@article{19498, abstract = {A dynamic interplay between fast synaptic signals and slower neuromodulatory signals controls the excitatory/inhibitory (E/I) balance within neuronal circuits. The mechanisms by which neuropeptide signaling is regulated to maintain E/I balance remain uncertain. We designed a genetic screen to isolate genes involved in the peptidergic maintenance of the E/I balance in the C. elegans motor circuit. This screen identified the C. elegans orthologs of the presynaptic phosphoprotein synapsin (snn-1) and the protein phosphatase 1 (PP1) regulatory subunit PHACTR1 (phac-1). We demonstrate that both phac-1 and snn-1 alter the motor behavior of C. elegans, and genetic interactions suggest that SNN-1 contributes to PP1-PHAC-1 holoenzyme signaling. De novo variants of human PHACTR1, associated with early-onset epilepsies [developmental and epileptic encephalopathy 70 (DEE70)], when expressed in C. elegans resulted in constitutive PP1-PHAC-1 holoenzyme activity. Unregulated PP1-PHAC-1 signaling alters the synapsin and actin cytoskeleton and increases neuropeptide release by cholinergic motor neurons, which secondarily affects the presynaptic vesicle cycle. Together, these results clarify the dominant mechanisms of action of the DEE70 alleles and suggest that altered neuropeptide release may alter E/I balance in DEE70.}, author = {Stratigi, Aikaterini and Soler-García, Miguel and Krout, Mia and Shukla, Shikha and De Bono, Mario and Richmond, Janet E. and Laurent, Patrick}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {13}, publisher = {Society for Neuroscience}, title = {{Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans}}, doi = {10.1523/JNEUROSCI.1767-23.2024}, volume = {45}, year = {2025}, } @article{18305, abstract = {Motor circuits represent the main output of the central nervous system and produce dynamic behaviors ranging from relatively simple rhythmic activities like swimming in fish and breathing in mammals to highly sophisticated dexterous movements in humans. Despite decades of research, the development and function of motor circuits remain poorly understood. Breakthroughs in the field recently provided new tools and tractable model systems that set the stage to discover the molecular mechanisms and circuit logic underlying motor control. Here, we describe recent advances from both vertebrate (mouse, frog) and invertebrate (nematode, fruit fly) systems on cellular and molecular mechanisms that enable motor circuits to develop and function and highlight conserved and divergent mechanisms necessary for motor circuit development.}, author = {Kratsios, Paschalis and Zampieri, Niccolò and Carrillo, Robert and Mizumoto, Kota and Sweeney, Lora Beatrice Jaeger and Philippidou, Polyxeni}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {40}, publisher = {Society for Neuroscience}, title = {{Molecular and cellular mechanisms of motor circuit development}}, doi = {10.1523/JNEUROSCI.1238-24.2024}, volume = {44}, year = {2024}, } @article{17092, abstract = {Memories are thought to be stored in neural ensembles known as engrams that are specifically reactivated during memory recall. Recent studies have found that memory engrams of two events that happened close in time tend to overlap in the hippocampus and the amygdala, and these overlaps have been shown to support memory linking. It has been hypothesized that engram overlaps arise from the mechanisms that regulate memory allocation itself, involving neural excitability, but the exact process remains unclear. Indeed, most theoretical studies focus on synaptic plasticity and little is known about the role of intrinsic plasticity, which could be mediated by neural excitability and serve as a complementary mechanism for forming memory engrams. Here, we developed a rate-based recurrent neural network that includes both synaptic plasticity and neural excitability. We obtained structural and functional overlap of memory engrams for contexts that are presented close in time, consistent with experimental and computational studies. We then investigated the role of excitability in memory allocation at the network level and unveiled competitive mechanisms driven by inhibition. This work suggests mechanisms underlying the role of intrinsic excitability in memory allocation and linking, and yields predictions regarding the formation and the overlap of memory engrams.