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Behavioral consequences of abnormal cortical development: insights into developmental disabilities
J Berger-Sweeney1, C F Hohmann
1Department of Biological Sciences, Wellesley College, MA 02181, USA. jberger-sween@wellesley.edu
Insights
Disruptions in cerebral cortical development, particularly during differentiation, can cause anatomical and behavioral abnormalities. Animal models reveal how neurotransmitter systems like norepinephrine and dopamine impact development and behavior, offering insights into human developmental disabilities.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurodevelopmental Disorders
Background:
- Cerebral cortical development involves neurogenesis, neuronal migration, and differentiation during prenatal and early postnatal periods.
- Insults during these stages can result in cortical hypoplasia, ectopias, and dysplasias.
- Animal models are crucial for studying the long-term consequences of disrupted cortical development.
Purpose of the Study:
- To review animal models of disrupted cortical development, focusing on differentiation.
- To compare anatomical, neurochemical, and behavioral abnormalities resulting from insults to specific neurotransmitter systems.
- To explore sex differences in developmental insult responses and their relevance to human conditions.
Main Methods:
- Examination of extensively-studied animal models of disrupted cortical development.
- Analysis of long-term anatomical, neurochemical, and behavioral outcomes.
- Focus on developmental manipulations affecting neurotransmitter afferent systems (norepinephrine, serotonin, dopamine, acetylcholine).
Main Results:
- Developmental insults lead to a range of behavioral alterations, from motor to cognitive deficits.
- Disruptions in specific neurotransmitter systems (norepinephrine, dopamine, serotonin, acetylcholine) yield distinct anatomical and neurochemical changes.
- Perinatal insults can differentially affect males and females, impacting developmental trajectories.
Conclusions:
- Animal models provide valuable insights into the cellular and neurochemical underpinnings of behavioral abnormalities following developmental insults.
- Understanding these mechanisms is critical for addressing human developmental disabilities.
- The timing and specific neurotransmitter system affected by insults significantly influence outcomes.
Abstract:
Cerebral cortical development occurs in precisely-timed stages that can be divided into neurogenesis, neuronal migration and neuronal differentiation. These events occur during discrete time windows that span the late prenatal and early postnatal periods in both rodents and primates, including humans. Insults at particular developmental stages can lead to distinctive cortical abnormalities including cortical hypoplasia (reduced cell number), cortical ectopias (abnormalities in migration) and cortical dysplasias (abnormalities in the shapes or numbers of dendrites). In this review, we examine some of the most extensively-studied animal models of disrupted stages of cortical development and we compare long-term anatomical, neurochemical, and behavior abnormalities in these models. The behavioral abnormalities in these models range from alterations in simple motor behaviors to food hoarding and maternal behaviors as well as cognitive behaviors. Although we examine concisely animal models of cortical hypoplasia and cortical ectopias, we focus here on developmental manipulations that affect cortical differentiation, particularly, those that interrupt the normal ontogeny of the neurotransmitter-defined cortical afferent systems: norepinephrine, serotonin, dopamine and acetylcholine. All of these afferents presumably play a critical role in the maturation of their cortical targets; the timing of the afferents' entry into the cortex and their effects on their cortical targets, however, are different. We, therefore, compare the specific anatomical, neurochemical and behavioral effects of manipulations of the different cortical afferents. Because of the considerable evidence that cortical development proceeds differently in the two sexes, when data are available, we address whether perinatal insults differentially affect the sexes. Finally, we discuss how these developmental studies provide insights into cellular and neurochemical correlates of behavioral functional abnormalities and the relevance of these data to understanding developmental disabilities in humans.