The proposed experiments are a comprehensive plan for determining how gestational malnutrition affects development and maintenance of neuronal plasticity in the hippocampal formation. Using our well established malnutrition model we are proposing to study the effects of prenatal protein deprivation on the ontogeny of two forms of electrophysiological plasticity: (1) long-term plasticity by measuring the establishment and maintenance of long-term potentiation (LTP) in the dentate gyrus and (2) short-term plasticity by measuring the effects of vigilance states on field potentials and recurrent inhibition in the dentate gyrus. LTP is a form of synaptic plasticity regarded as a putative substrate for learning and memory and is the simplest paradigm yet developed where use alone leads to an increase in synaptic efficacy that lasts for weeks or months. Our previous studies using anesthetized normal and prenatally malnourished rats revealed that prenatal malnutrition leads to a deficit in the ability to potentiate the synaptic component of LTP (population EPSP) but not the cell firing component (population spike). In our first series of experiments we plan to examine this finding in the chronically implanted, freely moving animal in order to study LTP over a longer time course in the awake preparation in terms of its development and maintenance. In our second series of studies on short-term, vigilance state-dependent plasticity in the dentate gyrus we will use the paired-pulse technique to simultaneously monitor the effect of sleep/waking state on field potentials and recurrent inhibition. In this regard, it has been well established that field potentials throughout the hippocampal trisynaptic circuit are vigilance state dependent. However, the role of hippocampal interneurons in these effects have been largely ignored. Our paired pulse experiments will provide new information on the local circuit mechanisms by which sleep- waking states exert their influence on field potentials in the dentate gyrus. These studies are thus expected to show how prenatal protein malnutrition may lead to alterations in the function of local circuit interneurons. Overall, these experiments will reveal how malnutrition may affect specific neuronal circuits in the hippocampus and how a prenatal stressor can affect neuronal plasticity in adulthood even when dietary rehabilitation is initiated at birth.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD023338-01
Application #
3323466
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-09-01
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
01545
Attardi, Barbara J; Marck, Brett T; Matsumoto, Alvin M et al. (2011) Long-term effects of dimethandrolone 17ýý-undecanoate and 11ýý-methyl-19-nortestosterone 17ýý-dodecylcarbonate on body composition, bone mineral density, serum gonadotropins, and androgenic/anabolic activity in castrated male rats. J Androl 32:183-92
Attardi, Barbara J; Engbring, Jean A; Gropp, David et al. (2011) Development of dimethandrolone 17beta-undecanoate (DMAU) as an oral male hormonal contraceptive: induction of infertility and recovery of fertility in adult male rabbits. J Androl 32:530-40
Attardi, Barbara J; Koduri, Sailaja; Hild, Sheri A (2010) Relative progestational and androgenic activity of four progestins used for male hormonal contraception assessed in vitro in relation to their ability to suppress LH secretion in the castrate male rat. Mol Cell Endocrinol 328:16-21
Attardi, Barbara J; Page, Stephanie T; Hild, Sheri A et al. (2010) Mechanism of action of bolandiol (19-nortestosterone-3beta,17beta-diol), a unique anabolic steroid with androgenic, estrogenic, and progestational activities. J Steroid Biochem Mol Biol 118:151-61
Attardi, Barbara J; Hild, Sheri A; Koduri, Sailaja et al. (2010) The potent synthetic androgens, dimethandrolone (7?,11?-dimethyl-19-nortestosterone) and 11?-methyl-19-nortestosterone, do not require 5?-reduction to exert their maximal androgenic effects. J Steroid Biochem Mol Biol 122:212-8
Hild, Sheri Ann; Attardi, Barbara J; Koduri, Sailaja et al. (2010) Effects of synthetic androgens on liver function using the rabbit as a model. J Androl 31:472-81
Tash, Joseph S; Attardi, Barbara; Hild, Sheri A et al. (2008) A novel potent indazole carboxylic acid derivative blocks spermatogenesis and is contraceptive in rats after a single oral dose. Biol Reprod 78:1127-38
Koduri, Sailaja; Hild, Sheri Ann; Pessaint, Laurent et al. (2008) Mechanism of action of l-CDB-4022, a potential nonhormonal male contraceptive, in the seminiferous epithelium of the rat testis. Endocrinology 149:1850-60
Attardi, Barbara J; Pham, Trung C; Radler, Lisa C et al. (2008) Dimethandrolone (7alpha,11beta-dimethyl-19-nortestosterone) and 11beta-methyl-19-nortestosterone are not converted to aromatic A-ring products in the presence of recombinant human aromatase. J Steroid Biochem Mol Biol 110:214-22
Hild, Sheri Ann; Reel, Jerry R; Dykstra, Michael J et al. (2007) Acute adverse effects of the indenopyridine CDB-4022 on the ultrastructure of sertoli cells, spermatocytes, and spermatids in rat testes: comparison to the known sertoli cell toxicant Di-n-pentylphthalate (DPP). J Androl 28:621-9

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