Auditory System Development: Primary Auditory Neurons and Their Targets

Abstract

The neurons of the cochlear ganglion transmit acoustic information between the inner ear and the brain. These placodally derived neurons must produce a topographically precise pattern of connections in both the inner ear and the brain. In this review, we consider the current state of knowledge concerning the development of these neurons, their peripheral and central connections, and their influences on peripheral and central target cells. Relatively little is known about the cellular and molecular regulation of migration or the establishment of precise topographic connection to the hair cells or cochlear nucleus (CN) neurons. Studies of mice with neurotrophin deletions are beginning to yield increasing understanding of variations in ganglion cell survival and resulting innervation patterns, however. Finally, existing evidence suggests that while ganglion cells have little influence on the differentiation of their hair cell targets, quite the opposite is true in the brain. Ganglion cell innervation and synaptic activity are essential for normal development of neurons in the cochlear nucleus.

Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system

“…As compared to normal adult cats, the CN of neonatally deafened cats showed marked reduction in the total volume of the CN to 76% of normal and reduction in the mean cross-sectional area of AVCN spherical cells to about 75% of normal (Lustig et al, 1994;Osofsky et al, 2001). These degenerative changes are consistent with many previous studies showing that neonatal auditory deprivation results in profound adverse effects within the cochlear nucleus (Coleman and O'Connor, 1979;Coleman et al, 1982;Rubel et al, 1984;Rubel and Fritzsch, 2002;Trune, 1982;Webster, 1983;1988;Webster and Webster, 1977; for review see Harris and Rubel, 2006).…”

“…Neurotrophins include NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5, each of which binds to specific high-affinity receptors, the Trk family of receptors. Neurotrophins are particularly relevant to our studies of SG cell survival in neonatally-deafened animals because they regulate neuronal differentiation and survival during development (Korsching, 1993;Gao et al, 1995;Farinas et al, 2001;Fritzsch et al, 1999;Rubel and Fritsch, 2002) and are also involved in the development and maturation of the central auditory system (for review, see Fritzsch et al, 1999;Rubel and Fritzsch, 2002). Within the developing cochlea, neurotrophins are differentially distributed, with NT-3 expressed predominantly in the supporting cells of the organ of Corti, and BDNF expressed only in hair cells (Farinas, et al, 2001).…”

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

“…Because neurotrophins regulate neuronal differentiation and survival during development (Fariñas et al 2001;Fritzsch et al 1999;Gao et al 1995;Korsching 1993;Rubel and Fritzsch 2002;Tessarollo et al 2004;Yang et al 2011), we hypothesized that exogenous NTs might be particularly effective in our developing animals, after early-onset hearing loss. In our initial study, cats were deafened as neonates, implanted unilaterally and received 10 weeks of intracochlear BDNF starting at 4 weeks of age.…”

Topography of Auditory Nerve Projections to the Cochlear Nucleus in Cats after Neonatal Deafness and Electrical Stimulation by a Cochlear Implant

“…However, there is little agreement about the specific roles of molecular cues and neuronal activity in the subsequent development and refinement of various topographic maps in the central nervous system (Rubel and Cramer 2002). In the auditory system, several lines of evidence suggest that patterns of neural connections are essentially correctly organized from the time of their initial arrival at target locations (Rubel and Fritzsch 2002). In chickens, a tonotopically ordered map of the auditory nerve axons projecting within the CN analogue (nucleus magnocellularis) is present from early embryonic ages, even before the formation of hair cell synapses (Molea and Rubel 2003).…”

“…Thus, relatively accurate tonotopic maps likely form initially through processes independent of activity and guided by specific molecular mechanisms (Rubel and Fritzsch 2002;Fritzsch et al 2005Fritzsch et al , 2006. Eph/ephrin signaling is of particular interest because of its well-established role in formation of topographic maps in other sensory systems, including the visual system (Feldheim et al 2000), the somatosensory (Prakash et al 2000), and olfactory systems (Cutforth et al 2003).…”