التفاصيل البيبلوغرافية
| العنوان: |
Acetylcholine modulates cerebellar granule cell spiking by regulating the balance of synaptic excitation and inhibition |
| المؤلفون: |
Benjamin N. Taylor, Nicolas Brunel, Court Hull, Taylor R. Fore |
| المصدر: |
J Neurosci |
| بيانات النشر: |
Cold Spring Harbor Laboratory, 2019. |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
Male, 0301 basic medicine, Cerebellum, Population, Models, Neurological, Neural Inhibition, Neurotransmission, Synaptic Transmission, Rats, Sprague-Dawley, Mice, 03 medical and health sciences, 0302 clinical medicine, Golgi cell, Muscarinic acetylcholine receptor, medicine, Animals, education, Research Articles, 030304 developmental biology, Neurons, 0303 health sciences, education.field_of_study, Chemistry, General Neuroscience, Depolarization, Granule cell, Acetylcholine, Rats, Nicotinic agonist, 030104 developmental biology, medicine.anatomical_structure, Female, Neuroscience, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: |
Sensorimotor integration in the cerebellum is essential for refining motor output, and the first stage of this processing occurs in the granule cell layer. Recent evidence suggests that granule cell layer synaptic integration can be contextually modified, though the circuit mechanisms that could mediate such modulation remain largely unknown. Here we investigate the role of Acetylcholine (ACh) in regulating granule cell layer synaptic integration. We find that Golgi cells, interneurons that provide the sole source of inhibition to the granule cell layer, express both nicotinic and muscarinic cholinergic receptors. While acute ACh application can modestly depolarize some Golgi cells, the net effect of longer, optogenetically induced ACh release is to strongly hyperpolarize Golgi cells. Golgi cell hyperpolarization by ACh leads to a significant reduction in both tonic and evoked granule cell synaptic inhibition. ACh also reduces glutamate release from mossy fibers by acting on presynaptic muscarinic receptors. Surprisingly, despite these consistent effects on Golgi cells and mossy fibers, ACh can either increase or decrease the spike probability of granule cells as measured by non-invasive cell attached recordings. By constructing an integrate and fire model of granule cell layer population activity, we find that the direction of spike rate modulation can be accounted for predominately by the initial balance of excitation and inhibition onto individual granule cells. Together, these experiments demonstrate that ACh can modulate population-level granule cell responses by altering the ratios of excitation and inhibition at the first stage of cerebellar processing.Significance StatementThe cerebellum plays a key role in motor control and motor learning. While it is known that behavioral context can modify motor learning, the circuit basis of such modulation has remained unclear. Here we find that a key neuromodulator, Acetylcholine (ACh), can alter the balance of excitation and inhibition at the first stage of cerebellar processing. These results suggest that ACh could play a key role in altering cerebellar learning by modifying how sensorimotor input is represented at the input layer of the cerebellum. |
| اللغة: |
English |
| DOI: |
10.1101/760223 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c8554d026f4af96559b04b377b64dc4 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....9c8554d026f4af96559b04b377b64dc4 |
| قاعدة البيانات: |
OpenAIRE |