Neuronal excitability as a regulator of circuit remodeling.

Autor:	Mayseless O; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel., Shapira G; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, 7610001 Rehovot, Israel., Rachad EY; Department of Molecular Neurobiology of Behavior, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, University of Göttingen, 37077 Göttingen, Germany., Fiala A; Department of Molecular Neurobiology of Behavior, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, University of Göttingen, 37077 Göttingen, Germany., Schuldiner O; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address: oren.schuldiner@weizmann.ac.il.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2023 Mar 13; Vol. 33 (5), pp. 981-989.e3. Date of Electronic Publication: 2023 Feb 08.
DOI:	10.1016/j.cub.2023.01.032
Abstrakt:	Postnatal remodeling of neuronal connectivity shapes mature nervous systems. ¹ ^, ² ^, ³ The pruning of exuberant connections involves cell-autonomous and non-cell-autonomous mechanisms, such as neuronal activity. Indeed, experience-dependent competition sculpts various excitatory neuronal circuits. ⁴ ^, ⁵ ^, ⁶ ^, ⁷ ^, ⁸ ^, ⁹ Moreover, activity has been shown to regulate growth cone motility and the stability of neurites and synaptic connections. ¹⁰ ^, ¹¹ ^, ¹² ^, ¹³ ^, ¹⁴ However, whether inhibitory activity influences the remodeling of neuronal connectivity or how activity influences remodeling in systems in which competition is not clearly apparent is not fully understood. Here, we use the Drosophila mushroom body (MB) as a model to examine the role of neuronal activity in the developmental axon pruning of γ-Kenyon cells. The MB is a neuronal structure in insects, implicated in associative learning and memory, ¹⁵ ^, ¹⁶ which receives mostly olfactory input from the antennal lobe. ¹⁷ ^, ¹⁸ The MB circuit includes intrinsic neurons, called Kenyon cells (KCs), which receive inhibitory input from the GABAergic anterior paired lateral (APL) neuron among other inputs. The γ-KCs undergo stereotypic, steroid-hormone-dependent remodeling ¹⁹ ^, ²⁰ that involves the pruning of larval neurites followed by regrowth to form adult connections. ²¹ We demonstrate that silencing neuronal activity is required for γ-KC pruning. Furthermore, we show that this is mechanistically achieved by cell-autonomous expression of the inward rectifying potassium channel 1 (irk1) combined with inhibition by APL neuron activity likely via GABA-B-R1 signaling. These results support the Hebbian-like rule "use it or lose it," where inhibition can destabilize connectivity and promote pruning while excitability stabilizes existing connections. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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