There is growing evidence that moderate exposure to alcohol during development can lead to behavioral and cognitive deficits that can persist throughout the lifespan. The cognitive impairments associated with Fetal Alcohol Spectrum Disorders (FASDs) include abnormalities in learning and memory, executive control and social behaviors^""""""""^ and are often characterized by a hyper-focus on one particular task or aspect of a task, to the detriment of other important behaviors. Measures of cortically-mediated cognition have been shown to be sensitive to high dose ethanol (EtOH) exposure during development in rodents, but little is known regarding the mechanisms responsible for executive function alterations associated with FASD. We propose to investigate the impact of prenatal ethanol exposure on corticostriatal-mediated behavior and learning related cortical and striatal physiology by integrating highly translatable touch-screen behavioral measures previously shown to recruit dorsal striatum and orbitofrontal cortex with in vivo and ex vivo electrophysiology in prenatally exposed and control mice. We hypothesize that moderate prenatal EtOH exposure will decrease activation of neuronal circuits in the orbito-frontal cortex (OFC) impairing executive control behavior and releasing the dorsal striatal (dS) from cortical control, resulting in hyper-focused, unregulated learning. In order to test this hypothesis we propose three specific aims. First, we will investigate whether moderate prenatal ethanol exposure impairs reversal learning by measuring choice learning and shifting in adolescent mice after moderate prenatal alcohol exposure using touch screen paradigm. Next, we will examine whether this ethanol exposure impairs the function of dS neuronal circuits by both performing in vivo multi-electrode array electrophysiological recording to examine dS neuronal firing activity during choice learning and shifting and utilizing in vitro slice electrophysiological techniques to examine synaptic transmission and plasticity in the dS after choice learning and shifting. Finally, we will investigate whether PAE impairs the function of OFC neuronal circuits during reversal learning by performing in vivo recording of OFC neuronal firing activity during choice learning and shifting and performing in vitro slice electrophysiology to measure synaptic transmission and AMPAR/NMDAR ratios in the OFC after choice learning and shifting. Taken together, the completion of these aims will allow us to better understand the mechanisms of cognitive impairment in FASD and provide an important tool for developing more effective therapies for executive dysfunction.

Public Health Relevance

There is growing evidence that moderate prenatal alcohol exposure can lead to behavioral and cognitive deficits that can persist throughout the lifespan. However, little is known regarding the mechanisms responsible for these deficits in Fetal Alcohol Spectrum Disorder. This project seeks to understand how prenatal alcohol exposure disrupts normal brain circuitry leading to behavioral impairments and provide important tools for developing more effective therapies for executive dysfunction.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Specialized Center (P50)
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Special Emphasis Panel (ZAA1-GG (50))
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University of New Mexico Health Sciences Center
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Rodriguez, Carlos I; Davies, Suzy; Calhoun, Vince et al. (2016) Moderate Prenatal Alcohol Exposure Alters Functional Connectivity in the Adult Rat Brain. Alcohol Clin Exp Res 40:2134-2146
Marquardt, Kristin; Brigman, Jonathan L (2016) The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: Insights from rodent models. Alcohol 51:1-15
Morton, Russell A; Valenzuela, C Fernando (2016) Further characterization of the effect of ethanol on voltage-gated Ca(2+) channel function in developing CA3 hippocampal pyramidal neurons. Brain Res 1633:19-26
Kajimoto, Kenta; Valenzuela, C Fernando; Allan, Andrea M et al. (2016) Prenatal alcohol exposure alters synaptic activity of adult hippocampal dentate granule cells under conditions of enriched environment. Hippocampus 26:1078-87
Morton, Russell A; Valenzuela, C Fernando (2016) Third Trimester Equivalent Alcohol Exposure Reduces Modulation of Glutamatergic Synaptic Transmission by 5-HT1A Receptors in the Rat Hippocampal CA3 Region. Front Neurosci 10:266
Welch, J H; Mayfield, J J; Leibowitz, A L et al. (2016) Third trimester-equivalent ethanol exposure causes micro-hemorrhages in the rat brain. Neuroscience 324:107-18
Nirgudkar, Pranita; Taylor, Devin H; Yanagawa, Yuchio et al. (2016) Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis. Neurosci Lett 632:86-91
Weick, Jason P (2016) Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease. Stem Cells Int 2016:4190438
Izquierdo, A; Brigman, J L; Radke, A K et al. (2016) The neural basis of reversal learning: An updated perspective. Neuroscience :
Topper, Lauren A; Baculis, Brian C; Valenzuela, C Fernando (2015) Exposure of neonatal rats to alcohol has differential effects on neuroinflammation and neuronal survival in the cerebellum and hippocampus. J Neuroinflammation 12:160

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