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Functional brain repair in songbirds: the role of neurogenesis and FoxP2, a gene implicated in a human speech impairment

Kirill Tokarev, Doctoral Student.

The present project aims to investigate the relationship between behavioral recovery and brain repair. Research during the last 25 years has established that nerve cells, neurons, continue to be born in the adult brain of many vertebrate species, including humans. Why some types of neurons die and get replaced while other neurons function throughout the lifespan of an organism remains one of the enigmas of modern neuroscience.

Songbirds provide an excellent model to study the regulation and function of adult neurogenesis, which cannot be investigated experimentally in humans. Songbirds, like humans and unlike most other animals, use imitative learning to acquire their communication sounds [1, 2]. A brain region that is essential for this learned singing behavior, called HVC, continuously incorporates new neurons throughout adulthood [3, 4]. Experimentally induced neuronal death in HVC leads to severe song deficits that recover to varying degrees over time, concomitant with compensatory rates of increased neuronal replacement of the experimentally ablated neurons [4]. However, whether neuronal replacement in HVC is the cause for behavioral changes has not been tested directly.

To address the relationship between behavioral recovery and brain repair, I am testing whether the song recovery after experimental ablation of certain neuron types depends on the subsequent replacement of these neurons. Experimental manipulation of the time-course of neuronal incorporation into HVC allows me to investigate concomitant changes in the time course of behavioral recovery. I am also focusing on a the regulatory role of the transcription factor FoxP2, which is essential for normal human speech to develop [5] and together with its nearest homologue FoxP1 plays an important role in vocal learning in songbirds [6,7]. Whether this role is mediated via a regulatory influence on neurogenesis, neural differentiation or neuronal survival is not known yet.

(1) Doupe, A.J., Kuhl, P.K. BIRDSONG AND HUMAN SPEECH: Common Themes and Mechanisms. Annu. Rev. Neurosci. 1999. 22:567–631. (2) Jarvis, E.D. Learned Birdsong and the Neurobiology of Human Language. Ann.N.Y.Acad.Sci. (2004)1016: 749-777. (3) Nottebohm, F. The Road We Travelled Discovery, Choreography, and Significance of Brain Replaceable Neurons Ann. N.Y. Acad. Sci. (2004). 1016: 628–658. (4) Scharff, C., Kirn, J.R., Grossman, M., Macklis, J.D., and Nottebohm F. Targeted Neuronal Death Affects Neuronal Replacement and Vocal Behavior in Adult Songbirds, Neuron (2000) Vol. 25, 481–492. (5) Fisher, S.E., Lai, C.S.L. and Monaco, A.P. DECIPHERING THE GENETIC BASIS OF SPEECH AND LANGUAGE DISORDERS. Annu. Rev. Neurosci. 2003. 26:57–80. (6) Teramitsu, I., Kudo, L.C., London, S.E., Geschwind, D.H., and White, S.A. Parallel FoxP1 and FoxP2 Expression in Songbird and Human Brain Predicts Functional Interaction The Journal of Neuroscience (2004) 24(13):3152–3163.