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Automatic Xrefs. ChEBI Name. Supplier Information. Find compounds which contain this structure Find compounds which resemble this structure Take structure to the Advanced Search. Read full article at Wikipedia. Average Mass. Monoisotopic Mass. In brief, birds were anesthetized and euthanized by decapitation. After recovery, the slices were individually isolated in a recording chamber and superfused with oxygenated ACSF 2. RA PNs were identified based on distinct electrophysiological properties as described previously Spiro et al.
The following experiments were performed using conventional whole-cell patch recordings under current-clamp configurations. RA PNs with a resting membrane potential greater i. These drugs were obtained from Sigma-Aldrich. The effects of these drugs on RA PNs were tested by bath perfusion. The software pClamp Electrophysiological properties were measured according to the procedures defined by Farries and Perkel and reported in our previous study Meng et al.
The membrane time constant was calculated by fitting a single exponential curve to the membrane potential change in response to pA hyperpolarizing pulses. The membrane capacitance was calculated by dividing the membrane time constant by the membrane input resistance Meitzen et al.
The membrane input resistance was measured by a series of ms hyperpolarizing current steps from to 0 pA, step 20 pA with 10 s intervals. The slope of the current-voltage curve is designated as the membrane input resistance. The results showed that muscarine significantly decreased the number of spikes from 9.
Moreover, muscarine markedly increased the evoked AP latency from Meanwhile, muscarine induced the hyperpolarization of membrane potential from The line at the top indicates the drug present in the bath. B The traces illustrate the responses with consecutive treatment in a representative neuron.
We further tested the effects of muscarine on the activity of RA PNs using another pattern of depolarizing stimulus — ramp, which increased in intensity from 0 to pA linearly over ms Yao et al. The results showed that muscarine increased the evoked ramped AP latency from In addition, muscarine also induced the hyperpolarization of the membrane potential from These results further suggested that the muscarine-induced reduction of RA PN excitability may be due to membrane hyperpolarization.
A Sample traces of AP firing evoked by a ramp before, during and after muscarine application. The results showed a gradual recovery of the significantly hyperpolarized membrane potential Table 1. It was accompanied with an increase in the AHP peak amplitude and AHP time to peak during muscarine application, and return to the control level following muscarine washout Table 1 and Figures 3B,C.
However, the AP threshold, peak amplitude and half-width were unaffected Table 1. A Representative AP recordings in response to a depolarizing pulse of pA at 5 ms duration before and during muscarine application. D Voltage responses of a neuron to a series of hyperpolarizing current steps before, during and after muscarine application. TABLE 1. In addition, we also tested the roles of muscarine on membrane input resistance, membrane time constant and membrane capacitance of RA PNs.
The results showed that the membrane input resistance was decreased during muscarine application, and recovered to the control level after muscarine washout Table 1 and Figures 3D—F. The membrane time constant was decreased as well during muscarine application, and recovered gradually after muscarine washout Table 1. However, the membrane capacitance was unaffected Table 1. The results showed that carbachol had no effect on the number of evoked spikes in the presence of atropine pre: The combination of carbachol and atropine had no effect on the evoked AP latency pre: 9.
The combination of carbachol and atropine also had no effect on the membrane potential pre: The line at the top indicates the drugs present in the bath. The results showed that nicotine application has no effect on the number of evoked spikes pre: 8. Meanwhile, nicotine also had no effect on the membrane potential pre: Previous studies showed that nicotine increased the frequency of evoked and spontaneous action potentials in RA neurons Salgado-Commissariat et al.
However, the type of neurons recorded within RA was unclear in the study of Salgado-Commissariat et al. The results showed that similar to the effects of nicotine, DMPP application had no effect on the number of evoked spikes pre: 7.
DMPP also had no effect on the membrane potential pre: The results showed that similar to the effects of carbachol alone, the combination of carbachol and mecamylamine significantly decreased the number of evoked spikes pre: 8. Similar to the effects of carbachol alone, the use of carbachol combined with mecamylamine significantly increased the evoked ramped AP latency pre: 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. Brainard, M. What songbirds teach us about learning. Nature , — Chi, Z. Temporal precision and temporal drift in brain and behavior of zebra finch song. Neuron 32, — Conner, J.
Unique contributions of distinct cholinergic projections to motor cortical plasticity and learning. Cortex 20, — Farries, M. Electrophysiological properties of avian basal ganglia neurons recorded in vitro. Google Scholar. Foster, E. Lesions of a telencephalic nucleus in male zebra finches: influences on vocal behavior in juveniles and adults. Gigout, S.
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