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Open research questions in Memory and Neural Mechanisms

296 unresolved questions extracted from the limitations and future-work sections of 1,088 Memory and Neural Mechanisms papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Some of the rats did not complete all fifteen sessions due to the loss of their recording head stage or distractions from the cable tether, - Small sample size, n = 9, - Limited to rats, Long Evans

    Reconfiguration of prefrontal-striatal-hippocampal networks during rule-based category learning in rats · 2026 · DOI

  • Investigate the neural mechanisms of category learning in other species, - Examine the effects of lesions or inactivation of specific brain regions on category learning, - Develop more complex category learning tasks to further understand the neural basis of categorization

    Reconfiguration of prefrontal-striatal-hippocampal networks during rule-based category learning in rats · 2026 · DOI

  • Further studies need to investigate the conditions under which an improvement on the psychophysiological and behavioral levels can be achieved as well. Studies should investigate the long-term effects of VPA in combination with fear-memory retrieval prior to exposure therapy. Research should be conducted to determine the optimal dosage and administration schedule of VPA for enhancing symptom improvement in the treatment of phobias.

    Effects of the histone deacetylase inhibitor valproic acid in combination with fear-memory retrieval before exposure therapy for spider phobia: A randomized controlled trial · 2025 · DOI

  • The return of fear after successful exposure therapy for a phobia is a common clinical challenge, - The original fear memory remains intact and can return over time, - There is a need to enhance symptom improvement at the subjective level in the treatment of phobias

    Effects of the histone deacetylase inhibitor valproic acid in combination with fear-memory retrieval before exposure therapy for spider phobia: A randomized controlled trial · 2025 · DOI

  • limited empirical research examines developmental theories of anxiety, - small sample size, - no significant differences emerged between adults and adolescents in gender, anxiety symptom severity, or sleep duration or quality between visits

    Late positive potential reveals sustained threat contingencies despite extinction in adolescents but not adults · 2024 · DOI

  • Limited empirical research examines the neurobiological theories of anxiety. Scarce research on adolescence-specific patterns of neural responding during threat learning. A need to investigate the link between anxiety severity and neural responses to threat extinction.

    Late positive potential reveals sustained threat contingencies despite extinction in adolescents but not adults · 2024 · DOI

  • Existing memories can be updated with new information through a process known as reconsolidation, though the molecular mechanisms underlying this process are poorly understood.

    Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation · 2026 · DOI

  • Additionally, memory updating is impaired with aging, but little is known about how this impairment occurs.

    Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation · 2026 · DOI

  • The laminar anatomy of the hippocampal microcircuit is conserved across mammals, and its physiology has been characterized extensively in rodents, yet how this circuitry is organized physiologically in the primate brain remains poorly understood.

    Physiological landmarks reveal the laminar organization of the primate hippocampus · 2026 · DOI

  • Maladaptive fear memories are a core feature of stress-related disorders and are often accompanied by cognitive and affective disturbances; yet, it remains unclear whether the same neuronal ensembles link maladaptive fear to these behavioural alterations.

    High-intensity fear engrams extend beyond threat processing to drive cognitive and affective dysfunction · 2026 · DOI

  • Vasoactive intestinal peptide-expressing interneurons (VIP-INs) gate hippocampal inhibition during novel experience, but the long-range signals that engage these cells remain poorly understood.

    Median raphe input to dorsal CA1 shapes VIP interneuron recruitment and novelty-guided spatial memory · 2026 · DOI

  • Linearization, defined as the mapping of parallel and recursive syntactic configurations onto a temporally constrained sequence of words, constitutes a fundamental problem for language production, yet its neurocognitive implementation remains insufficiently explained.

    Sequencing thought into speech: Hippocampal functions in linguistic linearization · 2026 · DOI

  • However, the upstream circuits controlling projection-defined basal forebrain cholinergic populations remain incompletely understood.

    Subregion-specific input organization of prefrontal-projecting basal forebrain cholinergic neurons and weakened striatal–NBM inhibitory transmission in 5xFAD mice · 2026 · DOI

  • Direct retrieval-window evidence remains limited to two local baclofen studies in male mice using morphine conditioned place preference; both reported retrieval dependence, but only the agranular insular cortex study included a delayed-treatment comparison.

    GABAB receptor modulation during drug-memory reconsolidation: current evidence and translational priorities for relapse prevention · 2026 · DOI

  • However, it remains unknown how 40 Hz flicker affects neural codes essential for memory.

    40 Hz sensory stimulation enhances CA3–CA1 coordination and prospective coding during navigation in a mouse model of Alzheimer’s disease · 2025 · DOI

  • However, the mechanism underlying the prefrontal coordination with HPC and PPC during spatial learning is poorly understood.

    Prefrontal cortex synchronization with the hippocampus and parietal cortex is strategy-dependent during spatial learning · 2025 · DOI

  • This phenomenon-repulsion-is not accounted for by most theories of the hippocampus, and the conditions that trigger repulsion remain poorly understood.

    Repulsion of hippocampal representations driven by distinct internal beliefs · 2025 · DOI

  • When external landmarks are scarce, place cells use self-motion (idiothetic) information to track location based on distance traveled (distance coding).

    An independent coding scheme for idiothetic distance in the hippocampus · 2025 · DOI

  • 18 However, few studies have examined the role of grid cell firing during active navigation.

    Grid cell distortion is associated with increased distance estimation error in polarized environments · 2025 · DOI

  • Yet, how such relative value signals are acquired during learning remains poorly known.

    Modulation of relative aversive and safety learning by D2-expressing neurons of the anterior paraventricular nucleus of the thalamus · 2025 · DOI

  • However, the role of the projections of ACC neurons to subcortical areas and their influence on sensory processing are not fully investigated.

    Anterior cingulate cross-hemispheric inhibition via the claustrum resolves painful sensory conflict · 2024 · DOI

  • We show that this time-mapping ability requires experience and is lacking in inexperienced bats.

    Time-mapping and future-oriented behavior in free-ranging wild fruit bats · 2024 · DOI

  • However, OFC- and DH-specific contributions to the different functional properties of hierarchical associations remain controversial.

    Partially dissociable roles of the orbitofrontal cortex and dorsal hippocampus in context-dependent hierarchical associations · 2024 · DOI

  • In contrast, DH's role appears limited to the contextual learning bias conferred by hierarchical associations.

    Partially dissociable roles of the orbitofrontal cortex and dorsal hippocampus in context-dependent hierarchical associations · 2024 · DOI

  • However, little is known whether this cross-frequency interaction exists in the Hp of birds during navigation.

    Phase–Amplitude Coupling between Theta Rhythm and High-Frequency Oscillations in the Hippocampus of Pigeons during Navigation · 2024 · DOI

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296 open questions have been extracted from the limitations and future-work passages of 1,088 Memory and Neural Mechanisms papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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