Hyperpolarization-Activated Currents and Subthreshold Resonance in Granule Cells of the Olfactory Bulb

An important contribution to neural circuit oscillatory dynamics is the ongoing activation and inactivation of hyperpolarization-activated currents (I_h). Network synchrony dynamics play an important role in the initial processing of odor signals by the main olfactory bulb (MOB) and accessory olfactory bulb (AOB). In the mouse olfactory bulb, we show that I_h is present in granule cells (GCs), the most prominent inhibitory neuron in the olfactory bulb, and that I_h underlies subthreshold resonance in GCs. In accord with the properties of I_h, the currents exhibited sensitivity to changes in extracellular K⁺ concentration and ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidin chloride), a blocker of I_h. ZD7288 also caused GCs to hyperpolarize and increase their input resistance, suggesting that I_h is active at rest in GCs. The inclusion of cAMP in the intracellular solution shifted the activation of I_h to less negative potentials in the MOB, but not in the AOB, suggesting that channels with different subunit composition mediate I_h in these regions. Furthermore, we show that mature GCs exhibit I_h-dependent subthreshold resonance in the theta frequency range (4-12 Hz). Another inhibitory subtype in the MOB, the periglomerular cells, exhibited I_h-dependent subthreshold resonance in the delta range (1-4 Hz), while principal neurons, the mitral cells, do not exhibit I_h-dependent subthreshold resonance. Importantly, I_h size, as well as the strength and frequency of resonance in GCs, exhibited a postnatal developmental progression, suggesting that this development of I_h in GCs may differentially contribute to their integration of sensory input and contribution to oscillatory circuit dynamics.