scholarly journals CaMKII holoenzyme mechanisms that govern the LTP versus LTD decision

2021 ◽  
Vol 7 (16) ◽  
pp. eabe2300
Author(s):  
Sarah G. Cook ◽  
Olivia R. Buonarati ◽  
Steven J. Coultrap ◽  
K. Ulrich Bayer
Keyword(s):  
Stimulus Frequency ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Brain Functions ◽  
Term Potentiation ◽  
Autonomous Activity ◽  
And Function ◽  
Higher Brain Functions ◽  
Feed Forward Inhibition

Higher brain functions are thought to require synaptic frequency decoding that can lead to long-term potentiation (LTP) or depression (LTD). We show that the LTP versus LTD decision is determined by complex cross-regulation of T286 and T305/306 autophosphorylation within the 12meric CaMKII holoenzyme, which enabled molecular computation of stimulus frequency, amplitude, and duration. Both LTP and LTD require T286 phosphorylation, but T305/306 phosphorylation selectively promoted LTD. In response to excitatory LTP versus LTD stimuli, the differential T305/306 phosphorylation directed CaMKII movement to either excitatory or inhibitory synapses, thereby coordinating plasticity at both synapse types. Fast T305/306 phosphorylation required prior T286 phosphorylation and then curbed CaMKII activity by two mechanisms: (i) a cis-subunit reaction reduced both Ca2+ stimulation and autonomous activity and (ii) a trans-subunit reaction enabled complete activity shutdown and feed-forward inhibition of further T286 phosphorylation. These are fundamental additions to the long-studied CaMKII regulation and function in neuronal plasticity.

Induction of long-term potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex

1991 ◽  
Vol 65 (1) ◽  
pp. 20-32 ◽  
Author(s):  
Y. Komatsu ◽  
S. Nakajima ◽  
K. Toyama
Keyword(s):  
Nmda Receptors ◽  
Stimulus Frequency ◽  
Low Frequency ◽  
Nmda Antagonist ◽  
Long Term Potentiation ◽  
Conditioning Stimulation ◽  
Postsynaptic Potential ◽  
Term Potentiation ◽  
Stimulation Of

1. Intracellular recording was made from layer II-III cells in slice preparations of kitten (30-40 days old) visual cortex. Low-frequency (0.1 Hz) stimulation of white matter (WM) usually evoked an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). The postsynaptic potentials (PSPs) showed strong dependence on stimulus frequency. Early component of EPSP and IPSP evoked by weak stimulation both decreased monotonically at frequencies greater than 0.5-1 Hz. Strong stimulation similarly depressed the early EPSP at higher frequencies (greater than 2 Hz) and replaced the IPSP with a late EPSP, which had a maximum amplitude in the stimulus frequency range of 2-5 Hz. 2. Very weak WM stimulation sometimes evoked EPSPs in isolation from IPSPs. The falling phase of the EPSP revealed voltage dependence characteristic to the responses mediated by N-methyl-D-aspartate (NMDA) receptors and was depressed by application of an NMDA antagonist DL-2-amino-5-phosphonovalerate (APV), whereas the rising phase of the EPSP was insensitive to APV. 3. The early EPSPs followed by IPSPs were insensitive to APV but were replaced with a slow depolarizing potential by application of a non-NMDA antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX), indicating that the early EPSP is mediated by non-NMDA receptors. The slow depolarization was mediated by NMDA receptors because it was depressed by membrane hyperpolarization or addition of APV. 4. The late EPSP evoked by higher-frequency stimulation was abolished by APV, indicating that it is mediated by NMDA receptors, which are located either on the recorded cell or on presynaptic cells to the recorded cells. 5. Long-term potentiation (LTP) of EPSPs was examined in cells perfused with solutions containing 1 microM bicuculline methiodide (BIM), a gamma-aminobutyric acid (GABA) antagonist. WM was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes were tested by low-frequency (0.1 Hz) stimulation of WM. 6. LTP of early EPSPs occurred in more than one-half of the cells (8/13) after strong conditioning stimulation. The rising slope of the EPSP was increased 1.6 times on average. 7. To test involvement of NMDA receptors in the induction of LTP in the early EPSP, the effect of conditioning stimulation was studied in a solution containing 100 microM APV, which was sufficient to block completely synaptic transmission mediated by NMDA receptors. LTP occurred in the same frequency and magnitude as in control solution.

scholarly journals Phosphorylation of the AMPAR-TARP Complex in Synaptic Plasticity

Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 40 ◽  
Author(s):  
Joongkyu Park
Keyword(s):  
Synaptic Plasticity ◽  
Drug Addiction ◽  
Ampa Receptor ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Regulatory Proteins ◽  
Cellular Models ◽  
Brain Functions ◽  
Term Potentiation

Synaptic plasticity has been considered a key mechanism underlying many brain functions including learning, memory, and drug addiction. An increase or decrease in synaptic activity of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complex mediates the phenomena as shown in the cellular models of synaptic plasticity, long-term potentiation (LTP), and depression (LTD). In particular, protein phosphorylation shares the spotlight in expressing the synaptic plasticity. This review summarizes the studies on phosphorylation of the AMPAR pore-forming subunits and auxiliary proteins including transmembrane AMPA receptor regulatory proteins (TARPs) and discusses its role in synaptic plasticity.

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

scholarly journals Poststress Block of Kappa Opioid Receptors Rescues Long-Term Potentiation of Inhibitory Synapses and Prevents Reinstatement of Cocaine Seeking

2014 ◽  
Vol 76 (10) ◽  
pp. 785-793 ◽  
Author(s):  
Abigail M. Polter ◽  
Rachel A. Bishop ◽  
Lisa A. Briand ◽  
Nicholas M. Graziane ◽  
R. Christopher Pierce ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Term Potentiation ◽  
Cocaine Seeking

[P3-141]: FOLATE PREVENTS THE DETRIMENTAL EFFECTS OF OLIGOMERIC Aβ ON INSULIN RECEPTOR LOCALIZATION AND FUNCTION AND LONG-TERM POTENTIATION

2017 ◽  
Vol 13 (7S_Part_20) ◽  
pp. P989-P989
Author(s):  
Athena Ching Jung Wang ◽  
Ron Freund ◽  
Christina M. Coughlan ◽  
Esteban M. Lucero ◽  
Mark DellAcqua ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Long Term Potentiation ◽  
Receptor Localization ◽  
Term Potentiation ◽  
And Function

scholarly journals A physiological role for GABAA receptor desensitization – induction of long-term potentiation at inhibitory synapses

2020 ◽  
Author(s):  
Martin Field ◽  
Philip Thomas ◽  
Trevor G Smart
Keyword(s):  
Physiological Role ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Structural Basis ◽  
Inhibitory Neurotransmission ◽  
Term Potentiation ◽  
Physiological Relevance ◽  
Kinetic Effects ◽  
Physiological Impact

AbstractGABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring new form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 hrs following desensitization of GABAARs in response to prolonged agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a new physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.

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