The role of H-current in regulating strength and frequency of thalamic network oscillations

Abstract

Intrathalamic oscillations related to sleep and epilepsy depend on interactions between synaptic mechanisms and intrinsic membrane excitability. One intrinsic conductance implicated in the genesis of thalamic oscillations is the H-current – a cationic current activated by membrane hyperpolarization. Activation of H-current promotes rebound excitation of thalamic relay neurons and can thus enhance recurrent network activity.

We examined the effects of H-current modulation on bicuculline-enhanced network oscillations (2–4 Hz) in rat thalamic slices. The adrenergic agonist norepinephrine, a known regulator of H-current, caused an alteration of the internal structure of the oscillations – they were enhanced and accelerated as the interval between bursts was shortened. The acceleration was blocked by the β-adrenergic antagonist propranolol. The β-agonist isoproterenol mimicked the effect of norepinephrine on oscillation frequency and truncated the responses suggesting that a β-adrenergic up-regulation of H-current modifies the internal structure (frequency) of thalamic oscillations. Consistent with this, we found that H-channel blockade by Cs⁺ or ZD7288 could decelerate the oscillations and produce more robust (longer lasting) responses. High concentrations of either Cs⁺ or ZD7288 blocked the oscillations.

These results indicate that a critical amount of H-current is necessary for optimal intrathalamic oscillations in the delta frequency range. Up- or down-regulation of H-current alter not only the oscillation frequency but also retard or promote the development of thalamic synchronous oscillations. This conclusion has important implications regarding the development of epilepsy in thalamocortical circuits.