Deleting the HCN1 Subunit of Hyperpolarization-Activated Ion Channels in Mice Impairs Acoustic Startle Reflexes, Gap...

It has been proposed that the high temporal and spatial acuities of human listeners and animals tested in the hearing laboratory depend in part on the short time constants of auditory neurons that are able to preserve or sharpen the information conveyed in the timing of firing of auditory nerve fibers. We tested this hypothesis in a series of in vivo experiments, based on previous in vitro experiments showing that neuronal time constants are raised in brainstem slices when HCN1 channels are blocked or in slices obtained from Hcn1 ^-/- null mutant mice. We compared Hcn1 ^-/- and Hcn1 ^+/+ mice on auditory brainstem responses (ABRs) and behavioral measures. Those measures included temporal integration for acoustic startle responses (ASRs), ASR depression by noise offset, and ASR inhibition by gaps in noise and by shifts of a noise source along the azimuth as measures of temporal and spatial acuity. Hcn1 ^-/- mice had less sensitive ABR thresholds at 32 and 48 kHz. Their wavelet P1b was delayed, and wave 2 was absent in the 16 kHz/90 SPL waveform, indicating that groups of neurons early in the auditory pathways were delayed and fired asynchronously. Baseline ASR levels were lower in Hcn1 ^-/- mice, temporal integration was delayed, time constants for ASR depression by noise offset were higher, and their sensitivity to brief gaps and spatial acuity was diminished. HCN1 channels are also present in vestibular, cutaneous, digestive, and cardiac neurons that variously may contribute to the deficits in spatial acuity and possibly in ASR levels.