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

---

Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences

Journal of Neuroscience, Journal Year: 2018, Volume and Issue: 38(24), P. 5441 - 5455

Published: May 21, 2018

Neocortical pyramidal neurons with somata in layers 5 and 6 are among the most visually striking enigmatic brain. These deep-layer (DLPNs) integrate a plethora of cortical extracortical synaptic inputs along their impressive dendritic arbors. The pattern output to both local long-distance targets is sculpted by unique physiological properties specific DLPN subpopulations. Here we revisit two broad subpopulations: those that send axons within telencephalon (intratelencephalic neurons) project additional target areas outside (extratelencephalic neurons). While neuroscientists across many subdisciplines have characterized intrinsic subpopulations, our increasing ability selectively manipulate these neuron subtypes advances understanding distinct functional contributions. This Viewpoints article summarizes current knowledge about DLPNs highlights recent work elucidating differences between

Language: Английский

---

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

---

Early-life stress impairs postnatal oligodendrogenesis and adult emotional behaviour through activity-dependent mechanisms

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 25(6), P. 1159 - 1174

Published: Aug. 22, 2019

Exposure to stress during early life (infancy/childhood) has long-term effects on the structure and function of prefrontal cortex (PFC), increases risk for adult depression anxiety disorders. However, little is known about molecular cellular mechanisms these effects. Here, we focused changes induced by chronic maternal separation first 2 weeks postnatal life. Unbiased mRNA expression profiling in medial PFC (mPFC) maternally separated (MS) pups identified an increased myelin-related genes a decreased immediate genes. Oligodendrocyte lineage markers birthdating experiments indicated precocious oligodendrocyte differentiation mPFC at P15, leading depletion progenitor pool MS adults. We tested role neuronal activity oligodendrogenesis, using designed receptors exclusively activated drugs (DREADDs) techniques. hM4Di or hM3Dq constructs were transfected into neurons fast-acting AAV8 viruses. Reduction neuron excitability caused premature oligodendrocytes similar pups, while chemogenetic activation normalised it animals. Bidirectional manipulation P2–P14 period had long lasting emotional behaviours temporal object recognition: mimicked effects, prevented pro-depressive short-term memory impairment MS. Thus, our results identify as critical target early-life demonstrate its controlling both oligodendrogenesis mPFC-related behaviours.

Language: Английский

---

Microglia: Brain cells on the move

Progress in Neurobiology, Journal Year: 2019, Volume and Issue: 178, P. 101612 - 101612

Published: April 4, 2019

Language: Английский

---

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

---

Whole-brain mapping of effective connectivity by fMRI with cortex-wide patterned optogenetics

Neuron, Journal Year: 2023, Volume and Issue: 111(11), P. 1732 - 1747.e6

Published: March 30, 2023

Language: Английский

---

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

---

Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density

Journal of Neuroscience Research, Journal Year: 2018, Volume and Issue: 97(5), P. 620 - 638

Published: Dec. 26, 2018

Abstract Electrical stimulation of the brain has become a mainstay fundamental neuroscience research and an increasingly prevalent clinical therapy. Despite decades use in basic growing prevalence neuromodulation therapies, gaps knowledge regarding activation or inactivation neural elements over time have limited its ability to adequately interpret evoked downstream responses fine‐tune parameters focus on desired responses. In this work, vivo two‐photon microscopy was used image neuronal calcium activity layer 2/3 neurons somatosensory cortex (S1) male C57BL/6J‐Tg(Thy1‐GCaMP6s)GP4.3Dkim/J mice during 30 s continuous electrical at varying frequencies. We show frequency–dependent differences spatial temporal somatic stimulation. Our results elucidate conflicting from prior studies reporting either dense spherical somas biased toward those near electrode, sparse distance via axons electrode. These findings indicate that element specific response local stimulating electrode changes as function applied charge density frequency. need be considered properly circuit determining mechanisms action science experiments therapeutic applications.

Language: Английский

---

Modulation of Neocortical Development by Early Neuronal Activity: Physiology and Pathophysiology

Frontiers in Cellular Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: Nov. 29, 2017

Animal and human studies revealed that patterned neuronal activity is an inherent feature of developing nervous systems. This review summarizes our current knowledge about the mechanisms generating early electrical patterns their impact on structural functional development cerebral cortex. All neocortical areas display distinct spontaneous sensory-driven already at phases development. At embryonic stages, intermittent synchronized within small networks, becoming more complex with further transition accompanied by a gradual shift from to chemical synaptic transmission, particular role non-synaptic tonic currents before onset phasic activity. In this article we first describe impacts classical neurotransmitters (GABA, glutamate) modulatory systems (e.g. acetylcholine) activities in neocortex special emphasis synapses, nonsynaptic currents. Early influences probably all developmental processes crucial for proper formation circuits. second part review, illustrate how specific might interfere neurodevelopmental like proliferation, migration, axonal dendritic sprouting, synapse neurotransmitter specification. Finally, present evidence transient alterations during restricted perinatal periods can lead persistent changes connectivity therefore underlie manifestation neurological neuropsychiatric diseases.

Language: Английский

---