Developmental alcohol exposure has been shown to affect the hippocampus, a brain region involved in learning and memory. Long-lasting alterations in synaptic plasticity and AMPA receptor (AMPAR) function have been shown to be a consequence of developmental ethanol (EtOH) exposure. Precocious AMPAfication of synaptic connections can prematurely stabilize neuronal connections. Previous studies in the neonatal hippocampus have demonstrated that alcohol exposure increases network activity, strengthens AMPAR-mediated transmission in a neurosteroid-dependent manner, and decreases cells displaying silent synapses. Together, these data implicate that EtOH alters the normal developmental course of AMPAR- mediated synaptic transmission in CA1 hippocampal pyramidal neurons, and therefore it is hypothesized that developmental exposure to EtOH will strengthen AMPAR-mediated function in CA1 hippocampal pyramidal neurons during the third trimester equivalent of human pregnancy.
Specific aim 1 : is to determine if developmental EtOH exposure alters AMPAR function and subunit expression in CA1 pyramidal neurons. Using the rat alcohol vapor inhalation paradigm, EtOH exposure during the human third-trimester equivalent will be modeled. AMPAR function and expression will be investigated using whole-cell patch-clamp and immunohistochemical techniques. AMPAR-mediated synaptic currents, current- voltage (IV) relationships, and AMPAR subunit expression will be investigated.
Specific aim 2 : is to determine if developmental EtOH exposure affects plasticity in CA1 pyramidal neurons. Studies of long term potentiation (LTP), as well as neuronal expression of silent synapses will be used to address this possibility. The proposed studies will lead to a better understanding of the effects of EtOH on AMPAR- mediated function in the immature hippocampus, making contributions to the FASD as well as the developmental fields, and eventually may lead to the discovery of effective therapies for the life-long consequences of FASD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30AA017813-02
Application #
7669084
Study Section
Special Emphasis Panel (ZAA1-CC (12))
Program Officer
Liu, Qi-Ying
Project Start
2008-08-01
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
2
Fiscal Year
2009
Total Cost
$32,730
Indirect Cost
Name
University of New Mexico
Department
Neurosciences
Type
Schools of Medicine
DUNS #
868853094
City
Albuquerque
State
NM
Country
United States
Zip Code
87131