This seminar is open to all NACS students.

Speaker: Ruilong Hu
Title: Hyperpolarization-activated currents and subthreshold resonance in granule cells of the olfactory bulb
Abstract: In sensory systems, neural circuits exhibit oscillatory dynamics driven by sensory input, extrinsic regulation, and intrinsic circuit properties. Activation and inactivation of hyperpolarization-activated currents (Ih), is thought to participate in generating membrane potential oscillations in neurons and contribute to network oscillatory dynamics. In the olfactory system, initial processing of odor signals occurs in the olfactory bulb (OB) where network synchrony, an important aspect of odor processing, arises from the activity of reciprocal synapses between output neurons, the mitral and tufted cells (MCs herein), and inhibitory intrinsic neurons, the granule cells (GCs). In addition, theta oscillations entrained by the respiratory cycle are also present. Interestingly, MCs exhibit varying expression of Ih, suggesting a contribution of this current to the fidelity of information coding by MCs. In contrast, the presence of Ih in the GC population is poorly characterized. Here, using whole-cell patch clamp recordings, we characterize Ih in GCs of the OB. In accord with Ih characterized in neurons in other oscillatory systems, Ih in OB GCs exhibit sensitivity to changes in extracellular K+ concentration, and blockage by ZD7288 (30 μM). Inclusion of cAMP (0.5 mM) in the intracellular pipette solution shifted the activation curve of Ih to less negative potentials in GCs in the main olfactory bulb (MOB), but not the accessory olfactory bulb (AOB), suggesting different HCN subunit composition between the two regions. Bath perfusion of ZD7288 increased input resistance and hyperpolarized GCs in both AOB and MOB, suggesting that at rest, Ih contributes to the resting membrane potential. In agreement with this possibility, application of ZD7288 also modifies the kinetics of spontaneous and evoked postsynaptic potentials (PSPs). Further, to examine the contribution of GCs’ Ih to circuit level oscillations, we examined subthreshold resonance, where we found heterogeneity across AOB and MOB GCs. However, when characterizing Ih and subthreshold resonance as a function of postnatal development, we found contrasting characteristics between AOB and MOB GCs in their resonance profiles and voltage dependencies, with mature MOB GCs able to resonate in the theta frequency range (6-10 Hz), suggesting that Ih in GCs may play an important role in dendritic integration and filtering of oscillatory inputs. These results suggest that the expression of Ih across different cell types, including GCs and MCs, may impart unique features to odor processing in the OB and facilitate oscillatory network activity in both the main olfactory and Vomeronasal systems.