The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed a novel behavioral procedure to study object memory load in mice by progressively increasing the stimulus set size in the spontaneous object recognition task. Using this procedure, we demonstrated that naive mice have a memory span, which is the number of elements they can remember for a short-time interval, of about six objects. Then, we showed that excitotoxic selective lesions of the dorsal hippocampus did not impair novel object discrimination in the condition of low memory load. In contrast, the same lesion impaired novel object discrimination in the high memory load condition, and reduced the object memory span to four objects. These results have important heuristic and clinical implications because they open new perspective toward the understanding of the role of the hippocampus in item memory and in memory span deficits occurring in human pathologies, such as Alzheimer's disease and schizophrenia.

Autophagy agonists have been proposed to slow down neurodegeneration. Spermidine, a polyamine that acts as an autophagy agonist, is currently under clinical trial for the treatment of age‐related memory decline. How Spermidine and other autophagy agonists regulate memory and synaptic plasticity is under investigation. We set up a novel mouse model of mild cognitive impairment (MCI), in which middle‐aged (12‐month‐old) mice exhibit impaired memory capacity, lysosomes engulfed with amyloid fibrils (β‐amyloid and α‐synuclein) and impaired task‐induced GluA1 hippocampal post‐translation modifications. Subchronic treatment with Spermidine as well as the autophagy agonist TAT‐Beclin 1 rescued memory capacity and GluA1 post‐translational modifications by favouring the autophagy/lysosomal‐mediated degradation of amyloid fibrils. These findings provide new mechanistic evidence on the therapeutic relevance of autophagy enhancers which, by improving the degradation of misfolded proteins, slow down age‐related memory decline.

Goal-directed navigation can be based on world-centered (allocentric) or body-centered (egocentric) representations of the environment, mediated by a wide network of interconnected brain regions, including hippocampus, striatum and prefrontal cortex. The relative contribution of these regions to navigation from novel or familiar routes, that demand a different degree of flexibility in the use of the stored spatial representations, has not been completely explored. To address this issue, we trained mice to find a reward relying on allocentric or egocentric information, in a modified version of the cross-maze task. Then we used Zif268 expression to map brain activation when well-trained mice were required to find the goal from a novel or familiar location. Successful navigation was correlated with the activation of CA1, posterior-dorsomedial striatum, nucleus accumbens core and infralimbic cortex when allocentric-trained mice needed to use a novel route. Allocentric navigation from a familiar route activated dorsomedial striatum, nucleus accumbens, prelimbic and infralimbic cortex. None of the structures analyzed was significantly activated in egocentric-trained mice, irrespective of the starting position. These data suggest that a flexible use of stored allocentric information, that allows goal finding even from a location never explored during training, induces a shift from fronto-striatal to hippocampal circuits.

The restriction imposed worldwide for limiting the spread of coronavirus disease 2019 (COVID-19) globally impacted our lives, decreasing people’s wellbeing, causing increased anxiety, depression, and stress and affecting cognitive functions, such as memory. Recent studies reported decreased working memory (WM) and prospective memory (PM), which are pivotal for the ability to plan and perform future activities. Although the number of studies documenting the COVID-19 effects has recently blossomed, most of them employed self-reported questionnaires as the assessment method. The main aim of our study was to use standardized tests to evaluate WM and PM in a population of young students. A sample of 150 female psychology students was recruited online for the administration of two self-reported questionnaires that investigated psychological wellbeing (DASS-21), prospective, and retrospective memory (PRMQ). Subjects were also administered two standardized tests for WM (PASAT) and PM (MIST). We found increased anxiety, depression, and stress and decreased PM as measured by self-reports. The perceived memory failures agreed with the results from the standardized tests, which demonstrated a decrease in both WM and PM. Thus, COVID-19 restriction has strongly impacted on students’ mental health and memory abilities, leaving an urgent need for psychological and cognitive recovery plans.