Abstract

Neurogenesis continues in the adult songbird brain. Many telencephalic song control regions incorporate new neurons into their existing circuits in adulthood. One song nucleus that receives many new neurons is Area X. Because this striatal region is crucial for song learning and song maintenance the recruitment of new neurons into Area X could influence these processes. As an entry point into addressing this possibility, we investigated the maturation and connectivity within the song circuit and behavioral activation of newly generated Area X neurons. Using BrdU birth dating and virally mediated GFP expression we followed adult-generated neurons from their place of birth in the ventricle to their place of incorporation into Area X. We show that newborn neurons receive glutamatergic input from pallial/cortical song nuclei. Additionally, backfills revealed that the new neurons connect to pallidal-like projection neurons that innervate the thalamus. Using in situ hybridization, we found that new neurons express the mRNA for D1- and D2-type dopamine receptors. Employing DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32 kDa) and EGR-1 (early growth response protein 1) as markers for neural maturation and activation, we established that at 42 days after labeling approximately 80% of new neurons were mature medium spiny neurons (MSNs) and could be activated by singing behavior. Finally, we compared the MSN density in Area X of birds up to seven years of age and found a significant increase with age, indicating that new neurons are constantly added to the nucleus. In summary, we provide evidence that newborn MSNs in Area X constantly functionally integrate into the circuit and are thus likely to play a role in the maintenance and regulation of adult song.

Highlights

  • To investigate whether and when newborn neurons in Area X are integrated into existing circuits, we used a lentivirally mediated approach to label progenitor cells in the striatal ventricular zone of adult male zebra finches (Figures 2A,B)

  • We investigated key features of adultgenerated medium spiny neurons (MSNs) that integrate into the avian striatal song nucleus Area X

  • We tested whether newborn MSNs in Area X receive this input by searching for glutamatergic presynaptic terminals on green fluorescent protein (GFP)-labeled newborn neurons after their migration from the ventricular zone

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Summary

Introduction

Some neurons continue to be generated in adulthood whereas the majority are born during development and persist throughout the animal’s life. Why these differences exist is still not known but much progress has been made elucidating the mechanism and function of adult neurogenesis during the past decades (Song et al, 2016). Neurons born in adulthood originate in regions adjacent to the ventricles that give rise to neurons during development From these neurogenic niches, neural precursors delaminate and migrate through the dense parenchyma, incorporate into functional circuits and influence behavior (Paredes et al, 2016) Neural precursors delaminate and migrate through the dense parenchyma, incorporate into functional circuits and influence behavior (Paredes et al, 2016).

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