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Ciocca, D.

Publications and source records attributed to Ciocca, D..

3 recordsLinked to original sources

Medial prefrontal cortex encodes implicit temporal expectations in mice

Temporal prediction allows animals to align their actions with upcoming events, yet most work has focused on explicit duration judgments rather than the implicit timing that shapes ongoing behavior. Here, we ask how medial prefrontal cortex implements such latent temporal expectations and how cerebellar input contributes. Head-fixed mice learned a cued water-delivery task in which reward occurred after either a short or long delay, or after a single fixed delay. During variable delays, running and licking became anticipatory, and medial prefrontal local field potentials and single neurons showed ramping and reward-locked activity patterns aligned to expected reward time. Switching to a fixed delay rapidly sharpened behavioral anticipation and temporal coding. Optogenetic activation of cerebellar Purkinje cells selectively perturbed these dynamics and biased behavior around the earliest possible reward time. These results identify a cerebello-prefrontal circuit that encodes implicit temporal predictions on the sub-second scale.

neuroscience↗

Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption in mice, in part through hippocampal thyroid hormone signaling.

The consumption of calorie-rich diet has adverse effects on short and long-term memory, especially when introduced early in life when the brain is still maturing. Time-restricted feeding (TRF) without calorie restriction has proven to be an efficient strategy to reduce the deleterious effects of diet-induced obesity on metabolism. TRF was also shown to be beneficial to restore long-term memory in Alzheimer rodent models. Here, we provide evidence that four weeks of TRF restore the rhythmicity of some metabolic parameters together with short and long-term memory in mice fed a high fat-high sucrose (HFS) diet since weaning. Hippocampal translatome analyses indicated that impaired memory of mice under ad libitum HFS diet is accompanied by changes in genes associated with thyroid hormone signaling and astrocytic genes involved in the regulation of glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intra-hippocampal infusion of T3, the active form of thyroid hormone, rescued the memory performances of ad libitum HFS diet-fed mice. Thus, TRF demonstrates positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity and its related comorbidities in mice. The analogous time-restricted eating in humans is an easy to implement lifestyle intervention that should now be tested in obese adolescents with memory alterations.

neuroscience↗

Abca4 inhibition in a cone-rich rodent leads to Stargardt Disease type 1-like retinal degeneration

Mutations in the gene ABCA4 coding for photoreceptor-specific ATP-binding cassette subfamily A member 4, are responsible for the most common form of inherited macular degeneration known as Stargardt Disease type 1 (STGD1). STGD1 typically declares early in life and leads to severe visual handicap. Abca4 gene deletion mouse models of STGD1 show increased accumulation of lipofuscin, a hallmark of the disease, but unlike the human disease show mostly no photoreceptor degeneration or functional decline (an albino Abca4-/- mouse exhibits photoreceptor degeneration although functional parameters were not studied). Reasoning that the small cone population of mice (<3%) might compromise more faithful modelling of human maculopathies, we performed subretinal injections of CRISPR/Cas9-Abca4 recombinant Adeno-Associated Virus constructs into young Fat Sand Rats (Psammomys obesus), a diurnal rodent containing >30% cones. Sanger sequencing of the CRISPR-targeted sequence showed clear edition of the Abca4 gene. At 2 months post- injection, non-invasive fundus imaging showed widespread photoreceptor loss, confirmed by optical coherence tomography. Functional recording by scotopic and photopic single flash, and photopic flicker electroretinography, showed significant decline in photopic (cone) but not scotopic (rod) light responses. Post-mortem real-time PCR, immunohistochemistry and western blotting showed significant decrease of cone-specific (MW cone opsin) but not rod- specific (rhodopsin) markers. Transmission electron microscopy showed large numbers of lipid inclusions in treated but not control retinal pigmented epithelium. Finally, ultrahigh performance liquid chromatographic analysis of whole P. obesus eyes showed the presence of all-trans retinal-dimer, also seen in Abca4-/- mice but not normal rod-rich mouse or rat eyes. In conclusion, this animal model of STGD1 more accurately reflects human STGD1 and should be valuable for characterizing pathogenic pathways and exploring treatment options.

pathology↗