scholarly journals Lifelong reductions of PKMζ in ventral hippocampus of nonhuman primates exposed to early-life adversity due to unpredictable maternal care

2021 ◽  
Vol 28 (9) ◽  
pp. 341-347
Author(s):  
Sasha L. Fulton ◽  
Changchi Hsieh ◽  
Tobias Atkin ◽  
Ryan Norris ◽  
Eric Schoenfeld ◽  
...  
Keyword(s):  
Maternal Care ◽  
Early Life ◽  
Long Term Potentiation ◽  
Emotional Memory ◽  
Ventral Hippocampus ◽  
Long Term Memory ◽  
Early Life Adversity ◽  
Protein Kinase Mζ ◽  
Maternal Variable

Protein kinase Mζ (PKMζ) maintains long-term potentiation (LTP) and long-term memory through persistent increases in kinase expression. Early-life adversity is a precursor to adult mood and anxiety disorders, in part, through persistent disruption of emotional memory throughout life. Here we subjected 10- to 16-wk-old male bonnet macaques to adversity by a maternal variable-foraging demand paradigm. We then examined PKMζ expression in their ventral hippocampi as 7- to 12-yr-old adults. Quantitative immunohistochemistry reveals decreased PKMζ in dentate gyrus, CA1, and subiculum of subjects who had experienced early-life adversity due to the unpredictability of maternal care. Adult animals with persistent decrements of PKMζ in ventral hippocampus express timid rather than confrontational responses to a human intruder. Persistent down-regulation of PKMζ in the ventral hippocampus might reduce the capacity for emotional memory maintenance and contribute to the long-lasting emotional effects of early-life adversity.

scholarly journals A Unique Mouse Model of Early Life Exercise Enables Hippocampal Memory and Synaptic Plasticity

2019 ◽  
Author(s):  
Autumn S. Ivy ◽  
Tim Yu ◽  
Enikö Kramár ◽  
Sonia Parievsky ◽  
Fred Sohn ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Memory Task ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Critical Periods ◽  
Juvenile Period ◽  
Cognitive Benefits

AbstractAerobic exercise is a powerful modulator of learning and memory. Molecular mechanisms underlying the cognitive benefits of exercise are well documented in adult rodents. Animal models of exercise targeting specific postnatal periods of hippocampal development and plasticity are lacking. Here we characterize a model of early-life exercise (ELE) in male and female mice designed with the goal of identifying critical periods by which exercise may have a lasting impact on hippocampal memory and synaptic plasticity. Mice freely accessed a running wheel during three postnatal periods: the 4th postnatal week (juvenile ELE, P21-27), 6th postnatal week (adolescent ELE, P35-41), or 4th-6th postnatal weeks (juvenile-adolescent ELE, P21-41). All exercise groups significantly increased their running distances over time. When exposed to a weak learning stimulus, mice that had exercised during the juvenile period were able to form lasting long-term memory for a hippocampus-dependent spatial memory task. Electrophysiological experiments revealed enhanced long-term potentiation in hippocampal CA1 the juvenile-adolescent ELE group only. Furthermore, basal synaptic transmission was significantly increased in all mice that exercised during the juvenile period. Our results suggest early-life exercise can enable hippocampal memory, synaptic plasticity, and basal synaptic physiology when occurring during postnatal periods of hippocampal maturation.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

scholarly journals Early-life adversity programs long-term cytokine and microglia expression within the HPA axis in female Japanese quail

2019 ◽  
Vol 222 (6) ◽  
pp. jeb187039 ◽  
Author(s):  
David J. Walker ◽  
Cédric Zimmer ◽  
Maria Larriva ◽  
Susan D. Healy ◽  
Karen A. Spencer
Keyword(s):  
Hpa Axis ◽  
Japanese Quail ◽  
Early Life ◽  
Early Life Adversity

scholarly journals Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory

2019 ◽  
Vol 4 (40) ◽  
pp. eaay5199 ◽  
Author(s):  
Miguel Ribeiro ◽  
Helena C. Brigas ◽  
Mariana Temido-Ferreira ◽  
Paula A. Pousinha ◽  
Tommy Regen ◽  
...  
Keyword(s):  
T Cell ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Interleukin 17 ◽  
Γδ T Cell ◽  
Short Term ◽  
Functional Link ◽  
Term Memory

