Details

Autor(en) / Beteiligte

• Marrs, Glen S.
• Spirou, George A.

Titel

Embryonic assembly of auditory circuits: spiral ganglion and brainstem

Ist Teil von

• The Journal of physiology, 2012-05, Vol.590 (10), p.2391-2408

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2012

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Key points  •  Neural activity in sensory systems is important for proper assembly of neural circuits during early development. •  In the auditory system, the timing for functional synapse formation and reliance of central circuit formation on peripherally generated activity are unknown. •  We used a novel whole‐head slice preparation and genetically labelled auditory neurons to provide the first assay of cells at embryonic ages and reveal a peripheral‐to‐central maturation sequence. •  Auditory nerve fibres generate spontaneous action potentials by embryonic day 14 and drive third order central neurons by embryonic day 17, nearly 2 weeks before hearing onset. •  This information provides a timeline for initial auditory circuit assembly and the basis to explore mechanisms for initial sensory circuit assembly.   During early development, peripheral sensory systems generate physiological activity prior to exposure to normal environmental stimuli. This activity is thought to facilitate maturation of these neurons and their connections, perhaps even promoting efficacy or modifying downstream circuitry. In the mammalian auditory system, initial connections form at embryonic ages, but the functional characteristics of these early neural connections have not been assayed. We investigated processes of embryonic auditory development using a whole‐head slice preparation that preserved connectivity between peripheral and brainstem stations of the auditory pathway. Transgenic mice expressing fluorescent protein provided observation of spiral ganglion and cochlear nucleus neurons to facilitate targeted electrophysiological recording. Here we demonstrate an apparent peripheral‐to‐central order for circuit maturation. Spiral ganglion cells acquire action potential‐generating capacity at embryonic day 14 (E14), the earliest age tested, and action potential waveforms begin to mature in advance of comparable states for neurons of the ventral cochlear nucleus (VCN) and medial nucleus of the trapezoid body (MNTB). In accordance, auditory nerve synapses in the VCN are functional at E15, prior to VCN connectivity with the MNTB, which occurs at least 1 day later. Spiral ganglion neurons exhibit spontaneous activity at least by E14 and are able to drive third‐order auditory brainstem neurons by E17. This activity precedes cochlear‐generated wave activity by 4 days and ear canal opening by at least 2 weeks. Together, these findings reveal a previously unknown initial developmental phase for auditory maturation, and further implicate the spiral ganglion as a potential controlling centre in this process.