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Nicotinic ?5 subunits drive developmental changes in the activation and morphology of prefrontal cortex layer VI neurons.


ABSTRACT: Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of ?5 subunits into ?4?2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of ?5 subunits in the development of the prefrontal cortex is not known.We sought to answer this question by examining nicotinic currents and neuronal morphology in layer VI neurons of medial prefrontal cortex of wild-type and ?5 subunit knockout (?5(-/-)) mice during postnatal development and in adulthood.In wild-type but not in ?5(-/-) mice, there is a developmental peak in nicotinic acetylcholine currents in the third postnatal week. At this juvenile time period, the majority of neurons in all mice have long apical dendrites extending into cortical layer I. Yet, by early adulthood, wild-type but not ?5(-/-) mice show a pronounced shift toward shorter apical dendrites. This cellular difference occurs in the absence of genotype differences in overall cortical morphology.Normal developmental changes in nicotinic signaling and dendritic morphology in prefrontal cortex depend on ?5-comprising nicotinic acetylcholine receptors. It appears that these receptors mediate a specific developmental retraction of apical dendrites in layer VI neurons. This finding provides novel insight into the cellular mechanisms underlying the known attention deficits in ?5(-/-) mice and potentially also into the pathophysiology of developmental neuropsychiatric disorders such as attention-deficit disorder and autism.

SUBMITTER: Bailey CD 

PROVIDER: S-EPMC3788582 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Nicotinic α5 subunits drive developmental changes in the activation and morphology of prefrontal cortex layer VI neurons.

Bailey Craig D C CD   Alves Nyresa C NC   Nashmi Raad R   De Biasi Mariella M   Lambe Evelyn K EK  

Biological psychiatry 20111025 2


<h4>Background</h4>Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of α5 subunits into α4β2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of α5 subunits in the development of the prefrontal cortex is not known.<h4>Methods</h4>We sought to answer this question by examining nicotinic curr  ...[more]

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