The notion of “immune privilege” of the brain has been revised to accommodate its infiltration, at steady state, by immune cells that participate in normal neurophysiology. However, the immune mechanisms that regulate learning and memory remain poorly understood. Here, we show that noninflammatory interleukin-17 (IL-17) derived from a previously unknown fetal-derived meningeal-resident γδ T cell subset promotes cognition. When tested in classical spatial learning paradigms, mice lacking γδ T cells or IL-17 displayed deficient short-term memory while retaining long-term memory. The plasticity of glutamatergic synapses was reduced in the absence of IL-17, resulting in impaired long-term potentiation in the hippocampus. Conversely, IL-17 enhanced glial cell production of brain-derived neurotropic factor, whose exogenous provision rescued the synaptic and behavioral phenotypes of IL-17–deficient animals. Together, our work provides previously unknown clues on the mechanisms that regulate short-term versus long-term memory and on the evolutionary and functional link between the immune and nervous systems.

scholarly journals Neuro-Transistor Based on UV-Treated Charge Trapping in MoTe2 for Artificial Synaptic Features

Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2326
Author(s):  
Shania Rehman ◽  
Muhammad Farooq Khan ◽  
Mehr Khalid Rahmani ◽  
Honggyun Kim ◽  
Harshada Patil ◽  
...  
Keyword(s):  
Field Effect Transistors ◽  
Charge Trapping ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Long Term Memory ◽  
Ambient Conditions ◽  
Time Constants ◽  
Brain Functions ◽  
Gate Pulse

The diversity of brain functions depend on the release of neurotransmitters in chemical synapses. The back gated three terminal field effect transistors (FETs) are auspicious candidates for the emulation of biological functions to recognize the proficient neuromorphic computing systems. In order to encourage the hysteresis loops, we treated the bottom side of MoTe2 flake with deep ultraviolet light in ambient conditions. Here, we modulate the short-term and long-term memory effects due to the trapping and de-trapping of electron events in few layers of a MoTe2 transistor. However, MoTe2 FETs are investigated to reveal the time constants of electron trapping/de-trapping while applying the gate-voltage pulses. Our devices exploit the hysteresis effect in the transfer curves of MoTe2 FETs to explore the excitatory/inhibitory post-synaptic currents (EPSC/IPSC), long-term potentiation (LTP), long-term depression (LTD), spike timing/amplitude-dependent plasticity (STDP/SADP), and paired pulse facilitation (PPF). Further, the time constants for potentiation and depression is found to be 0.6 and 0.9 s, respectively which seems plausible for biological synapses. In addition, the change of synaptic weight in MoTe2 conductance is found to be 41% at negative gate pulse and 38% for positive gate pulse, respectively. Our findings can provide an essential role in the advancement of smart neuromorphic electronics.

scholarly journals Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses

2016 ◽  
Vol 28 (9) ◽  
pp. 1317-1329 ◽  
Author(s):  
J. E. Medland ◽  
C. S. Pohl ◽  
L. L. Edwards ◽  
S. Frandsen ◽  
K. Bagley ◽  
...  
Keyword(s):  
Nervous System ◽  
Early Life ◽  
Early Life Adversity

scholarly journals Gradation (approx. 10 size states) of synaptic strength by quantal addition of structural modules

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160328 ◽  
Author(s):  
Kang K. L. Liu ◽  
Michael F. Hagan ◽  
John E. Lisman
Keyword(s):  
Functional Module ◽  
Late Phase ◽  
Matrix Material ◽  
Super Resolution ◽  
Long Term Potentiation ◽  
Information Storage ◽  
Homeostatic Plasticity ◽  
Memory Storage ◽  
Long Term Memory

Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes. Other recent evidence using super-resolution microscopy has revealed that synapses are composed of stereotyped nanoclusters of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and scaffolding proteins; furthermore, synapse size varies linearly with the number of nanoclusters. Here we have sought to develop a model of synapse structure and growth that is consistent with both the EM and super-resolution data. We argue that synapses are composed of modules consisting of matrix material and potentially one nanocluster. LTP induction can add a trans-synaptic nanocluster to a module, thereby converting a silent module to an AMPA functional module. LTP can also add modules by a linear process, thereby producing an approximately 10-fold gradation in synapse size and strength. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

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