Spatial and Temporal Organization of Composite Receptive Fields in the Songbird Auditory Forebrain

The mechanisms underlying how single auditory neurons and neuron populations encode natural and acoustically complex vocal signals, such as human speech or bird songs, are not well understood. Classical models focus on individual neurons, whose spike rates vary systematically as a function of change in a small number of simple acoustic dimensions. However, neurons in the caudal medial nidopallium (NCM), an auditory forebrain region in songbirds that is analogous to the secondary auditory cortex in mammals, have composite receptive fields (CRFs) that comprise multiple acoustic features tied to both increases and decreases in firing rates. Here, we investigated the anatomical organization and temporal activation patterns of auditory CRFs in European starlings exposed to natural vocal communication signals (songs). We recorded extracellular electrophysiological responses to various bird songs at auditory NCM sites, including both single and multiple neurons, and we then applied a quadratic model to extract large sets of CRF features that were tied to excitatory and suppressive responses at each measurement site. We found that the superset of CRF features yielded spatially and temporally distributed, generalizable representations of a conspecific song. Individual sites responded to acoustically diverse features, as there was no discernable organization of features across anatomically ordered sites. The CRF features at each site yielded broad, temporally distributed responses that spanned the entire duration of many starling songs, which can last for 50 s or more. Based on these results, we estimated that a nearly complete representation of any conspecific song, regardless of length, can be obtained by evaluating populations as small as 100 neurons. We conclude that natural acoustic communication signals drive a distributed yet highly redundant representation across the songbird auditory forebrain, in which adjacent neurons contribute to the encoding of multiple diverse and time-varying spectro-temporal features.

Expression of oxytocin receptors in the zebra finch brain during vocal development

Juvenile male zebra finches memorize and learn to sing the song of a male caregiver, or “tutor”, during a complex vocal learning process. Juveniles are highly motivated to interact socially with their tutor, and these interactions are required for effective vocal learning. It is currently unknown what neurological mechanisms underlie attraction to tutors, but social motivation and affiliation in this and other species may be mediated by oxytocin and related nonapeptides. Here, we used qPCR to quantify expression of oxytocin receptor (OTR) mRNA in the lateral septum, auditory forebrain, and regions of the song control system in zebra finches throughout post-hatch development and vocal learning. We found that zebra finches express OTR mRNA in these regions from post-hatch day 5 to adulthood, encompassing the entire period of auditory and sensorimotor learning. We also mapped the binding of 125I-ornithine vasotocin, an oxytocin receptor antagonist that binds to oxytocin receptors in songbird brain, to understand the neuroanatomical distribution of oxytocin-like action during vocal development. This study provides the groundwork for the use of zebra finches as a model for understanding the mechanisms underlying social motivation and its role in vocal development.

Acute social isolation alters neurogenomic state in songbird forebrain

Prolonged social isolation has negative effects on brain and behavior in humans and other social organisms, but neural mechanisms leading to these effects are not understood. Here we tested the hypothesis that even brief periods of social isolation can alter gene expression and DNA methylation in higher cognitive centers of the brain, focusing on the auditory/associative forebrain of the highly social zebra finch. Using RNA sequencing, we first identified genes that individually increase or decrease expression after isolation and observed general repression of gene sets annotated for neurotrophin pathways and axonal guidance functions. We then pursued 4 genes of large effect size: EGR1 and BDNF (decreased by isolation) and FKBP5 and UTS2B (increased). By in situ hybridization, each gene responded in different cell subsets, arguing against a single cellular mechanism. To test whether effects were specific to the social component of the isolation experience, we compared gene expression in birds isolated either alone or with a single familiar partner. Partner inclusion ameliorated the effect of solo isolation on EGR1 and BDNF, but not on FKBP5 and UTS2B nor on circulating corticosterone. By bisulfite sequencing analysis of auditory forebrain DNA, isolation caused changes in methylation of a subset of differentially expressed genes, including BDNF. Thus, social isolation has rapid consequences on gene activity in a higher integrative center of the brain, triggering epigenetic mechanisms that may influence processing of ongoing experience.

Functional connectivity strength within the auditory forebrain is altered by song learning and predicts song stereotypy in developing male zebra finches

Much as humans acquire speech in early childhood, the zebra finch (Taeniopygia guttata) songbird learns to sing from an adult “tutor” during the first three months of life. Within a well-defined critical period (CP), juvenile zebra finches memorize a tutor song that will guide subsequent motor patterning. This sensory learning process is mediated by tutor experience-dependent neuroplasticity within the auditory forebrain. Here, we used longitudinal resting-state fMRI analyses to investigate whether tutor experience also modifies patterns of functional connectivity (FC) within the juvenile zebra finch brain. Eighteen male zebra finches (only males sing) were scanned before, during, and at the end of the CP, as well as at the young adult stage. Prior to the onset of the CP, birds were separated into rearing conditions: Normal (aviary-housed; N=5), Tutored (one adult male tutor and one adult female; N=7), and Isolate (two adult females, isolated from male song; N=6). Brain-wide voxel-wise analyses identified a single cluster overlapping the left caudomedial nidopallium (NCM) of the auditory forebrain that showed developmentally decreasing FC strength in Isolates but stable or increasing FC in Normal and Tutored birds. Additionally, FC between left NCM and left dorsal cerebellum showed a parallel developmental difference. Developmental changes in left NCM FC strength statistically mediated condition-related differences in song stereotypy. These results extend previous reports of tutor experience-dependent plasticity in NCM at epigenetic, genomic, molecular, and cellular levels to the whole-brain functional network level by demonstrating that tutor experience also influences the development of NCM FC. Moreover, these results link NCM FC to the emergence of song stereotypy.