Prefrontal Cortex Development in Health and Disease: Lessons from Rodents and Humans

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 44(3), P. 227 - 240

Published: Nov. 24, 2020

The role of the prefrontal cortex (PFC) takes center stage among unanswered questions in modern neuroscience. PFC has a Janus-faced nature: it enables sophisticated cognitive and social abilities that reach their maximum expression humans, yet underlies some devastating symptoms psychiatric disorders. Accordingly, appropriate development is crucial for many high-order dysregulation this process been linked to various neuropsychiatric diseases. Reviewing recent advances field, with primary focus on rodents we highlight why, despite differences across species, cross-species approach fruitful strategy understanding development. We briefly review developmental contribution molecules extensively discuss how electrical activity controls early maturation wiring areas, as well emergence refinement input-output circuitry involved processing. Finally, mechanisms dysfunction relevance

Language: Английский

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Dendritic Spine Plasticity: Function and Mechanisms

Frontiers in Synaptic Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: Aug. 28, 2020

Dendritic spines are small protrusions studding neuronal dendrites, first described in 1888 by Ramón y Cajal using his famous Golgi stainings. Around fifty years later the advance of electron microscopy confirmed Cajal's intuition that constitute postsynaptic site most excitatory synapses mammalian brain. The finding spine density decreases between young and adult ages fixed tissues suggested dynamic. It is only a decade ago two-photon has unambiguously proven dynamic nature spines, through repeated imaging single live animals. Spine dynamics comprise formation, disappearance stabilization modulated activity developmental age. Here we review several emerging concepts field start to answer following key questions: What external signals triggering molecular mechanisms involved? is, return, role circuit rewiring, learning neuropsychiatric disorders?

Language: Английский

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The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Aug. 27, 2020

Schizophrenia is a disorder with heterogeneous etiology involving complex interplay between genetic and environmental risk factors. The immune system now known to play vital roles in nervous function pathology through regulating neuronal glial development, synaptic plasticity, behavior. In this regard, the positioned as common link seemingly diverse factors for schizophrenia. Synthesizing information about how immune-brain axis affected by multiple these might interact schizophrenia necessary better understand pathogenesis of disease. Such knowledge will aid development more translatable animal models that may lead effective therapeutic interventions. Here, we provide an overview modulate function. We also explore including exposure pollution, gut dysbiosis, maternal activation early-life stress, consequences are linked microglial dysfunction. propose morphological signaling deficits blood-brain barrier, observed some individuals schizophrenia, can act gateway peripheral central inflammation, thus affecting microglia their essential functions. Finally, describe response neuroinflammation impact on brain homeostasis, well pathophysiology.

Language: Английский

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An increase of inhibition drives the developmental decorrelation of neural activity

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Aug. 17, 2022

Throughout development, the brain transits from early highly synchronous activity patterns to a mature state with sparse and decorrelated neural activity, yet mechanisms underlying this process are poorly understood. The developmental transition has important functional consequences, as latter is thought allow for more efficient storage, retrieval, processing of information. Here, we show that, in mouse medial prefrontal cortex (mPFC), during first two postnatal weeks decorrelates following specific spatial patterns. This accompanied by concomitant tilting excitation-inhibition (E-I) ratio toward inhibition. Using optogenetic manipulations network modeling, that phenomena mechanistically linked, relative increase inhibition drives decorrelation activity. Accordingly, mice mimicking etiology neurodevelopmental disorders, subtle alterations E-I associated impairments correlational structure spike trains. Finally, capitalizing on EEG data newborn babies, an analogous takes place also human brain. Thus, changes control (de)correlation and, these means, its imbalance might contribute pathogenesis disorders.

Language: Английский

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The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: July 29, 2022

Gamma oscillation is the synchronization with a frequency of 30-90 Hz neural oscillations, which are rhythmic electric processes neuron groups in brain. The inhibitory interneuron network necessary for production gamma but certain disruptions such as brain inflammation, oxidative stress, and metabolic imbalances can cause this to malfunction. oscillations specifically control connectivity between different regions, crucial perception, movement, memory, emotion. Studies have linked abnormal conditions central nervous system, including Alzheimer's disease, Parkinson's schizophrenia. Evidence suggests that entrainment using sensory stimuli (GENUS) provides significant neuroprotection. This review discusses function advanced activities from both physiological pathological standpoint, it emphasizes potential therapeutic approach range neuropsychiatric diseases.

