Tonotopic reorganization of developing auditory brainstem circuits

Abstract

A fundamental organizing principle of auditory brain circuits is tonotopy, the orderly representation of the sound frequency to which neurons are most sensitive. Tonotopy arises from the coding of frequency along the cochlea and the topographic organization of auditory pathways. The mechanisms that underlie the establishment of tonotopy are poorly understood. In auditory brainstem pathways, topographic precision is present at very early stages in development, which may suggest that synaptic reorganization contributes little to the construction of precise tonotopic maps. Accumulating evidence from several brainstem nuclei, however, is now changing this view by demonstrating that developing auditory brainstem circuits undergo a marked degree of refinement on both a subcellular and circuit level.Increasing the topographic organization of synaptic connections via activity-dependent refinement is a major milestone in the maturation of neuronal circuits 1 . In the developing auditory system, experience-dependent refinement of tonotopic maps has been well demonstrated in the auditory cortex and in multimodal-integration brain areas [2][3][4][5] . In contrast, primary auditory circuits in the brainstem are assembled with high topographic (tonotopic) precision early in development and show little evidence of subsequent refinement. This picture is based on a wealth of anatomical tracing studies in both birds and mammals that have shown that growing axons innervate their topographically correct target areas from the outset and do not establish aberrant, transient connections to incorrect nuclei [6][7][8][9] . Likewise, physiological studies indicate that a precise tonotopic organization is present as soon as central auditory pathways can be activated by sound [10][11][12] . Even if the formation of a projection is induced by embryonic otocyst (an ectodermal invagination that constitutes the primordium of the internal ear) removal, the projection is tonotopically organized 13 .Recently, however, this traditional picture of a developmentally predetermined and 'hardwired' auditory brainstem has undergone a substantial revision. It is becoming increasingly apparent that auditory synapses in the brainstem can express activity-dependent synaptic plasticity [14][15][16] and that auditory brainstem circuits undergo an unexpected degree of synaptic reorganization. Here we summarize recent evidence from the cochlear nucleus and primary © 2009 Nature America, Inc. All rights reserved.Correspondence should be addressed to K.K. (kkarl@pitt.edu).. (Fig. 1) that support the view that the emergence of precise tonotopy depends on circuit refinement, and discuss potential underlying mechanisms. NIH Public Access Auditory nerve projections to the cochlear nucleusCochlear hair cells, the sensory cells that transform sound energy into electrical signals, are connected to the brain by spiral ganglion neurons whose centrally directed axons form the auditory nerve. After entering the brain, each auditory nerve fiber branches to innervate...

Synaptic Refinement of an Inhibitory Topographic Map in the Auditory Brainstem Requires Functional CaV1.3 Calcium Channels

“…Not much is known about the mechanisms that establish an initially crude topography in the auditory brainstem, but Eph protein signaling appears to be involved (Huffman and Cramer, 2007). Which steps of the development of topography in the auditory brainstem are influenced by cochlea-driven activity is subject to an ongoing discussion (Kandler et al, 2009). Our results of a less precise topography in Ca V 1.3 Ϫ/Ϫ than in WT provide further evidence for the role of activity in fine tuning neuronal circuitry.…”

Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem

“…In the auditory system, patterned firing activity was observed before hearing onset in several nuclei along the ascending auditory pathway (Walsh and McGee, 1988;Rüb-samen and Schäfer, 1990;Lippe, 1994;Jones et al, 2007;Sonntag et al, 2009). Such activity is likely to support survival of target neurons, tonotopic refinement of afferent connections, and adjustment of synaptic strength (Friauf and Lohmann, 1999;Rubel and Fritzsch, 2002;Leake et al, 2006;McKay and Oleskevich, 2007;Kandler et al, 2009). Before the onset of hearing, ATPmediated activation of the cochlear inner hair cells evokes APs in the spiral ganglion neurons (SGNs) , which provide synaptic inputs to second-order neurons in the cochlear nucleus (CN) (Feldman and Harrison, 1969;Fekete et al, 1984;Liberman and Oliver, 1984).…”

Dendritic Eph organizes dendrodendritic segregation in discrete olfactory map formation in Drosophila

“…One of the key steps for establishing a functional neural circuit is to construct a precise connection between the axons and dendrites of presynaptic and postsynaptic neurons, respectively. In the visual and auditory systems, neighboring neurons in the input field target the neighboring regions in the output field (Flanagan 2006;Kandler et al 2009). In the olfactory systems of mammals and insects, the axons of the primary olfactory receptor neurons (ORNs) that express the same olfactory or ionotropic receptors converge to one specific glomerulus in the primary olfactory center (Couto et al 2005;Sakano 2010;Silbering et al 2011).…”