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1.
Cell ; 186(9): 1950-1967.e25, 2023 04 27.
Article in English | MEDLINE | ID: mdl-36996814

ABSTRACT

Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.


Subject(s)
Amino Acids, Neutral , Large Neutral Amino Acid-Transporter 1 , Female , Humans , Pregnancy , Amino Acids, Neutral/genetics , Amino Acids, Neutral/metabolism , Brain/metabolism , Large Neutral Amino Acid-Transporter 1/genetics , Large Neutral Amino Acid-Transporter 1/metabolism , Mutation , Neurons/metabolism , Animals , Mice
2.
Hum Brain Mapp ; 41(7): 1904-1919, 2020 05.
Article in English | MEDLINE | ID: mdl-31904899

ABSTRACT

Odors can increase memory performance when presented as context during both encoding and retrieval phases. Since information from different sensory modalities is integrated into a unified conceptual knowledge, we hypothesize that the social information from body odors and faces would be integrated during encoding. The integration of such social information would enhance retrieval more so than when the encoding occurs in the context of common odors. To examine this hypothesis and to further explore the underlying neural correlates of this behavior, we have conducted a functional magnetic resonance imaging study in which participants performed an encoding-retrieval memory task for faces during the presentation of common odor, body odor or clean air. At the behavioral level, results show that participants were less biased and faster in recognizing faces when presented in concomitance with the body odor compared to the common odor. At the neural level, the encoding of faces in the body odor condition, compared to common odor and clean air conditions, showed greater activation in areas related to associative memory (dorsolateral prefrontal cortex), odor perception and multisensory integration (orbitofrontal cortex). These results suggest that face and body odor information were integrated and as a result, participants were faster in recognizing previously presented material.


Subject(s)
Face , Mental Recall/physiology , Odorants , Recognition, Psychology/physiology , Adolescent , Adult , Affect , Association Learning , Female , Human Body , Humans , Magnetic Resonance Imaging , Male , Memory, Episodic , Olfactory Perception/physiology , Prefrontal Cortex/physiology , Psychomotor Performance/physiology , Young Adult
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