The Maternal Brain: An Organ with Peripartal Plasticity

The time of pregnancy, birth, and lactation, is characterized by numerous specific alterations in several systems of the maternal body. Peripartum-associated changes in physiology and behavior, as well as their underlying molecular mechanisms, have been the focus of research since decades, but are still far from being entirely understood. Also, there is growing evidence that pregnancy and lactation are associated with a variety of alterations in neural plasticity, including adult neurogenesis, functional and structural synaptic plasticity, and dendritic remodeling in different brain regions. All of the mentioned changes are not only believed to be a prerequisite for the proper fetal and neonatal development, but moreover to be crucial for the physiological and mental health of the mother. The underlying mechanisms apparently need to be under tight control, since in cases of dysregulation, a certain percentage of women develop disorders like preeclampsia or postpartum mood and anxiety disorders during the course of pregnancy and lactation. This review describes common peripartum adaptations in physiology and behavior. Moreover, it concentrates on different forms of peripartum-associated plasticity including changes in neurogenesis and their possible underlying molecular mechanisms. Finally, consequences of malfunction in those systems are discussed.

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Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning

Scientific Reports ◽

10.1038/s41598-021-91495-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Matthew R. Baker ◽

Ryan Y. Wong

Keyword(s):

Neural Plasticity ◽

Coping Style ◽

Molecular Mechanisms ◽

Conditioned Fear ◽

Coping Styles ◽

Brain Regions ◽

Contextual Fear Conditioning ◽

Fear Learning ◽

Stress Coping ◽

Contextual Fear

AbstractLearning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive–reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4a and gabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.

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Roles of Gasotransmitters in Synaptic Plasticity and Neuropsychiatric Conditions

Neural Plasticity ◽

10.1155/2018/1824713 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 13

Author(s):

Ulfuara Shefa ◽

Dokyoung Kim ◽

Min-Sik Kim ◽

Na Young Jeong ◽

Junyang Jung

Keyword(s):

Nervous System ◽

Synaptic Plasticity ◽

Neural Plasticity ◽

Molecular Mechanisms ◽

Electrical Signal ◽

The Body ◽

Major Depressive ◽

Essential Information ◽

The Central Nervous System ◽

Neuropsychiatric Conditions

Synaptic plasticity is important for maintaining normal neuronal activity and proper neuronal functioning in the nervous system. It is crucial for regulating synaptic transmission or electrical signal transduction to neuronal networks, for sharing essential information among neurons, and for maintaining homeostasis in the body. Moreover, changes in synaptic or neural plasticity are associated with many neuropsychiatric conditions, such as schizophrenia (SCZ), bipolar disorder (BP), major depressive disorder (MDD), and Alzheimer’s disease (AD). The improper maintenance of neural plasticity causes incorrect neurotransmitter transmission, which can also cause neuropsychiatric conditions. Gas neurotransmitters (gasotransmitters), such as hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO), play roles in maintaining synaptic plasticity and in helping to restore such plasticity in the neuronal architecture in the central nervous system (CNS). Indeed, the upregulation or downregulation of these gasotransmitters may cause neuropsychiatric conditions, and their amelioration may restore synaptic plasticity and proper neuronal functioning and thereby improve such conditions. Understanding the specific molecular mechanisms underpinning these effects can help identify ways to treat these neuropsychiatric conditions.

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Neural plasticity and emotional memory

Development and Psychopathology ◽

10.1017/s0954579498001898 ◽

1998 ◽

Vol 10 (4) ◽

pp. 829-855 ◽

Cited By ~ 47

Author(s):

R. M. POST ◽

S. R. B. WEISS ◽

H. LI ◽

M. A. SMITH ◽

L. X. ZHANG ◽

...

