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Frontiers in Neuroendocrinology Jul 2022Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that the facilitation of long-term synaptic... (Review)
Review
Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that the facilitation of long-term synaptic potentiation (LTP)-related pathways, by products induced by physical exercise (i.e., exerkines), is a crucial aspect of the exercise-effect on the brain. This review summarizes synaptic pathways that are activated by exerkines and may potentiate LTP. For a total of 16 exerkines, we indicated how blood and brain exerkine levels are altered depending on the type of physical exercise (i.e., cardiovascular or resistance exercise) and how they respond to a single bout (i.e., acute exercise) or multiple bouts of physical exercise (i.e., chronic exercise). This information may be used for designing individualized physical exercise programs. Finally, this review may serve to direct future research towards fundamental gaps in our current knowledge regarding the biophysical interactions between muscle activity and the brain at both cellular and system levels.
Topics: Cognition; Exercise; Hippocampus; Long-Term Potentiation; Neuronal Plasticity
PubMed: 35283168
DOI: 10.1016/j.yfrne.2022.100993 -
Cold Spring Harbor Perspectives in... Jun 2012Long-term potentiation and long-term depression (LTP/LTD) can be elicited by activating N-methyl-d-aspartate (NMDA)-type glutamate receptors, typically by the coincident...
Long-term potentiation and long-term depression (LTP/LTD) can be elicited by activating N-methyl-d-aspartate (NMDA)-type glutamate receptors, typically by the coincident activity of pre- and postsynaptic neurons. The early phases of expression are mediated by a redistribution of AMPA-type glutamate receptors: More receptors are added to potentiate the synapse or receptors are removed to weaken synapses. With time, structural changes become apparent, which in general require the synthesis of new proteins. The investigation of the molecular and cellular mechanisms underlying these forms of synaptic plasticity has received much attention, because NMDA receptor-dependent LTP and LTD may constitute cellular substrates of learning and memory.
Topics: Humans; Learning; Long-Term Potentiation; Long-Term Synaptic Depression; Memory; Receptors, N-Methyl-D-Aspartate; Signal Transduction
PubMed: 22510460
DOI: 10.1101/cshperspect.a005710 -
Physiological Reviews Oct 2023Ca/calmodulin-dependent protein kinase II (CaMKII) and long-term potentiation (LTP) were discovered within a decade of each other and have been inextricably intertwined... (Review)
Review
Ca/calmodulin-dependent protein kinase II (CaMKII) and long-term potentiation (LTP) were discovered within a decade of each other and have been inextricably intertwined ever since. However, like many marriages, it has had its up and downs. Based on the unique biochemical properties of CaMKII, it was proposed as a memory molecule before any physiological linkage was made to LTP. However, as reviewed here, the convincing linkage of CaMKII to synaptic physiology and behavior took many decades. New technologies were critical in this journey, including in vitro brain slices, mouse genetics, single-cell molecular genetics, pharmacological reagents, protein structure, and two-photon microscopy, as were new investigators attracted by the exciting challenge. This review tracks this journey and assesses the state of this marriage 40 years on. The collective literature impels us to propose a relatively simple model for synaptic memory involving the following steps that drive the process: ) Ca entry through -methyl-d-aspartate (NMDA) receptors activates CaMKII. ) CaMKII undergoes autophosphorylation resulting in constitutive, Ca-independent activity and exposure of a binding site for the NMDA receptor subunit GluN2B. ) Active CaMKII translocates to the postsynaptic density (PSD) and binds to the cytoplasmic C-tail of GluN2B. ) The CaMKII-GluN2B complex initiates a structural rearrangement of the PSD that may involve liquid-liquid phase separation. ) This rearrangement involves the PSD-95 scaffolding protein, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), and their transmembrane AMPAR-regulatory protein (TARP) auxiliary subunits, resulting in an accumulation of AMPARs in the PSD that underlies synaptic potentiation. ) The stability of the modified PSD is maintained by the stability of the CaMKII-GluN2B complex. ) By a process of subunit exchange or interholoenzyme phosphorylation CaMKII maintains synaptic potentiation in the face of CaMKII protein turnover. There are many other important proteins that participate in enlargement of the synaptic spine or modulation of the steps that drive and maintain the potentiation. In this review we critically discuss the data underlying each of the steps. As will become clear, some of these steps are more firmly grounded than others, and we provide suggestions as to how the evidence supporting these steps can be strengthened or, based on the new data, be replaced. Although the journey has been a long one, the prospect of having a detailed cellular and molecular understanding of learning and memory is at hand.
