These results suggested that mecamylamine failed to inhibit the effects of carbachol on RA PNs. Similar to the effects of carbachol alone, the AHP peak amplitude and AHP time to peak were increased during the application of carbachol plus mecamylamine, and returned to the control level after carbachol plus mecamylamine washout Table 2 and Figures 9B,C , along with significant hyperpolarization of the membrane potential and gradual recovery Table 2.
However, the AP threshold, peak amplitude and half-width were unaffected Table 2. In addition, membrane input resistance, membrane time constant and membrane capacitance were significantly decreased following application of carbachol and mecamylamine, and restored eventually after the washout Table 2 and Figures 9D—F. TABLE 2. In the present study, we observed strong effects of cholinergic agents on the PNs in the song premotor nucleus RA of adult male zebra finches. We found that the effects of the cholinergic analog carbachol on RA PNs were mimicked by the mAChR agonist muscarine, which significantly decreased the evoked AP firing frequency, along with hyperpolarization of the membrane potential, increase in the evoked AP latency, AHP peak amplitude and AHP time to peak, and decrease in the membrane input resistance and membrane time constant.
The AP threshold, peak amplitude, half-width and membrane capacitance were not affected by muscarine. Furthermore, the mAChR antagonist atropine blocked the effects of carbachol.
However, the nAChR antagonist mecamylamine failed to block the effects of carbachol. Songbird RA PNs are similar to pyramidal tract neurons in the lower layer 5 of mammalian motor cortex Pfenning et al. ACh plays an important role in the regulation of mammalian cortex activity Kalmbach and Waters, In mammals, local cholinergic activation within the motor cortex modulates cortical map plasticity and motor learning Conner et al.
In addition, the previous study employing cell-attached recording by Yang et al. It was reported that multiple types of response to carbachol in rat parafascicular neurons were mainly mediated via direct activation of post-synaptic mAChRs Ye et al. An early quantitative autoradiographic study showed that either high or low levels of mAChR labels were detected in song control nuclei of songbirds, including nucleus RA Ball et al. Further studies suggested that presynaptic ACh receptors may also mediate the regulation of synaptic transmission and neuronal activity Gigout et al.
For example, in the basolateral amygdaloid pyramidal-type neurons of rats, carbachol rapidly excited presynaptic GABAergic interneurons by binding to mAChRs, and depressed the excitability of post-synaptic neurons Washburn and Moises, Interestingly, Zhang and Warren reported that ACh or carbachol affect presynaptic mAChRs and nAChRs, respectively, in rat nucleus accumbens nAcb neurons during postnatal development, and decrease or increase glutamatergic neurotransmission.
Thus, these studies provide multiple possible explanations for our results. A further study is needed to validate these findings. The study of Salgado-Commissariat et al. RA includes two types of neurons: PNs and interneurons, and the previous study does not elucidate the type of neuron investigated. Co-application of carbachol and atropine, which is supposed to activate nAChRs alone, also had no effect on the excitability of RA PNs.
Furthermore, the Mello lab zebra finch in situ hybridization database suggests the expression of muscarinic receptors but not nicotinic receptors in RA Lovell et al.
Robust nucleus of the arcopallium is a key nucleus of songbirds involved in the regulation of song behavior. PNs occurring in the premotor nucleus RA project to vocal and respiratory control nuclei in the midbrain and brainstem.
Our results, acquired from the brain slices of adult male zebra finch, demonstrate that cholinergic neurotransmitters modulate the activity of RA PNs by affecting intrinsic membrane properties via activation of mAChRs. Intrinsic membrane properties play a major role in the regulation of neuronal behavior Surges et al. Thus, our studies provide in vitro electrophysiological evidence supporting the cholinergic modulation of RA PNs, and also provide a cellular mechanism underlying the cholinergic regulation of song behavior.
The study of Shea and Margoliash shows that injections of carbachol or muscarine into HVC of anesthetized zebra finches significantly altered the discharge rates and auditory responsiveness in both HVC and RA, and nicotine produced similar effects in HVC. Shea et al. Therefore, under physiological conditions, ACh affects song behavior by modulating the activities of song premotor nuclei.
The cholinergic system, arising from the basal forebrain of songbirds, is involved in the regulation of song motor control and song learning. These findings contribute to the understanding of mechanisms associated with cholinergic regulation in birdsong production. WM and SW contributed equally to this study.
WM and SW designed and performed the experiments, analyzed the data and wrote this manuscript. LY and NZ were involved in analyzing a portion of the data. DL contributed reagents, materials and analytical tools. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ball, G. Muscarinic cholinergic receptors in the songbird and quail brain: a quantitative autoradiographic study.
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