Serotonin drives striatal synaptic plasticity in a sex-related manner

Plasticity at corticostriatal synapses is a key substrate for a variety of brain functions – including motor control, learning and reward processing – and is often disrupted in disease conditions. Despite intense research pointing toward a dynamic interplay between glutamate, dopamine (DA), and sero...

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Vydáno v:Neurobiology of disease Ročník 158; s. 105448
Hlavní autoři: Campanelli, Federica, Marino, Gioia, Barsotti, Noemi, Natale, Giuseppina, Calabrese, Valeria, Cardinale, Antonella, Ghiglieri, Veronica, Maddaloni, Giacomo, Usiello, Alessandro, Calabresi, Paolo, Pasqualetti, Massimo, Picconi, Barbara
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 01.10.2021
Elsevier
Témata:
Animals
Animals, Genetically Modified
Dopamine
Electrophysiological Phenomena
Female
Functional recovery
Glutamic Acid - physiology
Long-Term Potentiation
Male
Mice
Neostriatum - physiology
Nerve Fibers
Neuronal Plasticity - physiology
Parkinson Disease, Secondary - physiopathology
Serotonin
Serotonin - physiology
Sex Characteristics
Striatum
Synapses - physiology
Synaptic plasticity
Synaptic Transmission - physiology
Tph2
Tryptophan Hydroxylase - metabolism
Tph2
Striatum
Dopamine
Functional recovery
Serotonin
Synaptic plasticity
ISSN:0969-9961, 1095-953X, 1095-953X
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Shrnutí:Plasticity at corticostriatal synapses is a key substrate for a variety of brain functions – including motor control, learning and reward processing – and is often disrupted in disease conditions. Despite intense research pointing toward a dynamic interplay between glutamate, dopamine (DA), and serotonin (5-HT) neurotransmission, their precise circuit and synaptic mechanisms regulating their role in striatal plasticity are still unclear. Here, we analyze the role of serotonergic raphe-striatal innervation in the regulation of DA-dependent corticostriatal plasticity. Mice (males and females, 2–6 months of age) were housed in standard plexiglass cages at constant temperature (22 ± 1°C) and maintained on a 12/12h light/dark cycle with food and demineralized water ad libitum. In the present study, we used a knock-in mouse line in which the green fluorescent protein reporter gene (GFP) replaced the I Tph2 exon (Tph2GFP mice), allowing selective expression of GFP in the whole 5-HT system, highlighting both somata and neuritis of serotonergic neurons. Heterozygous, Tph2+/GFP, mice were intercrossed to obtain experimental cohorts, which included Wild-type (Tph2+/+), Heterozygous (Tph2+/GFP), and Mutant serotonin-depleted (Tph2GFP/GFP) animals. Using male and female mice, carrying on different Tph2 gene dosages, we show that Tph2 gene modulation results in sex-specific corticostriatal abnormalities, encompassing the abnormal amplitude of spontaneous glutamatergic transmission and the loss of Long Term Potentiation (LTP) in Tph2GFP/GFP mice of both sexes, while this form of plasticity is normally expressed in control mice (Tph2+/+). Once LTP is induced, only the Tph2+/GFP female mice present a loss of synaptic depotentiation. We showed a relevant role of the interaction between dopaminergic and serotonergic systems in controlling striatal synaptic plasticity. Overall, our data unveil that 5-HT plays a primary role in regulating DA-dependent corticostriatal plasticity in a sex-related manner and propose altered 5-HT levels as a critical determinant of disease-associated plasticity defects. •Tph2 catalyzes the rate-limiting step in 5-HT biosynthesis via subsequent decarboxylation.•Neurotransmitter systems (DA and 5-HT) are differently regulated between sexes.•Serotonergic and dopaminergic interplay modulates synaptic activity within the striatal nucleus.•Tph2 gene dosage exerts a primary role in modulating bidirectional synaptic plasticity in a sex-related manner.
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ISSN:0969-9961
1095-953X
1095-953X
DOI:10.1016/j.nbd.2021.105448