Keyword(s):

Neural Plasticity ◽

Molecular Mechanisms ◽

Emotional Memory ◽

Neonatal Rat ◽

Prior History ◽

Rat Pups ◽

Life Threatening ◽

History Of ◽

And Behavior

Posttraumatic stress disorder is the pathological replay of emotional memory formed in response to painful, life-threatening, or horrifying events. In contrast, depression is often precipitated by more social context-related stressors. New data suggest that different types of life experiences can differentially impact biochemistry, physiology, anatomy, and behavior at the level of changes in gene expression. Repeated separation of neonatal rat pups from their mother results in many long-lasting alterations in biology and behavior paralleling that in depression, including hypercortisolism. The role of the amygdala in modulating emotional memory is highlighted, as well as some of its unique properties such as metaplasticity (i.e., the differential direction of long-term adaptation, either potentiation or depression) in response to the same input as a function of the prior history of stimulation. The implications of these emerging data on the physiological and molecular mechanisms underlying emotional memory emphasize the particular importance of prevention and early intervention.

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Chronic restraint stress induces changes in the cerebral Galpha 12/13 and Rho-GTPase signaling network

Pharmacological Reports ◽

10.1007/s43440-021-00294-4 ◽

2021 ◽

Author(s):

Katarzyna Rafa-Zabłocka ◽

Agnieszka Zelek-Molik ◽

Beata Tepper ◽

Piotr Chmielarz ◽

Grzegorz Kreiner ◽

...

Keyword(s):

Mrna Expression ◽

Neural Plasticity ◽

Intracellular Signaling ◽

Restraint Stress ◽

Molecular Mechanisms ◽

Rho Gtpase ◽

Brain Regions ◽

Neuronal Morphology ◽

Stress Effects ◽

Neuropsychiatric Diseases

Abstract Background Evidence indicates that Gα12, Gα13, and its downstream effectors, RhoA and Rac1, regulate neuronal morphology affected by stress. This study was aimed at investigating whether repeated stress influences the expression of proteins related to the Gα12/13 intracellular signaling pathway in selected brain regions sensitive to the effects of stress. Furthermore, the therapeutic impact of β(1)adrenergic receptors (β1AR) blockade was assessed. Methods Restraint stress (RS) model in mice (2 h/14 days) was used to assess prolonged stress effects on the mRNA expression of Gα12, Gα13, RhoA, Rac1 in the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY). In a separate study, applying RS model in rats (3–4 h/1 day or 14 days), we evaluated stress effects on the expression of Gα12, Gα11, Gαq, RhoA, RhoB, RhoC, Rac1/2/3 in the HIP. Betaxolol (BET), a selective β1AR antagonist, was introduced (5 mg/kg/p.o./8–14 days) in the rat RS model to assess the role of β1AR in stress effects. RT-qPCR and Western Blot were used for mRNA and protein assessments, respectively. Results Chronic RS decreased mRNA expression of Gα12 and increased mRNA for Rac1 in the PFC of mice. In the mice AMY, decreased mRNA expression of Gα12, Gα13 and RhoA was observed. Fourteen days of RS exposure increased RhoA protein level in the rats’ HIP in the manner dependent on β1AR activity. Conclusions Together, these results suggest that repeated RS affects the expression of genes and proteins known to be engaged in neural plasticity, providing potential targets for further studies aimed at unraveling the molecular mechanisms of stress-related neuropsychiatric diseases.

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The Prolactin Family of Hormones as Regulators of Maternal Mood and Behavior

Frontiers in Global Women's Health ◽

10.3389/fgwh.2021.767467 ◽

2021 ◽

Vol 2 ◽

Author(s):

Teodora Georgescu ◽

Judith M. Swart ◽

David R. Grattan ◽

Rosemary S. E. Brown

Keyword(s):

Mental Health Problems ◽

Maternal Mental Health ◽

Brain Regions ◽

Placental Lactogen ◽

Hormonal Changes ◽

Aberrant Expression ◽

Major Barrier ◽

Pregnancy And Lactation ◽

Lactogenic Hormones ◽

And Behavior

Transition into motherhood involves profound physiological and behavioral adaptations that ensure the healthy development of offspring while maintaining maternal health. Dynamic fluctuations in key hormones during pregnancy and lactation induce these maternal adaptations by acting on neural circuits in the brain. Amongst these hormonal changes, lactogenic hormones (e.g., prolactin and its pregnancy-specific homolog, placental lactogen) are important regulators of these processes, and their receptors are located in key brain regions controlling emotional behaviors and maternal responses. With pregnancy and lactation also being associated with a marked elevation in the risk of developing mood disorders, it is important to understand how hormones are normally regulating mood and behavior during this time. It seems likely that pathological changes in mood could result from aberrant expression of these hormone-induced behavioral responses. Maternal mental health problems during pregnancy and the postpartum period represent a major barrier in developing healthy mother-infant interactions which are crucial for the child's development. In this review, we will examine the role lactogenic hormones play in driving a range of specific maternal behaviors, including motivation, protectiveness, and mother-pup interactions. Understanding how these hormones collectively act in a mother's brain to promote nurturing behaviors toward offspring will ultimately assist in treatment development and contribute to safeguarding a successful pregnancy.

