The role of hyperpolarization‐activated cationic current in spike‐time precision and intrinsic resonance in cortical neurons in vitro

Abstract

Non-technical summary We determined here the role of the hyperpolarization-activated cationic (h) current on the temporal organization of hippocampal activity in vitro. In CA1 pyramidal neurons the h-current has three main actions. In addition to setting intrinsic resonance frequency at ∼4 Hz, the h-current determines, through two main mechanisms, the temporal precision of action potentials evoked by excitatory postsynaptic potentials or following stimulation of inhibitory postsynaptic potentials (rebound spiking). We propose that h-channels participate in the fine tuning of oscillatory activity in hippocampal and neocortical networks.Abstract Hyperpolarization-activated cyclic nucleotide modulated current (I h ) sets resonance frequency within the θ-range (5-12 Hz) in pyramidal neurons. However, its precise contribution to the temporal fidelity of spike generation in response to stimulation of excitatory or inhibitory synapses remains unclear. In conditions where pharmacological blockade of I h does not affect synaptic transmission, we show that postsynaptic h-channels improve spike time precision in CA1 pyramidal neurons through two main mechanisms. I h enhances precision of excitatory postsynaptic potential (EPSP)-spike coupling because I h reduces peak EPSP duration. I h improves the precision of rebound spiking following inhibitory postsynaptic potentials (IPSPs) in CA1 pyramidal neurons and sets pacemaker activity in stratum oriens interneurons because I h accelerates the decay of both IPSPs and after-hyperpolarizing potentials (AHPs). The contribution of h-channels to intrinsic resonance and EPSP waveform was comparatively much smaller in CA3 pyramidal neurons. Our results indicate that the elementary mechanisms by which postsynaptic h-channels control fidelity of spike timing at the scale of individual neurons may account for the decreased theta-activity observed in hippocampal and neocortical networks when h-channel activity is pharmacologically reduced.

Different functions of hyperpolarization-activated cation channels for hippocampal sharp waves and ripples in vitro

“…In neurons lacking HCN channels postsynaptic potentials are prolonged and excitation-spike coupling is less precise (Pavlov et al, 2011;Gastrein et al, 2011). Therefore, we analyzed the temporal precision of spike entrainment by the oscillating field potential in CA1.…”

Axon Physiology

“…Outward voltage-gated currents with biophysical properties that sharpen physiological depolarizations, such as EPSPs, reduce the time window during which an action potential can be triggered and thus enhance spike precision (25,200,207). In contrast, outward currents that reduce the rate of depolarization leading to the generation of a spike decrease spike-time precision (131,503).…”

Dopamine neurons change the type of excitability in response to stimuli

“…This makes spiking more robust near the threshold. In addition to the contribution of Ih current to pacemaker activity, has been shown in DA neurons [72], as well as in the other neuronal types that Ih induces intrinsic subthreshold resonance [73][74][75]. Thus, augmentation of Ih current increases oscillatory behavior of the DA neurons, as well as their synchronization in response to excitatory pulses.…”