Open research questions in Neuroscience and Neuropharmacology Research
682 gap statements mined from Neuroscience and Neuropharmacology Research papers in our 7.9M-paper local library, which holds 2,608 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
The researchers need to overcome the difficulty of recording electrophysiological activity in hippocampal CA1 pyramidal neurons. The paper mentions the challenge of analyzing epileptiform activity in brain slices using custom-written scripts in Wolfram Mathematica.
Enhanced HCN-Dependent Regulation of Temporoammonic Integration and Entorhinal–Hippocampal Epileptiform Coupling Following Febrile Seizures · 2026 · DOIThe lack of understanding of the neurobiological basis of psychosis in PTSD. The need for novel therapeutic strategies for PTSD. The limited knowledge of the role of GABAergic transmission in dopamine dysregulation.
Enantiomer-specific modulation of GABAA receptors differentially regulates stress-induced dopamine dysregulation · 2026 · DOIThe variation in intracellular GABA immunoreactivity in the mouse main olfactory bulb is not well understood. The neuronal organization of the main olfactory bulb is complex and requires further investigation. The study aims to address this gap by analyzing the layer-specific variation in intracellular GABA immunoreactivity.
Layer-specific variation in intracellular GABA immunoreactivity in the neuronal organization of the mouse main olfactory bulb · 2026 · DOIThe exact mechanisms of how environmental toxins contribute to the development of PD are not fully understood. There is a need to investigate the effects of rotenone exposure on the development of PD in young adult rats. The study aims to fill this gap by exploring the potential ontogenetic origins of PD.
Rotenone Exposure During Development Conditions Parkinsonian Phenotype in Young Adult Rats · 2025 · DOIThe need for further investigations to fully clarify the mechanisms of excitotoxicity induced by substance-related disorders. The challenge of developing effective therapeutic interventions for neurodevelopmental and adult mental disorders.
Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders · 2024 · DOIThe need for further studies on the role of glutamate-induced excitotoxicity in neurodevelopmental and adult mental disorders. The limited clinical evidence for glutamatergic drugs in the treatment of mental diseases.
Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders · 2024 · DOIThere are few reviews on the effects of glutamine supplementation on emotional and cognitive functions. The mechanisms by which glutamine supplementation contributes to normalizing glutamatergic neurotransmission and the Glu-Gln cycle are not well understood.
It highlights the need to develop targeted therapeutic strategies to address these complex disorders. The paper notes that disruptions in the developmental regulation of NMDA receptors are linked to neurodevelopmental disorders, underscoring the importance of understanding these dynamics.
The lack of understanding of the interplay between inflammation and mitochondria in glutamate toxicity. The need for a comprehensive understanding of the mechanisms of glutamate regulation and its impact on mitochondrial function. The gap in current research on the role of inflammation in glutamate toxicity.
Pathological Interplay between Inflammation and Mitochondria Aggravates Glutamate Toxicity · 2024 · DOIThere is a lack of understanding of the distribution of synaptic and extrasynaptic NMDARs in AD. The paper identifies the need to study the subcellular localization of NMDAR subunits in relation to AD. The mechanisms of neurodegeneration occurring in Alzheimer's disease are not fully understood.
The mechanisms underlying the requisite control of DA amidst extensive axonal arborization remain unknown. The precise timing and spatial extent of DA release and diffusion are crucial factors for the modulation of activities of neurons and synapses in the striatum. The differences observed among striatal neuron types may reflect different mechanisms of DA transmission within the striatal interneurons.
Anterograde trans-neuronal labeling of striatal interneurons in relation to dopamine neurons in the substantia nigra pars compacta · 2024 · DOIParvalbumin-positive (PV) and somatostatin-positive (SOM) inhibitory interneurons play distinct and critical roles in cortical sensory processing, yet their activation dynamics during patterned input remain unclear.
Temporal modulation of cortical parvalbumin and somatostatin neurons shapes network activation and adaptation during microstimulation · 2026 · DOIPreviously, we demonstrated that LATS1 plays an important role in synapse development; however, the role of LATS2 remains poorly understood.
Despite this, little is known about the specific role or subcellular localization of the Large Tumor Suppressor kinases, LATS1 and LATS2, in postmitotic neurons.
Endogenous retroviruses (ERVs) comprise a substantial fraction of the human genome, yet whether their expression can directly alter human neuronal function remains unknown.
Endogenous retrovirus activation disrupts postsynaptic organization in human glutamatergic neurons · 2026 · DOIAlthough altered glutamatergic neurotransmission is considered a major contributor to epileptic hyperexcitability, the nanoscale organization of key synaptic proteins in the human epileptic cortex is still not well characterized.