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Neuromolecular and behavioral effects of ethanol deprivation in Drosophila

10.1101/2021.01.02.425101 ◽

2021 ◽

Author(s):

Natalie M. D’Silva ◽

Katie S. McCullar ◽

Ashley Conard ◽

Tyler Blackwater ◽

Reza Azanchi ◽

...

Keyword(s):

Neural Plasticity ◽

Molecular Mechanisms ◽

Social Behaviors ◽

Alcohol Exposure ◽

Brain Regions ◽

Exposure Model ◽

Brain Gene Expression ◽

Expression Of Genes ◽

Sensory Responses ◽

The Impact

AbstractAlcohol use disorder (AUD) is characterized by loss of control in limiting alcohol intake. This may involve intermittent periods of abstinence followed by alcohol seeking and, consequently, relapse. However, little is understood of the molecular mechanisms underlying the impact of alcohol deprivation on behavior. Using a new Drosophila melanogaster repeated intermittent alcohol exposure model, we sought to identify how ethanol deprivation alters spontaneous behavior, determine the associated neural structures, and reveal correlated changes in brain gene expression. We found that repeated intermittent ethanol exposures followed by ethanol-deprivation dynamically induces behaviors associated with a negative affect state. Although behavioral states broadly mapped to many brain regions, persistent changes in social behaviors mapped to the mushroom body and surrounding neuropil. This occurred concurrently with changes in expression of genes associated with sensory responses, neural plasticity, and immunity. Like social behaviors, immune response genes were upregulated following three-day repeated intermittent ethanol-exposures and persisted with one or two days of ethanol-deprivation, suggesting an enduring change in molecular function. Our study provides a framework for identifying how ethanol deprivation alters behavior with correlated underlying circuit and molecular changes.

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Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine

Life ◽

10.3390/life11070683 ◽

2021 ◽

Vol 11 (7) ◽

pp. 683

Author(s):

Zdenka Drastichova ◽

Lucie Hejnova ◽

Radka Moravcova ◽

Jiri Novotny

Keyword(s):

Synaptic Plasticity ◽

Proteomic Analysis ◽

Molecular Mechanisms ◽

Brain Regions ◽

Morphine Withdrawal ◽

Synaptic Proteins ◽

Label Free ◽

Presynaptic Nerve Terminal ◽

Cytoskeleton Organization ◽

Associated Proteins

Drug withdrawal is associated with abstinence symptoms including deficits in cognitive functions that may persist even after prolonged discontinuation of drug intake. Cognitive deficits are, at least partially, caused by alterations in synaptic plasticity but the precise molecular mechanisms have not yet been fully identified. In the present study, changes in proteomic and phosphoproteomic profiles of selected brain regions (cortex, hippocampus, striatum, and cerebellum) from rats abstaining for six months after cessation of chronic treatment with morphine were determined by label-free quantitative (LFQ) proteomic analysis. Interestingly, prolonged morphine withdrawal was found to be associated especially with alterations in protein phosphorylation and to a lesser extent in protein expression. Gene ontology (GO) term analysis revealed enrichment in biological processes related to synaptic plasticity, cytoskeleton organization, and GTPase activity. More specifically, significant changes were observed in proteins localized in synaptic vesicles (e.g., synapsin-1, SV2a, Rab3a), in the active zone of the presynaptic nerve terminal (e.g., Bassoon, Piccolo, Rims1), and in the postsynaptic density (e.g., cadherin 13, catenins, Arhgap35, Shank3, Arhgef7). Other differentially phosphorylated proteins were associated with microtubule dynamics (microtubule-associated proteins, Tppp, collapsin response mediator proteins) and the actin–spectrin network (e.g., spectrins, adducins, band 4.1-like protein 1). Taken together, a six-month morphine withdrawal was manifested by significant alterations in the phosphorylation of synaptic proteins. The altered phosphorylation patterns modulating the function of synaptic proteins may contribute to long-term neuroadaptations induced by drug use and withdrawal.

