Faculty Opinions recommendation of A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain.

The endocannabinoid system (ECS) is a crucial modulatory system in which interest has been increasing, particularly regarding the regulation of behavior and neuroplasticity. The adolescent–young adulthood phase of development comprises a critical period in the maturation of the nervous system and the ECS. Neurogenesis occurs in discrete regions of the adult brain, and this process is linked to the modulation of some behaviors. Since marijuana (cannabis) is the most consumed illegal drug globally and the highest consumption rate is observed during adolescence, it is of particular importance to understand the effects of ECS modulation in these early stages of adulthood. Thus, in this article, we sought to summarize recent evidence demonstrating the role of the ECS and exogenous cannabinoid consumption in the adolescent–young adulthood period; elucidate the effects of exogenous cannabinoid consumption on adult neurogenesis; and describe some essential and adaptive behaviors, such as stress, anxiety, learning, and memory. The data summarized in this work highlight the relevance of maintaining balance in the endocannabinoid modulatory system in the early and adult stages of life. Any ECS disturbance may induce significant modifications in the genesis of new neurons and may consequently modify behavioral outcomes.

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Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20143407 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3407 ◽

Cited By ~ 2

Author(s):

Paola Imbriani ◽

Annalisa Tassone ◽

Maria Meringolo ◽

Giulia Ponterio ◽

Graziella Madeo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Synaptic Plasticity ◽

Mouse Model ◽

Caspase 3 ◽

Cysteine Proteases ◽

Synaptic Function ◽

Adult Brain ◽

Striatal Slices

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.

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Estrogenic Regulation of Synaptic Actin Proteins and Plasticity

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0006 ◽

2020 ◽

pp. 69-82

Author(s):

Enikö A. Kramár

Keyword(s):

Synaptic Plasticity ◽

Long Term Potentiation ◽

Synaptic Strength ◽

Adult Brain ◽

Actin Dynamics ◽

Signaling Cascade ◽

Term Potentiation ◽

Estrogenic Regulation ◽

Estradiol Levels

Estrogens are rapid and potent facilitators of synaptic plasticity in the adult brain; however, the steps that link estrogens to factors that regulate synaptic strength remain unclear. The present chapter will first review the acute effects of 17β‎-estradiol on synaptic transmission and long-term potentiation (LTP). It will then describe a synaptic model used to study the substrates of LTP and provide evidence for the ability of estradiol to rapidly engage a selective actin signaling cascade associated with the consolidation of LTP. Finally, it will be shown that chronic reductions in estradiol levels disrupt LTP and actin dynamics but can be reversed by acute infusions of the hormone. It is concluded here that estradiol can promote learning-related plasticity by modifying the synaptic cytoskeleton.

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Pharmacological Manipulation of Critical Period Plasticity

The Oxford Handbook of Developmental Neural Plasticity ◽

10.1093/oxfordhb/9780190635374.013.10 ◽

2018 ◽

Author(s):

Ramon Guirado ◽

Eero Castrén

Keyword(s):

Critical Period ◽

Adult Brain ◽

Brain Disorders ◽

Critical Periods ◽

Pharmacological Treatments ◽

New Paradigm ◽

Early Postnatal Development ◽

Pharmacological Manipulation ◽

Efficient Recovery ◽

Activity Dependent

Neuronal networks are refined through an activity-dependent competition during critical periods of early postnatal development. Recent studies have shown that critical period plasticity is influenced by a number of environmental factors, including drugs that are widely used for the treatment of brain disorders. These findings suggest a new paradigm, where pharmacological treatments can be used to open critical period–like plasticity in the adult brain. The plastic networks can then be modified through rehabilitation or psychotherapy to rewire those abnormally wired during development. This kind of combination of pharmacotherapy with physical or psychological rehabilitation may open a new opportunity for a more efficient recovery of a number of neurological and neuropsychiatric disorders.

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Sleep and Synaptic Plasticity in the Developing and Adult Brain

Sleep, Neuronal Plasticity and Brain Function - Current Topics in Behavioral Neurosciences ◽

10.1007/7854_2014_305 ◽

2014 ◽

pp. 123-149 ◽

Cited By ~ 23

Author(s):

Marcos G. Frank

Keyword(s):

Synaptic Plasticity ◽

Adult Brain

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Neurons, Glia, Extracellular Matrix and Neurovascular Unit: A Systems Biology Approach to the Complexity of Synaptic Plasticity in Health and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21041539 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1539 ◽

Cited By ~ 11

Author(s):

Ciro De Luca ◽

Anna Maria Colangelo ◽

Assunta Virtuoso ◽

Lilia Alberghina ◽

Michele Papa

Keyword(s):

Extracellular Matrix ◽

Synaptic Plasticity ◽

Systems Biology ◽

Synapse Formation ◽

Neurovascular Unit ◽

Synaptic Cleft ◽

Adult Brain ◽

Molecular Networks ◽

Maladaptive Plasticity ◽

Health And Disease

The synaptic cleft has been vastly investigated in the last decades, leading to a novel and fascinating model of the functional and structural modifications linked to synaptic transmission and brain processing. The classic neurocentric model encompassing the neuronal pre- and post-synaptic terminals partly explains the fine-tuned plastic modifications under both pathological and physiological circumstances. Recent experimental evidence has incontrovertibly added oligodendrocytes, astrocytes, and microglia as pivotal elements for synapse formation and remodeling (tripartite synapse) in both the developing and adult brain. Moreover, synaptic plasticity and its pathological counterpart (maladaptive plasticity) have shown a deep connection with other molecular elements of the extracellular matrix (ECM), once considered as a mere extracellular structural scaffold altogether with the cellular glue (i.e., glia). The ECM adds another level of complexity to the modern model of the synapse, particularly, for the long-term plasticity and circuit maintenance. This model, called tetrapartite synapse, can be further implemented by including the neurovascular unit (NVU) and the immune system. Although they were considered so far as tightly separated from the central nervous system (CNS) plasticity, at least in physiological conditions, recent evidence endorsed these elements as structural and paramount actors in synaptic plasticity. This scenario is, as far as speculations and evidence have shown, a consistent model for both adaptive and maladaptive plasticity. However, a comprehensive understanding of brain processes and circuitry complexity is still lacking. Here we propose that a better interpretation of the CNS complexity can be granted by a systems biology approach through the construction of predictive molecular models that enable to enlighten the regulatory logic of the complex molecular networks underlying brain function in health and disease, thus opening the way to more effective treatments.

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