@article{23003, abstract = {The peripheral neural pathways that relay oral and post-ingestive chemo- and mechanosensory signals to the brain during food consumption are increasingly well understood. Far less is known about how these and other body signals are integrated and organized in the brainstem lateral parabrachial nucleus (LPBN), a key interoceptive sensory hub. We established methods for dense calcium imaging of 100s of neurons from mouse LPBN. Food consumption drove a seconds-long wave of activity across LPBN, with dynamics mirroring the movement of food through the upper gastrointestinal tract as observed using X-ray videofluoroscopy. By imaging the same neurons across days, we found that spatially clustered subsets of neurons encoded oral signals, stomach filling, visceral malaise, arousal, and/or body movement. Moreover, only certain subsets were modulated by cortical input. Together, these experiments establish a platform for understanding how peripheral and central interoceptive signals are integrated in the brainstem to guide behavior.}, author = {Essner, Rachel A. and Ruda, Kiersten and Choh, Hannah J. and Kücükdereli, Hakan and Amsalem, Oren and Edelhaus, Julia and Chahyadinata, Gracesenia and Grødem, Sverre and Lensjø, Kristian K. and Lever, Teresa E. and Andermann, Mark L.}, issn = {1097-4199}, journal = {Neuron}, publisher = {Cell Press}, title = {{Brainstem sensing of multiple body signals during food consumption}}, doi = {10.1016/j.neuron.2026.08.015}, year = {2026}, } @article{19506, abstract = {Hippocampal reactivation of waking neuronal assemblies in sleep is a key initial step of systems consolidation. Nevertheless, it is unclear whether reactivated assemblies are static or whether they reorganize gradually over prolonged sleep. We tracked reactivated CA1 assembly patterns over ∼20 h of sleep/rest periods and related them to assemblies seen before or after in a spatial learning paradigm using rats. We found that reactivated assembly patterns were gradually transformed and started to resemble those seen in the subsequent recall session. Periods of rapid eye movement (REM) sleep and non-REM (NREM) had antagonistic roles: whereas NREM accelerated the assembly drift, REM countered it. Moreover, only a subset of rate-changing pyramidal cells contributed to the drift, whereas stable-firing-rate cells maintained unaltered reactivation patterns. Our data suggest that prolonged sleep promotes the spontaneous reorganization of spatial assemblies, which can contribute to daily cognitive map changes or encoding new learning situations.}, author = {Bollmann, Lars and Baracskay, Peter and Stella, Federico and Csicsvari, Jozsef L}, issn = {1097-4199}, journal = {Neuron}, number = {9}, pages = {1446--1459.e6}, publisher = {Cell Press}, title = {{Sleep stages antagonistically modulate reactivation drift}}, doi = {10.1016/j.neuron.2025.02.025}, volume = {113}, year = {2025}, } @article{15381, abstract = {Cholecystokinin-expressing interneurons (CCKIs) are hypothesized to shape pyramidal cell-firing patterns and regulate network oscillations and related network state transitions. To directly probe their role in the CA1 region, we silenced their activity using optogenetic and chemogenetic tools in mice. Opto-tagged CCKIs revealed a heterogeneous population, and their optogenetic silencing triggered wide disinhibitory network changes affecting both pyramidal cells and other interneurons. CCKI silencing enhanced pyramidal cell burst firing and altered the temporal coding of place cells: theta phase precession was disrupted, whereas sequence reactivation was enhanced. Chemogenetic CCKI silencing did not alter the acquisition of spatial reference memories on the Morris water maze but enhanced the recall of contextual fear memories and enabled selective recall when similar environments were tested. This work suggests the key involvement of CCKIs in the control of place-cell temporal coding and the formation of contextual memories.