Biology subjects

Bashir, Z. I.

Publications and source records attributed to Bashir, Z. I..

5 recordsLinked to original sources

bioRxiv2025

Novel object-place configurations increase excitability of layer 5 lateral entorhinal cortex engram cells

Associative recognition memory is essential for everyday life, forming cognitive representations of and recalling relationships between things we encounter and their environments. Object-place associations are represented in the lateral entorhinal and medial prefrontal cortices, however the identity of neurons in which these associations are formed, the cellular mechanisms supporting them, and how these representations react to change are not understood. Here we labelled associative recognition memory engrams, finding that engram neuron reactivation by memory recall correlated with behavioural performance only in the dorsolateral subregion of entorhinal cortex, where reactivation was overrepresented in layer 5/6. Electrophysiology from ex vivo slices prepared directly following memory recall revealed increased excitability in layer 5 lateral entorhinal cortex engram cells, which only occurred when engram-specific objects were reconfigured. These data identify deep layer lateral entorhinal cortex neurons as key loci of object-place associations and proposes a plastic mechanism by which pre-existing neural representations are updated. Significance statementAssociative recognition memory is key to our normal everyday lives, but how these memories are updated and which neurons support these memories remain poorly understood. We identify a population of neurons in the deep-layers of lateral entorhinal cortex which are activated by memory encoding and whose reactivation is correlated with, and necessary for, memory retrieval, thus identifying them as engram neurons. These entorhinal neurons demonstrate increased firing following presentation of familiar cues in a novel configuration, revealing a mechanism for integrating new information into existing memories. By identifying a specific cell type and plasticity process underlying memory updating, this work advances understanding of how flexible object-place representations are maintained in the brain.

neuroscience↗

bioRxiv2025

Medial prefrontal cortex input to lateral entorhinal cortex supports both encoding and retrieval of associative recognition memory

Associative recognition memory allows us to form representations of items and their environment and to judge the novelty of such representations. This memory is dependent on a brain circuit that includes interactions between medial prefrontal cortex (mPFC) and lateral entorhinal cortex (LEC); however it is unknown whether the interaction of these brain areas is required for memory encoding, retrieval or both processes. Furthermore, little is known as to whether indirect or direct mPFC-LEC connections are critical for associative recognition memory and, if the latter, in which direction information travels. To address these questions, we first performed pharmacological disconnection of mPFC and LEC, finding that mPFC-LEC interaction is required for both memory encoding and retrieval. Next, we optogenetically inhibited projections from mPFC to LEC, showing that this projection was crucial for both encoding and retrieval of both object-in-place and object-in-context recognition memory when a 1 h, but not a 5 min, memory retention delay was used. These data show that a direct connection from mPFC to LEC is critical for associative recognition memory, in a delay-dependent manner.

neuroscience↗

bioRxiv2023

A framework for decolonising and diversifying biomedical sciences curricula: rediscovery, representation and readiness

To date, most efforts to decolonise curricula have focussed on the arts and humanities, with many believing that science subjects are objective, unbiased, and unaffected by colonial legacies. However, research is shaped by cultural and historical context, and inequities exist in funding, publishing and acknowledging scientific achievements. Our curricula reflect these inequities, perpetuating bias to future generations of scientists. We examined attitudes and understanding towards decolonising and diversifying the curriculum among students and teaching staff in the biomedical sciences at the University of Bristol, to discover whether our current teaching practice is perceived as inclusive. We used a mixed methods study including surveys of staff (N=71) and students (N=121) and focus groups. Quantitative data showed that staff and students think decolonising the curriculum is important, but this is more important to female respondents (p<0.001). Students are less aware than staff of current efforts to decolonise the curriculum, while students from minority ethnic groups feel less represented by the curriculum than white students. Thematic analysis of qualitative data revealed three themes that are important for a decolonised curriculum: rediscovery, representation and readiness. We propose that this 3Rs framework could guide future efforts to decolonise and diversify the curriculum in the biomedical sciences and beyond.

scientific communication and education↗

bioRxiv2021

Why do hippocampal mossy cells matter? It depends on the frequency and context.

The discrimination of similar episodes and places, and their representation as distinct memories, depend on a process called pattern separation that relies on the circuitry of the hippocampal dentate gyrus (DG). Mossy cells (MCs) are key neurons in the circuitry, but how they influence DG network dynamics, function, and seizure risk has not been fully elucidated. We found the net impact of MCs was inhibitory at physiological frequencies connected with learning and behaviour, and their absence associated with deficits in pattern separation and spatial memory; at higher frequencies, their net impact was excitatory, and their absence protected against seizures. Thus, MCs influence DG outputs in a highly dynamic manner that varies with frequency and context. One-Sentence SummaryHippocampal mossy cells are required for learning and memory; but their absence protects against seizures.

neuroscience↗

bioRxiv2020

Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2

The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies we have performed unbiased proteomics to identify new neuronal SNX27-dependent cargoes, and identified proteins linked to excitotoxicity (SLC1A3, SLC4A7, SLC6A11), epilepsy, intellectual disabilities and working memory deficits (KCNT2, ADAM22, KIDINS220, LRFN2). Focusing on the synaptic adhesion molecule leucine-rich repeat and fibronectin type-III domain-containing protein 2 (LRFN2), we establish that SNX27 binds to LRFN2 and is responsible for regulating its endosomal sorting. LRFN2 associates with AMPA receptors and knockdown of LRFN2 phenocopies SNX27 depletion in decreasing surface expression of AMPA receptors, reducing synaptic activity and attenuating hippocampal long-term potentiation. Our evidence suggests that, in contrast to previous reports, SNX27 does not directly bind to AMPA receptors, and instead controls AMPA receptor-mediated synaptic transmission and plasticity indirectly through the endosomal sorting of LRFN2. Overall, our study provides new molecular insight into the perturbed function of SNX27 and LRFN2 in a range of neurological conditions.

molecular biology↗