Pleiotropic Effects of Neurotransmission during Development: Modulators of Modularity

Abstract

The formation and function of the mammalian cerebral cortex relies on the complex interplay of a variety of genetic and environmental factors through protracted periods of gestational and postnatal development. Biogenic amine systems are important neuromodulators, both in the adult nervous system, and during critical epochs of brain development. Abnormalities in developmental programming likely contribute to developmental delays and multiple neurological and psychiatric disorders, often with symptom onset much later than the actual induction of pathology. We review several genetic and pharmacological models of dopamine and serotonin modulation during development, each of which produces permanent changes in cerebral cortical structure and function. These models clearly illustrate the ability of these neurotransmitters to function beyond their classic roles and show their involvement in the development and modulation of fine brain circuitry that is sensitive to numerous effectors. Furthermore, these studies demonstrate the need to consider not only gene by environment interactions, but also gene by environment by developmental time interactions.

Susceptibility to a parkinsonian toxin varies during primate development

“…It is known that the gestational environment can alter neurodevelopment, and furthermore, there is evidence that certain perturbations during the prenatal period can render an individual susceptible to neurodegenerative or neuropsychiatric disorders later in life, with the risk being further modified by the adulthood environment and genetics (Barlow, et al, 2007, Brown, 2011, Johnston, 1995, Thompson and Stanwood, 2009). …”

Probabilistic epigenesis: An alternative causal model for conduct disorders in children and adolescents

“…In these animal models, environmental enrichment during the peripubertal period indeed leads to a functional reversal of the effects of maternal separation (HPA and behavioural response) through compensation rather than reversal of the neural effects of early life adversity (Francis et al, 2002). These studies therefore demonstrate the need to consider not only gene by environment interactions, but also gene by environment by developmental time interactions, as it is hypothesised in pleiotropic effects of neurotransmission during development (Thompson and Stanwood, 2009). …”

ttime: an R Package for Translating the Timing of Brain Development Across Mammalian Species

“…The frequent use of the web-service (>40,000 page accesses) by the research community since its publication (Clancy et al 2007b) establishes its usefulness. The web-service and data sets (Clancy et al 2007a, b) have been cited widely (> 100 citations) across varied scientific disciplines including neuropharmacology (Vorhees et al 2007; Skelton et al 2008; Meyer et al 2010), perinatal pain and anesthesia (Rothstein et al 2008; Sanders et al 2008; Fitzgerald and Walker 2009; McCann and Soriano 2009), neuromodulator development (Thompson and Stanwood 2009; Nordquist and Oreland 2010) and nutrition (Rosales et al 2009). Our tracking statistics indicate over 500 national and international universities, medical centers, and research labs have accessed the web-service, and many of these use the site on a regular basis.…”