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Selected publications
Selected publications
Maddaloni G, Chang YJ, Senft RA, Dymecki SM. Adaptation to photoperiod via dynamic neurotransmitter segregation. Nature 632, 147–156 (2024).
In this paradigm shift paper, we define a previously uncharacterized circuit in the mouse brain that adjusts circadian and sleep/wake rhythms to changes in day length, or photoperiod. We also uncover a novel form of neurotransmitter plasticity, where dual serotonin-glutamate neurons dynamically deploy serotonin vs. glutamate to different axonal branches as a function of daylength, and this plasticity is essential for photoperiod habituation. This work lays the foundation of the lab future work on the neurobiology of seasonal rhythms.
Maddaloni G*, Barsotti N, Migliarini S, Giordano M, Nazzi S, Picchi M, Errico F, Usiello A, Pasqualetti M*. Impact of Serotonin Deficiency on Circadian Dopaminergic Rhythms. International Journal of Molecular Sciences. 25(12):6475 (2024) *corresponding authors
In this paper, we discover that daily rhythms in the expression of the dopamine biosynthetic enzyme Tyrosine Hydroxylase, or TH, is controlled by serotonin. In mice depleted of brain serotonin, daily oscillation of TH are blunted, generating a behavioral phenotype that resembles bipolar disorder associated manic states.
Nazzi S*, Maddaloni G*, Pratelli M, Pasqualetti M. Fluoxetine Induces Morphological Rearrangements of Serotonergic Fibers in the Hippocampus. ACS Chemical Neuroscience. 10(7):3218-3224 (2019) *co-first authorship
Here we show for the first time that the antidepressant Fluoxetine, which blocks the synaptic reuptake of serotonin, induces morphological rearrangements of serotonin axons themselves, highlighting a previously unappreciated structural effect that might contribute to the antidepressant action.
Maddaloni G, ... , Pasqualetti M. Serotonin depletion causes valproate-responsive manic-like condition and increased hippocampal neuroplasticity that are reversed by stress. Scientific Reports. 7;8(1):11847 (2018)
Here we identified in mice a transcriptomic program that is engaged in the hippocampus in response to chronic, inescapable stress and is essential for the animal’s ability to cope with it. The timing of such response is modulated by 5-HT – if 5-HT is disrupted genetically, a stress-related transcriptomic response takes place in the absence of any stress, resulting in aberrant, manic-like behavior; when exposed to chronic stress, transgenic mice fail to engage adaptive responses and exhibit aggravated depressive-like phenotypes resembling human bipolar disorder. This work revealed previously unappreciated molecules, circuits, and gene modules that might be dysregulated in bipolar disorder.
Maddaloni G*, Bertero A*, Pratelli M*, Barsotti N, Boonstra A, Giorgi A, Migliarini S, Pasqualetti M. Development of Serotonergic Fibers in the Post-Natal Mouse Brain. Frontiers in Cellular Neuroscience. 11:202 (2017) *co-first authorship
In this manuscript we provide the first high-resolution reconstruction of the maturation trajectory of serotonin axons innervating different brain targets. While we found a common morphological refinement of axons – from thick and dot shaped to thinner and smoother – we uncovered previously unreported region- and time-specific developmental patterns characterized by either progressive increase in axon sprouting or a transient one that is followed by secondary pruning. More broadly, our work has uncovered novel critical periods of plasticity where fine-tuned serotonin signaling might be required for proper circuit maturation
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