Inhibition of phosphatase and tensin homolog induces chemical long-term potentiation in the dentate gyrus of hippocampus.

Phosphatase and Tensin Homolog (PTEN) is a tumor suppressor gene that regulates cell growth, proliferation, and survival. Although the role of PTEN in cellular processes has been well-established, its involvement in synaptic plasticity is still poorly understood. This study examined the impact of bisperoxovanadium (bpV, PTEN inhibitor, 10 µM) on basal synaptic transmission and metaplasticity in the dentate gyrus of the hippocampus. A total of 48 male Wistar rats weighing between 240 and 360 g were used for all experiments. We recorded extracellular postsynaptic potentials (EPSPs) in the dentate gyrus by stimulating the perforant path of the hippocampus. To evaluate basal synaptic function, we applied constant stimuli of 0.175 ms at a frequency of 0.33 Hz, delivered at 30 s intervals. The metaplasticity responses were induced using a low-frequency stimulus (LFS) at 1 Hz for 5 min, followed by a high-frequency stimulus (HFS) consisting of four trains at 100 Hz. Saline (control) or bpV was administered into the dentate gyrus via a Hamilton syringe, started after the 15-minute initial recording, and lasted 60 min. To assess the molecular effects of bpV, Western blot and PCR analyses were used to measure the protein levels of the PI3K pathway and related gene expression. Infusion of bpV enhanced the baseline population spikes evoked by test stimulation but did not change population spike (PS) amplitude and EPSP slope in metaplasticity responses. The results showed that inhibition of PTEN led to increased basal synaptic transmission, and bpV induced a chemical form of long-term potentiation, a process associated with synaptic strengthening. Based on these findings, PTEN could function as a negative regulator in synaptic plasticity modification.