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Lodovichi, C.

Publications and source records attributed to Lodovichi, C..

4 recordsLinked to original sources

High sensitivity imaging of intracellular Cl- reveals the spatiotemporal evolution of GABAergic chloride fluxes in vitro and in vivo

Fast GABAergic inhibition in the brain is mediated by chloride currents whose driving force depends on intracellular Chloride concentration ([Cl-]i). Resolving the spatiotemporal dynamics of [Cl-]i in neurons requires a sensor combining high Cl- affinity, pH independence, and photostability - properties no existing tool achieves simultaneously. Here we introduce iClima (improved Chloride Imaging), a ratiometric genetically encoded sensor with high Cl- affinity (Kd=3.5 mM at pH 7.2), pH-insensitive under physiological conditions, and markedly improved photostability compared to existing sensors. These properties enable dynamic Cl- imaging without simultaneous pH correction. We demonstrate that iClima resolves GABAA-driven Cl- transients in cultured neurons, detects discrete Cl- hotspots along dendrites, and captures sensory-evoked Cl- transients in vivo. Finally, exploiting the spectral compatibility of iClima with GCaMP6f, we measure in interleaved trials Cl- and Ca2+ transients in the same neurons in vivo, revealing a divergence between the somatic inhibitory drive and the neuronal excitation state as reported by Ca2+ dynamics.

neuroscience↗

Effects of Tilia tomentosa on sleep architecture and circadian rhythm

Tilia extract has been used for centuries as a sedative and hypnotic compound. The impact of Tilia on sleep architecture and circadian rhythm remained, however, elusive. Here, we addressed these open questions by analysing the behaviour and the EEG signals recorded in freely moving mice fed an enriched diet with Tilia extracts. We found that Tilia significantly increased the amount of sleep, mostly during the dark hours, which correspond to the most active phase in nocturnal animals, such as mice. Furthermore, in darkness, the length of wake episodes did not increase as in controls. Spectral analyses of the EEG showed that the features of the sleep and wake signals remained unaltered upon Tilia treatment. Interestingly, the power in the gamma band resulted significantly decrease while the theta band power resulted increased in treated mice. Altogether, our data demonstrated a clear effect of Tilia on sleep architecture, highlighting its dependency on the circadian rhythm.

neuroscience↗

Male violence disrupts estrogen receptor β signaling in the female hippocampus

Women are the main target of intimate partner violence (IPV), which is escalating worldwide. Mechanisms subtending IPV-related disorders, such as anxiety, depression and PTSD, remain unclear. We employed a mouse model molded on an IPV scenario (male vs. female prolonged violent interaction) to unearth the neuroendocrine alterations triggered by an aggressive male mouse on the female murine brain. Experimental IPV (EIPV) prompted marked anxiety-like behavior in young female mice, coincident with high circulating/cerebral corticosterone levels. The hippocampus of EIPV-inflicted female animals displayed neuronal loss, reduced BrdU-DCX-positive nuclei, decreased mature DCX-positive cells, and diminished dendritic arborization level in the dentate gyrus (DG), features denoting impaired neurogenesis and neuronal differentiation. These hallmarks were associated with marked down-regulation of estrogen receptor {beta} (ER{beta}) density in the hippocampus, especially in the DG and dependent prosurvival ERK signaling. Conversely, ER expression was unchanged. After EIPV, the DG harbored lowered local BDNF pools, diminished TrkB phosphorylation, and elevated glucocorticoid receptor phosphorylation. In unison, ER{beta} KO mice had heightened anxiety-like behavior and curtailed BDNF levels at baseline, despite enhanced circulating estradiol levels, while dying prematurely during EIPV. Thus, reiterated male-to-female violence jeopardizes hippocampal homeostasis in the female brain, perturbing ER{beta}/BDNF signaling, thus instigating anxiety and chronic stress.

neuroscience↗

A Cre-amplifier to generate and detect genetic mosaics in vivo

Cre-Lox manipulation is the gold standard for cell-specific expression or knockout of selected genes. However, it is not unusual to deal with conditions of low Cre expression or transient activation, which can often go undetected by conventional Cre-reporters. We designed Beatrix, a general-purpose tool specifically devised to amplify weak Cre recombinase activity, and we used it to develop a powerful approach for the in vivo generation and detection of sparse mosaics of mutant and wild type cells.

neuroscience↗