Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors

An anti-Hebbian form of LTP is observed at excitatory synapses made with some hippocampal interneurons. LTP induction is facilitated when postsynaptic interneurons are hyperpolarized, presumably because Ca(2+) entry through Ca(2+)-permeable glutamate receptors is enhanced. The contribution of modulatory transmitters to anti-Hebbian LTP induction remains to be established. Activation of group I metabotropic receptors (mGluRs) is required for anti-Hebbian LTP induction in interneurons with cell bodies in the CA1 stratum oriens. This region receives a strong cholinergic innervation from the septum, and muscarinic acetylcholine receptors (mAChRs) share some signaling pathways and cooperate with mGluRs in the control of neuronal excitability.We therefore examined possible interactions between group I mGluRs and mAChRs in anti-Hebbian LTP at synapses which excite oriens interneurons in rat brain slices. We found that blockade of either group I mGluRs or M1 mAChRs prevented the induction of anti-Hebbian LTP by pairing presynaptic activity with postsynaptic hyperpolarization. Blocking either receptor also suppressed long-term effects of activation of the other G-protein coupled receptor on interneuron membrane potential. However, no crossed blockade was detected for mGluR or mAchR effects on interneuron after-burst potentials or on the frequency of miniature EPSPs. Paired recordings between pyramidal neurons and oriens interneurons were obtained to determine whether LTP could be induced without concurrent stimulation of cholinergic axons. Exogenous activation of mAChRs led to LTP, with changes in EPSP amplitude distributions consistent with a presynaptic locus of expression. LTP, however, required noninvasive presynaptic and postsynaptic recordings

Monosynaptic GABAergic Signaling from Dentate to CA3 with a Pharmacological and Physiological Profile Typical of Mossy Fiber Synapses

AbstractMossy fibers are the sole excitatory projection from dentate gyrus granule cells to the hippocampus, where they release glutamate, dynorphin, and zinc. In addition, mossy fiber terminals show intense immunoreactivity for the inhibitory neurotransmitter GABA. Fast inhibitory transmission at mossy fiber synapses, however, has not previously been reported. Here, we show that electrical or chemical stimuli that recruit dentate granule cells elicit monosynaptic GABAA receptor–mediated synaptic signals in CA3 pyramidal neurons. These inhibitory signals satisfy the criteria that distinguish mossy fiber–CA3 synapses: high sensitivity to metabotropic glutamate receptor agonists, facilitation during repetitive stimulation, and NMDA receptor–independent long-term potentiation. GABAergic transmission from the dentate gyrus to CA3 has major implications not only for information flow into the hippocampus but also for developmental and pathological processes involving the hippocampus

Analog modulation of mossy fiber transmission is uncoupled from changes in presynaptic Ca2+

Subthreshold somatic depolarization has been shown recently to modulate presynaptic neurotransmitter release in cortical neurons. To understand the mechanisms underlying this mode of signaling in the axons of dentate granule cells (hippocampal mossy fibers), we have combined two- photon Ca2+ imaging with dual-patch recordings from somata and giant boutons forming synapses on CA3 pyramidal cells. In intact axons, subthreshold depolarization propagates both orthodromically and antidromically, with an estimated length constant of 200-600 mu m depending on the signal waveform. Surprisingly, presynaptic depolarization sufficient to enhance glutamate release at mossy fiber-CA3 pyramidal cell synapses has no detectable effect on either basal Ca2+-dependent fluorescence or action-potential-evoked fluorescence transients in giant boutons. We further estimate that neurotransmitter release varies with presynaptic Ca2+ entry with a 2.5-power relationship and that depolarization-induced synaptic facilitation remains intact in the presence of high-affinity presynaptic Ca2+ buffers or after blockade of local Ca2+ stores. We conclude that depolarization-dependent modulation of transmission at these boutons does not rely on changes in presynaptic Ca2+

Sustainability of sanitation in rural Bangladesh

This is a report on a study of 53 Bangladesh unions declared “100% sanitized” more than 4.5 years earlier under the auspices of a broad-based national sanitation campaign. Union Chairmen received awards if their populations achieved the goal. Findings were generally positive, with 89.5% of surveyed households using some type of improved latrine (shared or not). A dramatic change in social norms was found. Two-thirds of union chairmen were still working on sanitation. Other achievements were the emergence of private sector latrine parts producers and an increase in latrine pit cleaning services. A significant problem was the unclean condition of 56% of improved household latrines. Other challenges are discussed. Recommendations include: Establish quality standards for latrine parts manufacture; Monitor sanitation coverage in all unions in the future; Offer low-interest loans to poor households for latrine purchases; and Keep local government involved and responsible for continuing rural sanitation improvements

Exploiting Resolution-based Representations for MaxSAT Solving

Most recent MaxSAT algorithms rely on a succession of calls to a SAT solver in order to find an optimal solution. In particular, several algorithms take advantage of the ability of SAT solvers to identify unsatisfiable subformulas. Usually, these MaxSAT algorithms perform better when small unsatisfiable subformulas are found early. However, this is not the case in many problem instances, since the whole formula is given to the SAT solver in each call. In this paper, we propose to partition the MaxSAT formula using a resolution-based graph representation. Partitions are then iteratively joined by using a proximity measure extracted from the graph representation of the formula. The algorithm ends when only one partition remains and the optimal solution is found. Experimental results show that this new approach further enhances a state of the art MaxSAT solver to optimally solve a larger set of industrial problem instances

Finite-time fluctuations in the degree statistics of growing networks

This paper presents a comprehensive analysis of the degree statistics in models for growing networks where new nodes enter one at a time and attach to one earlier node according to a stochastic rule. The models with uniform attachment, linear attachment (the Barab\'asi-Albert model), and generalized preferential attachment with initial attractiveness are successively considered. The main emphasis is on finite-size (i.e., finite-time) effects, which are shown to exhibit different behaviors in three regimes of the size-degree plane: stationary, finite-size scaling, large deviations.Comment: 33 pages, 7 figures, 1 tabl

Financial correlations at ultra-high frequency: theoretical models and empirical estimation

A detailed analysis of correlation between stock returns at high frequency is compared with simple models of random walks. We focus in particular on the dependence of correlations on time scales - the so-called Epps effect. This provides a characterization of stochastic models of stock price returns which is appropriate at very high frequency.Comment: 22 pages, 8 figures, 1 table, version to appear in EPJ

Independent regulation of Basal neurotransmitter release efficacy by variable Ca²+ influx and bouton size at small central synapses.

The efficacy of action potential evoked neurotransmitter release varies widely even among synapses supplied by the same axon, and the number of release-ready vesicles at each synapse is a major determinant of this heterogeneity. Here we identify a second, equally important, mechanism for release heterogeneity at small hippocampal synapses, the inter-synaptic variation of the exocytosis probability of release-ready vesicles. Using concurrent measurements of vesicular pool sizes, vesicular exocytosis rates, and presynaptic Ca²⁺ dynamics, in the same small hippocampal boutons, we show that the average fusion probability of release-ready vesicles varies among synapses supplied by the same axon with the size of the spike-evoked Ca²⁺ concentration transient. We further show that synapses with a high vesicular release probability exhibit a lower Ca²⁺ cooperativity, arguing that this is a direct consequence of increased Ca²⁺ influx at the active zone. We conclude that variability of neurotransmitter release under basal conditions at small central synapses is accounted for not only by the number of release-ready vesicles, but also by their fusion probabilities, which are set independently of bouton size by variable spike-evoked presynaptic Ca²⁺ influx