}, author = {Rangel Guerrero, Dámaris K and Balueva, Kira and Barayeu, Uladzislau and Baracskay, Peter and Gridchyn, Igor and Nardin, Michele and Roth, Chiara N and Wulff, Peer and Csicsvari, Jozsef L}, issn = {1097-4199}, journal = {Neuron}, number = {12}, pages = {2045--2061.e10}, publisher = {Cell Press}, title = {{Hippocampal cholecystokinin-expressing interneurons regulate temporal coding and contextual learning}}, doi = {10.1016/j.neuron.2024.03.019}, volume = {112}, 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}, } @article{12542, abstract = {In this issue of Neuron, Espinosa-Medina et al.1 present the TEMPO (Temporal Encoding and Manipulation in a Predefined Order) system, which enables the marking and genetic manipulation of sequentially generated cell lineages in vertebrate species in vivo.}, author = {Villalba Requena, Ana and Hippenmeyer, Simon}, issn = {1097-4199}, journal = {Neuron}, number = {3}, pages = {291--293}, publisher = {Elsevier}, title = {{Going back in time with TEMPO}}, doi = {10.1016/j.neuron.2023.01.006}, volume = {111}, year = {2023}, } @article{10753, abstract = {This is a comment on "Meta-learning synaptic plasticity and memory addressing for continual familiarity detection." Neuron. 2022 Feb 2;110(3):544-557.e8.}, author = {Confavreux, Basile J and Vogels, Tim P}, issn = {1097-4199}, journal = {Neuron}, number = {3}, pages = {361--362}, publisher = {Elsevier}, title = {{A familiar thought: Machines that replace us?}}, doi = {10.1016/j.neuron.2022.01.014}, volume = {110}, year = {2022}, } @article{8544, abstract = {The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis.}, author = {Takeo, Yukari H. and Shuster, S. Andrew and Jiang, Linnie and Hu, Miley and Luginbuhl, David J. and Rülicke, Thomas and Contreras, Ximena and Hippenmeyer, Simon and Wagner, Mark J. and Ganguli, Surya and Luo, Liqun}, issn = {1097-4199}, journal = {Neuron}, number = {4}, pages = {P629--644.E8}, publisher = {Elsevier}, title = {{GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells}}, doi = {10.1016/j.neuron.2020.11.028}, volume = {109}, year = {2021}, } @article{9793, abstract = {Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate developmental processes among one another to parse out the synaptic neuropil and form non-overlapping territories is unknown. Here we identify a molecular mechanism regulating astrocyte-astrocyte interactions during development to coordinate astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked, astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for territory and morphological complexity in the developing mouse cortex. Furthermore, conditional deletion of Hepacam from developing astrocytes significantly impairs gap junction coupling between astrocytes and disrupts the balance between synaptic excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy with subcortical cysts in humans. Therefore, our findings suggest that disruption of astrocyte self-organization mechanisms could be an underlying cause of neural pathology.}, author = {Baldwin, Katherine T. and Tan, Christabel X. and Strader, Samuel T. and Jiang, Changyu and Savage, Justin T. and Elorza-Vidal, Xabier and Contreras, Ximena and Rülicke, Thomas and Hippenmeyer, Simon and Estévez, Raúl and Ji, Ru-Rong and Eroglu, Cagla}, issn = {1097-4199}, journal = {Neuron}, number = {15}, pages = {2427--2442.e10}, publisher = {Elsevier}, title = {{HepaCAM controls astrocyte self-organization and coupling}}, doi = {10.1016/j.neuron.2021.05.025}, volume = {109}, year = {2021}, } @article{7684, author = {Gridchyn, Igor and Schönenberger, Philipp and O'Neill, Joseph and Csicsvari, Jozsef L}, issn = {1097-4199}, journal = {Neuron}, number = {2}, pages = {291--300.e6}, publisher = {Elsevier}, title = {{Assembly-specific disruption of hippocampal replay leads to selective memory deficit}}, doi = {10.1016/j.neuron.2020.01.021}, volume = {106}, year = {2020}, } @article{8674, abstract = {Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localization reveal that LTP induction thus prompts spatial retreat of astroglial glutamate transporters, boosting glutamate spillover and NMDA-receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which a memory trace at one synapse could alter signal handling by multiple neighboring connections.