}, author = {Delamare, Geoffroy and Feitosa Tomé, Douglas and Clopath, Claudia}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {21}, publisher = {Society for Neuroscience}, title = {{Intrinsic neural excitability biases allocation and overlap of memory engrams}}, doi = {10.1523/JNEUROSCI.0846-23.2024}, volume = {44}, year = {2024}, } @article{13202, abstract = {Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role in neuronal activities through interaction with various proteins involved in signaling at membranes. However, the distribution pattern of PI(4,5)P2 and the association with these proteins on the neuronal cell membranes remain elusive. In this study, we established a method for visualizing PI(4,5)P2 by SDS-digested freeze-fracture replica labeling (SDS-FRL) to investigate the quantitative nanoscale distribution of PI(4,5)P2 in cryo-fixed brain. We demonstrate that PI(4,5)P2 forms tiny clusters with a mean size of ∼1000 nm2 rather than randomly distributed in cerebellar neuronal membranes in male C57BL/6J mice. These clusters show preferential accumulation in specific membrane compartments of different cell types, in particular, in Purkinje cell (PC) spines and granule cell (GC) presynaptic active zones. Furthermore, we revealed extensive association of PI(4,5)P2 with CaV2.1 and GIRK3 across different membrane compartments, whereas its association with mGluR1α was compartment specific. These results suggest that our SDS-FRL method provides valuable insights into the physiological functions of PI(4,5)P2 in neurons.}, author = {Eguchi, Kohgaku and Le Monnier, Elodie and Shigemoto, Ryuichi}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {23}, pages = {4197--4216}, publisher = {Society for Neuroscience}, title = {{Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons}}, doi = {10.1523/JNEUROSCI.1514-22.2023}, volume = {43}, year = {2023}, } @article{14656, abstract = {Although much is known about how single neurons in the hippocampus represent an animal's position, how circuit interactions contribute to spatial coding is less well understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured CA1 cell-cell interactions in male rats during open field exploration. The statistics of these interactions depend on whether the animal is in a familiar or novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the informativeness of their spatial inputs. This structure facilitates linear decodability, making the information easy to read out by downstream circuits. Overall, our findings suggest that the efficient coding hypothesis is not only applicable to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain.}, author = {Nardin, Michele and Csicsvari, Jozsef L and Tkačik, Gašper and Savin, Cristina}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {48}, pages = {8140--8156}, publisher = {Society for Neuroscience}, title = {{The structure of hippocampal CA1 interactions optimizes spatial coding across experience}}, doi = {10.1523/JNEUROSCI.0194-23.2023}, volume = {43}, year = {2023}, } @article{9073, abstract = {The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention.}, author = {Hanganu-Opatz, Ileana L. and Butt, Simon J. B. and Hippenmeyer, Simon and De Marco García, Natalia V. and Cardin, Jessica A. and Voytek, Bradley and Muotri, Alysson R.}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, keywords = {General Neuroscience}, number = {5}, pages = {813--822}, publisher = {Society for Neuroscience}, title = {{The logic of developing neocortical circuits in health and disease}}, doi = {10.1523/jneurosci.1655-20.2020}, volume = {41}, year = {2021}, } @article{10051, abstract = {Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics during high-frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in BCs of RIM-BP2-deficient mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization.