Biology subjects

London, S. E.

Publications and source records attributed to London, S. E..

5 recordsLinked to original sources

bioRxiv2026

Shared Neuroanatomy, Separate Mechanism: in vivo ERK and mTOR Manipulations Reveal Female-Specific Molecular Signaling for Auditory Forebrain-Dependent Learning in Juveniles

Developmental experience can produce lasting changes in neural function and behavior. Zebra finch offers a powerful model for identifying the molecular mechanisms underlying this process. Both juvenile male and female zebra finches perform developmental sensory song learning that influences their adult behaviors: in males, the structure of the song they sing and in female, the song preferences they exhibit (females cannot sing). The auditory forebrain, a region distinct from but connected to nodes of the male singing circuitry, is required for male sensory song learning. Song experience induces epigenetic, genomic, molecular, cellular and systems-level alterations in the auditory forebrain of males. Much less evidence is available for females. Although epigenetic and molecular data implicate the auditory forebrain in female sensory song learning, there has been no causal test of its role. Further, molecular evidence indicates the potential for distinct mechanisms for male and female sensory song learning, even though they learn during a largely overlapping developmental period. We used pharmacological manipulations of the ERK and mTOR cascades in the auditory forebrain of juvenile females during controlled tutoring, and an operant assay for adult song preference, to test the causal role of the auditory forebrain and the two cascades known to be required for male sensory song learning. We demonstrate that the auditory forebrain is required for female sensory song learning, and that while ERK signaling is necessary for both sexes, that of mTOR is sex specific. Results raise implications for alternative molecular cascade cross-talks and protein synthesis processes that successfully support the developmental learning at the same age and brain region.

neuroscience↗

bioRxiv2019

Inhibitory cell populations depend on age, sex, and prior experience across a neural network for Critical Period learning

In many ways, the complement of cell subtypes determines the information processing that a local brain circuit can perform. For example, the balance of excitatory and inhibitory (E/I) signaling within a brain region contributes to response magnitude and specificity in ways that influence the effectiveness of information processing. An extreme example of response changes to sensory information occur across Critical Periods (CPs). In primary mammalian visual cortex, GAD65 and parvalbumin inhibitory cell types in particular control experience-dependent responses during a CP. Here, we test how the density of GAD65- and parvalbumin-expressing cells may inform on a CP for complex behavioral learning. Juvenile male zebra finch songbirds (females cannot sing) learn to sing through coordinated sensory, sensorimotor, and motor learning processes distributed throughout a well-defined neural network. There is a CP is for sensory learning, the stage during which a young male forms a memory of his \"tutors\" song, which is then used to guide the young birds emerging song structure. We quantified the effect of sex and experience with a tutor on the cell densities of GAD65- and parvalbumin-expressing cells across major nodes of the song network, using ages that span the CP for tutor song memorization. As a resource, we also include whole-brain mapping data for both genes. Results indicate that inhibitory cell populations differ across sex, age, and experiential conditions, but not always in the ways we predicted.

neuroscience↗

bioRxiv2019

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.

neuroscience↗

bioRxiv2018

Interhemispheric Integration for Complex Behaviors, Absent the Corpus Callosum in Normal Ontogeny

Functional homotopy, or synchronous spontaneous activity between symmetric, contralateral brain regions, is a fundamental characteristic of the mammalian brains functional architecture(1-6). In mammals, functional homotopy may be predominantly mediated by the corpus callosum (CC), a white matter structure thought to balance the interhemispheric coordination and hemispheric specialization critical for many complex brain functions, including lateralized human language abilities(7, 8). The CC first emerged with the Eutherian (placental) mammals ~160 MYA and is not found in other vertebrates(9, 10). Despite this, other vertebrates also exhibit complex brain functions requiring bilateral integration and lateralization(11). For example, much as humans acquire speech, the zebra finch (Taeniopygia guttata) songbird learns to sing from tutors and must balance hemispheric specialization(12) with interhemispheric coordination to successfully learn and produce song(13). We therefore tested whether the zebra finch brain also exhibits functional homotopy despite lacking the CC. Implementing custom resting-state fMRI (rs-fMRI) functional connectivity (FC) analyses, we demonstrate widespread functional homotopy between pairs of contralateral brain regions required for learned song but which lack direct anatomical projections (i.e., structural connectivity; SC). We believe this is the first demonstration of functional homotopy in a non-Eutherian vertebrate; however, it is unlikely to be the only instance of it. The remarkable congruence between functional homotopy in the zebra finch and Eutherian brains indicates that alternative mechanisms must exist for balanced interhemispheric coordination in the absence of a CC. This insight may have broad implications for understanding complex, bilateral neural processing across phylogeny and how information is integrated between hemispheres.\n\nSignificance StatementThe mammalian brain exhibits strongly synchronized hemodynamic activity (i.e., functional connectivity) between symmetric, contralateral (i.e., homotopic) brain regions. This pattern is thought to be largely mediated by the corpus callosum (CC), a large white matter tract unique to mammals, which balances interhemispheric coordination and lateralization. Many complex brain functions, including human language, are thought to critically rely upon this balance. Despite lacking the CC, the zebra finch exhibits a song learning process with striking parallels to human speech acquisition, including lateralization and interhemispheric coordination. Using resting-state fMRI, we show that the zebra finch brain exhibits widespread homotopic functional connectivity within a network critical for learned song, suggesting that this symmetrical activity pattern may phylogenetically precede the evolution of the CC.

neuroscience↗

bioRxiv2018

The variability of song variability in wild and domesticated zebra finches Taeniopygia guttata

Birdsong is a classic example of a learned social behavior. Like many traits of interest, however, song production is also influenced by genetic factors and understanding the relative contributions of genetic and environmental influences remains a major research goal. In this study we take advantage of genetic variation among captive zebra finch populations to examine variation in a population-level song trait: song variability. We find that zebra finch populations differ in levels of song variability. Domesticated T. g. castanotis populations displayed higher song diversity than more recently wild-derived populations of both zebra finch subspecies T. g. castanotis and T. g. guttata, the Timor zebra finch. To determine whether these differences could have a genetic basis, we cross-fostered domesticated T. g. castanotis and Timor zebra finches to Bengalese finches Lonchura striata domestica. Following cross-fostering, domesticated T. g. castanotis maintained a higher level of song diversity than T. g. guttata. We suggest that the high song variability of domesticated zebra finches may be a consequence of reduced purifying selection acting on song traits. Intraspecific differences in the mechanisms underlying song variability therefore represent an untapped opportunity for probing the mechanisms of song learning and production.

animal behavior and cognition↗