}, author = {Henneberger, Christian and Bard, Lucie and Panatier, Aude and Reynolds, James P. and Kopach, Olga and Medvedev, Nikolay I. and Minge, Daniel and Herde, Michel K. and Anders, Stefanie and Kraev, Igor and Heller, Janosch P. and Rama, Sylvain and Zheng, Kaiyu and Jensen, Thomas P. and Sanchez-Romero, Inmaculada and Jackson, Colin J. and Janovjak, Harald L and Ottersen, Ole Petter and Nagelhus, Erlend Arnulf and Oliet, Stephane H.R. and Stewart, Michael G. and Nägerl, U. VAlentin and Rusakov, Dmitri A. }, issn = {1097-4199}, journal = {Neuron}, number = {5}, pages = {P919--936.E11}, publisher = {Elsevier}, title = {{LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia}}, doi = {10.1016/j.neuron.2020.08.030}, volume = {108}, year = {2020}, } @article{6454, abstract = {Adult neural stem cells and multiciliated ependymalcells are glial cells essential for neurological func-tions. Together, they make up the adult neurogenicniche. Using both high-throughput clonal analysisand single-cell resolution of progenitor division pat-terns and fate, we show that these two componentsof the neurogenic niche are lineally related: adult neu-ral stem cells are sister cells to ependymal cells,whereas most ependymal cells arise from the termi-nal symmetric divisions of the lineage. Unexpectedly,we found that the antagonist regulators of DNA repli-cation, GemC1 and Geminin, can tune the proportionof neural stem cells and ependymal cells. Our find-ings reveal the controlled dynamic of the neurogenicniche ontogeny and identify the Geminin familymembers as key regulators of the initial pool of adultneural stem cells.}, author = {Ortiz-Álvarez, G and Daclin, M and Shihavuddin, A and Lansade, P and Fortoul, A and Faucourt, M and Clavreul, S and Lalioti, ME and Taraviras, S and Hippenmeyer, Simon and Livet, J and Meunier, A and Genovesio, A and Spassky, N}, issn = {1097-4199}, journal = {Neuron}, number = {1}, pages = {159--172.e7}, publisher = {Elsevier}, title = {{Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the Geminin family members}}, doi = {10.1016/j.neuron.2019.01.051}, volume = {102}, year = {2019}, } @article{6830, author = {Contreras, Ximena and Hippenmeyer, Simon}, issn = {1097-4199}, journal = {Neuron}, number = {5}, pages = {750--752}, publisher = {Elsevier}, title = {{Memo1 tiles the radial glial cell grid}}, doi = {10.1016/j.neuron.2019.08.021}, volume = {103}, year = {2019}, } @article{1546, abstract = {Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.}, author = {Nakamura, Yukihiro and Harada, Harumi and Kamasawa, Naomi and Matsui, Ko and Rothman, Jason and Shigemoto, Ryuichi and Silver, R Angus and Digregorio, David and Takahashi, Tomoyuki}, issn = {1097-4199}, journal = {Neuron}, number = {1}, pages = {145 -- 158}, publisher = {Elsevier}, title = {{Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development}}, doi = {10.1016/j.neuron.2014.11.019}, volume = {85}, year = {2015}, } @article{1791, abstract = {Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing brain is a powerful technique to study genetic function; however, discrepancies between knockdown and knockout murine phenotypes have left unanswered questions. For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical neuronal migration phenotype. Here we report that in utero electroporation of shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx knockouts akin to the effect in wild-type mice, suggestingshRNA-mediated off-target toxicity. This effect wasnot limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-specific effect. Profiling RNAs from electroporated cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or Dicer recapitulated the migration defect. The results suggest that shRNA-mediated knockdown can produce untoward migration effects by altering endogenous miRNA pathways.