ArticleFrontiers in cellular neuroscience2014
Leptin potentiates GABAergic synaptic transmission in the developing rodent hippocampus.
Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Neuroendocrine response to GABA-B receptor agonism in alcohol-dependent individuals: Results from a combined outpatient and human laboratory experiment.Neuropharmacology · 2018Trial
- Hippocampal Leptin Resistance and Cognitive Decline: Mechanisms, Therapeutic Strategies and Clinical Implications.Biomedicines · 2024Review
- Food for Thought: Leptin and Hippocampal Synaptic Function.Frontiers in pharmacology · 2022Review
- Leptin increases GABAergic synaptogenesis through the Rho guanine exchange factor β-PIX in developing hippocampal neurons.Science signaling · 2021Article
- Leptin down-regulates KCC2 activity and controls chloride homeostasis in the neonatal rat hippocampus.Molecular brain · 2020Article
- Sonic Hedgehog Signaling Agonist (SAG) Triggers BDNF Secretion and Promotes the Maturation of GABAergic Networks in the Postnatal Rat Hippocampus.Frontiers in cellular neuroscience · 2020Article
- Developmental Switch of Leptin Action on Network Driven Activity in the Neonatal Rat Hippocampus.Frontiers in cellular neuroscience · 2019Article
- Zebrafish Mutants Carrying Leptin a (lepa) Gene Deficiency Display Obesity, Anxiety, Less Aggression and Fear, and Circadian Rhythm and Color Preference Dysregulation.International journal of molecular sciences · 2018Article
- Article
- [Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2017Article
- Loss of Leptin-Induced Modulation of Hippocampal Synaptic Trasmission and Signal Transduction in High-Fat Diet-Fed Mice.Frontiers in cellular neuroscience · 2017Article
- Combination treatment with leptin and pioglitazone in a mouse model of Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2017Article
- Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice.Nutrition (Burbank, Los Angeles County, Calif.) · 2016Article
- GABAergic regulation of the HPA and HPG axes and the impact of stress on reproductive function.The Journal of steroid biochemistry and molecular biology · 2016Review
- Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Impairs Synaptic Plasticity and Hippocampal-Dependent Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons.Frontiers in molecular neuroscience · 2016Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
It is becoming increasingly clear that leptin is not only a hormone regulating energy homeostasis but also a neurotrophic factor impacting a number of brain regions, including the hippocampus. Although leptin promotes the development of GABAergic transmission in the hypothalamus, little is known about its action on the GABAergic system in the hippocampus. Here we show that leptin modulates GABAergic transmission onto developing CA3 pyramidal cells of newborn rats. Specifically, leptin induces a long-lasting potentiation (LLP-GABAA) of miniature GABAA receptor-mediated postsynaptic current (GABAA-PSC) frequency. Leptin also increases the amplitude of evoked GABAA-PSCs in a subset of neurons along with a decrease in the coefficient of variation and no change in the paired-pulse ratio, pointing to an increased recruitment of functional synapses. Adding pharmacological blockers to the recording pipette showed that the leptin-induced LLP-GABAA requires postsynaptic calcium released from internal stores, as well as postsynaptic MAPK/ERK kinases 1 and/or 2 (MEK1/2), phosphoinositide 3 kinase (PI3K) and calcium-calmodulin kinase kinase (CaMKK). Finally, study of CA3 pyramidal cells in leptin-deficient ob/ob mice revealed a reduction in the basal frequency of miniature GABAA-PSCs compared to wild type littermates. In addition, presynaptic GAD65 immunostaining was reduced in the CA3 stratum pyramidale of mutant animals, both results converging to suggest a decreased number of functional GABAergic synapses in ob/ob mice. Overall, these results show that leptin potentiates and promotes the development of GABAergic synaptic transmission in the developing hippocampus likely via an increase in the number of functional synapses, and provide insights into the intracellular pathways mediating this effect. This study further extends the scope of leptin's neurotrophic action to a key regulator of hippocampal development and function, namely GABAergic transmission.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.