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Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
LTP is triggered by activation of NMDA glutamate receptors (NMDARs) concomitant with depolarization of the postsynaptic membrane. As mentioned earlier, the NMDA channel is blocked at the resting voltage by extracellular Mg2+. High-frequency stimulation causes prolonged depolarization of the postsynaptic membrane that removes the blockage, so that the glutamate-activated channel of the NMDA receptor conducts and allows the influx of Ca2+ and Na+ (Figure 6.14). The ensuing rise in [Ca2+]i triggers LTP through several mechanisms; the dominant one seems to be through CaMKII and, to a lesser extent, through PKC (Section 6.3.1). An interesting property of CaMKII is that its 12 subunits not only phosphorylate other proteins but can also phosphorylate each other. Because of this autophosphorylation, the activity of CaMKII can persist long after [Ca2+]i returns to its normal level. CaMKII phosphorylates AMPA receptors (AMPARs), thereby increasing the conductance of this receptor channel.
Treatment of Chronic Fatigue Syndrome
Published in Jay A. Goldstein, Chronic Fatigue Syndromes, 2020
Nitric oxide may also mediate post-synaptic regulation of presynaptic transmitter release. This phenomenon has been studied in the production of long-term potentiation (LTP) by glutamate binding to non-NMDA receptors in the hippocampus. This induction of LTP is dependent on post-synaptic depolarization, calcium influx, and activation of protein and calmodulin kinases. For maintenance of LTP, however, the post-synaptic neuron stimulates the firing pre-synaptic neurons to secrete more transmitter, in this case glutamate. This stimulation may occur by the post-synaptic secretion of nitric oxide which diffuses into the pre-synaptic terminals and stimulates guanylyl cyclase enhancement of transmitter release to maintain LTP106 (see Figure 3). Multiple firing presynaptic neurons in a neural network could thus cause an integrated increase in transmission via nitric oxide.
Advances in Understanding the Mechanisms Underlying Synaptic Plasticity
Published in Avital Schurr, Benjamin M. Rigor, BRAIN SLICES in BASIC and CLINICAL RESEARCH, 2020
Timothy J. Teyler, Idil Cavus, Chris Coussens, Pascal DiScenna, Lawrence Grover, Yi-Ping Lee, Zeb Little
The original descriptions of LTP were made in the hippocampus, particularly area CA1, and most mechanistic studies of LTP have been done in this region. Central to understanding the mechanisms underlying LTP is the role of the N-methyl-d-aspartate (NMDA) glutamate receptor subtype. When appropriately activated, the NMDA receptor (NMDAr) gates Ca2+ into the postsynaptic cell where Ca2+-dependent biochemical processes responsible for the expression of this enduring form of increased synaptic efficacy are activated. We shall term this form NMDA LTP. More recently, a second form of LTP was described that is independent of the NMDAr. This form of LTP gates Ca2+ into the cell through voltage-dependent calcium channels (VDCCs). We shall refer to this form as non-NMDA LTP. For both forms of LTP, the metabotropic glutamate receptor (mGLUr) may also play a role in the maintenance of the potentiated response. The most prevalent form of LTD is seen at synapses subjected to a long, low-frequency stimulus train (homosynaptic LTD). Heterosynaptic LTD is less reliably seen at inactive synapses when other synapses on the same cell are activated. Like LTP, LTD is a Ca2+-dependent phenomenon. The central question of this chapter concerns how a common second messenger, Ca2+, can initiate different physiological responses in the same cell.
Emerging drugs for the treatment of hereditary angioedema due to C1-inhibitor deficiency
Published in Expert Opinion on Emerging Drugs, 2022
Andrea Zanichelli, Vincenzo Montinaro, Massimo Triggiani, Francesco Arcoleo, Debora Visigalli, Mauro Cancian
Some new drugs partially overcoming these drawbacks were recently approved as LTP: a plasma-derived C1-INH for subcutaneous use (twice weekly) approved in the US (Haegarda®), in Europe (Berinert s.c.®), and in other countries [14];a subcutaneous monoclonal antibody (1–2 injections per month) inhibiting the proteolytic activity of active plasma kallikrein (lanadelumab, TakhzyroTM) [15].an oral kallikrein inhibitor (one capsule per day) recently approved by FDA and EMA, but not yet on the market in several countries (berotralstat, OrladeyoTM) [16].
Is tDCS a potential first line treatment for major depression?
Published in International Review of Psychiatry, 2021
Rachel Woodham, Rachael M. Rimmer, Julian Mutz, Cynthia H. Y. Fu
The neurophysiological effects of tDCS typically last beyond the immediate stimulation period (Nitsche et al., 2003a, 2003b). Long-term potentiation (LTP) describes the sustained increase in synaptic transmission that is the cellular correlate of learning and memory, first described in neuronal cells in the hippocampus (Bliss & Lømo, 1973). Cortical LTP and long-term depression (LTD)-like changes are modulated by glutamatergic and GABAergic neurons (Trepel & Racine, 2000). Anodal tDCS-enhanced excitability in the primary motor cortex is LTP-like, which is dependent on N-methyl-D-aspartate (NMDA) receptor and calcium channel activity (Liebetanz et al., 2002; Monte-Silva et al., 2013). Stimulation strength, duration and direction have a non-linear relationship impact on whether excitatory or inhibitory effects are generated (Batsikadze et al., 2013; Jamil et al., 2017; Monte-Silva et al., 2013).
Acute enhancing effect of a standardized extract of Centella asiatica (ECa 233) on synaptic plasticity: an investigation via hippocampal long-term potentiation
Published in Pharmaceutical Biology, 2021
Yingrak Boondam, Mayuree H. Tantisira, Kanokwan Tilokskulchai, Sompol Tapechum, Narawut Pakaprot
The hippocampal LTP is a cellular model of the synaptic plasticity that represents hippocampal synapse strengthening, which is the basic mechanism of learning-and-memory formation. The stimulus intensity of the half-maximal fEPSP amplitude determined from the I-O curve of each slice was used on that hippocampal slice throughout the experiment. Recordings were still made in response to a single constant current stimulation once every 30 s. After 10 min of direct perfusion at approximately 1.5 mL/min with a tested substance (ACSF, 0.01% DMSO, 10 µg/mL ECa 233 in 0.01% DMSO, or 100 µg/mL ECa 233 in 0.01% DMSO), we recorded the baseline activity for 20 min. To induce LTP, we delivered high-frequency stimulation (HFS) containing two trains of tetanic stimulation (100 Hz of 100 pulses) of the same stimulus intensity and continually recorded the neuronal activity for 60 min (LTP phase). Thereafter, we reverted the solution to ACSF and continually recorded the activity for 15 min (washed-out phase). Next, we calculated the peak slope of the rising phase of the fEPSPs (1 ms duration). Figure 1 illustrates the experimental protocol.