}, author = {Baek, Seungtae and Kerjan, Géraldine and Bielas, Stephanie and Lee, Jieun and Fenstermaker, Ali and Novarino, Gaia and Gleeson, Joseph}, issn = {1097-4199}, journal = {Neuron}, number = {6}, pages = {1255 -- 1262}, publisher = {Elsevier}, title = {{Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation}}, doi = {10.1016/j.neuron.2014.04.036}, volume = {82}, year = {2014}, } @article{3823, abstract = {Two studies in this issue of Neuron (Kwon and Castillo and Rebola et al.) show that the mossy fiber-CA3 pyramidal neuron synapse, a hippocampal synapse well known for its presynaptic plasticity, exhibits a novel form of long-term potentiation of NMDAR-mediated currents, which is induced and expressed postsynaptically.}, author = {Kerr, Angharad and Jonas, Peter M}, issn = {1097-4199}, journal = {Neuron}, number = {1}, pages = {5 -- 7}, publisher = {Elsevier}, title = {{The two sides of hippocampal mossy fiber plasticity (Review)}}, doi = {10.1016/j.neuron.2007.12.015}, volume = {57}, year = {2008}, } @article{3824, abstract = {It is generally thought that transmitter release at mammalian central synapses is triggered by Ca2+ microdomains, implying loose coupling between presynaptic Ca2+ channels and Ca2+ sensors of exocytosis. Here we show that Ca2+ channel subunit immunoreactivity is highly concentrated in the active zone of GABAergic presynaptic terminals of putative parvalbumin-containing basket cells in the hippocampus. Paired recording combined with presynaptic patch pipette perfusion revealed that GABA release at basket cell-granule cell synapses is sensitive to millimolar concentrations of the fast Ca2+ chelator BAPTA but insensitive to the slow Ca2+ chelator EGTA. These results show that Ca2+ source and Ca2+ sensor are tightly coupled at this synapse, with distances in the range of 10-20 nm. Models of Ca2+ inflow-exocytosis coupling further reveal that the tightness of coupling increases efficacy, speed, and temporal precision of transmitter release. Thus, tight coupling contributes to fast feedforward and feedback inhibition in the hippocampal network.}, author = {Bucurenciu, Iancu and Kulik, Ákos and Schwaller, Beat and Frotscher, Michael and Jonas, Peter M}, issn = {1097-4199}, journal = {Neuron}, number = {4}, pages = {536 -- 45}, publisher = {Elsevier}, title = {{Nanodomain coupling between Ca(2+) channels and Ca2+ sensors promotes fast and efficient transmitter release at a cortical GABAergic synapse}}, doi = {10.1016/j.neuron.2007.12.026}, volume = {57}, year = {2008}, } @article{3811, abstract = {Networks of GABAergic neurons are key elements in the generation of gamma oscillations in the brain. Computational studies suggested that the emergence of coherent oscillations requires hyperpolarizing inhibition. Here, we show that GABA(A) receptor-mediated inhibition in mature interneurons of the hippocampal dentate gyrus is shunting rather than hyperpolarizing. Unexpectedly, when shunting inhibition is incorporated into a structured interneuron network model with fast and strong synapses, coherent oscillations emerge. In comparison to hyperpolarizing inhibition, networks with shunting inhibition show several advantages. First, oscillations are generated with smaller tonic excitatory drive. Second, network frequencies are tuned to the gamma band. Finally, robustness against heterogeneity in the excitatory drive is markedly improved. In single interneurons, shunting inhibition shortens the interspike interval for low levels of drive but prolongs it for high levels, leading to homogenization of neuronal firing rates. Thus, shunting inhibition may confer increased robustness to gamma oscillations in the brain.