Temporal patterns of gene expression during calyx of held development

Abstract

Relating changes in gene expression to discrete developmental events remains an elusive challenge in neuroscience, in part because most neural territories are comprised of multiple cell types that mature over extended periods of time. The medial nucleus of the trapezoid body (MNTB) is an attractive vertebrate model system that contains a nearly homogeneous population of neurons, which are innervated by large glutamatergic nerve terminals called calyces of Held (CH). Key steps in maturation of CHs and MNTB neurons, including CH growth and competition, occur very quickly for most cells between postnatal days (P)2 and P6. Therefore, we characterized genome-wide changes in this system, with dense temporal sampling during the first postnatal week. We identified 541 genes whose expression changed significantly between P0–6 and clustered them into eight groups based on temporal expression profiles. Candidate genes from each of the eight profile groups were validated in separate samples by qPCR. Our tissue sample permitted comparison of known glial and neuronal transcripts and revealed that monotonically increasing or decreasing expression profiles tended to be associated with glia and neurons, respectively. Gene ontology revealed enrichment of genes involved in axon pathfinding, cell differentiation, cell adhesion and extracellular matrix. The latter category included elements of perineuronal nets, a prominent feature of MNTB neurons that is morphologically distinct by P6, when CH growth and competition are resolved onto nearly all MNTB neurons. These results provide a genetic framework for investigation of general mechanisms responsible for nerve terminal growth and maturation.

In vivo matching of postsynaptic excitability with spontaneous synaptic inputs during formation of the rat calyx of Held synapse

“…; Kolson et al . ). Our fit results showed an increase of all three conductances during development, but only for g LTK was the developmental trend statistically significant (Fig.…”

“…; Kolson et al . ). A similar developmental increase in low‐threshold K + channels has also been observed at other auditory synapses (Kuba et al .…”

“…; Kolson et al . ), including the low‐threshold K + channels Kv1, hyperpolarization‐activated cation channels I h and leak channels (Leao et al . ; Berntson & Walmsley, ; Gao & Lu, ).…”

Developmental plasticity shapes synaptic phenotypes of autism-associated neuroligin-3 mutations in the calyx of Held

“…After ruling out NL1, we focused on Cbln1 as a lead candidate because it functions as a neurexin ligand similar to NL3, 3 and because it is expressed developmentally early in pre- and postsynaptic calyx neurons (Figure 4a, Supplementary Fig. S2C, see also ref. 55).…”

Myelin development, plasticity, and pathology in the auditory system

“…Similar to humans, myelination of the murine central auditory pathway also coincides with the onset of hearing, which takes place between postnatal days 10 and 12 (Ehret, ). Within the mouse brainstem, Olig2‐positive oligodendrocyte progenitors can be seen in auditory nuclei at birth (Dinh et al, ), but the onset of myelin gene expression does not begin until about the second postnatal week and becomes detectable throughout the brainstem and auditory cortex during this time period (Hackett et al, ; Kolson et al, ). As myelin gene expression increases, myelin thickness and conduction velocity also increase in parts of the auditory brainstem, reaching adult‐like levels by P35 (Sinclair et al, ).…”