Language: Английский

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Histamine, Neuroinflammation and Neurodevelopment: A Review

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: July 14, 2021

The biogenic amine, histamine, has been shown to critically modulate inflammatory processes as well the properties of neurons and synapses in brain, is also implicated emergence neurodevelopmental disorders. Indeed, a reduction synthesis this neuromodulator associated with disorders Tourette's syndrome obsessive-compulsive disorder, evidence that may be through disruption corticostriatal circuitry during development. Furthermore, neuroinflammation alterations brain development, e.g., impacting synaptic plasticity synaptogenesis, there are suggestions histamine deficiency leave developing more vulnerable proinflammatory insults. While most studies have focused on neuronal sources it remains unclear what extent other (non-neuronal) from mast cells sources, can impact few started exploring

Language: Английский

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A transient developmental increase in prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice

Neuron, Journal Year: 2021, Volume and Issue: 109(8), P. 1350 - 1364.e6

Published: March 7, 2021

Disturbed neuronal activity in neuropsychiatric pathologies emerges during development and might cause multifold dysfunction by interfering with apoptosis, dendritic growth, synapse formation. However, how altered electrical early life affects function behavior adults is unknown. Here, we address this question transiently increasing the coordinated of layer 2/3 pyramidal neurons medial prefrontal cortex neonatal mice monitoring long-term functional behavioral consequences. We show that increased causes premature maturation interneuronal density. Consequently, inhibitory feedback fast-spiking interneurons excitation/inhibition imbalance circuits young result weaker evoked synchronization gamma frequency. These structural changes ultimately lead to poorer mnemonic social abilities. Thus, actively controls cognitive performance be critical for symptoms diseases.

Language: Английский

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Episodic memory development: Bridging animal and human research

Neuron, Journal Year: 2024, Volume and Issue: 112(7), P. 1060 - 1080

Published: Feb. 14, 2024

Human episodic memory is not functionally evident until about 2 years of age and continues to develop into the school years. Behavioral studies have elucidated this developmental timeline its constituent processes. In tandem, lesion neurophysiological in non-human primates rodents identified key neural substrates circuit mechanisms that may underlie development. Despite progress, collaborative efforts between psychologists neuroscientists remain limited, hindering progress. Here, we seek bridge human development research by offering a comparative review using humans, primates, rodents. We highlight critical theoretical methodological issues limit cross-fertilization propose common framework, adaptable different species, facilitate cross-species endeavors.

Language: Английский

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Gamma activity accelerates during prefrontal development

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 18, 2020

Gamma oscillations are a prominent activity pattern in the cerebral cortex. While gamma rhythms have been extensively studied adult prefrontal cortex context of cognitive (dys)functions, little is known about their development. We addressed this issue by using extracellular recordings and optogenetic stimulations mice across postnatal show that fast rhythmic becomes during second week. initially at 15 Hz, oscillatory progressively accelerates with age stabilizes within frequency range (30-80 Hz) fourth Activation layer 2/3 pyramidal neurons drives throughout development, yet acceleration follows similar temporal dynamics as maturation fast-spiking interneurons. These findings uncover development provide framework to examine origin abnormal neurodevelopmental disorders.

Language: Английский

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Systemic LPS-induced microglial activation results in increased GABAergic tone: A mechanism of protection against neuroinflammation in the medial prefrontal cortex in mice

Brain Behavior and Immunity, Journal Year: 2021, Volume and Issue: 99, P. 53 - 69

Published: Sept. 27, 2021

Neuroinflammation with excess microglial activation and synaptic dysfunction are early symptoms of most neurological diseases. However, how microglia-associated neuroinflammation regulates activity remains obscure. We report here that acute induced by intraperitoneal injection lipopolysaccharide (LPS) results in cell-type-specific increases inhibitory postsynaptic currents the glutamatergic, but not GABAergic, neurons medial prefrontal cortex (mPFC), coinciding excessive activation. LPS causes upregulation levels GABAAR subunits, glutamine synthetase vesicular GABA transporter, downregulation brain-derived neurotrophic factor (BDNF) its receptor, pTrkB. Blockage minocycline ameliorates LPS-induced abnormal expression signaling-related proteins network. Moreover, prevents mice from aberrant behavior, such as a reduction total distance time spent centre open field test; decreases entries into arm elevated-plus maze consumption sucrose; increased immobility tail suspension test. Furthermore, signaling tiagabine also behavior. This study illustrates mode bidirectional constitutive between neural immune compartments brain, suggests mPFC is an important area for brain-immune system communication. present highlights GABAergic key therapeutic target mitigating neuroinflammation-induced mPFC, together associated behavioral abnormalities.

Language: Английский

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