micedid not impair cognitive flexibilityasmeasuredbya spatial reversallearning task.

doi:10.1016/j.ntt.2012.05.046

NBTS P08Perinatal choline supplementation improves spatial learning andincreases cholinergic neuron density in the medial septal nucleusin the Ts65Dn mouse model of Down syndrome

Ramon Velazqueza, Jessica Asha, Christy Kelleyb, Brian Powersa, MylaStrawdermana, Elliot Mufsonb, Stephen Ginsbergc, Barbara StruppaaCornell University, Ithaca, NY, United StatesbRush University, Chicago, IL, United StatescNathan Kline Institute/NYU Langone Medical Center, Orangeburg, NY,United States

In addition to mental retardation, individuals with Down syndrome(DS) develop neuropathological hallmarks of Alzheimer's disease (AD)by early adulthood. A murine model of DS and AD (the Ts65Dn mouse)exhibits key features of these disorders, including age-dependentdegeneration of basal forebrain cholinergic neurons (BFCNs) andimpairments in the cognitive functions dependent on these neuronsand their projections to hippocampus and frontal cortex; i.e., explicitmemory and attention. Effective treatment regimens are lacking for bothDS and AD. Recently, our lab demonstrated that supplementing thematernal diet with additional choline markedly improved attention inthe adult Ts65Dn offspring, possibly via protection of BFCNs and theirprojections to frontal cortex. The present study was designed to extendthese findings by testing the hypothesis that this regimen also benefitsfunctions dependent onBFCNsprojections to the hippocampus. PregnantTs65Dnmiceweremaintainedoneither normal rodent chow(containing1.1 g/kg choline chloride) or the same diet supplementedwith additionalcholine (5 g/kg choline chloride) from conception until weaning of thepups. The trisomic offspring and disomic (2 N) littermate controls wereassessed between 13.5 and 17.0 months of age in a radial armwatermaze(RAWM) task, in which the mice learned to find a hidden platform. Atsacrifice, brains were fixation perfused, 40-μm tissue sections wereimmunolabeled for choline acetyltransferase (ChAT, 1:1000, Millipore,Billerica, MA), and analyzed by stereology to determine medial septalnucleus (MSN) area and ChAT-positive neuron number and density.Unsupplemented Ts65Dn mice were impaired relative to the 2N mice inthe acquisition of this spatial navigation task. Perinatal cholinesupplementation significantly improved the performance of the trisomicmice in the RAWM; they learned the task significantly faster than theirunsupplemented counterparts, although their performance was stillinferior to that of the 2N controls. This improved performance may beattributable to the 46% increase in ChAT-positive neuron density in theMSNof the supplemented Ts65Dnmice relative to their unsupplementedcounterparts. In sum, these data suggest that maternal cholinesupplementation may improve cognitive functioning and reduce loss ofMSN neurons in DS, and by extension also in AD.

doi:10.1016/j.ntt.2012.05.047

NBTS P09Perinatal choline supplementation improves learning andattention in Ts65Dnmice and disomic littermates without alteringthe nucleus basalis cholinergic neuronal phenotype

Brian Powersa, Christy Kelleyb, Jessica Asha, Ramon Velazqueza, MylaStrawdermana, Elliot Mufsonb, Stephen Ginsbergc, Barbara StruppaaCornell University, Ithaca, NY, United States

bRush University Medical Center, Chicago, IL, United StatescNathan Kline Institute/New York University Langone Medical Center,Orangeburg, NY, United States

Individuals with Down syndrome (DS) exhibit mental retardationand early-onset Alzheimer's disease (AD). The Ts65Dn mouse modelexhibits key features of DS and AD, including early degeneration of basalforebrain cholinergic neurons (BFCNs) and impairments in the cognitivefunctions dependent on these neurons and their projection systems.Currently, there are no effective treatments for DS or AD. However,recent experiments in our lab demonstrated that maternal cholinesupplementation (MCS) improved performance in various attentiontasks in both trisomic (Ts65Dn) offspring and disomic (2N) littermatecontrols. The present study tested the hypothesis that the improvedperformanceof Ts65Dnand2Nmice supplementedwith cholineearly inlife is due to alterations of cholinergic neurons in the nucleus basalis ofMeynert/substantia innominata (NBM/SI). Ts65Dn dams were main-tained on diets containing either 1.1 g/kg or 5.0 g/kg choline chloride. At12 months, the offspring were assessed on a series of visual attentiontasks. Following sacrifice (14.7–18.6 months), brains were fixationperfused; 40-μm tissue sections were immunolabeled for cholineacetyltransferase (ChAT) and the pan-neurotrophin receptor (p75NTR)and analyzed using unbiased stereology for ChAT-positive and p75NTR-immunoreactive BFCN number, density, and region area within theNBM/SI. Unsupplemented Ts65Dn mice were slower to learn theattention task than 2N mice and exhibited impaired attention duringthe asymptotic phase of performance. MCS significantly improvedlearning of the attention task for both Ts65Dn and 2Nmice. Despite thelearning and attentional benefits of MCS for the Ts65Dn and 2N mice,this early intervention did not produce lasting changes in cholinergicneuron number or density in the NBM/SI. By contrast, cholinergicneurons within themedial septum (MS) of siblings of thesemice testedin a water maze were significantly increased by MCS. The apparentdissociation between the NBM/SI and the MS may be related to theneuroplastic nature of theMS cholinergic system compared to theNBM/SI. Future studieswill be directed to elucidate themolecular and cellularfactors underlying the differential effects of MCS on these BFCNs. Thesebehavioral data suggest that MCS may be a safe and inexpensive meansof improving cognitive functioning in DS and AD.

doi:10.1016/j.ntt.2012.05.048

NBTS P10Prenatal drug exposure and maternal behavior have distinct andpersistent effects on offspring behavior

Lindsay Silva, Diana Dow-EdwardsState University of New York, Downstate Medical Center, School ofGraduate Studies, Program in Neural and Behavioral Science, Brooklyn,NY, United States

Theuse ofmultiple drugs of abuseduringpregnancyhas been shownto have severe adverse effects on offspring behavior. Additionally,gestational drug use can alter the maternal response to offspring cuesleading to altered maternal behavior (MB), which has also been shownto affect offspring behavior. The changes caused by altered MB and/orprenatal drug exposure (PDE) are persistent and can bedetected even inadult offspring. Thepresent studyexamines theeffects of PDEandMBonoffspring performance in a pre-pulse inhibition (PPI) test and on theelevated plus maze (EPM) during adolescence (P 43–44). PPI is ameasure of sensorimotor gating (abnormal in schizophrenia) and theEPM assesses anxiety. Prior to mating, polydrug-treated dams areimplantedwith a 2.0 mg/kg/day nicotine osmotic pump, intubatedwith30 mg/kg cocaine and 25% ethanol and injected sc with 10 mg/kg delta-

NBTS 2012 Abstracts 383