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66 P.P. Kale, V. Addepalli / Int. J. D

abies virus mediated tracing of synapses onto adult generatedeurons

. Deshpande 1,∗, M. Bergami 1, K. Conzelmann 3, M. Götz 1,2, B.erninger 1,2

Department of Physiological Genomics, Institute of Physiology,udwig-Maximilians University Munich, GermanyInstitute for Stem Cell Research, National Research Center for Envi-onment and Health, GermanyMax von Pettenkofer Institute and Gene Center, Ludwig-Maximiliansniversity Munich, Germany

-mail address: Aditi.Deshpande@med.uni-muenchen.de (A. Desh-ande).

In the adult brain, newborn neurons are constantly integrated inhe dentate gyrus (DG) of the hippocampus and the olfactory bulb.owever, much remains to be explored about the precise sequencef events underlying this integration and the cellular identity ofre- and postsynaptic partners, pertaining to both local and distantonnections. Here we aimed at tracing monosynaptic connectionsnto adult generated neurons by modifying a method of retro-rade tracing using an EnvA-pseudotyped rabies virus (EnvA-RV).o target newborn neurons, we used a retrovirus engineered toxpress two proteins – the EnvA receptor, TVA, and the rabies viruslycoprotein – crucial to infection and trans-synaptic transportf EnvA-RV, respectively. Thus only progenitors transduced withhe retrovirus will get infected by EnvA-RV and can subsequentlyransport the virus to their presynaptic partners. We performedtereotaxic injections of the TVA–glycoprotein encoding retrovirusollowed by EnvA-RV 3–5 weeks later, into the DG of adult mice.his resulted in double-labeling of newborn granule cells withetrovirus and EnvA-RV. We also found local interneurons in theG labeled with EnvA-RV alone, presumably via presynaptic inputsnto newborn granule cells. Moreover, we obtained monosynapticracing of distant connections from neurons in the entorhinal cor-ex, a well known source of excitatory input to granule cells, as wells neurons residing in the basal forebrain.

A similar strategy of stereotactic injection of TVA–glycoproteinncoding retrovirus into the SEZ, followed by EnvA-RV into theostral migratory stream to target migrating neuroblasts, resultedn double-labeling of granule cells (GCs), periglomerular cells andabeling of diverse types of interneurons in the olfactory bulb (OB)

ith EnvA-RV alone. Surprisingly, we observed monosynaptic trac-ng of neurons in the anterior olfactory nucleus (AON), known toroject to GCs in the OB, demonstrating that one of the earliestxcitatory synaptic inputs newborn neurons in the OB receive, orig-

nate from the AON.

oi:10.1016/j.ijdevneu.2012.03.317

uroscience 30 (2012) 640–671

MRI versus US as a predictor of neuro-developmental outcomein preterms with mild white matter abnormalities

Maya Weinstein a,f, Liat Ben Sira a, Vicki Myers a, Moran Artzi a,b,Varda Gross-Tsur d, Irit Berger e, Ronella Marom e, Yael Leitner b,c,Shimrit Uliel c, Ronny Geva f, Dafna Ben Bashat a,∗

a The Functional Brain Center, The Wohl Institute for Advanced Imag-ing, TASMC, Israelb Sackler Faculty of Medicine, Tel Aviv University, Israelc Pediatric Neurology and Child Development Unit, TASMC, Israeld Neuropediatric Unit, Shaare-Zedek Medical Center, Israele Department of Neonatology, Lis Maternity Hospital, TASMC, Israelf Department of Psychology, Gonda Multidisciplinary Brain ResearchCenter, Bar Ilan University, Israel

E-mail address: dafnab@tasmc.health.gov.il (D. Ben Bashat).Introduction: Prematurity is a risk factor for mild to severe

neuro-developmental impairments, which occur in more than50% of preterm infants. Increased periventricular echogenicity isoften detected in preterms using cranial ultrasound (cUS). Punc-tuate lesions and diffuse excessive high signal intensity (DEHSI)have recently been documented in MRI. Yet little is known aboutthe correlation between imaging findings obtained via these twomodalities and their clinical relevance.

Methods: 33 premature infants born at <34 weeks’ gestationalage with mild to moderate echogenicity identified on routine cUSunderwent MRI at 36–40 weeks, on a 3T MRI system. Diffuse andfocal echogenic regions were defined on the first US (cUS1) and onthe US closest to the MRI (cUS2). Regions with DEHSI or punctuatelesions were defined on T1 and T2 weighted MRI images. Theseparameters were defined separately for frontal, periventricular,parietal and occipital areas. Identical rating criteria were applied onboth modalities and a total score of white matter (WM) injury wascalculated. Behavioural outcome measures were assessed at oneyear of age in 10 children, using the Griffiths Mental DevelopmentScales.

Results: No significant correlations in WM injury scores weredetected between the two US exams and between cUS and MRIfindings. WM injury scores were higher on cUS1 than on cUS2,implying that some of the echogenicity is transient, as expected.Only WM injury scores calculated on MRI significantly correlatedwith outcome, specifically with personal–social and hearing andlanguage scales.

Discussion: Although cUS is performed routinely in all prema-ture infants, it neither correlated with WM injury as demonstratedon MRI, nor served as a good predictor of development in oursample. Our preliminary results show that MRI performed at termin preterms with mild WM abnormalities, may predict neuro-

developmental outcome at one year of age.

doi:10.1016/j.ijdevneu.2012.03.318