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Is Sleep Essential for Neural Plasticity in Humans, and How Does It Affect Motor and Cognitive Recovery?

Neural Plasticity ◽

10.1155/2013/103949 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 26

Author(s):

Maurizio Gorgoni ◽

Aurora D'Atri ◽

Giulia Lauri ◽

Paolo Maria Rossini ◽

Fabio Ferlazzo ◽

...

Keyword(s):

Synaptic Plasticity ◽

Sleep Quality ◽

Beneficial Effect ◽

Neural Plasticity ◽

Point Of View ◽

Specific Nature ◽

Synaptic Homeostasis ◽

Recovery Processes ◽

Cortical Topography ◽

Underlying Mechanisms

There is a general consensus that sleep is strictly linked to memory, learning, and, in general, to the mechanisms of neural plasticity, and that this link may directly affect recovery processes. In fact, a coherent pattern of empirical findings points to beneficial effect of sleep on learning and plastic processes, and changes in synaptic plasticity during wakefulness induce coherent modifications in EEG slow wave cortical topography during subsequent sleep. However, the specific nature of the relation between sleep and synaptic plasticity is not clear yet. We reported findings in line with two models conflicting with respect to the underlying mechanisms, that is, the “synaptic homeostasis hypothesis” and the “consolidation” hypothesis, and some recent results that may reconcile them. Independently from the specific mechanisms involved, sleep loss is associated with detrimental effects on plastic processes at a molecular and electrophysiological level. Finally, we reviewed growing evidence supporting the notion that plasticity-dependent recovery could be improved managing sleep quality, while monitoring EEG during sleep may help to explain how specific rehabilitative paradigms work. We conclude that a better understanding of the sleep-plasticity link could be crucial from a rehabilitative point of view.

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Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning

10.1101/2020.11.24.396887 ◽

2020 ◽

Author(s):

Matthew R Baker ◽

Ryan Y Wong

Keyword(s):

Neural Plasticity ◽

Coping Style ◽

Molecular Mechanisms ◽

Conditioned Fear ◽

Coping Styles ◽

Brain Regions ◽

Contextual Fear Conditioning ◽

Fear Learning ◽

Stress Coping ◽

Contextual Fear

AbstractLearning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive-reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4a and gabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the magnitude of expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.

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The emergence of molecular systems neuroscience

Molecular Brain ◽

10.1186/s13041-021-00885-5 ◽

2022 ◽

Vol 15 (1) ◽

Author(s):

Yang Shen ◽

Alessandro Luchetti ◽

Giselle Fernandes ◽

Won Do Heo ◽

Alcino J. Silva

Keyword(s):

Molecular Mechanisms ◽

Brain Regions ◽

Spatial And Temporal Patterns ◽

Molecular Systems ◽

Systems Neuroscience ◽

Molecular Approaches ◽

Electrophysiological Recordings ◽

Brain States ◽

And Behavior ◽

The Brain

AbstractSystems neuroscience is focused on how ensemble properties in the brain, such as the activity of neuronal circuits, gives rise to internal brain states and behavior. Many of the studies in this field have traditionally involved electrophysiological recordings and computational approaches that attempt to decode how the brain transforms inputs into functional outputs. More recently, systems neuroscience has received an infusion of approaches and techniques that allow the manipulation (e.g., optogenetics, chemogenetics) and imaging (e.g., two-photon imaging, head mounted fluorescent microscopes) of neurons, neurocircuits, their inputs and outputs. Here, we will review novel approaches that allow the manipulation and imaging of specific molecular mechanisms in specific cells (not just neurons), cell ensembles and brain regions. These molecular approaches, with the specificity and temporal resolution appropriate for systems studies, promise to infuse the field with novel ideas, emphases and directions, and are motivating the emergence of a molecularly oriented systems neuroscience, a new discipline that studies how the spatial and temporal patterns of molecular systems modulate circuits and brain networks, and consequently shape the properties of brain states and behavior.

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