{"abstract_id":1048,"unique_id":"fens-24/presynaptic-mechanisms-underlying-gabab-f18512a3","title":"Presynaptic mechanisms underlying GABAB receptor-mediated heterosynaptic depression at hippocampal mossy fiber bouton to CA3 pyramidal neuron synapses","authors":"Peipeng Lin, Katharina Lichter, Yuji Okamoto, Peter Jonas","author_affil":[{"auth_name":"Peipeng Lin","affiliation":"Institute of Science and Technology Austria"},{"auth_name":"Katharina Lichter","affiliation":"Institute of Science and Technology Austria"},{"auth_name":"Yuji Okamoto","affiliation":"Akita University"},{"auth_name":"Peter Jonas","affiliation":"Institute of Science and Technology Austria"}],"session_date":"6","poster_board_id":"361","session_id":"6","abstract":"The hippocampal mossy fiber bouton to CA3 pyramidal neuron (MFB-PN) synapse has an important role in information processing and storage, whose efficacy is under profound modulation. Activation of presynaptic GABAB receptors (GABABRs) reduces extracellularly evoked EPSC amplitudes and mediates heterosynaptic depression at MFB-PN synapses.1,2 To decipher the mechanisms underlying GABABR-mediated modulation at these synapses, we performed paired pre-postsynaptic patch-clamp recordings and ultrastructural analysis using cryo-fixation and 2D electron microscopy (EM) in acute slices of mouse hippocampus. 50µM of the GABABR agonist baclofen suppressed the evoked EPSC amplitudes by 88.3±2.2%. Coefficient-of-variation analysis indicated that baclofen had a presynaptic site of action. The presynaptic Ca2+ current was reduced by 27.7%, only partially accounting for the reduction in EPSC. Cumulative EPSC analysis using train stimulation revealed that presynaptic GABABR activation significantly reduced the size of readily releasable pool (RRP) by 72.1±6.9%. Moreover, the RRP refilling rate was reduced by 33.0±6.8%, while the release probability of a single vesicle dropped by 54.6±4.4%. EM analysis of baclofen-incubated (50µM, 5min) and cryo-fixated acute slices revealed a median of 0.27 docked vesicles per 100nm profile length, suggesting that baclofen might decrease the number of docked vesicles at the active zone. Preliminary experiments with pre-postsynaptic recording combined with optogenetic stimulation of hippocampal interneurons suggested that synaptically released GABA might also inhibit MFB-PN EPSCs, implying a physiological role of GABABR-mediated regulation. Collectively, our results suggest that presynaptic GABABRs, activated by endogenous GABA, shape synaptic efficacy via regulation of vesicular release mechanisms at hippocampal MFB-PN synapses.References:1. Vogt KE, Nicoll RA. Glutamate and gamma-aminobutyric acid mediate a heterosynaptic depression at mossy fiber synapses in the hippocampus. Proc Natl Acad Sci U S A. 1999;96(3):1118-1122. doi:10.1073/pnas.96.3.11182. Guetg N, Seddik R, Vigot R, et al. The GABA B1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses. Journal of Neuroscience. 2009;29(5):1414-1423. doi:10.1523/JNEUROSCI.3697-08.2009","doi":"10.57736/86ac-cbac","url_link":"https://www.world-wide.org/fens-24/presynaptic-mechanisms-underlying-gabab-f18512a3","similar_abstracts":[{"abstract_id":606,"title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","authors_mini":"Peter Koppensteiner, Pradeep Bhandari, ..., Ryuichi Shigemoto","url_link":"https://www.world-wide.org/fens-24/gabab-receptors-induce-phasic-release-eb6514a4","nexus":"

Common Ground: Both studies investigate GABAB receptor modulation of synaptic transmission in the brain, focusing on presynaptic mechanisms.
Key Differences: Current study focuses on hippocampal MFB-PN synapses and heterosynaptic depression, whereas the recommended study examines medial habenula terminals and phasic release potentiation.
Methodologies: Current study uses patch-clamp recordings, 2D electron microscopy; recommended study employs Flash and Freeze-fracture, synaptoporin and CAPS2 gene deletion.
Complementary Aspects: Current study highlights reduction in RRP size and vesicle docking, while the recommended study shows an increase in these parameters under GABABR activation in a different brain region.
Potential Impact: Combining insights could elucidate diverse GABABR functions in synaptic regulation across different brain regions.