}, author = {Vida, Imre and Bartos, Marlene and Jonas, Peter M}, issn = {1097-4199}, journal = {Neuron}, number = {1}, pages = {107 -- 17}, publisher = {Elsevier}, title = {{Shunting inhibition improves robustness of gamma oscillations in hippocampal interneuron networks by homogenizing firing rates}}, doi = {10.1016/j.neuron.2005.11.036}, volume = {49}, year = {2006}, } @article{3522, abstract = {We observed sharp wave/ripples (SWR) during exploration within brief (< 2.4 s) interruptions of or during theta oscillations. CA1 network responses of SWRs occurring during exploration (eSWR) and SWRs detected in waking immobility or sleep were similar. However, neuronal activity during eSWR was location dependent, and eSWR-related firing was stronger inside the place field than outside. The eSPW-related firing increase was stronger than the baseline increase inside compared to outside, suggesting a “supralinear” summation of eSWR and place-selective inputs. Pairs of cells with similar place fields and/or correlated firing during exploration showed stronger coactivation during eSWRs and subsequent sleep-SWRs. Sequential activation of place cells was not required for the reactivation of waking co-firing patterns; cell pairs with symmetrical cross-correlations still showed reactivated waking co-firing patterns during sleep-SWRs. We suggest that place-selective firing during eSWRs facilitates initial associations between cells with similar place fields that enable place-related ensemble patterns to recur during subsequent sleep-SWRs.}, author = {O'Neill, Joseph and Senior, Timothy and Csicsvari, Jozsef L}, issn = {1097-4199}, journal = {Neuron}, number = {1}, pages = {143 -- 155}, publisher = {Elsevier}, title = {{Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior}}, doi = {10.1016/j.neuron.2005.10.037}, volume = {49}, year = {2006}, } @article{3808, abstract = {Action potentials in central neurons are initiated near the axon initial segment, propagate into the axon, and finally invade the presynaptic terminals, where they trigger transmitter release. Voltage-gated Na(+) channels are key determinants of excitability, but Na(+) channel density and properties in axons and presynaptic terminals of cortical neurons have not been examined yet. In hippocampal mossy fiber boutons, which emerge from parent axons en passant, Na(+) channels are very abundant, with an estimated number of approximately 2000 channels per bouton. Presynaptic Na(+) channels show faster inactivation kinetics than somatic channels, suggesting differences between subcellular compartments of the same cell. Computational analysis of action potential propagation in axon-multibouton structures reveals that Na(+) channels in boutons preferentially amplify the presynaptic action potential and enhance Ca(2+) inflow, whereas Na(+) channels in axons control the reliability and speed of propagation. Thus, presynaptic and axonal Na(+) channels contribute differentially to mossy fiber synaptic transmission.}, author = {Engel, Dominique and Jonas, Peter M}, issn = {1097-4199}, journal = {Neuron}, number = {3}, pages = {405 -- 17}, publisher = {Elsevier}, title = {{Presynaptic action potential amplification by voltage-gated Na+ channels in hippocampal mossy fiber boutons}}, doi = {10.1016/j.neuron.2004.12.048 }, volume = {45}, year = {2005}, } @article{3528, abstract = {Gamma frequency oscillations (30-100 Hz) have been suggested to underlie various cognitive and motor functions. Here, we examine the generation of gamma oscillation currents in the hippocampus, using two-dimensional, 96-site silicon probes. Two gamma generators were identified, one in the dentate gyrus and another in the CA3-CA1 regions. The coupling strength between the two oscillators varied during both theta and nontheta states. Both pyramidal cells and interneurons were phase-locked to gamma waves. Anatomical connectivity, rather than physical distance, determined the coupling strength of the oscillating neurons. CA3 pyramidal neurons discharged CA3 and CA1 interneurons at latencies indicative of monosynaptic connections. Intrahippocampal gamma oscillation emerges in the CA3 recurrent system, which entrains the CA1 region via its interneurons.}, author = {Csicsvari, Jozsef L and Jamieson, Brian and Wise, Kensall and Buzsáki, György}, issn = {1097-4199}, journal = {Neuron}, number = {2}, pages = {311 -- 322}, publisher = {Elsevier}, title = {{Mechanisms of gamma oscillations in the hippocampus of the behaving rat}}, doi = {10.1016/S0896-6273(02)01169-8}, volume = {37}, year = {2003}, }