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Cortical remodelling induced by activity of ventral tegmental dopamine neurons


Representations of sensory stimuli in the cerebral cortex can undergo progressive remodelling according to the behavioural importance of the stimuli1,2. The cortex receives widespread projections from dopamine neurons in the ventral tegmental area (VTA)3,4,5, which are activated by new stimuli or unpredicted rewards6,7, and are believed to provide a reinforcement signal for such learning-related cortical reorganization8. In the primary auditory cortex (AI) dopamine release has been observed during auditory learning that remodels the sound-frequency representations9,10. Furthermore, dopamine modulates long-term potentiation11,12, a putative cellular mechanism underlying plasticity13. Here we show that stimulating the VTA together with an auditory stimulus of a particular tone increases the cortical area and selectivity of the neural responses to that sound stimulus in AI. Conversely, the AI representations of nearby sound frequencies are selectively decreased. Strong, sharply tuned responses to the paired tones also emerge in a second cortical area, whereas the same stimuli evoke only poor or non-selective responses in this second cortical field in naive animals. In addition, we found that strong long-range coherence of neuronal discharge emerges between AI and this secondary auditory cortical area.

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Figure 1: Representative cortical tonotopic best frequency maps and frequency-intensity receptive fields.
Figure 2: Reorganization of the auditory cortex by VTA microstimulation paired with a 9-kHz pulsed tone.
Figure 3: VTA/tone-pairing increases neuronal synchrony between the ventroposterior region and the 9-kHz-representing AI area.
Figure 4: VTA stimulation effects are temporally asymmetrical.


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We thank D. Blake for many informative suggestions; L. I. Zhang and F. Strata for discussions; and C. Garabedian and T. Moallem for comments on the manuscript. This work was supported by an NIH grant, the Coleman Fund, the Mental Insight Foundation, and Hearing Research.

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Correspondence to Michael M. Merzenich.

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Figure 1

(GIF 7.82 KB)

Tone exposure or VTA-stimulation alone does not change cortical topographic best-frequency map. Stimulation (ANOVA, p > 0.5). b, Percent of the auditory cortex that is tuned to each frequency band. No difference was found in a, The size of cortical area that was selectively responsive to pure tones was not changed by either tone exposure or VTA any of the eight frequency bands (p > 0.1).

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Bao, S., Chan, V. & Merzenich, M. Cortical remodelling induced by activity of ventral tegmental dopamine neurons. Nature 412, 79–83 (2001).

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