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Long-term potentiation (LTP) is a highly studied cellular process yet determining the transduction and GABAergic pathways that are the essential vs. modulatory for LTP elicited by theta-burst stimulation (TBS) in the hippocampal CA1 area is still elusive, due to the use of different TBS intensities, patterns, or different rodent/cellular models. We now characterized the developmental maturation and the transduction and GABAergic pathways required for mild TBS-induced LTP in hippocampal CA1 area in male rats. LTP induced by TBS (5×4) (5 bursts of 4 pulses delivered at 100Hz) lasted for up to 3h and was increasingly larger from weaning to adulthood. Stronger TBS patterns - TBS (15×4) or three TBS (15×4) separated by 6 min induced nearly maximal LTP not being the best choice to study the value of LTP-enhancing drugs. LTP induced by TBS (5×4) in young adults was fully dependent on NMDA receptor and CaMKII activity but independent of PKA or PKC activity. Furthermore, it was partially dependent on GABA_B receptor activation and was potentiated by GABA_A receptor blockade and less by GAT-1 transporter blockade. AMPA GluA1 phosphorylation on Ser₈₃₁ (CaMKII target) but not GluA1 Ser₈₄₅ (PKA target) was essential for LTP expression. The phosphorylation of the Kv4.2 channel was observed at Ser₄₃₈ (CaMKII target) but not at Thr₆₀₂ or Thr₆₀₇ (ERK/MAPK pathway target). This suggests that cellular kinases like PKA, PKC or kinases of the ERK/MAPK family although important modulators of TBS (5×4)-induced LTP may not be essential for its expression in the CA1 area of the hippocampus.

LTP induced by theta …