A common feature in Fetal Alcohol Spectrum Disorders (FASD) is an inability to focus attention appropriately and inhibit responding to stimuli that are similar to, but distinct from, those that reliably lead to positive outcomes. Continuous performance tasks have been used to measure both attention and response inhibition in human subjects and the Five Choice Continuous Performance task (5C-CPT) was developed to examine these processes in an analogous manner in rodents. Together with our collaborators, we have recently validated this task behaviorally in mice and human subjects and our current data shows that the 5C-CPT recruits similar EEG signal from frontal and parietal cortex in rodents and healthy human subjects. Here, we propose to test whether moderate ethanol exposure during the first and second trimester equivalents impairs attention and response inhibition on the touch-screen 5C-CPT. Next, we will perform simultaneous EEG-like dura-resting local field potential (LFP) and depth recording of frontal and parietal cortex to examine whether moderate PAE significantly alters frontal and parietal signaling, and if this signaling is related to alteration in neuronal firing pattern or timing. The combination of these approaches will allow us to look at both individual unit firing and regional activity and compare it to a clinically relevant measure of brain activity. Finally, given evidence that LFP oscillatory signaling is controlled by the activity of fast-spiking parvalbumin positive (FS-PV+) interneurons, we will perform targeted in vivo recording of FS-PV+ neurons, immunohistochemistry and ex vivo electrophysiology to examine whether deficits in cognitive control are mediated by alterations in interneuron number and excitatory tone. Our hypothesis is that PAE leads to inappropriate parietal oscillatory tone via loss of interneuron signaling, with the overall outcome being impaired cognitive control. Taken together, the completion of these aims will allow us to better understand the mechanisms of the long-lasting impairments in cognitive control seen in FASD and provide targets for more effective therapies for executive dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA022534-07
Application #
9980243
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of New Mexico Health Sciences Center
Department
Type
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Caldwell, Kevin K; Solomon, Elizabeth R; Smoake, Jane J W et al. (2018) Sex-specific deficits in biochemical but not behavioral responses to delay fear conditioning in prenatal alcohol exposure mice. Neurobiol Learn Mem 156:1-16
Robinson, Shenandoah; Winer, Jesse L; Chan, Lindsay A S et al. (2018) Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats. Front Neurol 9:451
Oliver, R J; Brigman, J L; Bolognani, F et al. (2018) Neuronal RNA-binding protein HuD regulates addiction-related gene expression and behavior. Genes Brain Behav 17:e12454
Vanderwall, Arden G; Noor, Shahani; Sun, Melody S et al. (2018) Effects of spinal non-viral interleukin-10 gene therapy formulated with d-mannose in neuropathic interleukin-10 deficient mice: Behavioral characterization, mRNA and protein analysis in pain relevant tissues. Brain Behav Immun 69:91-112
Kenton, Johnny A; Castillo, Rebecca; Holmes, Andrew et al. (2018) Cortico-hippocampal GluN2B is essential for efficient visual-spatial discrimination learning in a touchscreen paradigm. Neurobiol Learn Mem 156:60-67
Thompson, Shannon M; Berkowitz, Laura E; Clark, Benjamin J (2018) Behavioral and Neural Subsystems of Rodent Exploration. Learn Motiv 61:3-15
Clark, Benjamin J; Simmons, Christine M; Berkowitz, Laura E et al. (2018) The retrosplenial-parietal network and reference frame coordination for spatial navigation. Behav Neurosci 132:416-429
van Erp, Theo G M; Walton, Esther; Hibar, Derrek P et al. (2018) Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biol Psychiatry 84:644-654
Bird, C W; Baculis, B C; Mayfield, J J et al. (2018) The brain-derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus. Genes Brain Behav :e12484
Gustus, Kymberly C; Li, Lu; Chander, Praveen et al. (2018) Genetic inactivation of synaptosomal-associated protein 25 (SNAP-25) in adult hippocampal neural progenitors impairs pattern discrimination learning but not survival or structural maturation of newborn dentate granule cells. Hippocampus 28:735-744

Showing the most recent 10 out of 46 publications