Long‐term high‐intensity sound stimulation inhibits h current (I_h) in CA1 pyramidal neurons

Abstract

Afferent neurotransmission to hippocampal pyramidal cells can lead to long-term changes to their intrinsic membrane properties and affect many ion currents. One of the most plastic neuronal currents is the hyperpolarization-activated cationic current (I ), which changes in CA1 pyramidal cells in response to many types of physiological and pathological processes, including auditory stimulation. Recently, we demonstrated that long-term potentiation (LTP) in rat hippocampal Schaffer-CA1 synapses is depressed by high-intensity sound stimulation. Here, we investigated whether a long-term high-intensity sound stimulation could affect intrinsic membrane properties of rat CA1 pyramidal neurons. Our results showed that I is depressed by long-term high-intensity sound exposure (1 min of 110 dB sound, applied two times per day for 10 days). This resulted in a decreased resting membrane potential, increased membrane input resistance and time constant, and decreased action potential threshold. In addition, CA1 pyramidal neurons from sound-exposed animals fired more action potentials than neurons from control animals; however, this effect was not caused by a decreased I . On the other hand, a single episode (1 min) of 110 dB sound stimulation which also inhibits hippocampal LTP did not affect I and firing in pyramidal neurons, suggesting that effects on I are long-term responses to high-intensity sound exposure. Our results show that prolonged exposure to high-intensity sound affects intrinsic membrane properties of hippocampal pyramidal neurons, mainly by decreasing the amplitude of I .

Increased hippocampal GABAergic inhibition after long-term high-intensity sound exposure

“…We have shown previously that the Schaffer-CA1 LTP was inhibited in animals one week after exposure to the same sound exposure protocol used in this investigation [18]. We also observed a diminished h current in CA1 pyramidal neurons, which hyperpolarized the membrane, and increased the membrane time constant [19]. The membrane hyperpolarization could negatively affect action potential firing in response to the train of EPSPs used to induce LTP, affecting the coincidence of pre and post-synaptic firing necessary for inducing associative LTP in the hippocampus [22].…”

“…This increased GABAergic tone is a potential contributor to the inhibited LTP after high intensity sound stimulation, however, at this moment we cannot make any causal conclusion about the mechanism of LTP inhibition. It is possible that this effect is a compensatory mechanism for the increased firing of the pyramidal neurons after high-intensity sound stimulation, for instance [19]. More studies are being carried out in order to elucidate the mechanism of LTP inhibition by high intensity sound exposure.…”

“…Acute traumatic noise (106-115 dB, 30-60 minutes) alters place cell activity in the hippocampus [16] and increases arc expression, an immediate early gene related to synaptic plasticity, in the hippocampi of rats [17]. Work from our group has shown that long-term (10 days, 2 minute a day) stimulation with high intensity broadband sound inhibits LTP in the Schaffer-CA1 hippocampus of rats [18] and hyperpolarizes CA1 pyramidal neurons by decreasing the expression of the h current (I h ), while increasing the firing of these neurons by an unknown ionic mechanism [19]. The effect on LTP, but not on the membrane intrinsic properties of CA1 neurons, was also observed after a single one-minute 110 dB broadband sound stimulus [20].…”

Mechanisms of high-intensity sound exposure on inhibiting hippocampal long-term potentiation: role of brain-derived neurotrophic factor

“…However, no potentiated GABAergic transmission was observed after a single episode of 110 dB sound, differently to the potentiated GABAergic transmission after ten days of stimulation (Cunha et al, 2019). This suggests that the potentiated GABAergic transmission is a late response to high-intensity sound stimulation and probably compensates the late increased excitability of CA1 pyramidal neurons observed after the prolonged exposure to high-intensity sound (Cunha et al, 2018). Thus, this indicates that the effects of high-intensity sound are distinct in both models of high-intensity sound exposure.…”

“…In order to investigate the possible mechanisms of this effect on the hippocampi of Wistar rats, we performed experiments studying the synaptic transmission on the CA1 pyramidal neurons and their intrinsic electrophysiological properties (Cunha et al, 2018(Cunha et al, , 2019. The mechanisms of the inhibition of LTP by the prolonged exposure to high-intensity sound might be related, at least partially, to an increase in membrane resistance and decrease in action potential threshold, by a reduction in the expression of Ih in CA1 pyramidal neurons (Cunha et al, 2018) and a potentiation of GABAergic transmission (Cunha et al, 2019). However, in the animals subjected to one minute of high-intensity sound, we did not find differences in the intrinsic properties of CA1 pyramidal neurons (Cunha et al, 2018) showing that the impact of high-intensity sound in the hippocampus is dependent on the length of sound exposure.…”