@article{22229,
  abstract     = {Hippocampal CA3 pyramidal neurons (PNs) form the largest autoassociative network in the mammalian brain. Whether CA3–CA3 recurrent connectivity is genetically preconfigured or environmentally shaped during ongoing memory storage is currently unknown. To address this question, we performed multicellular patch-clamp-based circuit mapping of up to eight CA3 PNs in the mouse hippocampus at multiple postnatal time points (P7–8, P18–25, and P45–50). Here, we show that the hippocampal CA3 network undergoes a developmental transformation from local, dense, and random connectivity to a distributed, sparse, and structured configuration. Thus, sparse and structured connectivity may emerge via experience-dependent mechanisms. In parallel, the strength of single synapses is downregulated; single synaptic events are sufficient to trigger postsynaptic spiking early in development, whereas spatial summation of several inputs is required at later time points. Biologically inspired models of memory storage by Hebbian synaptic plasticity and retrieval via pattern completion suggest that developmental changes improve specific aspects of memory storage and retrieval. Our results imply a developmental transformation of the neuronal code and the memory functions in the hippocampal CA3 network.</jats:p>},
  author       = {Vargas Barroso, Victor M and Watson, Jake and Navas Olivé, Andrea C and Schlögl, Alois and Jonas, Peter M},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit}},
  doi          = {10.1038/s41467-026-71914-x},
  volume       = {17},
  year         = {2026},
}

@misc{21442,
  author       = {Schlögl, Alois},
  keywords     = {hypocampus, ca3 simulations, modelling},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{CA3Simu v1.06 (vargas2026v1)}},
  doi          = {10.15479/AT-ISTA-21442},
  year         = {2026},
}

@phdthesis{22735,
  author       = {Lin, Peipeng},
  isbn         = {978-3-99078-088-6},
  issn         = {2663-337X},
  pages        = {88},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses}},
  doi          = {10.15479/AT-ISTA-22735},
  year         = {2026},
}

@phdthesis{22775,
  author       = {Jamrichova, Silvia},
  isbn         = {978-3-99078-085-5},
  issn         = {2663-337X},
  pages        = {153},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Timing and strength of synaptic transmission at hippocampal mossy fiber synapses in mice and humans}},
  doi          = {10.15479/AT-ISTA-22775},
  year         = {2026},
}

@article{20099,
  abstract     = {The hippocampus, critical for learning and memory, is dogmatically described as a trisynaptic circuit where dentate gyrus granule cells (GCs), CA3 pyramidal neurons (PNs), and CA1 PNs are serially connected. However, CA3 also forms an autoassociative network, and its PNs have diverse morphologies, intrinsic properties, and GC input levels. How PN subtypes compose this recurrent network is unknown. To determine the synaptic arrangement of identified CA3 PNs, we combine multicellular patch-clamp recording and post hoc morphological analysis in mouse hippocampal slices. PNs can be divided into distinct “superficial” and “deep” subclasses, the latter including previously reported “athorny” cells. Subclasses have distinct input-output transformations and asymmetric connectivity, which is more abundant from superficial to deep PNs, splitting CA3 locally into two parallel recurrent networks. Coincident spontaneous inhibition occurs frequently within but not between subclasses, implying subclass-specific inhibitory innervation. Our results suggest two separately controlled sublayers for parallel information processing in hippocampal CA3.},
  author       = {Watson, Jake and Vargas Barroso, Victor M and Jonas, Peter M},
  issn         = {2211-1247},
  journal      = {Cell Reports},
  number       = {8},
  publisher    = {Cell Press},
  title        = {{Cell-specific wiring routes information flow through hippocampal CA3}},
  doi          = {10.1016/j.celrep.2025.116080},
  volume       = {44},
  year         = {2025},
}

@article{18603,
  abstract     = {It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse.},
  author       = {Kim, Olena and Okamoto, Yuji and Kaufmann, Walter and Brose, Nils and Shigemoto, Ryuichi and Jonas, Peter M},
  issn         = {1545-7885},
  journal      = {PLoS Biology},
  number       = {11},
  publisher    = {Public Library of Science},
  title        = {{Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons}},
  doi          = {10.1371/journal.pbio.3002879},
  volume       = {22},
  year         = {2024},
}

@article{15117,
  abstract     = {The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.},
  author       = {Vandael, David H and Jonas, Peter M},
  issn         = {1095-9203},
  journal      = {Science},
  number       = {6687},
  pages        = {eadg6757},
  publisher    = {AAAS},
  title        = {{Structure, biophysics, and circuit function of a "giant" cortical presynaptic terminal}},
  doi          = {10.1126/science.adg6757},
  volume       = {383},
  year         = {2024},
}

@article{14843,
  abstract     = {The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.},
  author       = {Chen, JingJing and Kaufmann, Walter and Chen, Chong and Arai, Itaru and Kim, Olena and Shigemoto, Ryuichi and Jonas, Peter M},
  issn         = {1097-4199},
  journal      = {Neuron},
  number       = {5},
  pages        = {755--771.e9},
  publisher    = {Elsevier},
  title        = {{Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse}},
  doi          = {10.1016/j.neuron.2023.12.002},
  volume       = {112},
  year         = {2024},
}

@phdthesis{15101,
  abstract     = {The coupling between presynaptic Ca2+ channels and release sensors is a key factor that
determines speed and efficacy of synapse transmission. At some excitatory synapses,
channel–sensor coupling becomes tighter during development, and tightening is often
associated with a switch in the reliance on different Ca2+ channel subtypes. However, the
coupling topography at many synapses remains unknown, and it is unclear how it changes
during development. To address this question, we analyzed the coupling configuration at the
cerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,
combining biophysical analysis, structural analysis, and modeling.
Quantal analysis of BC–PC indicated that release probability decreased, while the
number of functional sites increased during development. Although transmitter release
persistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects
of the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased
during development, indicative of tightening of source-sensor coupling. Furthermore,
presynaptic action potentials became shorter during development, suggesting reduced
efficacy of Ca2+ channel activation.
Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron
microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters
throughout development, whereas docked vesicles were only clustered at later
developmental stages. The number of functional release sites correlated better with the AZ
number early in development, but match better with the Ca2+ channel cluster number at later
stages.
Modeling suggested a developmental transformation from a more random to a more
clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches
a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic
transmission.},
  author       = {Chen, JingJing},
  issn         = {2663-337X},
  pages        = {84},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse}},
  doi          = {10.15479/at:ista:15101},
  year         = {2024},
}