Poster abstracts
Poster number 74 submitted by Nidhi Devasthali
Neural stem cell-expressed excitatory amino acid transporter 1 supports normal hippocampal functioning
Nidhi Devasthali (Neuroscience Graduate Program), Emma Corbett (Department of Psychology, The Ohio State University), Liz Kirby (Department of Psychology, The Ohio State University)
Abstract:
The subgranular zone of the hippocampus is one of two neurogenic niches in the adult mammalian brain where neural stem cells (NSCs) reside and can proliferate to give rise to functional neurons. These newly-born neurons integrate into existing hippocampal circuitry where they support learning, memory, and affect regulation. NSCs abundantly express excitatory amino acid transporter 1 (EAAT1), which transports the neurotransmitter glutamate from the extracellular space to inside the cell. We have found NSC-EAAT1 is expressed in the NSC bodies and likely in the molecular layer terminals that wrap around and ensheathe glutamatergic synapses on dentate granule cells. NSC-EAAT1 may therefore have contact with peri-synaptic and extra-synaptic glutamate from a variety of sources. Clearance of glutamate is an essential process in maintaining effective synaptic function and in the DG may be critical to maintaining low levels of activity hypothesized to underpin effective pattern separation. Most previous work on the role of EAATs in glutamate clearance to date has focused on the role of EAAT2 expressed by astrocytes. The contribution of NSC-expressed EAAT1 to normal hippocampal functioning is unclear. We therefore investigated the hypothesis that NSC-EAAT1 modulates hippocampal functioning. To investigate this, we used CRISPR technology to generate a new EAAT1fl/fl mouse, in which a critical exon of EAAT1 was bracketed by LoxP sites. Crossing EAAT1fl/fl mice with NestinCreERT2+/- mice yielded a tamoxifen (TAM) sensitive NSC-specific knockout of the EAAT1 gene. TAM treated EAAT1fl/fl;NestinCreERT2+/- mice (EAAT1cKO) showed significant loss of EAAT1 protein in NSCs compared to Cre-negative littermates (Wt). EAAT1cKO resulted in increased granule cell activity after a cognitive task compared to similarly treated Wt mice, as measured by immunolabelling for the immediate early gene cFos. Additionally, EAAT1cKO mice showed a trend for impaired hippocampus-dependent memory in a Y-maze task compared to Wt mice. Together, these findings suggest that NSC-EAAT1 is required to maintain sparse firing of dentate granule cells, and may support hippocampus-dependent memory.
Keywords: Neuroscience