Evidence map›Paper›PMID 41154175›Full record

ArticleBrain sciences2025

miR-218 Regulates the Excitability of VTA Dopamine Neurons and the Mesoaccumbens Pathway in Mice.

Salvatore Pulcrano, Sebastian L D'Addario, Mauro Federici, Nicola B Mercuri, Patrizia Longone, Gian Carlo Bellenchi, Ezia Guatteo

Abstract read
In one paragraph

Article in Brain sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Salvatore PulcranoSanta Lucia Foundation IRCCS, Experimental Neurology Laboratory, Via del Fosso di Fiorano 64, 00143 Rome, Italy.ORCID 0000-0002-5324-8689
Sebastian L D'AddarioSanta Lucia Foundation IRCCS, Experimental Neurology Laboratory, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Mauro FedericiSanta Lucia Foundation IRCCS, Experimental Neurology Laboratory, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Nicola B MercuriSanta Lucia Foundation IRCCS, Experimental Neurology Laboratory, Via del Fosso di Fiorano 64, 00143 Rome, Italy.ORCID 0000-0001-6700-7491
Patrizia LongoneSanta Lucia Foundation IRCCS, Molecular Neurobiology Laboratory, Via del Fosso di Fiorano 64, 00143 Rome, Italy.ORCID 0000-0001-8964-1637
Gian Carlo BellenchiSanta Lucia Foundation IRCCS, Experimental Neurology Laboratory, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Ezia GuatteoSanta Lucia Foundation IRCCS, Experimental Neurology Laboratory, Via del Fosso di Fiorano 64, 00143 Rome, Italy.ORCID 0000-0001-6338-1793

Funding

Ministry of University and Research (MUR) PRIN 2022 PNRR-P2022K5PTKMinistry of University and Research (MUR), National Recovery and Resilience Plan (NRRP) project MNESYS PE0000006
6 · The paper itself

Abstract

backgroundMiR-218 is a micro-RNA expressed in two isoforms (miR-218-1 and miR-218-2) in the brain and, within the mesencephalic area, it represents a specific regulator of differentiation and functional maturation of the dopamine-releasing neurons (DAn). Deletion of miR-218 isoforms within the midbrain alters the expression of synaptic mRNAs, the neuronal excitability of DAn of the substantia nigra pars compacta (SNpc), and their ability to release dopamine (DA) within the dorsal striatum.

objectivesHere we have investigated if miR-218 impacts the function of the DAn population adjacent to SNpc, the mesencephalic ventral tegmental area (VTA) innervating the nucleus accumbens (NAcc), and the medial prefrontal cortex.

methodsWith the use of miR-218-1, miR-218-2, and double conditional knock-out mice (KO1, c-KO2, c-dKO), we performed electrophysiological recordings in VTA DAn to investigate firing activity, measurements of DA release in NAcc slices by constant potential amperometry (CPA), and in vivo behavioral analysis.

resultsWe find that KO1 VTA neurons display hyperexcitability in comparison with c-KO2, c-dKO, and wild type (WT) neurons. DA efflux in the NAcc core and shell is reduced in all single- and double-conditional KO striatal slices in comparison with controls. The KO1 mice display a tendency toward an anxiety-like trait, as revealed by the elevated plus maze test.

conclusionsOur data indicate that miR-218-1 is the isoform that mainly regulates VTA DA neuron excitability whereas both miR-218-1 and miR-218-2 impair DA release in the mesoaccumbens pathway.

Indexed as

amperometrybehaviordopamine neuron maturationdopamine releasegene expression regulationmiR-218neuronal excitabilityventral tegmental area

Identifiers

PMID41154175
PMCPMC12563713

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