In VivoReversible Regulation of Dendritic Patterning by Afferent Input in Bipolar Auditory Neurons

Abstract

Afferent input regulates neuronal dendritic patterning locally and globally through distinct mechanisms. To begin to understand these mechanisms, we differentially manipulate afferent input in vivo and assess effects on dendritic patterning of individual neurons in chicken nucleus laminaris (NL). Dendrites of NL neurons segregate into dorsal and ventral domains, receiving excitatory input from the ipsilateral and contralateral ears, respectively, via nucleus magnocellularis (NM). Blocking action potentials from one ear, by either cochlea removal or temporary treatment with tetrodotoxin (TTX), leads to rapid and significant retraction of affected NL dendrites (dorsal ipsilaterally and ventral contralaterally) within 8h as compared to the other dendrites of the same neurons. The degree of retraction is comparable to that induced by direct deafferentation resulting from transection of NM axons. Importantly, when inner ear activity is allowed to recover from TTX treatments, retracted NL dendrites regrow to their normal length within 48h. The retraction and growth involve elimination of terminal branches and addition of new branches. Examination of changes in NL dendrites at 96h following unilateral cochlear removal, a manipulation that induces cell loss in NM and persistent blockage of afferent excitatory action potentials, reveals a significant correlation between cell death in the ipsilateral NM and the degree of dendritic retraction in NL. These results demonstrate that presynaptic action potentials rapidly and reversibly regulate dendritic patterning of postsynaptic neurons in a compartment specific manner, while long-term dendritic maintenance may be regulated in a way that is correlated with the presence of silent presynaptic appositions.

Mechanisms underlying auditory processing deficits in Fragile X syndrome

“…High‐resolution imaging studies demonstrated intense dendritic localization of FMRP, particularly in dendritic branch points and distal endings, in NL (chicken and alligator) and MSO (gerbil and human) . In the chicken NL, the branching points are thought to be a site for initiating activity‐dependent dendritic reorganization . A proteomic study specifically targeting the chicken NL identified a number of dendritic proteins whose mRNAs are potential FMRP targets .…”

Development of Dendritic Form and Function

“…Organelles such as ribosomes, the secretory endoplasmic reticulum, and the Golgi complex are trafficked by minus end-directed transport and are thus enriched in dendrites, where they contribute to branch initiation and differentiation. The endoplasmic reticulum exhibits zones of structural complexity in dendrites that spatially correlate with both insertion of proteins into the plasma membrane and branch formation (Cui- Wang et al 2012). The Golgi complex influences branching through discrete and mobile structures called Golgi outposts, which regulate postGolgi trafficking and facilitate microtubule nucleation at nascent branch points (Horton et al 2005, Ori-McKenney et al 2012, Ye et al 2007).…”

“…In some systems, loss of neural activity is responsible for the changes. In chick auditory brainstem, removal of the cochlea or spike suppression by tetrodotoxin (TTX) causes site-specific dendrite shrinkage in the NL similar to that observed after afferent ablation (Wang & Rubel 2012). As the NL is two synapses upstream from the cochlea, these manipulations do not directly remove afferents but instead reduce their activity.…”

“…If one of the NL inputs is stimulated with an electrode, the dendritic tuft innervated by the stimulated pathway grows while the other shrinks (Sorensen & Rubel 2011). Strikingly, most of these effects are detectable within hours and, upon TTX withdrawal, are reversible on a similar time scale, suggesting that dendrite size can be exquisitely sensitive to presynaptic activity during development (Wang & Rubel 2012). Manipulating activity using electrodes or TTX can affect both excitatory and inhibitory neurotransmission.…”

Illuminating the Multifaceted Roles of Neurotransmission in Shaping Neuronal Circuitry

“…For example in the chick auditory brainstem, ipsilateral and contralateral afferents from the Nucleus Magnocellularis contact the dorsal and ventral arbors of the Nucleus Laminaris neurons respectively (Parks and Rubel, 1975 and Figure 4A). Accordingly, for these neurons, perturbing transmission from one set of afferents leads to connectivity changes only in their contacted dendritic arbor (Benes et al, 1977; Sorensen and Rubel, 2006; Wang and Rubel, 2012). Some activity-dependent competitive interactions occur between parallel fibers and climbing fibers that overlap marginally (Figure 4A) on the dendritic arbor of cerebellar Purkinje cells (Hashimoto et al, 2001; Ichikawa et al, 2002; Miyazaki et al, 2004; Uemura et al, 2007; Watanabe and Kano, 2011).…”