Mehreen Inayat

Bio: Mehreen Inayat is an academic researcher from University of Toronto. The author has co-authored 1 publications.

Promoting and Optimizing the Use of 3D-Printed Objects in Spontaneous Recognition Memory Tasks in Rodents: A Method for Improving Rigor and Reproducibility.

Abstract: Spontaneous recognition memory tasks are widely used to assess cognitive function in rodents and have become commonplace in the characterization of rodent models of neurodegenerative, neuropsychiatric and neurodevelopmental disorders. Leveraging an animal’s innate preference for novelty, these tasks use object exploration to capture the what, where and when components of recognition memory. Choosing and optimizing objects is a key feature when designing recognition memory tasks. Although the range of objects used in these tasks varies extensively across studies, object features can bias exploration, influence task difficulty and alter brain circuit recruitment. Here, we discuss the advantages of using 3D printed objects in rodent spontaneous recognition memory tasks. We provide strategies for optimizing their design and usage, and offer a repository of tested, open-source designs for use with commonly used rodent species. The easy accessibility, low-cost, renewability and flexibility of 3D printed open-source designs make this approach an important step toward improving rigor and reproducibility in rodent spontaneous recognition memory tasks. Significance statement Spontaneous recognition memory tasks are becoming standard in neuroscience labs studying cognitive function and using preclinical models of neurodegenerative, neuropsychiatric and neurodevelopmental disorders. Yet, variability in object selection across labs hinders cross-lab comparisons and consensus across the field. Here we discuss the advantages of, and optimization strategies for, the use of 3D-printed objects in rodent spontaneous recognition memory tasks, with the goal of increasing accessibility, reproducibility and rigor when running these tasks. We also share tested, open-source object designs for rats and mice with the broader scientific community.

Assessing the importance of sex in a hippocampus-dependent behavioral test battery in C57BL/6NTac mice.

Abstract: Inclusion of male and female subjects in behavioral neuroscience research requires a concerted effort to characterize sex differences in standardized behavioral assays. Sex differences in hippocampus-dependent assays have been widely reported but are still poorly characterized. In the present study, we conducted a parametric analysis of spontaneous alternation, object recognition, and fear conditioning in a commonly used control strain, C57BL/6NTac. Our findings show largely similar performance between males and females across the majority of behavioral end points. However, we identified an important difference in nonassociative fear sensitization, whereby females showed an enhanced fear response to the 75-dB tone that is used as the conditional stimulus. In addition, we observed an impairment in object location performance in females that was ameliorated by more extensive habituation to handling. Together, these findings argue that sex differences in nonassociative fear responses to both novel auditory cues and novel objects need to be considered when designing and interpreting cognitive assays in C57BL/6 mice. Furthermore, this elevated fear sensitization could serve as a novel approach to model the increased incidence of anxiety disorders in women.

Environmental conditions of recognition memory testing induce neurovascular changes in the hippocampus in a sex-specific manner in mice

Abstract: Abstract Experiences are linked to emotions impacting memory consolidation and associated brain neuronal circuits. Posttraumatic stress disorder is an example of strong negative emotions affecting memory processes by flashbacks of past traumas. Stress-related memory deficits are also observed in major depressive disorder (MDD). We recently highlighted that sex-specific blood-brain barrier (BBB) alterations underlie stress responses in mice and human depression. However, little is known about the relationship between emotional valence, memory encoding and BBB function. Here, we investigated the effects of novel object recognition (NOR) test, an experience considered of neutral emotional valence, on BBB properties in dorsal vs ventral hippocampus in the context of various environmental conditions (arena size, handling, age). The hippocampus is a brain area central for learning and memory processes with the dorsal and ventral subregions being associated with working memory vs reference memory retrieval, respectively. Expression of genes related to BBB integrity are altered in line with learning and memory processes in a region- and sex-specific manner. We observed correlations between poor learning, anxiety, stress-induced corticosterone release and changes in BBB-associated gene expression. Comparison of BBB transcriptomes between sexes also revealed profound differences at baseline in both ventral and dorsal hippocampus. Finally, we identified circulating vascular biomarkers, such as sE-selectin and Mmp-9, altered following NOR exposure supporting that recognition memory formation has an impact on the neurovasculature. Although deemed as a neutral valence test, NOR experimental conditions impact performance, highlighting the need to minimize anxiety when performing this commonly used test in mice. Significance Statement With this study, we aim to investigate the blood-brain barrier’s (BBB) role in memory acquisition and consolidation to unravel new mechanisms and decipher the involvement of non-neuronal cell types in these processes. For this purpose, male and female mice were subjected to a recognition memory test associated with a neutral emotional experience and impact on the transcriptomic profile of the BBB along with blood vascular biomarkers were evaluated under various experimental conditions. Crossing the BBB remains an important challenge to develop therapeutic drugs including in the context of memory deficits driven by psychiatric disorders or neurodegenerative diseases and thus, the possibility to directly target this barrier by better understanding its biology is attractive and innovating.

Ecologically mapped neuronal identity: Towards standardizing activity across heterogeneous experiments

Abstract: The brain's diversity of neurons enables a rich behavioral repertoire and flexible adaptation to new situations. Assuming that the ecological pressure has optimized this neuronal variety, we propose exploiting na\"ive behavior to map the neuronal identity. Here we investigate the feasibility of identifying neurons"ecologically"using their activation for natural behavioral and environmental parameters. Such a neuronal ECO-marker might give a finer granularity than possible with genetic or molecular markers, thereby facilitating the comparison of the functional characteristics of individual neurons across animals. In contrast to a potential mapping using artificial stimuli and trained behavior which have an unlimited parameter space, an ecological mapping is experimentally feasible since it is bounded by the ecology. Home-cage environment is an excellent basis for this ECO-mapping covering an extensive behavioral repertoire and since home-cage behavior is similar across laboratories. We review the possibility of adding area-specific environmental enrichment and automatized behavioral tasks to identify neurons in specific brain areas. In this work, we focus on the visual cortex, motor cortex, prefrontal cortex, and hippocampus. Fundamental to achieving this identification is to take advantage of state-of-the-art behavioral tracking, sensory stimulation protocols, and the plethora of creative behavioral solutions for rodents. We find that motor areas might be easiest to address, followed by prefrontal, hippocampal, and visual areas. The possibility of acquiring a near-complete ecological identification with minimal animal handling, minimal constraints on the main experiment, and data compatibility across laboratories might outweigh the necessity of implanting electrodes or imaging devices.