The origin of spontaneous activity in the developing auditory system

Spontaneous activity in developing sensory systems has been shown to be important for the growth and survival of projection neurons, as well as the establishment, refinement and maintenance of sensory maps in the brain. In the developing cochlea, bursts of action potentials occur in primary afferent neurons prior to the onset of hearing.  This activity is thought to originate within the cochlea, but the mechanisms responsible for initiating auditory nerve firing in the absence of sound are poorly understood. In this study we show that a group of supporting cells within the developing mammalian cochlea spontaneously release adenosine 5’-triphosphate (ATP), which triggers large current oscillations and widespread intracellular Ca2+ waves by activating purinergic autoreceptors. This ATP-dependent activity causes supporting cells to shrink, allowing ATP release events to be monitored through intrinsic optical imaging. Moreover, this spontaneous release of ATP causes neighboring inner hair cells to depolarize and release glutamate, triggering discrete bursts of action potentials in primary auditory neurons. This endogenous purinergic signaling synchronizes the output of neighboring inner hair cells, which may help refine tonotopic maps in the brain. Spontaneous ATP-dependent signaling rapidly subsides after the onset of hearing, thereby preventing this experience–independent activity from interfering with accurate encoding of sound. These data indicate that supporting cells in the organ of Corti initiate electrical activity in auditory nerves before hearing, pointing to an essential role for peripheral, non-sensory cells in the development of central auditory pathways.

Nicolas X. Tritsch, Eunyoung Yi, Jonathan E. Gale, Elisabeth Glowatzki & Dwight E. Bergles (2007) The origin of spontaneous activity in the developing auditory system. Nature 450, 50-5

Spontaneous optical changes in the developing organ of Corti. This difference movie highlights the changes in optical properties of the tissue, and was created by subtracting from each raw image the image that occurred 5 seconds before. The movie has been accelerated 20 times. (postnatal day 10 cochlea)

ATP release triggers bursts of action potentials in auditory nerve fibers. Time lapse imaging of spontaneous optical waves in the developing cochlea (subtracted movie, thresholded to highlight changing pixels, accelerated 10x). The clicks on the soundtrack correspond to spontaneous action potentials that were recorded from a spiral ganglion cell that received input from a hair cell located near the middle of the field of view.