"},{"abstract_id":3063,"title":"Ex-vivo and in-vivo analysis of hippocampal pathology in a murine model of anti-GABAB autoimmune encephalitis","authors_mini":"Eleonora Anna Loi, Josefine Sell, Christian Geis","url_link":"https://www.world-wide.org/fens-24/ex-vivo-in-vivo-analysis-hippocampal-84f753bf","nexus":"

Common Ground: Both studies investigate the role of GABAB receptors in synaptic transmission and neural pathology.
Key Differences: The current study focuses on presynaptic mechanisms at hippocampal synapses, while the recommended study examines autoimmune responses affecting GABAB receptors and their impact on cognitive and epileptic pathways.
Methodologies: Current study uses patch-clamp recordings, cryo-fixation, and electron microscopy. Recommended study employs in-vivo EEG, ex-vivo field potentials, super-resolution microscopy, and behavioral tests.
Complementary Aspects: The current study elucidates basic presynaptic mechanisms, while the recommended study explores pathophysiological effects of disrupted GABAB receptor function.
Potential Impact: Combined insights could advance understanding of GABAB receptor modulation in both neurophysiological and pathological contexts.

"},{"abstract_id":2548,"title":"Presynaptic plasticity and memory encoding in hippocampal circuits","authors_mini":"Catherine Marneffe, Noelle Grosjean, ..., Christophe Mulle","url_link":"https://www.world-wide.org/fens-24/presynaptic-plasticity-memory-encoding-4332625e","nexus":"

Common Ground: Both studies focus on presynaptic mechanisms at hippocampal mossy fiber to CA3 pyramidal neuron synapses.
Key Differences: The current study examines GABAB receptor-mediated heterosynaptic depression and regulatory mechanisms via baclofen; the recommended study explores Syt7-dependent presynaptic facilitation related to memory encoding and circuit dynamics.
Methodologies: The current study uses paired patch-clamp recordings, cryo-fixation, and 2D electron microscopy; the recommended study employs conditional KO mice, hippocampal slicing, and silicon probe recordings.
Complementary Aspects: The current study elucidates GABAB receptor effects on synaptic transmission; the recommended study highlights calcium sensor roles in synaptic plasticity.
Potential Impact: Combining findings may elucidate comprehensive presynaptic modulation mechanisms and enhance understanding of synaptic plasticity in memory encoding.

"},{"abstract_id":1513,"title":"Neuromodulators trigger the formation of inhibitory boutons in hippocampus via activation of cAMP/PKA signaling","authors_mini":"Ségolène Bompierre, Seeger Deerenberg, ..., Corette Wierenga","url_link":"https://www.world-wide.org/fens-24/neuromodulators-trigger-formation-inhibitory-8d2d7693","nexus":"

Common Ground: Both studies investigate synaptic modulation in the hippocampus, focusing on the role of specific receptors and their downstream signaling pathways.
Key Differences: Current study explores GABABR-mediated heterosynaptic depression at MFB-PN synapses, while the recommended study examines neuromodulator-induced inhibitory bouton formation through cAMP/PKA signaling.
Methodologies: Current study uses patch-clamp recordings, ultrastructural analysis by cryo-fixation, and 2D electron microscopy. Recommended study employs two-photon microscopy and biosensors for cAMP/PKA dynamics in organotypic brain slices.
Complementary Aspects: Current study details GABAB receptor's effects on presynaptic vesicle dynamics; recommended study focuses on neuromodulators influencing inhibitory synapse formation via the same signaling cascade (cAMP/PKA).
Potential Impact: Combining findings may enhance understanding of presynaptic inhibition and synapse formation, suggesting convergent roles for cAMP/PKA in synaptic regulation.\n

