Incorporation of newborn neurons in vocal learning

NIH RePORTER · NIH · R15 · $489,336 · view on reporter.nih.gov ↗

Abstract

We propose a novel research program in which we aim to understand the diversity of neurons that are produced in the adult songbird brain. Songbirds are the only warm-blooded vertebrates that add new neurons to well-defined motor circuits underlying the control of an easily quantifiable behavior, birdsong. Adult male zebra finches – which learn to sing a highly reproducible song and maintain it throughout life – continually produce adult-born neurons that are incorporated into the vocal motor pathway originating in HVC, the sensorimotor region that underlies the song production. One class of neurons in HVC project to RA (HVCRA) as part of the vocal motor pathway, are continually produced in adulthood, and are active in song production. Mature HVCRA neurons have uniquely sparse and temporally precise firing properties that underlie song stability, and yet we know very little about their functional maturation from neuroblast to differentiated neuron. Our first hypothesis is that the sparse and precise firing pattern of mature HVCRA neurons develops from a more excitable electrophysiology that becomes more restrained due to increased potassium conductances and inhibitory synaptic inputs. We will accomplish this by using a retroviral approach to fluorescently label adult born neurons and subsequently record their developing, immature electrophysiology in brain slices. We can then compare them to mature HVCRA neurons to see how these neurons change over the course of their maturation. Interestingly, HVCRA neurons only constitute about 50% of all adult-born HVC neurons. These remaining unidentified adult-born HVC neurons are not RA-projecting, nor are they local inhibitory interneurons. Preliminary data from our laboratory suggests that these unidentified neurons transiently express DARPP-32, a marker of dopaminoceptive neurons, and do not project to RA. Our second hypothesis is that DARPP-32+ adult born neurons in HVC comprise a unique population of local excitatory interneurons that do not project to RA, and that DA plays a transient role in the development and modulation of these adult-born neurons. This study is innovative because it seeks to identify a previously unknown population of adult born neurons in an otherwise well-defined and widely-studied brain region that has served as arguably the best studied model of vocal learning available. Understanding the functional roles of all adult born neurons in HVC will improve our understanding of how neuronal circuits improve and maintain behavioral precision and stability.

Key facts

NIH application ID
10292179
Project number
1R15NS123921-01
Recipient
WESLEYAN UNIVERSITY
Principal Investigator
Gloster Aaron
Activity code
R15
Funding institute
NIH
Fiscal year
2021
Award amount
$489,336
Award type
1
Project period
2021-09-01 → 2025-08-31