}, author = {Butola, Tanvi and Alvanos, Theocharis and Hintze, Anika and Koppensteiner, Peter and Kleindienst, David and Shigemoto, Ryuichi and Wichmann, Carolin and Moser, Tobias}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {37}, pages = {7742--7767}, publisher = {Society for Neuroscience}, title = {{RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse}}, doi = {10.1523/JNEUROSCI.0586-21.2021}, volume = {41}, year = {2021}, } @article{7339, abstract = {Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin) dynamically support cell structure and functions. In central presynaptic terminals, F-actin is expressed along the release edge and reportedly plays diverse functional roles, but whether axonal MTs extend deep into terminals and play any physiological role remains controversial. At the calyx of Held in rats of either sex, confocal and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological analysis demonstrated that depolymerization of MTs specifically prolonged the slow-recovery time component of EPSCs from short-term depression induced by a train of high-frequency stimulation, whereas depolymerization of F-actin specifically prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic action potential recordings, depolymerization of MTs or F-actin significantly impaired the fidelity of high-frequency neurotransmission. We conclude that MTs and F-actin differentially contribute to slow and fast SV replenishment, thereby maintaining high-frequency neurotransmission.}, author = {Piriya Ananda Babu, Lashmi and Wang, Han Ying and Eguchi, Kohgaku and Guillaud, Laurent and Takahashi, Tomoyuki}, issn = {1529-2401}, journal = {Journal of neuroscience}, number = {1}, pages = {131--142}, publisher = {Society for Neuroscience}, title = {{Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission}}, doi = {10.1523/JNEUROSCI.1571-19.2019}, volume = {40}, year = {2020}, } @article{7908, abstract = {Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.}, author = {Wang, Han Ying and Eguchi, Kohgaku and Yamashita, Takayuki and Takahashi, Tomoyuki}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {21}, pages = {4103--4115}, publisher = {Society for Neuroscience}, title = {{Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms}}, doi = {10.1523/JNEUROSCI.2946-19.2020}, volume = {40}, year = {2020}, } @article{8084, abstract = {Origin and functions of intermittent transitions among sleep stages, including brief awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing sleep on scales of seconds and minutes results from intrinsic non-equilibrium critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms exhibit complex temporal organization, with long-range correlations and robust duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, features typical of non-equilibrium systems self-organizing at criticality. We show that such non-equilibrium behavior relates to anti-correlated coupling between θ- and δ-bursts, persists across a range of time scales, and is independent of the dominant physiologic state; indications of a basic principle in sleep regulation. Further, we find that VLPO lesions lead to a modulation of cortical dynamics resulting in altered dynamical parameters of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings and model simulations demonstrate that θ–δ coupling is essential for the emerging non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate that VLPO neurons may have dual role for both sleep and arousal/brief wake activation. The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates a mechanism essential for the micro-architecture of spontaneous sleep-stage and arousal transitions within a novel, non-homeostatic paradigm of sleep regulation.}, author = {Lombardi, Fabrizio and Gómez-Extremera, Manuel and Bernaola-Galván, Pedro and Vetrivelan, Ramalingam and Saper, Clifford B. and Scammell, Thomas E. and Ivanov, Plamen Ch.}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {1}, pages = {171--190}, publisher = {Society for Neuroscience}, title = {{Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake}}, doi = {10.1523/jneurosci.1278-19.2019}, volume = {40}, year = {2020}, } @article{8126, abstract = {Cortical areas comprise multiple types of inhibitory interneurons with stereotypical connectivity motifs, but their combined effect on postsynaptic dynamics has been largely unexplored. Here, we analyse the response of a single postsynaptic model neuron receiving tuned excitatory connections alongside inhibition from two plastic populations. Depending on the inhibitory plasticity rule, synapses remain unspecific (flat), become anti-correlated to, or mirror excitatory synapses. Crucially, the neuron’s receptive field, i.e., its response to presynaptic stimuli, depends on the modulatory state of inhibition. When both inhibitory populations are active, inhibition balances excitation, resulting in uncorrelated postsynaptic responses regardless of the inhibitory tuning profiles. Modulating the activity of a given inhibitory population produces strong correlations to either preferred or non-preferred inputs, in line with recent experimental findings showing dramatic context-dependent changes of neurons’ receptive fields. We thus confirm that a neuron’s receptive field doesn’t follow directly from the weight profiles of its presynaptic afferents.