title: Altered postnatal development of cortico-hippocampal neuronal electric activity in mice deficient for the mitochondrial aspartate-glutamate transporter.
abstract: The deficiency in the mitochondrial aspartate/glutamate transporter Aralar/AGC1 results in a loss of the malate-aspartate NADH shuttle in the brain neurons, hypomyelination, and additional defects in the brain metabolism. We studied the development of cortico/hippocampal local field potential (LFP) in Aralar/AGC1 knockout (KO) mice. Laminar profiles of LFP, evoked potentials, and unit activity were recorded under anesthesia in young (P15 to P22) Aralar-KO and control mice as well as control adults. While LFP power increased 3 to 7 times in both cortex and hippocampus of control animals during P15 to P22, the Aralar-KO specimens hardly progressed. The divergence was more pronounced in the CA3/hilus region. In parallel, spontaneous multiunit activity declined severely in KO mice. Postnatal growth of hippocampal-evoked potentials was delayed in KO mice, and indicated abnormal synaptic and spike electrogenesis and reduced output at P20 to P22. The lack of LFP development in KO mice was accompanied by the gradual appearance of epileptic activity in the CA3/hilus region that evolved to status epilepticus. Strikingly, CA3 bursts were poorly conducted to the CA1 field. We conclude that disturbed substrate supply to neuronal mitochondria impairs development of cortico-hippocampal LFPs. Aberrant neuronal electrogenesis and reduced neuron output may explain circuit dysfunction and phenotype deficiencies.
authors.affiliation: Department of Systems Neuroscience, Cajal Institute-CSIC, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gómez-Galán
authors.forename: Julia
authors.initials: J
authors.lastname: Makarova
authors.forename: Irene
authors.initials: I
authors.lastname: Llorente-Folch
authors.forename: Takeyori
authors.initials: T
authors.lastname: Saheki
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pardo
authors.forename: Jorgina
authors.initials: J
authors.lastname: Satrústegui
authors.forename: Oscar
authors.initials: O
authors.lastname: Herreras
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D033681:Mitochondrial Membrane Transport Proteins; C491956:Slc25a12 protein, mouse; D005968:Glutamate Decarboxylase