Topics: Mice; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Memory; Long-Term Potentiation; Learning; Hippocampus
PubMed: 37290118
DOI: 10.1152/physrev.00034.2022 -
Neuron Sep 2004LTP and LTD, the long-term potentiation and depression of excitatory synaptic transmission, are widespread phenomena expressed at possibly every excitatory synapse in... (Review)
Review
LTP and LTD, the long-term potentiation and depression of excitatory synaptic transmission, are widespread phenomena expressed at possibly every excitatory synapse in the mammalian brain. It is now clear that "LTP" and "LTD" are not unitary phenomena. Their mechanisms vary depending on the synapses and circuits in which they operate. Here we review those forms of LTP and LTD for which mechanisms have been most firmly established. Examples are provided that show how these mechanisms can contribute to experience-dependent modifications of brain function.
Topics: Animals; Brain; Humans; Long-Term Potentiation; Long-Term Synaptic Depression; Neuronal Plasticity
PubMed: 15450156
DOI: 10.1016/j.neuron.2004.09.012 -
Neurobiology of Learning and Memory Dec 2022Experience-dependent modulation of the visual evoked potential (VEP) has emerged as a promising non-invasive proxy for assaying long term potentiation (LTP)-like...
OBJECTIVE
Experience-dependent modulation of the visual evoked potential (VEP) has emerged as a promising non-invasive proxy for assaying long term potentiation (LTP)-like plasticity in the cerebral cortex. LTP is considered the principal candidate mechanism underlying learning and memory. There is, however, a paucity of evidence exploring associations between LTP-like plasticity and performance-based learning and memory. The present study aimed to explore the relationship between VEP-plasticity and higher-order learning and memory in healthy adults.
METHOD
Visual and verbal learning and memory was assessed using the Aggie Figures Learning Test (AFLT) and the Rey Auditory Verbal Learning Test (RAVLT). The study included 111 healthy adults (61.1% females; mean age 37.6 years, range 17-71) who underwent a VEP paradigm employing visual high-frequency stimulation to induce a change in visual evoked responses recorded by scalp EEG. In addition, a more comprehensive neuropsychological assessment was administered.
RESULTS
Several significant moderate age-corrected positive correlations were found between modulation of the later VEP components (N1 and P1-N1 peak-to-peak) and both visual and verbal learning and memory performance. Further, there were significant differences in learning and memory performance between participants showing a higher degree of modulation (>1 SD above mean) compared to participants showing a lower degree of modulation. No significant associations were found between VEP-plasticity and other neurocognitive domains.
CONCLUSIONS
The current results suggest that LTP-like plasticity indexed by VEP modulation reflect processes specific to learning and memory. Future research is needed to further delineate the complex relationship between neural plasticity and learning and memory, specifically concerning possible clinical implications in populations with deficits in learning and memory function.
Topics: Adult; Female; Humans; Adolescent; Young Adult; Middle Aged; Aged; Male; Long-Term Potentiation; Evoked Potentials, Visual; Neuronal Plasticity; Electroencephalography; Photic Stimulation
PubMed: 36368635
DOI: 10.1016/j.nlm.2022.107696 -
Learning & Memory (Cold Spring Harbor,... Jun 2022A critical role of protein modifications such as phosphorylation and acetylation in synaptic plasticity and memory is well documented. Tyrosine sulfation plays important...
