Inactivation mode of sodium channels defines the different maximal firing rates of conventional versus atypical midbrain dopamine neurons
| Autor: | Carmen C. Canavier, Tabea Ines Ziouziou, Niklas Hammer, Jochen Roeper, Christopher J. Knowlton |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Patch-Clamp Techniques Physiology Dopamine Action Potentials Gating Striatum Voltage-Gated Sodium Channels Biochemistry Ion Channels Sodium Channels Midbrain Mice Catecholamines Mesencephalon Animal Cells Medicine and Health Sciences Amines Biology (General) Membrane potential Neurons education.field_of_study Ecology Chemistry Organic Compounds Physics Brain Depolarization Neurochemistry Neurotransmitters Markov Chains Electrophysiology Computational Theory and Mathematics Modeling and Simulation Physical Sciences Cellular Types Anatomy Ion Channel Gating Brainstem medicine.drug Research Article Biogenic Amines QH301-705.5 Population Models Neurological Biophysics Neurophysiology Nucleus accumbens In Vitro Techniques Membrane Potential Cellular and Molecular Neuroscience Genetics medicine Animals education Molecular Biology Ecology Evolution Behavior and Systematics Sodium channel Dopaminergic Neurons Long-Term Synaptic Depression Organic Chemistry Chemical Compounds Computational Biology Biology and Life Sciences Proteins Cell Biology Hormones Electrophysiological Phenomena Mice Inbred C57BL Cellular Neuroscience Calcium Channels Neuroscience |
| Zdroj: | PLoS Computational Biology, Vol 17, Iss 9, p e1009371 (2021) PLoS Computational Biology |
| ISSN: | 1553-7358 |
| Popis: | Two subpopulations of midbrain dopamine (DA) neurons are known to have different dynamic firing ranges in vitro that correspond to distinct projection targets: the originally identified conventional DA neurons project to the dorsal striatum and the lateral shell of the nucleus accumbens, whereas an atypical DA population with higher maximum firing frequencies projects to prefrontal regions and other limbic regions including the medial shell of nucleus accumbens. Using a computational model, we show that previously identified differences in biophysical properties do not fully account for the larger dynamic range of the atypical population and predict that the major difference is that originally identified conventional cells have larger occupancy of voltage-gated sodium channels in a long-term inactivated state that recovers slowly; stronger sodium and potassium conductances during action potential firing are also predicted for the conventional compared to the atypical DA population. These differences in sodium channel gating imply that longer intervals between spikes are required in the conventional population for full recovery from long-term inactivation induced by the preceding spike, hence the lower maximum frequency. These same differences can also change the bifurcation structure to account for distinct modes of entry into depolarization block: abrupt versus gradual. The model predicted that in cells that have entered depolarization block, it is much more likely that an additional depolarization can evoke an action potential in conventional DA population. New experiments comparing lateral to medial shell projecting neurons confirmed this model prediction, with implications for differential synaptic integration in the two populations. Author summary We developed a theoretical and mathematical framework that could explain the major electrophysiological differences between the conventional midbrain dopamine (DA) neurons with a low maximum firing rate, and the more recently identified atypical DA neurons. Testable predictions from this framework were then verified with in vitro patch-clamp recordings from DA neurons with identified phenotypes and projection targets. Since different subpopulations of DA neurons participate in different circuits, and these circuits are likely differentially dysregulated in diseases such as addiction, Parkinson disease, and schizophrenia, it is important to identify the differences of their intrinsic electrophysiological properties as a prelude to developing more precisely targeted therapies. |
| Databáze: | OpenAIRE |
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