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38 Symposium Abstracts ISDN 2012 / In

eurogenesis, through the identification of novel genes involved inhis process.

Moreover, it constitutes a unique model linking cortical devel-pment and evolution, as the mouse and human pathways oforticogenesis display many similarities but also striking dif-erences that may be related to species-specific developmentalrogrammes.

Finally, when grafted into the cerebral cortex of newborn mice,r lesioned cortex of adult mice, mouse and human ESC-derivedortical neurons develop complex and specific patterns of axonalnd dendritic projections corresponding to endogenous corticalrojections in vivo.

ttp://dx.doi.org/10.1016/j.ijdevneu.2012.10.098

SDN2012 0278

ragile X syndrome and the amygdala

umantra Chattarji ∗, Aparna Suvrathan, Sonal Kedia

National Centre for Biological Sciences, TIFR, Bangalore, IndiaFragile X syndrome (FXS), a common heritable form of autism

nd mental impairment, is caused by the absence of the fragile Xental retardation protein (FMRP) encoded by the fragile X mental

etardation 1 (Fmr1) gene. Although FXS is a single gene disorder,he absence of FMRP gives rise to a broad spectrum of psychiatricnd neurological problems including moderate to severe learn-ng disability, developmental delay, hyperactivity, and seizures.urrent understanding of the molecular and cellular mechanismsnderlying FXS symptoms is derived mainly from studies in the hip-ocampus and cortex. However, FXS is also associated with strongmotional symptoms, such as high social anxiety and unstableood, which are likely to involve changes in the amygdala. Unfortu-

ately, the synaptic basis of amygdalar dysfunction in FXS remainsargely unexplored. We will present recent findings from mouse

odels of FXS that have identified synaptic defects in the lateralmygdala that are in many respects distinct from those reportedarlier in the hippocampus.

Using whole-cell recordings in brain slices from adult Fmr1-KOice, we found mGluR-dependent long-term potentiation (LTP) to

e impaired at thalamic inputs to principal neurons in the lateralmygdala (LA). Consistent with this LTP deficit, surface expres-ion of AMPA-receptors in the LA is reduced in the LA of KO mice.urther, in contrast to the hippocampus, thalamic inputs to LA neu-ons also show reduced transmitter release probability, manifestedy a reduction in mEPSC frequency. Importantly, pharmacologi-al inactivation of mGluR5 failed to rescue either the deficit in LTPr surface AMPARs. However, the same acute treatment with anGluR5-antagonist reversed the pre-synaptic deficit. Thus, despite

he contrasting manifestations of abnormal synaptic transmissionnd plasticity in the amygdala versus hippocampus, our resultsuggest that synaptic defects in the amygdala of KO mice are stillmenable to pharmacological interventions against mGluR5, albeitn a manner not envisioned in the original framework based ontudies in the hippocampus. Of particular therapeutic significances the possibility that such reversal can be achieved pharmacologi-

ally even after the disease has had months to leave its mark in thedult brain.

ttp://dx.doi.org/10.1016/j.ijdevneu.2012.10.099

vl Neuroscience 30 (2012) 626–639

ISDN2012 0279

Cortical plasticity: Cell-specific circuits and disorders of braindevelopment

Mriganka Sur

Department of Brain and Cognitive Sciences, Picower Institute forLearning and Memory, Simons Initiative on Autism and the Brain,Massachusetts Institute of Technology, Cambridge, USA

The cerebral cortex not only has excitatory and inhibitory neu-rons, but many different subtypes of each class of neuron. Theseneurons differ in their structure and molecular signatures, but theextent to which they differ in function and circuitry has not beeneasy to resolve. Furthermore, the function of astrocytes, which com-prise over half of all cells in the cortex, has remained mysterious fora century. Novel tools such as molecule- and cell-specific geneticmarkers and transgenic animals, combined with technologies suchas two-photon imaging of structure and function in the intact brain,are transforming the analysis of cortical synapses, cells and circuits.We have used such approaches to reveal not only how circuits of thevisual cortex integrate inputs to make outputs, but also the mecha-nisms by which cortical circuits and synapses mediate remarkableactivity-dependent plasticity during brain development.

Screens for activity-dependent genes and micro-RNAs in visualcortex show that cortical plasticity is regulated by coordinatedmechanisms that influence specific components of plasticity. Manyof these mechanisms are also implicated in disorders of brain devel-opment. Mutant mice with deletions of particular genes implicatedin single-gene subsets of autism spectrum disorders express spe-cific deficits in plasticity. These findings have started to provide amechanism-based understanding of autism and related disordersof brain development.

http://dx.doi.org/10.1016/j.ijdevneu.2012.10.100

ISDN2012 0280

FGF8 specifies areas throughout the neocortex and controls thetopography of sensory maps within areas

Stavroula Assimacopoulos, Tina Kao, Naoum P. Issa, Elizabeth A.Grove

Department of Neurobiology, University of Chicago, Chicago, IL 60637,United States

Fibroblast Growth Factor (FGF) 8 regulates patterning of theneocortex, but an open question is whether FGF8 controls develop-ment only of frontal cortex, close to the FGF8 source, or whether agradient of FGF8 provides rostral to caudal (R/C) positional informa-tion that specifies the entire neocortical area map. To distinguishbetween these models, new sources of FGF8 were introduced atdifferent R/C positions in the mouse neocortical primordium (NP).FGF8 delivered to the lateral NP generated a sulcus, separating ros-tral and caudal parts of the NP. In the caudal part, ectopic FGF8 nearthe sulcus specified an inclusive area map, containing duplicatesof frontal cortex, primary somatosensory (S1) primary visual (V1)and primary auditory (A1) areas. Finally, duplicate S1 respondedto whisker input, and duplicate V1 to visual stimuli. These findingsindicate that an FGF8 gradient specifies areas throughout the neo-

cortex, and, further, initiates the organization of functional sensorymaps.

http://dx.doi.org/10.1016/j.ijdevneu.2012.10.101