}, author = {Agnes, Everton J. and Luppi, Andrea I. and Vogels, Tim P}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {50}, pages = {9634--9649}, publisher = {Society for Neuroscience}, title = {{Complementary inhibitory weight profiles emerge from plasticity and allow attentional switching of receptive fields}}, doi = {10.1523/JNEUROSCI.0276-20.2020}, volume = {40}, year = {2020}, } @article{2018, abstract = {Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic segments of target neurons. However, the neural circuits and functional roles of netrin-G isoform complexes remain unclear. Here, we use netrin-G-KO and NGL-KO mice to reveal that netrin-G1/NGL1 and netrin-G2/NGL2 interactions specify excitatory synapses in independent hippocampal pathways. In the hippocampal CA1 area, netrin-G1/NGL1 and netrin-G2/NGL2 were expressed in the temporoammonic and Schaffer collateral pathways, respectively. The lack of presynaptic netrin-Gs led to the dispersion of NGLs from postsynaptic membranes. In accord, netrin-G mutant synapses displayed opposing phenotypes in long-term and short-term plasticity through discrete biochemical pathways. The plasticity phenotypes in netrin-G-KOs were phenocopied in NGL-KOs, with a corresponding loss of netrin-Gs from presynaptic membranes. Our findings show that netrin-G/NGL interactions differentially control synaptic plasticity in distinct circuits via retrograde signaling mechanisms and explain how synaptic inputs are diversified to control neuronal activity.}, author = {Matsukawa, Hiroshi and Akiyoshi Nishimura, Sachiko and Zhang, Qi and Luján, Rafael and Yamaguchi, Kazuhiko and Goto, Hiromichi and Yaguchi, Kunio and Hashikawa, Tsutomu and Sano, Chie and Shigemoto, Ryuichi and Nakashiba, Toshiaki and Itohara, Shigeyoshi}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {47}, pages = {15779 -- 15792}, publisher = {Society for Neuroscience}, title = {{Netrin-G/NGL complexes encode functional synaptic diversification}}, doi = {10.1523/JNEUROSCI.1141-14.2014}, volume = {34}, year = {2014}, } @article{3826, abstract = {Gamma frequency (30-100 Hz) oscillations in the mature cortex underlie higher cognitive functions. Fast signaling in GABAergic interneuron networks plays a key role in the generation of these oscillations. During development of the rodent brain, gamma activity appears at the end of the first postnatal week, but frequency and synchrony reach adult levels only by the fourth week. However, the mechanisms underlying the maturation of gamma activity are unclear. Here we demonstrate that hippocampal basket cells (BCs), the proposed cellular substrate of gamma oscillations, undergo marked changes in their morphological, intrinsic, and synaptic properties between postnatal day 6 (P6) and P25. During maturation, action potential duration, propagation time, duration of the release period, and decay time constant of IPSCs decreases by approximately 30-60%. Thus, postnatal development converts BCs from slow into fast signaling devices. Computational analysis reveals that BC networks with young intrinsic and synaptic properties as well as reduced connectivity generate oscillations with moderate coherence in the lower gamma frequency range. In contrast, BC networks with mature properties and increased connectivity generate highly coherent activity in the upper gamma frequency band. Thus, late postnatal maturation of BCs enhances coherence in neuronal networks and will thereby contribute to the development of cognitive brain functions.