Biology subjects

Cavezza, D.

Publications and source records attributed to Cavezza, D..

3 recordsLinked to original sources

bioRxiv2025

Functional specialization of the hippocampus along its dorso-ventral axis: from span to supraspan in working memory capacity

Working memory (WM) is characterized by a limited capacity or span, beyond which performance deteriorates, the supraspan condition. Human neuropsychology and neuroimaging studies have implicated the medial temporal lobe (MTL), including the hippocampus (HPC), in WM particularly when memory load exceeds span, yet no animal model has been established to investigate supraspan mechanisms. Here, we present a novel rodent model of supraspan memory and examine the distinct roles of dorsal and ventral HPC. Using selective NMDA lesions in mice combined with object recognition tasks and a modified radial arm maze (RAM), we manipulated memory load and strategy constraints to assess span and supraspan performance. Dorsal HPC lesions impaired object memory span, while ventral lesions spared this ability. In the RAM, span performance (number of correct arm visits before the first error) was unaffected by either lesion under allocentric conditions. However, once animals exceeded span, following the first error, here defined as the supraspan condition, both dorsal and ventral lesions caused catastrophic disorientation and error escalation. Under free-choice conditions, ventral HPC lesions selectively reduced the occurrence of trials with no errors in the first 5 choices, increased errors overall, and disrupted sequential egocentric strategies. Together, these results demonstrate that supraspan performance can be modeled in rodents, revealing a dorsal contribution to object memory under high load, a ventral contribution to egocentric spatial strategies, and a shared hippocampal role in supraspan memory performance. This paradigm provides a translational framework for investigating supraspan deficits observed in MTL patients and Alzheimers disease.

neuroscience↗

bioRxiv2024

Tbx1 haploinsufficiency causes brain metabolic and behavioral anomalies in adult mice which are corrected by vitamin B12 treatment

IntroductionThe brain-related phenotypes observed in 22q11.2 deletion syndrome (22q11.2DS) are highly variable and their origin is poorly understood. Changes in brain metabolism may cause or contribute to the phenotypes, given that many of the deleted genes (approx. 10%) are implicated in metabolic processes, but this is currently unknown. It is clearly important to address this knowledge gap, but in humans, the primary material required for studying brain metabolism is inaccessible. For this reason, we sought to address the issue using two mouse models of 22q11.2DS. MethodsWe used three independent approaches to investigate brain metabolism in young adult mice, namely, mass spectrometry, nuclear magnetic resonance spectroscopy and transcriptomics. We selected to study primarily Tbx1 single gene mutants because it is the primary candidate disease gene. We then confirmed key findings in the multi-gene deletion mutant Df1/+. ResultsWe found that Tbx1 mutants have alterations of specific brain metabolites, including methylmalonic acid, which is highly brain-toxic, as well as a more general metabolomic imbalance. We provide transcriptomic evidence of an interaction genotype-vB12 treatment, and behavioural evidence of a response to vB12 treatment, which rescued some of the behavioural anomaly observed in Tbx1 mutants. We conclude that Tbx1 haploinsufficiency causes extensive brain metabolic anomalies, which are partially responsive to vB12 treatment. We suggest that alterations of glutamine-glutamate metabolism and fatty acid metabolism are key components of the metabolic phenotype in these mutants.

genetics↗

bioRxiv2021

Thalamo-hippocampal pathway regulates incidental memory load: insights from sex differences

Incidental memory can be challenged by increasing either the retention delay or the memory load. The dorsal hippocampus (dHP) appears to help with both consolidation from short-term (STM) to long-term memory (LTM), and higher memory loads, but the mechanism is not fully understood. Here we find that female mice, despite having the same STM capacity of 6 objects and higher resistance to distraction in our different object recognition task (DOT), when tested over 1h or 24h delays appear to transfer to LTM only 4 objects, whereas male mice have an STM capacity of 6 objects in this task. In male mice the dHP shows greater activation (as measured by c-Fos expression), whereas female mice show greater activation of the ventral midline thalamus (VMT). Optogenetic inhibition of the VMT-dHP pathway during off-line memory consolidation enables 6-object LTM retention in females, while chemogenetic VMT-activation impairs it in males. Thus, removing or enhancing sub-cortical inhibitory control over the hippocampus, leads to differences in incidental memory. One Sentence SummaryThe sex-dependent recruitment of a subcortical pathway regulates how many items are spontaneously memorized in mice.

neuroscience↗