Abstract
Ion channels activated around the subthreshold membrane potential determine the likelihood of neuronal firing in response to synaptic inputs, a process described as intrinsic neuronal excitability. Long-term plasticity of chemical synaptic transmission is traditionally considered the main cellular mechanism of information storage in the brain; however, voltage- and calcium-activated channels modulating the inputs or outputs of neurons are also subjects of plastic changes and play a major role in learning and memory formation. Gamma oscillations are associated with numerous higher cognitive functions such as learning and memory, but our knowledge of their dependence on intrinsic plasticity is by far limited. Here we investigated the roles of potassium and calcium channels activated at near subthreshold membrane potentials in cholinergically induced persistent gamma oscillations measured in the CA3 area of rat hippocampal slices. Among potassium channels, which are responsible for the afterhyperpolarization in CA3 pyramidal cells, we found that blockers of SK (KCa2) and KV7.2/7.3 (KCNQ2/3), but not the BK (KCa1.1) and IK (KCa3.1) channels, increased the power of gamma oscillations. On the contrary, activators of these channels had an attenuating effect without affecting the frequency. Pharmacological blockade of the low voltage-activated T-type calcium channels (CaV3.1–3.3) reduced gamma power and increased the oscillation peak frequency. Enhancement of these channels also inhibited the peak power without altering the frequency of the oscillations. The presented data suggest that voltage- and calcium-activated ion channels involved in intrinsic excitability strongly regulate the power of hippocampal gamma oscillations. Targeting these channels could represent a valuable pharmacological strategy against cognitive impairment.
Highlights
The intrinsic excitability of a neuron describes the probability of action potential firing in response to synaptic inputs (Dunn and Kaczorowski, 2019)
Lower concentrations (10 and 1 μM) concentration-dependently decreased gamma power while the frequency was unchanged. Since these results indicate that cholinergically induced gamma oscillations are highly dependent on KCNQ2/3 channels, we tried to induce neuronal oscillations with XE991 (10 μM) in CA3
Our results show for the first time that among these subthreshold channels, KCa2, Kv7.2/3, as well as T-type calcium channels can modulate the power and, in some cases, the peak frequency of hippocampal gamma oscillations and changes in neuronal networks
Summary
The intrinsic excitability of a neuron describes the probability of action potential firing in response to synaptic inputs (Dunn and Kaczorowski, 2019). The firstly described big-conductance KCa channel (BK, Slo, or KCa1.1) is the only one that is activated by voltage (Almássy and Nánási, 2019) It is expressed in the brain and contributes mainly to the repolarization phase of action potentials and the fast component of afterhyperpolarization (AHP; Contet et al, 2016). Three subtypes of the small conductance KCa channels (SK1-3 or KCa2.1-3) and one intermediate-conductance KCa (IK or KCa3.1) are known (Adelman et al, 2012) They are all voltage-independent, gated directly by submicromolar concentrations of intracellular Ca2+, and rapidly modulate the intrinsic excitability of neurons mainly by generating the slower components of the AHP (Bond et al, 2005; Pedarzani and Stocker, 2008). Blockade of KCa2 channels with apamine has been shown to improve hippocampusdependent learning in rodents (Deschaux et al, 1997; Stackman et al, 2002)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
