Regional distribution of neurotrophin receptors in the developing auditory brainstem

Abstract

Neuron survival and axonal regeneration become severely limited during early postnatal development. In conjunction with our recent organotypic analysis of regeneration in the auditory midbrain, we wished to determine whether neurotrophins could serve as a trophic substance during the postnatal period. Therefore, the current study examines the development of three neurotrophin receptor tyrosine kinases (TrkA, TrkB, and TrkC) in the gerbil auditory brainstem. Immunoreactivity to TrkA, the nerve growth-factor receptor, was observed in nonneuronal cells during the first two postnatal weeks. In the cochlear nucleus of mature animals, however, there was a TrkA-positive neuronal subpopulation. In contrast, immunoreactivity to TrkB and TrkC (the receptors for brain-derived neurotrophic factor and neurotrophin-3, respectively) displayed a widespread distribution in the auditory brainstem. At postnatal day 0, TrkB and TrkC staining was virtually absent from auditory nuclei, although immunopositive neurons were present in the mesencephalic trigeminal nucleus. By postnatal day 7, TrkB- and TrkC-positive neurons were present in most brainstem auditory nuclei. At postnatal day 15, TrkB immunoreactivity was observed throughout the inferior colliculus (IC), the cochlear nucleus, the medial and lateral nuclei of the trapezoid body, and the lateral superior olive, whereas TrkC labeled only a subpopulation of neurons within the central nucleus of the IC. The TrkB immunoreactivity was present on both neuronal somata and dendrites, whereas TrkC was generally restricted to cell bodies. At postnatal day 30, TrkB immunostaining was observed on most neurons of the IC. The medial and lateral nuclei of the trapezoid body displayed extremely strong TrkB staining, followed by the cochlear nucleus. In contrast, the TrkC immunostaining was decreased dramatically by postnatal day 21. Observations at the ultrastructural level confirmed a neuronal localization of TrkB and TrkC. Immunostaining for both receptors was restricted largely to the postsynaptic density of synaptic profiles in both dendrites and somata. In summary, this study illustrates a differential pattern of immunoreactivity between three neurotrophin receptors during development. The general increase of TrkB expression is well correlated with the onset of sound-evoked activity in this system, and its synaptic localization suggests that it may be involved in the modulation or maintenance of postsynaptic physiology.

Prevention of Normally Occurring and Deafferentation-Induced Neuronal Death in Chick Brainstem Auditory Neurons by Periodic Blockade of AMPA/Kainate Receptors

“…Although neurotrophins and their receptors are essential to the survival of peripheral auditory neurons (Ernfors et al, 1995), little is known about their role in developing central auditory pathways. Hafidi et al (1996) have shown recently that TrkB and TrkC receptors are localized at postsynaptic sites on central auditory neurons and that TrkB receptors develop in parallel with auditory function in the brainstem auditory system of the gerbil. These authors suggest that brain-derived neurotrophic factor and neurotrophin-3, the ligands for TrkB and TrkC receptors, respectively, may be regulated by neuronal activity in the auditory pathway and may act as survival signals for auditory neurons.…”

GABAB and Trk Receptor Signaling Mediates Long-Lasting Inhibitory Synaptic Depression

“…This finding suggested that GABAergic transmission could play a significant role during inhibitory synaptogenesis. Second, MNTB neurons express neurotrophins, and LSO neurons express their cognate receptors during development (Hafidi 1999;Hafidi et al 1996). Since neurotrophin/Trk signaling pathways have been shown to modulate synaptic transmission (Kang and Schuman 1995;Kim et al 1994;Levine et al 1998), they may be relevant to the plasticity displayed by MNTB synapses.…”

L-type Calcium Channel Cav1.2 Is Required for Maintenance of Auditory Brainstem Nuclei

“…Of note, L-VGCC-mediated signaling has been tightly linked to BDNF expression (87)(88)(89). However, BDNF (69) and its major receptor TrkB (70) are barely expressed at P0 throughout the auditory brainstem, and their expression increases up to P15, implying a role during the maturation of auditory neurons. Similar results have been obtained for NTF3, NTF4, and TrkC (70,69).…”

“…TrkA is not expressed at all (70). In contrast, p75NTR is expressed already in the perinatal auditory brainstem and present even at late embryonic stages (71).…”