EN
The 5‑HT7 receptor has been implicated in mood reg‑ ulation, circadian rhythmicity, and sleep, the disturbances of which are evident in the course of depressive disorders. Research into 5‑HT7 receptor signalling in the hippocam‑ pus has indicated that activation of the 5‑HT7 receptor increases the excitability of pyramidal neurons of the CA1 and CA3 areas. The aim of our study was to investigate ionic mechanisms underlying this effect. We performed whole‑cell current clamp recordings from rat CA1 pyrami‑ dal cells and tested the effects of 5‑HT7 agonists on neu‑ ronal excitability and spiking dynamics. Voltage clamp recordings were used to determine changes in voltage‑de‑ pendent currents following 5‑HT7 receptor activation. Finally, we stimulated Schaffer collaterals and recorded evoked AMPA currents to examine whether these newly discovered ionic mechanisms influence synaptic transmis‑ sion. Administration of 5‑HT7 receptor agonists increased the excitability of CA1 pyramidal neurons, in line with pre‑ vious findings. This was accompanied by a significant de‑ crease in the time needed for the cell to fire the first action potential following a depolarizing current pulse. Voltage clamp recordings confirmed that 5‑HT7 receptor activation significantly attenuated the A‑type current. Pharmacolog‑ ical block of Kv4.2/4.3 channel subunits prevented the in‑ crease in neuronal excitability and spiking latency, as well as the 5‑HT7‑mediated increase in evoked AMPA current amplitude. In the present study we demonstrate that the 5‑HT7 receptor‑mediated effects on excitability, spiking latency and synaptic transmission are directly associated with inhibition of the A‑type potassium current, which is a mechanism not previously associated with this receptor.