Spatial Learning Depends on Both the Addition and Removal of New Hippocampal Neurons

The role of adult hippocampal neurogenesis in spatial learning remains a matter of debate. Here, we show that spatial learning modifies neurogenesis by inducing a cascade of events that resembles the selective stabilization process characterizing development. Learning promotes survival of relatively mature neurons, apoptosis of more immature cells, and finally, proliferation of neural precursors. These are three interrelated events mediating learning. Thus, blocking apoptosis impairs memory and inhibits learning-induced cell survival and cell proliferation. In conclusion, during learning, similar to the selective stabilization process, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons

A Neuron-Glial Perspective for Computational Neuroscience

International audienceThere is growing excitement around glial cells, as compelling evidence point to new, previously unimaginable roles for these cells in information processing of the brain, with the potential to affect behavior and higher cognitive functions. Among their many possible functions, glial cells could be involved in practically every aspect of the brain physiology in health and disease. As a result, many investigators in the field welcome the notion of a Neuron-Glial paradigm of brain function, as opposed to Ramon y Cayal's more classical neuronal doctrine which identifies neurons as the prominent, if not the only, cells capable of a signaling role in the brain. The demonstration of a brain-wide Neuron-Glial paradigm however remains elusive and so does the notion of what neuron-glial interactions could be functionally relevant for the brain computational tasks. In this perspective, we present a selection of arguments inspired by available experimental and modeling studies with the aim to provide a biophysical and conceptual platform to computational neuroscience no longer as a mere prerogative of neuronal signaling but rather as the outcome of a complex interaction between neurons and glial cells

Cell Metab

Recent work from Bonvento and colleagues indicated that synaptic and memory deficits in early Alzheimer's disease (AD) are related to a shortage in L-serine production in astrocytes. Here, the authors, responding to correspondence from Chen and colleagues, discuss how this deficiency does not necessarily require a decrease in PHGDH expression and conclude that the primary event leading to lower serine production is more likely related to altered glycolytic flux in early AD than to PHGDH expression

Int J Mol Sci

Synaptic plasticity is an extensively studied cellular correlate of learning and memory in which NMDARs play a starring role. One of the most interesting features of NMDARs is their ability to act as a co-incident detector. It is unique amongst neurotransmitter receptors in this respect. Coincident detection is possible because the opening of NMDARs requires membrane depolarisation and the binding of glutamate. Opening of NMDARs also requires a co-agonist. Although the dynamic regulation of glutamate and membrane depolarization have been well studied in coincident detection, the role of the co-agonist site is unexplored. It turns out that non-neuronal glial cells, astrocytes, regulate co-agonist availability, giving them the ability to influence synaptic plasticity. The unique morphology and spatial arrangement of astrocytes at the synaptic level affords them the capacity to sample and integrate information originating from unrelated synapses, regardless of any pre-synaptic and post-synaptic commonality. As astrocytes are classically considered slow re-sponders, their influence at the synapse is widely recognized as modulatory. The aim herein is to reconsider the potential of astrocytes to participate directly in ongoing synaptic NMDAR activity and co-incident detection.Contribution des récepteurs IP3 et du réticulum endoplasmique à la signalisation Ca2+ dans les astrocytesExploration fonctionnelle du domaine astrocytair

Regulation of transmitter release by high-affinity group III mGluRs in the supraoptic nucleus of the rat hypothalamus.

We analyzed the subtypes of group III metabotropic glutamate receptors (mGluRs) modulating inhibitory and excitatory transmission in the rat supraoptic nucleus. Bath application of the agonist l-AP4 at 200 microM, a concentration that activates all group III mGluR subtypes, inhibited the frequency but not the amplitude of miniature inhibitory and excitatory postsynaptic currents, indicating a presynaptic site of action. l-AP4 at low concentrations (10 microM), as well as ACPT-1 (50 microM), a specific mGluR III agonist, inhibited transmission at GABAergic and glutamatergic synapses to the same extent as 200 microM l-AP4. Because the potency of l-AP4 and ACPT-1 is much higher on mGluR4 and mGluR8 than on mGluR7, these results are consistent with the presence of high-affinity group III mGluRs regulating transmitter release in this nucleus. In agreement with these findings, DCPG (30 microM), a selective mGluR8 agonist, induced a significant depression of inhibitory and excitatory synaptic currents. Group III mGluRs such as mGluR8, because of their high affinity for glutamate, are particularly well suited to detect small changes in the concentration of this excitatory amino acid in the extracellular space. Their presence, therefore, may favor the negative feedback control exerted by glutamate on its own release as well as the intersynaptic crosstalk mediated by glutamate spillover on adjacent synapses

Voltage-gated Ca2+ channel subtypes mediating GABAergic transmission in the rat supraoptic nucleus.: Ca2+ channels regulating GABA release in the SON

The supraoptic nucleus receives an abundant gamma-aminobutyric acid (GABA)ergic input which is inhibited by activation of various presynaptic metabotropic receptors. We here analysed the subtypes of voltage-gated Ca2+ channels intervening in the control of transmitter release at these synapses. To address this issue, we tested various specific inhibitors of Ca2+ channels on evoked inhibitory postsynaptic currents (IPSCs). Blocking N- and P-type voltage-gated Ca2+ channels with 1 micromomega-conotoxin-GVIA and 20 nmomega-agatoxin-IVA, respectively, dramatically reduced IPSC amplitude. Q- and L-type Ca2+ channels also contributed to GABAergic transmission, although to a lesser extent, as revealed by applications of 200 nmomega-agatoxin-IVA and of the dihydropyridines nifedipine (10 microm) and nimodipine (10 microm). Evoked IPSCs were insensitive to SNX-482 (300 nm), a blocker of some R-type Ca2+ channels. Analysis of selective blockade by the various antagonists suggested that multiple types of Ca2+ channels synergistically interact to trigger exocytosis at some individual GABA release sites. We next investigated whether inhibition of GABA release in response to the activation of metabotropic glutamate, GABA and adenosine receptors involved the modulation of these presynaptic Ca2+ channels. This was not the case, as the inhibitory actions of selective agonists of these receptors were unaffected by the presence of the different Ca2+ channel antagonists. This finding suggests that these metabotropic receptors modulate GABAergic transmission through a different mechanism, downstream of Ca2+ entry in the terminals, or upstream through the activation of K+ channels