The Neural Basis of Syllables and Syntax in Canary Song

Motor behavior involves interactions between cortical and basal ganglia circuits, and disorders in these brain pathways leads to diseases such as Parkinson’s and Huntington’s disease. Songbirds provide an outstanding model of this conserved circuit because they have a specialized region of the basal ganglia devoted to song learning. Current models are based on zebra finches, a species with highly stereotyped, linear song, and a single song motor circuit. However, recent results suggests that assumptions from these models may not generalize to organisms with more complex motor sequences, such as canaries. First, the canonical model postulates that adult song is controlled by a single cortico-thalamic loop. However, lesions to nuclei in the Anterior Forebrain Pathway (AFP) resulted in stuttering in adult songbirds with complex songs, suggesting that adult song is controlled by two cortico-thalamic loops, or an additional cortico-thalamo-basal ganglia loop. This result suggests that complex singers’ neural pathways more closely resemble mammalian models, where motor control is governed by multiple parallel circuits. We will test the role of the AFP in adult birdsong by performing excitotoxic lesions to two nuclei in this pathway (Area X and MMAN). We will determine the impact of the lesion by measuring changes to syllable repeat number and syllable transition probabilities. Then, we will examine the real-time effects to syllable transitions of optogenetic perturbations to MMAN during singing behavior. Our broad hypothesis is that basal ganglia (Area X) as well as anterior thalamocortical loops (MMAN) perform in real-time syntax control for complex singers. A second mismatch between the canonical model and experimental results occurs in the motor control circuit. As predicted by the attractor model, zebra finches’ premotor activity repeats with each action (syllable) repeat in song. However, complex singers show more complex premotor activity that appears to encode timing within a series of repeat motor actions, rather than firing for each repeated syllable. It is therefore unclear how birds with complex song structure control which motor element is sung (syllable identity), and in what order (syntax). In Aim 2, we will measure extracellular neural activity in the HVC of singing canaries, and use antidromic stimulation of downstream nuclei to differentiate between the information relayed to the descending motor pathway versus efferent information relayed to the basal ganglia. We hypothesize that the premotor nucleus HVC signals within-phrase timing to its downstream premotor and basal ganglia nuclei. Completion of these aims will produce novel insight into the neural pathways governing motor control in a species that generates sequenced behavior with complex dynamics, such as long-range syntax. The proposed experiments will position the canary as a promising model organism with complex motor behavior, but simple neural circuits, which will expand the field’s understanding of motor control. This will inform research investigating the neuropathologies of motor disorders, as well as inform and advance treatments for these disorders. Project Number: 1F31NS143396-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Miranda Hulsey-Vincent | Institution: UNIVERSITY OF OREGON, EUGENE, OR | Award Amount: $49,538 | Activity Code: F31 | Study Section: Special Emphasis Panel[ZRG1 F02B-E (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11166188