier and Ashwell, 1993]. Gold axonal impregnations in MAMtreated rats.…”

Section: Introductionmentioning

confidence: 99%

Abnormal Connections in the Malformed Cortex of Rats with Prenatal Treatment with Methylazoxymethanol May Support Hyperexcitability

et al. 1999

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Prenatal treatment with methylazoxymethanol (MAM) in rats generates animals with a diffuse cortical malformation associated with hyperexcitability. These alterations are reminiscent of the cortical malformations associated with epilepsy in children. We hypothesised that one of the mechanisms supporting hyperexcitability in MAM rats could be the presence of abnormal cortical connections in the malformed cortex. Using a variety of anatomical techniques, we provide evidences for three types of such abnormal connections: (i) tangential bundles of corticocortical fibres in and below the neocortical molecular layer; (ii) partial deafferentation of neocortical heterotopias by afferent cortical fibres whatever their location; (iii) exuberant innervation of hippocampal CA3 pyramidal cells by mossy fibres that form ectopic mossy boutons on their basal dendrites. We conclude that these abnormal intrinsic cortical connections may support the propagation of paroxymal activity in the neocortex of MAM-treated rats.

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Telencephalic cytoarchitectonics in the brains of rats with graded degrees of micrencephaly

Cited by 59 publications

References 15 publications

Neuronal migration disorders: Heterotopic neocortical neurons in CA1 provide a bridge between the hippocampus and the neocortex

Neuronal migration disorders: Heterotopic neocortical neurons in CA1 provide a bridge between the hippocampus and the neocortex

A Neurobehavioral Systems Analysis of Adult Rats Exposed to Methylazoxymethanol Acetate on E17: Implications for the Neuropathology of Schizophrenia

Abnormal Connections in the Malformed Cortex of Rats with Prenatal Treatment with Methylazoxymethanol May Support Hyperexcitability

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