Presynaptic NMDA Receptors and Spike Timing-Dependent Depression at Cortical Synapses

It has recently been discovered that some forms of timing-dependent long-term depression (t-LTD) require presynaptic N-methyl-d-aspartate (NMDA) receptors. In this review, we discuss the evidence for the presence of presynaptic NMDA receptors at cortical synapses and their possible role in the induction of t-LTD. Two basic models emerge for the induction of t-LTD at cortical synapses. In one model, coincident activation of presynaptic NMDA receptors and CB1 receptors mediates t-LTD. In a second model, CB1 receptors are not necessary, and the activation of presynaptic NMDA receptors alone appears to be sufficient for the induction of t-LTD

Hippocampal network oscillations - recent insights from in vitro experiments.

Network oscillations are present throughout the mammalian brain. They are important for certain cognitive functions, such as learning and memory. The hippocampus exhibits prominent oscillations similar to those seen in other parts of the cortex. Due to its highly organised lamellar structure, ex vivo and in vitro preparations from the hippocampus have provided experimental models within which to study network oscillations. As such, experiments in hippocampal slices continue to progress our understanding about both the mechanisms and functions of cortical network oscillations. Here, advances from the past two years are summarised, and the current state of the field discussed.The authors are grateful for research funding from the BBSRC, UK. JLB is supported by a CASE studentship from the BBSRC.This is the final published version. It is also available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0959438814001627#

The Hippocampal Cacophony: Multiple Layers of Communication

Locally generated gamma oscillations synchronize spikes, but the nature of coupling between regions remains unclear. In this issue of Neuron, Schomburg et al. (2014) show that afferent gamma input fails to entrain hippocampal output, suggesting limited propagation of gamma waves

The Many Tunes of Perisomatic Targeting Interneurons in the Hippocampal Network

The axonal targets of perisomatic targeting interneurons make them ideally suited to synchronize excitatory neurons. As such they have been implicated in rhythm generation of network activity in many brain regions including the hippocampus. However, several recent publications indicate that their roles extend beyond that of rhythm generation. Firstly, it has been shown that, in addition to rhythm generation, GABAergic perisomatic inhibition also serves as a current generator contributing significantly to hippocampal oscillatory EEG signals. Furthermore, GABAergic interneurons have a previously unrecognized role in the initiation of hippocampal population bursts, both in the developing and adult hippocampus. In this review, we describe these new observations in detail and discuss the implications they have for our understanding of the mechanisms underlying physiological and pathological hippocampal network activities. This review is part of the Frontiers in Cellular Neuroscience's special topic entitled “GABA signaling in health and disease” based on the meeting at the CNCR Amsterdam

Neuromodulation of Spike-Timing-Dependent Plasticity: Past, Present, and Future.

Spike-timing-dependent synaptic plasticity (STDP) is a leading cellular model for behavioral learning and memory with rich computational properties. However, the relationship between the millisecond-precision spike timing required for STDP and the much slower timescales of behavioral learning is not well understood. Neuromodulation offers an attractive mechanism to connect these different timescales, and there is now strong experimental evidence that STDP is under neuromodulatory control by acetylcholine, monoamines, and other signaling molecules. Here, we review neuromodulation of STDP, the underlying mechanisms, functional implications, and possible involvement in brain disorders.BBSR

Synaptic Plasticity and Memory: New Insights from Hippocampal Left-Right Asymmetries.

All synapses are not the same. They differ in their morphology, molecular constituents, and malleability. A striking left-right asymmetry in the distribution of different types of synapse was recently uncovered at the CA3-CA1 projection in the mouse hippocampus, whereby afferents from the CA3 in the left hemisphere innervate small, highly plastic synapses on the apical dendrites of CA1 pyramidal neurons, whereas those originating from the right CA3 target larger, more stable synapses. Activity-dependent modification of these synapses is thought to participate in circuit formation and remodeling during development, and further plastic changes may support memory encoding in adulthood. Therefore, exploiting the CA3-CA1 asymmetry provides a promising opportunity to investigate the roles that different types of synapse play in these fundamental properties of the CNS. Here we describe the discovery of these segregated synaptic populations in the mouse hippocampus, and discuss what we have already learnt about synaptic plasticity from this asymmetric arrangement. We then propose models for how the asymmetry could be generated during development, and how the adult hippocampus might use these distinct populations of synapses differentially during learning and memory. Finally, we outline the potential implications of this left-right asymmetry for human hippocampal function, as well as dysfunction in memory disorders such as Alzheimer's disease.The author's research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC), UK. M.E-­G. is supported by a BBSRC Studentship.This is the author accepted manuscript. The final version is available from Sage via http://dx.doi.org/10.1177/107385841455065

Fredsoperasjoner: erstatningsrettslig ansvar

Den foreliggende studie er en gjennomgang av de ertstatningsrettslige sidene av fredsoperasjoner. Det er stor uenighet om modeller og begreper for hvorledes slike operasjoner skal utføres og klassifiseres. Ueningheten kan lett resultere i misforståelser. I et miljø preget av moderne våpen som på kort tid kan påføre enorme skader, også på uskyldig tredjemann, er det viktig å minimalisere denne risikoen. I denne studien gjennomgås domstolenes kompetanse i internasjonale erstatningssaker. Videre gjennomgås betingelsene for erstatning, som følger f.eks. UN SOFA og NATO SOFA. Til slutt gjennomgås de rettsvalg som må foretas i internasjonale erstatningssaker. I tillegg finnes en kort gjennomgang av gjeldende modeller og begreper for interasjonale fredsoperasjoner. Her presenteres den rettslige forskjellen mellom freds- og tvangsoperasjoner, samt den rettslige forskjellen mellom fredsopprettende operasjoner og regulær krig

Comparison of three gamma oscillations in the mouse entorhinal-hippocampal system.

The entorhinal-hippocampal system is an important circuit in the brain, essential for certain cognitive tasks such as memory and navigation. Different gamma oscillations occur in this circuit, with the medial entorhinal cortex (mEC), CA3 and CA1 all generating gamma oscillations with different properties. These three gamma oscillations converge within CA1, where much work has gone into trying to isolate them from each other. Here, we compared the gamma generators in the mEC, CA3 and CA1 using optogenetically induced theta-gamma oscillations. Expressing channelrhodopsin-2 in principal neurons in each of the three regions allowed for the induction of gamma oscillations via sinusoidal blue light stimulation at theta frequency. Recording the oscillations in CA1 in vivo, we found that CA3 stimulation induced slower gamma oscillations than CA1 stimulation, matching in vivo reports of spontaneous CA3 and CA1 gamma oscillations. In brain slices ex vivo, optogenetic stimulation of CA3 induced slower gamma oscillations than stimulation of either mEC or CA1, whose gamma oscillations were of similar frequency. All three gamma oscillations had a current sink-source pair between the perisomatic and dendritic layers of the same region. Taking advantage of this model to analyse gamma frequency mechanisms in slice, we showed using pharmacology that all three gamma oscillations were dependent on the same types of synaptic receptor, being abolished by blockade of either type A γ-aminobutyric acid receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors, and insensitive to blockade of N-methyl-d-aspartate receptors. These results indicate that a fast excitatory-inhibitory feedback loop underlies the generation of gamma oscillations in all three regions

Acetylcholine-modulated plasticity in reward-driven navigation: a computational study.

Neuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour. We find that acetylcholine, by allowing learning from negative outcomes, enhances exploration over the action space. We show that this results in a variety of effects, depending on the structure of the model, the environment and the task. Interestingly, sequentially neuromodulated STDP also yields flexible learning, surpassing the performance of other reward-modulated plasticity rules