A critical role of protein modifications such as phosphorylation and acetylation in synaptic plasticity and memory is well documented. Tyrosine sulfation plays important roles in several biological processes. However, its role in synaptic plasticity and memory is not well understood. Here, we show that sulfation contributes to long-term potentiation (LTP) in the hippocampal slices. In addition, inhibition of sulfation impairs long-term memory in a spatial memory task without affecting acquisition or short-term memory. Furthermore, LTP-inducing stimulus enhances protein tyrosine sulfation. These results suggest an important role for tyrosine sulfation in LTP and memory.
Topics: Hippocampus; Long-Term Potentiation; Memory, Long-Term; Neuronal Plasticity; Sulfotransferases; Tyrosine
PubMed: 35589338
DOI: 10.1101/lm.053538.121 -
ELife Apr 2023The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here, we report that the...
The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here, we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP-EPAC-PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM1α, and thereby initiates the assembly of the Rab3A-RIM1α-Munc13-1 tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC-PKCε signaling abolishes presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapses and impairs basic performance and learning of cerebellar motor behavior. These results unveil a functional relevance of presynaptic plasticity that is regulated through a novel signaling cascade, thereby enriching the spectrum of cerebellar learning mechanisms.
Topics: Animals; Mice; Cerebellum; Guanine Nucleotide Exchange Factors; Long-Term Potentiation; Neurons; Purkinje Cells; Synapses
PubMed: 37159499
DOI: 10.7554/eLife.80875 -
Clinics (Sao Paulo, Brazil) 2011Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much... (Review)
Review
Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.
Topics: Animals; Central Nervous System Diseases; Electric Stimulation; Humans; Long-Term Potentiation; Long-Term Synaptic Depression; Photic Stimulation
PubMed: 21779718
DOI: 10.1590/s1807-59322011001300002 -
The Journal of Physiology Aug 2017
Topics: Analgesics, Opioid; Long-Term Potentiation; Receptors, Opioid, kappa; Synapses
PubMed: 28626995
DOI: 10.1113/JP274545 -
The European Journal of Neuroscience Dec 2022There is great interest in developing non-invasive approaches for studying cortical plasticity in humans. High-frequency presentation of auditory and visual stimuli, or... (Review)
Review
There is great interest in developing non-invasive approaches for studying cortical plasticity in humans. High-frequency presentation of auditory and visual stimuli, or sensory tetanisation, can induce long-term-potentiation-like (LTP-like) changes in cortical activity. However, contrasting effects across studies suggest that sensory tetanisation may be unreliable. We review these contrasting effects, conduct our own study of auditory and visual tetanisation, and perform meta-analyses to determine the average effect of sensory tetanisation across studies. We measured auditory-evoked amplitude changes in a group of younger (18-29 years of age) and older (55-83 years of age) adults following tetanisation to 1 and 4 kHz tone bursts and following a slow-presentation control. We also measured visual-evoked amplitude changes following tetanisation to horizontal and vertical sign gradients. Auditory and visual response amplitudes decreased following tetanisation, consistent with some studies but contrasting with others finding amplitude increases (i.e. LTP-like changes). Older adults exhibited more modest auditory-evoked amplitude decreases, but visual-evoked amplitude decreases like those of younger adults. Changes in response amplitude were not specific to tetanised stimuli. Importantly, slow presentation of auditory tone bursts produced response amplitude changes approximating those observed following tetanisation in younger adults. Meta-analyses of visual and auditory tetanisation studies found that the overall effect of sensory tetanisation was not significant across studies or study sites. The results suggest that sensory tetanisation may not produce reliable changes in cortical responses and more work is needed to determine the validity of sensory tetanisation as a method for inducing human cortical plasticity in vivo.
Topics: Humans; Aged; Long-Term Potentiation; Neuronal Plasticity
PubMed: 36227258
DOI: 10.1111/ejn.15847