Singing, but not seizure, inducessynaptotagmin IVin zebra finch song circuit nuclei

Abstract

Synaptotagmins are a family of proteins that function in membrane fusion events, including synaptic vesicle exocytosis. Within this family, synaptotagmin IV (Syt IV) is unique in being a depolarization-induced immediate early gene (IEG). Experimental perturbation of Syt IV modulates neurotransmitter release in mice, flies, and PC12 cells, and modulates learning in mice. Despite these features, induction of Syt IV expression by a natural behavior has not been previously reported. We used the zebra finch, a songbird species, to investigate Syt IV because song is a naturally learned behavior whose neuroanatomical basis is largely identified. We observed that, similar to rodents, Syt IV is inducible in songbirds. This induction was selective and depended on the nature of neuronal depolarization. Generalized seizures caused by the GABA(A) receptor antagonist, metrazole, induced the IEG, ZENK, in zebra finch brain. However, these same seizures failed to induce Syt IV in song control areas. In contrast, when nontreated birds sang, three song control areas showed striking Syt IV induction. Further, this induction appeared sensitive to the social context in which song was sung. Together, these data suggest that neural activity during singing can drive Syt IV expression within song circuitry whereas generalized seizure activity fails to do so even though song control areas are depolarized. Our findings indicate that, within this neural circuit for a procedurally learned sensorimotor behavior, Syt IV is selective and requires precisely patterned neural activity and/or neuromodulation associated with singing.

Molecular Microcircuitry Underlies Functional Specification in a Basal Ganglia Circuit Dedicated to Vocal Learning

“…Rather, as revealed here by WGCNA, the relevance of transcriptional activity in these regions to singing is determined more by region-specific co-expression relationships, which comprise ‘molecular microcircuitry’ that arises during a specific behavior (singing) within a specific brain region (area X) supporting that behavior. In line with the idea that mere neural activity levels do not account for the song-specialized gene modules, we previously found that activation of the IEG Synaptotagmin 4 ( Syt4 ), is not achieved by overall depolarization of neurons but rather requires the patterned activation underlying singing 22 .…”

Language‐related Cntnap2 gene is differentially expressed in sexually dimorphic song nuclei essential for vocal learning in songbirds

“…Thus, the dynamic expression in male song nuclei has been reported for “motor-driven” whose levels change during singing, first exemplified for the immediate early gene zenk ( zif -268, egr -1, NGFI -A and krox -24; Jarvis and Nottebohm, 1997) and now shown for several other genes (Poopatanapong et al, 2006; Wada et al, 2006). …”

Song Practice Promotes Acute Vocal Variability at a Key Stage of Sensorimotor Learning

“…In zebra finches, expression levels of a number of known genes (Arc, Egr-1, Fos, SytIV), change during UD singing [18]–[26], [29], including the speech and language-related gene, FoxP2 [27], [28], (Teramitsu et al companion article). This link between gene expression and mechanisms underlying song plasticity warrants investigation.…”