}, author = {Doischer, Daniel and Hosp, Jonas and Yanagawa, Yuchio and Obata, Kunihiko and Jonas, Peter M and Vida, Imre and Bartos, Marlene}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {48}, pages = {12956 -- 68}, publisher = {Society for Neuroscience}, title = {{Postnatal differentiation of basket cells from slow to fast signaling devices}}, doi = {10.1523/JNEUROSCI.2890-08.2008}, volume = {28}, year = {2008}, } @article{3804, abstract = {Kv3 channels are thought to be essential for the fast-spiking (FS) phenotype in GABAergic interneurons, but how these channels confer the ability to generate action potentials (APs) at high frequency is unknown. To address this question, we developed a fast dynamic-clamp system (approximately 50 kHz) that allowed us to add a Kv3 model conductance to CA1 oriens alveus (OA) interneurons in hippocampal slices. Selective pharmacological block of Kv3 channels by 0.3 mm 4-aminopyridine or 1 mm tetraethylammonium ions led to a marked broadening of APs during trains of short stimuli and a reduction in AP frequency during 1 sec stimuli. The addition of artificial Kv3 conductance restored the original AP pattern. Subtraction of Kv3 conductance by dynamic clamp mimicked the effects of the blockers. Application of artificial Kv3 conductance also led to FS in OA interneurons after complete K+ channel block and even induced FS in hippocampal pyramidal neurons in the absence of blockers. Adding artificial Kv3 conductance with altered deactivation kinetics revealed a nonmonotonic relationship between mean AP frequency and deactivation rate, with a maximum slightly above the original value. Insertion of artificial Kv3 conductance with either lowered activation threshold or inactivation also led to a reduction in the mean AP frequency. However, the mechanisms were distinct. Shifting the activation threshold induced adaptation, whereas adding inactivation caused frequency-dependent AP broadening. In conclusion, Kv3 channels are necessary for the FS phenotype of OA interneurons, and several of their gating properties appear to be optimized for high-frequency repetitive activity.}, author = {Lien, Cheng and Jonas, Peter M}, issn = {1529-2401}, journal = {Journal of Neuroscience}, keywords = {Kv3 channels, dynamic clamp, fast spiking, deactivation kinetics, OA interneurons, hippocampal slices, two electrode current clamp}, number = {6}, pages = {2058 -- 68}, publisher = {Society for Neuroscience}, title = {{Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons}}, doi = {10.1523/JNEUROSCI.23-06-02058.2003}, volume = {23}, year = {2003}, } @article{2635, abstract = {Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically. Using preembedding immunohistochemical methods combined with quantitative analysis of GABAB receptor subunit immunoreactivity, this study provides a detailed description of the cellular and subcellular localization of GABAB1a/b and GABA B2 in the rat hippocampus. At the light microscopic level, an overlapping distribution of GABAB1a/b and GABAB2 was revealed in the dendritic layers of the hippocampus. In addition, expression of the GABAB1a/b subunit was found in somata of CA1 pyramidal cells and of a subset of GABAergic interneurons. At the electron microscopic level, immunoreactivity for both subunits was observed on presynaptic and, more abundantly, on postsynaptic elements. Presynaptically, subunits were mainly detected in the extrasynaptic membrane and occasionally over the presynaptic membrane specialization of putative glutamatergic and, to a lesser extent, GABAergic axon terminals. Postsynaptically, the majority of GABAB receptor subunits were localized to the extrasynaptic plasma membrane of spines and dendritic shafts of principal cells and shafts of interneuron dendrites. Quantitative analysis revealed enrichment of GABAB1a/b around putative glutamatergic synapses on spines and an even distribution on dendritic shafts of pyramidal cells contacted by GABAergic boutons. The association of GABAB receptors with glutamatergic synapses at both presynaptic and postsynaptic sides indicates their intimate involvement in the modulation of glutamatergic neurotransmission. The dominant extrasynaptic localization of GABAB receptor subunits suggests that their activation is dependent on spillover of GABA requiring simultaneous activity of populations of GABAergic cells as it occurs during population oscillations or epileptic seizures.}, author = {Kulik, Ákos and Vida, Imre and Luján, Rafael and Haas, Carola and López Bendito, Guillermina and Shigemoto, Ryuichi and Frotscher, Michael}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {35}, pages = {11026 -- 11035}, publisher = {Society for Neuroscience}, title = {{Subcellular Localization of Metabotropic GABAB Receptor Subunits GABAB1a/b and GABAB2 in the Rat Hippocampus}}, doi = {10.1523/JNEUROSCI.23-35-11026.2003}, volume = {23}, year = {2003}, }