ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Lentiviral delivery of a vesicular glutamate transporter 1 (VGLUT1)-targeting short hairpin RNA vector into the mouse hippocampus impairs cognition.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 16 citations in OpenAlex.
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- Calbindin-D28k deficiency mediates tau-driven hippocampal hyperexcitement and cognitive impairment.Translational neurodegeneration · 2026Article
- A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons.Cell · 2025Article
- E2F2 induces microglial activation and augments depressive-like behavior in mice by repressing PTPN6 transcription.Cytotechnology · 2025Article
- Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia.International journal of molecular sciences · 2022Review
- Calbindin Deficits May Underlie Dissociable Effects of 5-HTMolecular neurobiology · 2020Article
- Characterization of Behavioral, Signaling and Cytokine Alterations in a Rat Neurodevelopmental Model for Schizophrenia, and Their Reversal by the 5-HTMolecular neurobiology · 2018Article
- Remembering to eat: hippocampal regulation of meal onset.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Review
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Authors and funding
13 authors at 4 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Glutamate is the principle excitatory neurotransmitter in the mammalian brain, and dysregulation of glutamatergic neurotransmission is implicated in the pathophysiology of several psychiatric and neurological diseases. This study utilized novel lentiviral short hairpin RNA (shRNA) vectors to target expression of the vesicular glutamate transporter 1 (VGLUT1) following injection into the dorsal hippocampus of adult mice, as partial reductions in VGLUT1 expression should attenuate glutamatergic signaling and similar reductions have been reported in schizophrenia. The VGLUT1-targeting vector attenuated tonic glutamate release in the dorsal hippocampus without affecting GABA, and selectively impaired novel object discrimination (NOD) and retention (but not acquisition) in the Morris water maze, without influencing contextual fear-motivated learning or causing any adverse locomotor or central immune effects. This pattern of cognitive impairment is consistent with the accumulating evidence for functional differentiation along the dorsoventral axis of the hippocampus, and supports the involvement of dorsal hippocampal glutamatergic neurotransmission in both spatial and nonspatial memory. Future use of this nonpharmacological VGLUT1 knockdown mouse model could improve our understanding of glutamatergic neurobiology and aid assessment of novel therapies for cognitive deficits such as those seen in schizophrenia.
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