Nanoscale remodeling of synaptic glutamate receptors and calcium channels in temporal lobe epilepsy · 2026 · DOIIn particular, it remains unclear whether pre- and postsynaptic proteins undergo synapse-type-specific remodeling in TLE.
Nanoscale remodeling of synaptic glutamate receptors and calcium channels in temporal lobe epilepsy · 2026 · DOIHowever, both the molecular organization defining presynaptic fusion sites and the mechanisms by which they are spatially coordinated with postsynaptic complexes remains unclear.
Nanoarchitecture of the presynaptic cell adhesion molecule PTPσ in relation to prospective vesicle fusion sites and postsynaptic NMDA receptors · 2026 · DOIYet the degree to which individual molecules serve distinct functions in synapse formation and maturation remains poorly understood.
Specific regulation of transsynaptic nanoalignment and postsynaptic assembly by a novel NCAM family synaptic adhesion molecule · 2026 · DOIDespite mossy fiber bouton's potential role in learning and memory processes, the precise underlying mechanisms leading to their strengthened synaptic connections are still not fully understood.
Using super-resolution STED microscopy, we demonstrate that these poorly defined postsynaptic specializations are frequently out of register with presynaptic release sites.
Specific regulation of transsynaptic nanoalignment and postsynaptic assembly by a novel NCAM family synaptic adhesion molecule · 2026 · DOIOnly male rats were studied, precluding assessment of sex-dependent effects; sex differences in outcomes following experimental hyperthermic seizures have been reported previously, - Recordings were restricted to a single developmental stage (P21-P23), and it remains unknown whether the observed enhancement of HCN function persists into adulthood, - Because hyperthermia was the seizure-inducing stimulus and no…
Enhanced HCN-Dependent Regulation of Temporoammonic Integration and Entorhinal–Hippocampal Epileptiform Coupling Following Febrile Seizures · 2026 · DOIFurther studies aimed at assessing the long-term effects of ROT exposure during various stages of gestation, breastfeeding in adulthood, and old age, - Studies to understand how specific changes in the epigenome in S.
Rotenone Exposure During Development Conditions Parkinsonian Phenotype in Young Adult Rats · 2025 · DOIInvestigating the effects of Gln supplementation on emotional and cognitive disorders, - Studying the neuropathological aspects of Gln supplementation, - Examining the antioxidant and anti-inflammatory effects of Gln in humans, - Analyzing the optimal dosage of Gln for different health…
Further studies on the distribution of NMDARs in synaptic and extrasynaptic membranes in the brains of individuals with AD, - Investigation of the effects of Aβ on NMDAR levels…
Most-cited papers in Neuroscience and Neuropharmacology Research
- Magnesium gates glutamate-activated channels in mouse central neurones · Nature · 1984 · 3,129 citations
- Oxidative Stress, Glutamate, and Neurodegenerative Disorders · Science · 1993 · 3,092 citations
- A mesoscale connectome of the mouse brain · Nature · 2014 · 2,678 citations
- Glycine potentiates the NMDA response in cultured mouse brain neurons · Nature · 1987 · 2,501 citations
- Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones · Nature · 1984 · 2,291 citations
- Long-Term Potentiation--A Decade of Progress? · Science · 1999 · 2,170 citations
- Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders · New England Journal of Medicine · 1994 · 2,140 citations
- Molecular Diversity of Glutamate Receptors and Implications for Brain Function · Science · 1992 · 2,099 citations
- Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes · Science · 1992 · 2,098 citations
- Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain · Nature · 1988 · 2,063 citations
Most recent work
- Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory across species · Nature Metabolism · 2026
- Correlative light and electron microscopy identifies circuit motifs underlying processing of noisy visual motion in larval zebrafish · bioRxiv · 2026
- Cortical astrocytes extend phasic norepinephrine signals and critically mediate learned behavior · bioRxiv · 2026
- Inter-individual variability of neurotransmitter receptor and transporter density in the human brain · Brain Structure and Function · 2026
- Molecular architects of memory: BDNF/TrkB signaling and trafficking in neuronal plasticity and memory · Molecular Psychiatry · 2026
- Ten3-Lphn2-mediated target selection across the extended hippocampal network demonstrates a repeated strategy for circuit assembly · Current Biology · 2026
- Glutamate Metabotropic Receptors-Linked Postsynaptic Density Proteins: An Emergent Hub for Antipsychotics’ Regulation of Synaptic Plasticity and Metaplasticity · Biomolecules · 2026
- Biochemical Insights Into the Conserved Interactions of NMD Factors From Budding Yeast to Humans · Journal of Molecular Biology · 2026
- Synapse-specific and plasticity-regulated AMPA receptor mobility tunes synaptic integration · Neuron · 2026
- The role of GABAA receptors in hippocampus-dependent cognitive functions · Neuroscience & Biobehavioral Reviews · 2026
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