"},{"abstract_id":4580,"title":"A novel form of endocannabinoid-mediated plasticity of tonic GABA inhibition","authors_mini":"Roberto Colangeli & Fiorenzo Conti","url_link":"https://www.world-wide.org/fens-24/novel-form-endocannabinoid-mediated-2870d16e","nexus":"

Common Ground: Both studies focus on the regulation of synaptic efficacy by targeting presynaptic mechanisms in the brain, specifically involving GABAergic inhibition.
Key Differences: The current study examines GABAB receptor-mediated heterosynaptic depression at hippocampal mossy fiber synapses, while the recommended study addresses endocannabinoid (eCB)-dependent plasticity of tonic GABA inhibition in the neocortex.
Methodologies: The current study employs paired pre-postsynaptic patch-clamp recordings, cryo-fixation, and 2D electron microscopy. The recommended study uses whole-cell patch-clamp recordings and manipulates CB1 receptor and 2-AG signaling.
Complementary Aspects: The current study provides insights into vesicular release mechanisms at hippocampal synapses, while the recommended study elucidates eCB signaling and neurosteroid action in GABAergic modulation.\n
Potential Impact: Merging findings may reveal broad mechanisms of presynaptic regulation, influencing future research on synaptic plasticity and neurotransmitter systems.\n

"},{"abstract_id":631,"title":"The role of neurotransmitter release in the formation of mossy fibre synapses","authors_mini":"Nathalie Higgs, Mizuki Tojo, ..., Laura Andreae","url_link":"https://www.world-wide.org/fens-24/role-neurotransmitter-release-formation-7b3a127e","nexus":"

Common Ground: Both studies focus on synaptic mechanisms in the hippocampus, particularly examining synaptic efficacy and formation in connections involving mossy fibers and CA3 pyramidal neurons.
Key Differences: The current study investigates GABAB receptor-mediated heterosynaptic depression at established synapses, while the recommended study explores neurotransmitter release mechanisms during synapse formation.
Methodologies: Current study uses paired patch-clamp recordings, cryo-fixation, and 2D electron microscopy in acute hippocampal slices. Recommended study employs inducible conditional mouse models to manipulate spontaneous release during development.
Complementary Aspects: While the current study elucidates presynaptic modulation at mature synapses, the recommended study provides insights into developmental processes that shape synaptic formation via neurotransmitter release.
Potential Impact: Combined findings could advance understanding of synaptic plasticity from formation to function, shaping future research on hippocampal circuitry.\n

"},{"abstract_id":4125,"title":"Group I metabotropic glutamate receptor-mediated modulation of mono- and disynaptic transmission in the human neocortex","authors_mini":"Joanna Sandle, Gábor Molnár, ..., Gábor Tamás","url_link":"https://www.world-wide.org/fens-24/group-metabotropic-glutamate-receptor-mediated-05c3e5f6","nexus":"

Common Ground: Both studies focus on synaptic modulation by different neurotransmitter receptors (GABAB and mGluR) in the brain and their impact on synaptic transmission.
Key Differences: Current study examines GABABR effects in the hippocampus using mouse models, while recommended study analyzes mGluR impacts in the neocortex using human cortical samples.
Methodologies: Current study uses paired patch-clamp recordings and 2D EM in mouse hippocampal slices; recommended study employs dual whole-cell patch clamp recordings in human neocortical layer 2/3 and parallel rat experiments.
Complementary Aspects: Findings reveal presynaptic modulation by different receptors, providing insight into specific synaptic plasticity and strength changes under distinct conditions across species and brain regions.
Potential Impact: Combined insights could lead to a broader understanding of neurotransmitter receptor roles in synaptic modulation, informing therapeutic strategies for neurological disorders.\n

