Regular PaperCa2+stores and hippocampal synaptic plasticity
Abstract
For many years the importance of internal calcium stores (ICSs) in excitation–contraction coupling and endocrine function has been well recognized. With the discovery of ICSs in the CNS, evidence has accumulated regarding their role in neuronal function, and in particular, synaptic plasticity. In this review we focus on the involvement of ICSs in synaptic plasticity in the hippocampus.
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Kainate receptors and mossy fiber LTP
2005, NeuroToxicologyThere is considerable interest in understanding long-term potentiation (LTP) of glutamatergic synaptic transmission because the molecular mechanisms involved in its induction and expression are believed to be critical for learning and memory. There are two distinct forms of LTP. One type is triggered by synaptic activation of NMDA receptors and the other is NMDA receptor-independent. The latter type of LTP has been mostly studied at mossy fiber/CA3 synapses. Here we summarise some of our recent studies concerning the mechanisms of the induction of the NMDA receptor-independent form of LTP at these CA3 synapses. This form of LTP is triggered by the synaptic activation of kainate receptors. We also address the importance of Ca2+ availability in the extracellular environment and the release of Ca2+ from intracellular stores for this form of LTP.
Compared with NMDA receptor-dependent LTP, much less is known about the mechanism of induction of NMDA receptor-independent LTP; the most extensively studied form of which is mossy fiber LTP in the hippocampus. In the present study we show that Ca2+-induced Ca2+ release from intracellular stores is involved in the induction of mossy fiber LTP. This release also contributes to the kainate receptor-dependent component of the pronounced synaptic facilitation that occurs during high-frequency stimulation. We also present evidence that the trigger for this Ca2+ release is Ca2+ permeation through kainate receptors. However, these novel synaptic mechanisms can be bypassed when the Ca2+ concentration is raised (from 2 to 4 mM), via a compensatory involvement of L-type Ca2+ channels. These findings suggest that presynaptic kainate receptors at mossy fiber synapses can initiate a cascade involving Ca2+ release from intracellular stores that is important in both short-term and long-term plasticity.
High frequency stimulation-induced dendritic calcium waves in rat hippocampal neurons
2002, Neuroscience LettersAn activity-dependent intracellular Ca2+ increase represents a key signal for the activation of mechanisms involved in synaptic long-term plasticity. Here we present data from confocal microscopic imaging in conjunction with electrophysiological studies, that local 100 Hz stimulations of the hippocampal Schaffer collateral fibers, usually used for the induction of synaptic long-term potentiation (LTP), elicits an intradendritic Ca2+ rise, that propagates as a short-distance wave within dendrites of CA1-neurons, which could be involved in triggering the dendritic (local signal cascade) machinery of LTP generation. Pharmacological investigations elucidated the coincidental involvement of N-methyl-d-aspartate- and of group I metabotropic glutamate receptors in the generation of the Ca2+ wave.
Modulation of spontaneous quantal release of neurotransmitters in the hippocampus
2001, Progress in NeurobiologyPresynaptic action potentials trigger the exocytosis of neurotransmitters. However, even in the absence of depolarisation-dependent Ca2+ entry nearby release sites, spontaneous vesicular release still occurs. Even though this happens at low rate, such spontaneous release may play a trophic role in maintaining the shape of dendritic structures. Like evoked responses, action potential-independent release is subject to modulation. This review describes some of the regulatory factors that rapidly and presynaptically regulate the ongoing Ca2+-independent release of neurotransmitters in the hippocampus. For instance, the electrical activity of the nerve ending, neurotransmitters, hypertonic solutions, neurotoxins, polycations, neurotrophic factors, immunoglobulins, cyclothiazide and psychotropic drugs can all modify the rate of spontaneous release. This can be achieved through various mechanisms that can be Ca2+-dependent or Ca2+-independent, protein kinase-dependent or independent. Since action potential-independent release contributes to the maintenance of dendritic structures, neuromodulators are likely to influence the density and/or length of dendritic spines, which in turn may modulate information processing in the central nervous system (CNS).
Evoked transmitter release depends upon calcium influx into synaptic boutons, but mechanisms regulating bouton calcium levels and spontaneous transmitter release are obscure. To understand these processes better, we monitored calcium transients in axons and presynaptic terminals of pyramidal neurons in hippocampal slice cultures. Action potentials reliably evoke calcium transients in axons and boutons. Calcium-induced calcium release (CICR) from internal stores contributes to the transients in boutons and to paired-pulse facilitation of EPSPs. Store depletion activates store-operated calcium channels, influencing the frequency of spontaneous transmitter release. Boutons display spontaneous Ca2+ transients; blocking CICR reduces the frequency of these transients and of spontaneous miniature synaptic events. Thus, spontaneous transmitter release is largely calcium mediated, driven by Ca2+ release from internal stores. Bouton store release is important for short-term synaptic plasticity and may also contribute to long-term plasticity.
Casein kinase 2 as a potentially important enzyme in the nervous system
2000, Progress in NeurobiologyProtein kinase CK2 is a ubiquitous and pleiotropic seryl/threonyl protein kinase which is highly conserved in evolution indicating a vital cellular role for this kinase. The holoenzyme is generally composed of two catalytic (α and/or α′) and two regulatory (β) subunits, but the free α/α′ subunits are catalytically active by themselves and can be present in cells under some circumstances. Special attention has been devoted to phosphorylation status and structure of these enzymic molecules, however, their regulation and roles remain intriguing. Until recently, CK2 was believed to represent a kinase especially required for cell cycle progression in non-neural cells. At present, with respect to recent findings, four essential features suggest potentially important roles for this enzyme in specific neural functions: (1) CK2 is much more abundant in brain than in any other tissue; (2) there appear to be a myriad of substrates for CK2 in both synaptic and nuclear compartments that have clear implications in development, neuritogenesis, synaptic transmission, synaptic plasticity, information storage and survival; (3) CK2 seems to be associated with mechanisms underlying long-term potentiation in hippocampus; and (4) neurotrophins stimulate activity of CK2 in hippocampus. In addition, some data are suggestive that CK2 might play a role in processes underlying progressive disorders due to Alzheimer's disease, ischemia, chronic alcohol exposure or immunodeficiency virus HIV. The present review focuses mainly on the latest data concerning the regulatory mechanisms and the possible neurophysiological functions of this enzyme.