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Our previous studies indicate that the hippocampus may be particularly vulnerable to GDH deficiency in central nervous system (CNS). Here, we first asked whether mice with a homozygous deletion of <jats:italic>Glud1<\/jats:italic> in CNS (CNS\u2010<jats:italic>Glud1<\/jats:italic> <jats:italic>\u2212\/\u2212<\/jats:italic> mice) express different levels of glutamate in hippocampus, and found elevated glutamate as well as glutamine in dorsal and ventral hippocampus, and increased glutamine in medial prefrontal cortex (mPFC). <jats:sc>l<\/jats:sc>\u2010serine and <jats:sc>d<\/jats:sc>\u2010serine, which contribute to glutamate homeostasis and NMDA receptor function, are increased in ventral but not dorsal hippocampus, and in mPFC. Protein expression levels of the GABA synthesis enzyme glutamate decarboxylase (GAD) GAD67 were decreased in the ventral hippocampus as well. Behavioral analysis revealed deficits in visual, spatial and social novelty recognition abilities, which require intact hippocampal\u2010prefrontal cortex circuitry. Finally, hippocampus\u2010dependent contextual fear retrieval was deficient in CNS\u2010<jats:italic>Glud1 \u2212\/\u2212<\/jats:italic> mice, and c\u2010Fos expression (indicative of neuronal activation) in the CA1 pyramidal layer was reduced immediately following this task. These data point to hippocampal subregion\u2010dependent disruption in glutamate homeostasis and excitatory\/inhibitory balance, and to behavioral deficits that support a decline in hippocampal\u2010prefrontal cortex connectivity. Together with our previous data, these findings also point to different patterns of basal and activity\u2010induced hippocampal abnormalities in these mice. In sum, GDH contributes to healthy hippocampal and PFC function; disturbed GDH function is relevant to several psychiatric and neurological disorders.<\/jats:p>","DOI":"10.1111\/gbb.12636","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T08:07:40Z","timestamp":1578038860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Glutamate dehydrogenase deficiency disrupts glutamate homeostasis in hippocampus and prefrontal cortex and impairs recognition memory"],"prefix":"10.1111","volume":"19","author":[{"given":"Sharon Sima","family":"Lander","sequence":"first","affiliation":[{"name":"Department of Psychology University of Haifa  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy","family":"Chornyy","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Haifa  Haifa 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