Pharmacological Inhibition

The NCM (caudomedial nidopallium), a region in the avian brain analogous to Wernicke's area in humans, contains (part of) the neural substrate for the representation of tutor song memory in zebra finches (Bolhuis et al. 2006). Premotor regions in the avian brain such as HVC are also implicated in vocal learning; their role may be to encode sensory information used for successful imitation of tutor song (Roberts et al. 2012). Bilateral lesions to the NCM in adult zebra finches result in impaired tutor-song recognition, while leaving song production unaffected (Gobes and Bolhuis 2007). Taken together, these results provide evidence for distinct neural pathways for auditory recognition and vocal production of tutor song.

Photomicrograph of NCM showing immunostaining of the IEG Zenk
Figure 1: Photomicrograph of the NCM showing immunostaining of the IEG Zenk. The robust Zenk expression seen in NCM upon re-exposure to tutor song (as compared to a novel song) in juvenile zebra finches (Gobes et al. 2010) illustrates the role of this brain region in auditory-recognition memory and its function as (part of) the neural substrate for tutor song memory.

In our laboratory, we use Immediate Early Genes (IEGs), such as Zenk, as a measure for neuronal activation. IEGs are transcribed within 30min after stimulus exposure, and the protein products of these genes can be detected with Immunocytochemistry (Figure 1). The number of Zenk-expressing neurons in the NCM upon re-exposure to the tutor's song is related to the fidelity of song imitation, and is left-lateralized (Bolhuis et al. 2000, 2001; Moorman, Gobes et al. 2012). Hemispheric dominance of the left-NCM seems to develop with experience and is not innate (Moorman et al. 2012; Chirathivat et al. 2015). Interestingly, bilateral pharmacological inhibition of the molecular pathway responsible for inducing IEGs in the NCM during tutoring sessions impairs song learning in juvenile zebra finches (London and Clayton 2008). We are currently investigating whether development of a left-lateralized neural substrate for song memory is required for forming an accurate template, or memory, of tutor song with a combination of pharmacological and behavioral techniques.

Rythm spectograms of bird songs
Figure 2A
Rythm spectograms of bird songs
Figure 2B
Figure 2: Rhythm spectrograms for tutor song (A) and zebra finch song in which the NCM was unilaterally inhibited (B). Spectrograms illustrate the power of different frequencies of sound present in a bird's song. The clearly defined red/orange bands present in the higher frequencies of the tutor's rhythm spectrogram are indicative of a highly stereotyped, crystallized song. The absence of these bands in the song represented in panel (B) reflect the effects of our experimental manipulations on the bird's ability to imitate song.

References:

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  2. Bolhuis JJ, Hetebrij E, den Boer-Visser AM, de Groot JH, Zijlstra GGO (2001) Localized immediate early gene expression related to the strength of song learning in socially reared zebra finches. Eur J Neurosci 13:2165–2170.
  3. Bolhuis JJ, Zijlstra GGO, den Boer-Visser AM, Van Der Zee EA (2000) Localized neu- ronal activation in the zebra finch brain is related to the strength of song learning. Proc Natl Acad Sci USA 97:2282–2285.
  4. Chirathivat N, Raja S. C, Gobes S. M. H. (2015) Hemispheric dominance underlying the neural substrate for learned vocalizations develops with experience. Sci Rep 5: 11359.
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  8. Moorman S., Gobes S. M. H., Kuijpers M., Kerkhofs A., Zandbergen M. A., Bolhuis J. J. (2012) Human-like brain hemispheric dominance in birdsong learning. Proc. Natl. Acad. Sci. U.S.A. 109: 12782–12787.
  9. Roberts, T. F., Gobes, S. M. H., Murugan, M., Ölveczky, B. P., & Mooney, R. (2012). Motor circuits are required to encode a sensory model for imitative learning. Nature Neuroscience, 15(10), 1454–1459.