Early Alcohol Exposure Induces Persistent Alteration of Cortical Columnar Organization and Reduced Orientation Selectivity in the Visual Cortex

Abstract

Fetal alcohol syndrome (FAS) is a major cause of learning and sensory deficits in children. The visual system in particular is markedly affected, with an elevated prevalence of poor visual perceptual skills. Developmental problems involving the neocortex are likely to make a major contribution to some of these abnormalities. Neuronal selectivity to stimulus orientation, a functional property thought to be crucial for normal vision, may be especially vulnerable to alcohol exposure because it starts developing even before eye opening. To address this issue, we examined the effects of early alcohol exposure on development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets were exposed to ethanol starting at postnatal day (P) 10, when the functional properties and connectivity of neocortical neurons start to develop. Alcohol exposure ended at P30, just before eye opening at P32. Following a prolonged alcohol-free period (15-35 days), long-term effects of early alcohol exposure on cortical orientation selectivity were examined at P48-P65, when orientation selectivity in normal ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in alcohol- but not saline-treated animals. Moreover, single-unit recordings revealed that early alcohol treatment weakened neuronal orientation selectivity while preserving robust visual responses. These findings indicate that alcohol exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in FAS.

Pre-administration of G9a/GLP inhibitor during synaptogenesis prevents postnatal ethanol-induced LTP deficits and neurobehavioral abnormalities in adult mice

“…It is possible that ethanol-induced activation of G9a and histone H3 modification during development disrupts the specific process involved in refinement of neuronal circuits, which leads to persistent synaptic dysfunction in adulthood. This could explain why some cortical maps (Margret, et al, 2006, Medina, et al, 2005, Powrozek and Zhou, 2005, Zhou, et al, 2005) and olfacto-hippocampal networks (Sadrian, et al, 2012, Wilson, et al, 2011) are altered in FASD models. Moreover, G9a-deficient mice display signs of severe developmental growth retardation and generally die between the embryonic days 9.5 and 12.5 (Tachibana, et al, 2002, Tachibana, et al, 2005).…”

Children with fetal alcohol spectrum disorder show an amblyopia‐like pattern of vision deficit

“…These typical amblyogenic precursors were not evident in our sample of children with FASD. However, research with animal models by Medina et al 10,30 showed that early alcohol exposure adversely affects the development of ocular dominance columns and neuronal orientation selectivity within the visual cortex. They exposed ferrets to alcohol from day P10 to P30, a postnatal period equivalent to the last trimester of human gestation, and assessed the effects at P48 to P65 when orientation selectivity in normal ferret cortex is mature.…”

GABAAReceptor-Mediated Signaling Alters the Structure of Spontaneous Activity in the Developing Retina

“…This may have profound implications for developing fetuses, in which it has been demonstrated in animal models of fetal alcohol syndrome that exposure to alcohol leads to a variety of neuropathologies, including alterations in the developing visual system (Stromland, 2004) such as a profound loss of plasticity in visual cortex (Medina et al, 2005). Understanding the susceptibility of developing networks to neuromodulatory substances will provide insights into the mechanisms by which exposure to substances such as alcohol impact the prenatal wiring of the nervous system.…”