Regulation of neocortical interneuron development and the implications for neurodevelopmental disorders

Levitt, Pat; Eagleson, Kathie L.; Powell, Elizabeth M.

doi:10.1016/j.tins.2004.05.008

Cited by 317 publications

(232 citation statements)

References 65 publications

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“…Cortical TH-IR neurons, at least some of which belong to the calretinin-containing subset of interneurons, may play a dopaergic role in cortical circuitry. Interneuron-related disorders may arise when cortical development goes awry (Levitt et al, 2004;Di Cristo, 2007). 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).…”

Section: Discussionmentioning

confidence: 99%

“…The heterogeneity of cortical interneuron morphology and neurochemistry presents a complex, incompletely understood picture of neural development (Wonders and Anderson, 2006). Moreover, cortical interneuron dysfunction has been implicated in several neurological disorders with developmental origins (Levitt et al, 2004;Di Cristo, 2007), 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). The current study examined a subpopulation of rat cortical interneurons that produced tyrosine hydroxylase (TH), the first, rate-limiting catecholaminergic enzyme.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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“…The involvement of Caspr2 in synchronicity of neuronal firing is consistent with the observed effects on inhibitory interneuron function given the role they have in coordination of neural network activity. 41 Interneuron function has also been implicated in disorders such as autism, 70 schizophrenia, 71,72 and epilepsy, 73 suggesting a possible shared mechanism by which CASPR2 could contribute to these neurological disorders.…”

Section: Caspr2 and Neuronal Networkmentioning

confidence: 99%

Shining a light on CNTNAP2: complex functions to complex disorders

2013

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The genetic basis of complex neurological disorders involving language are poorly understood, partly due to the multiple additive genetic risk factors that are thought to be responsible. Furthermore, these conditions are often syndromic in that they have a range of endophenotypes that may be associated with the disorder and that may be present in different combinations in patients. However, the emergence of individual genes implicated across multiple disorders has suggested that they might share similar underlying genetic mechanisms. The CNTNAP2 gene is an excellent example of this, as it has recently been implicated in a broad range of phenotypes including autism spectrum disorder (ASD), schizophrenia, intellectual disability, dyslexia and language impairment. This review considers the evidence implicating CNTNAP2 in these conditions, the genetic risk factors and mutations that have been identified in patient and population studies and how these relate to patient phenotypes. The role of CNTNAP2 is examined in the context of larger neurogenetic networks during development and disorder, given what is known regarding the regulation and function of this gene. Understanding the role of CNTNAP2 in diverse neurological disorders will further our understanding of how combinations of individual genetic risk factors can contribute to complex conditions.

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“…Therefore, contrary to all other cerebellar neurons, GABAergic interneurons derive from a pool of precursors generically committed to this type, but competent to develop specific phenotypic traits in response to spatiotemporally patterned instructive signals. Given the relevance of inhibitory mechanisms in the construction and shaping of neural circuits (Levitt et al, 2004;Hensch, 2005), such a strategy offers obvious advantages, because it allows to match types and numbers of interneurons to specific functional requirements of the developing cerebellar network. Figure 9.…”

Section: Potentiality Of the Cerebellar Gabaergic Interneuron Progenimentioning

confidence: 99%

Different Types of Cerebellar GABAergic Interneurons Originate from a Common Pool of Multipotent Progenitor Cells

et al. 2006

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Different cerebellar phenotypes are generated according to a precise spatiotemporal schedule, in which projection neurons precede local interneurons. Glutamatergic neurons develop from the rhombic lip, whereas GABAergic neurons originate from the ventricular neuroepithelium. Progenitors in these germinal layers are committed toward specific phenotypes already at early ontogenetic stages. GABAergic interneurons are thought to derive from a subset of ventricular zone cells, which migrate in the white matter and proliferate up to postnatal life. During this period, different interneuron categories are produced according to an inside-out sequence, from the deep nuclei to the molecular layer (we show here that nuclear interneurons are also born during late embryonic and early postnatal days, after glutamatergic and GABAergic projection neurons). To ask whether distinct interneuron phenotypes share common precursors or derive from multiple fate-restricted progenitors, we examined the behavior of embryonic and postnatal rat cerebellar cells heterotopically/ heterochronically transplanted to syngenic hosts. In all conditions, donor cells achieved a high degree of integration in the cerebellar cortex and deep nuclei and acquired GABAergic interneuron phenotypes appropriate for the host age and engraftment site. Therefore, contrary to other cerebellar types, which derive from dedicated precursors, GABAergic interneurons are produced by a common pool of progenitors, which maintain their full developmental potentialities up to late ontogenetic stages and adopt mature identities in response to local instructive cues. In this way, the numbers and types of inhibitory interneurons can be set by spatiotemporally patterned signals to match the functional requirements of developing cerebellar circuits.

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Regulation of neocortical interneuron development and the implications for neurodevelopmental disorders

Cited by 317 publications

References 65 publications

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

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

Shining a light on CNTNAP2: complex functions to complex disorders

Different Types of Cerebellar GABAergic Interneurons Originate from a Common Pool of Multipotent Progenitor Cells

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