"},{"abstract_id":5026,"title":"Synapsin role in presynaptic potentiation at hippocampal mossy fiber boutons","authors_mini":"Felicitas Bruentgens, Laura Moreno Velasquez, ..., Marta Orlando","url_link":"https://www.world-wide.org/fens-24/synapsin-role-presynaptic-potentiation-67b4d2ff","nexus":"

Common Ground: Both studies investigate hippocampal mossy fiber bouton (MFB) synapses and their role in synaptic plasticity.
Key Differences: Current study focuses on GABAB receptor-mediated heterosynaptic depression using baclofen. Recommended study examines synapsin's role in presynaptic potentiation using synapsin knockout mice.
Methodologies: Current study employs patch-clamp recordings, cryo-fixation, 2D electron microscopy. Recommended study uses transmission electron microscopy and local field potential recordings in synapsin knockout and wild-type mice.
Complementary Aspects: Current study provides detailed mechanisms of presynaptic inhibition; recommended study offers insights on presynaptic vesicle dynamics and plasticity.
Potential Impact: Combining these insights might reveal intricate presynaptic modulation mechanisms, informing targeted interventions for cognitive processes.

"},{"abstract_id":2757,"title":"Decreased synaptic GABAergic inhibition in the dentate gyrus of a mouse model of the neurodevelopmental disorder BBSOAS","authors_mini":"Eleonora Dallorto, Sara Bonzano, ..., Silvia De Marchis","url_link":"https://www.world-wide.org/fens-24/decreased-synaptic-gabaergic-inhibition-0d650a4b","nexus":"

Common Ground: Both studies investigate synaptic regulation in the hippocampus and its implications for neural function.
Key Differences: The current study examines GABAB receptor-mediated synaptic modulation in the mossy fiber-CA3 pathway, while the recommended study explores synaptic inhibition deficits in the dentate gyrus of a neurodevelopmental disorder model.
Methodologies: The current study uses paired patch-clamp recordings, cryo-fixation, and 2D electron microscopy. The recommended study employs in situ analyses, gene expression profiling, and electrophysiological recordings.
Complementary Aspects: The current study focuses on presynaptic mechanisms of GABAB receptors, while the recommended study highlights hippocampal inhibition deficits; both enhance understanding of synaptic regulation.
Potential Impact: Combining insights could inform therapeutic strategies for disorders involving altered hippocampal synaptic function.\n

"},{"abstract_id":5328,"title":"Two forms of presynaptic spike timing-dependent depression at entorhinal cortex-hippocampal synapses are mediated by astrocyte activity","authors_mini":"Irene Martínez Gallego, Heriberto Coatl Cuaya, Antonio Rodríguez Moreno","url_link":"https://www.world-wide.org/fens-24/forms-presynaptic-spike-timing-dependent-8ffbdd7e","nexus":"

Common Ground: Both studies investigate presynaptic mechanisms underlying synaptic modulation and plasticity in hippocampal circuits.
Key Differences: The current study focuses on GABAB receptor-mediated heterosynaptic depression at MFB-PN synapses, while the recommended study examines spike timing-dependent long-term depression (t-LTD) at EC-DG synapses.
Methodologies: The current study uses patch-clamp recordings and electron microscopy in mouse hippocampus. The recommended study employs electrophysiological recordings to characterize t-LTD and its dependency on astrocyte activity.
Complementary Aspects: Current study uncovers detailed presynaptic vesicle dynamics; recommended study identifies different t-LTD mechanisms involving NMDAR, mGluR, and astrocytes.
Potential Impact: Combining insights may clarify presynaptic regulation roles in synaptic plasticity, influencing memory and information processing research.

"}],"apa_citation":"Lin, P., Lichter, K., Okamoto, Y., & Jonas, P. (2024). Presynaptic mechanisms underlying GABAB receptor-mediated heterosynaptic depression at hippocampal mossy fiber bouton to CA3 pyramidal neuron synapses. Science Communications World Wide. doi:10.57736/86ac-cbac"}

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