AI Article Synopsis
- Researchers investigated the role of the PI3Kγ isoform in hippocampal synaptic plasticity and cognitive function, identifying its crucial involvement in NMDA receptor-mediated long-term depression (LTD).
- Both genetic deletion and pharmacological inhibition of PI3Kγ disrupted NMDAR LTD while not affecting other forms of synaptic plasticity.
- The impairment in NMDAR LTD due to PI3Kγ blockade was linked to deficits in behavioral flexibility, suggesting that different PI3K isoforms have unique roles that influence synaptic functions and behavior.
Article Abstract
Phosphatidylinositol 3-kinase (PI3K) has been implicated in synaptic plasticity and other neural functions in the brain. However, the role of individual PI3K isoforms in the brain is unclear. We investigated the role of PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateral-commissural synapses. Both genetic deletion and pharmacological inhibition of PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, is critical for NMDAR LTD and some forms of cognitive function. Thus, individual isoforms of PI3Ks may have distinct roles in different types of synaptic plasticity and may therefore influence various kinds of behavior.
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| http://dx.doi.org/10.1038/nn.2937 | DOI Listing |
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