Erich D. Jarvis Duke University Medical Center Howard Hughes Medical Institute

1. Of mice, birds, and humans: The mouse ultrasonic song system has features similar to humans and song-learning birds Erich D. Jarvis Duke University Medical Center Howard Hughes Medical Institute Department of Neurobiology • October 9th, 2012

2. Researchers – mouse song project Erich Jarvis, PhD Project leader Professor Duke Univ Senior-author Eric Zhou, BA Graduated May 2010 Now in Medical School 2nd-author Gustavo Arriaga, PhD (Graduate student) Graduated May 2011 1-st author

3. Convergent behavior: vocal learning – substrate for speech AVIAN FAMILY TREE only humans * * * Hackett et al 2008 tree * • Depends on auditory feedback, vocal critical periods, • cultural transmission, syntax,… • Deaf-induced vocal disorders, aphasias, • speech sound disorder, autism,… Vocal learners

4. Goal was to test hypothesis using vocal non-learning species: chicken for birds and mice for mammals Holy and Guo showed mice have songs with acoustic features like song learning birds? Mouse song in real time Mouse song slowed Individual differences Are mice vocal learners or not? Never tested! Holy and Guo 2005 PLoSBiol

5. 1. Mouse singing-driven gene expression M1 A1 brainatlas.mbi.ufl.edu Arriaga, Zhou, Jarvis2012 From Figure 2

6. Exclusively in Layer V neurons of singing-induced M1 cortex region M1 M2 I II III IV V VI Cg Arriaga, Zhou, Jarvis2012 From Figure 3

7. Singing activated M1 projects directly to vocal motor neurons (Amb) But projection is sparse: 1-2 axons per motor neuron Arriaga, Zhou, Jarvis2012 From Figure 3

8. 2. Mouse song system connectivity more similar to songbird and human Arriaga, Zhou, Jarvis2012 From Figure 1

9. 3. Posterior vocal motor pathway produces learned vocalizations X X X X EXPERIMENT 3: Motor cortex lesion (n=5) Visual cortex lesion (n=5) Sham surgery (n=6) Eliminate song/speech production Crying/laughing intact Eliminate song production Innate calls intact Nottebohm et al 1976 J Comp Neurol

10. Experiment 3. M1 laryngeal cortex lesions Record song, ibotenic acid lesion, record song again, backfill with PRV and verify lesion. down jumps up jumps Lead to greater singing variation: aphasia of song? Arriaga, Zhou, Jarvis2012 From Figure 4

11. Deafened mice show some song deterioration Caspase-3 a cystein proteases that play essential roles in programmed cell death. CASP3 KO causes loss of ear hair cells by 1 month (Takahasi et al 2001 Brain Res) Arriaga, Zhou, Jarvis2012 From Figure 5

12. 5. Song pitch convergence caused by competitive social experience Co-house adult C57 males + BxD males that sing at different pitches in the presence of either a C57 female or BxD female Arriaga, Zhou, Jarvis2012 From Figure 6

13. Traits unique to vocal learners *Vocal learners: e.g. humans, songbirds, parrots, hummingbirds. **Vocal non-learners: e.g. non-human primates, cat, chicken, pigeon Reviewed in: Doupe & Kuhl 1999 Ann Rev Neurosci; Hauser et al 2002 Science; Jarvis 2004 Ann NY AcadSci; Jurgens & Ehrenreich 2007 Brain Res; Fischer & Hammerschmidt 2010 Genes, Brain & Behav.

14. Summary • We propose that vocal learning is not dichotomous, but a continuous trait. Mice are limited vocal learners, in the middle. • Mice might serve as genetic models for some properties thought unique to humans for speech-language disorders. • Given the convergent behavior, neural networks, and genetics for vocal learning, it is theoretically possible to genetically enhance the circuit. chicken macaque mice songbird human Vocal learning and brain pathway continuum (not solely based on species related)

15. Funding for projects presented NIH Director’s Pioneer Award Howard Hughes Medical Institute NIDCD R01-DC007218

16. Big questions EITHER • Mice are more similar to humans and song learning birds for vocal communication traits than are non-human primates are to humans OR • Much of the last 50 years of research on differences between vocal learners and non-learners needs to be re-evaluated