Early postnatal development of pyramidal neurons across layers of the mouse medial prefrontal cortex

Kroon, Tim; Hugte, Eline J.H. van; Linge, Lola van; Mansvelder, Huibert D.; Meredith, Rhiannon M.

doi:10.1038/s41598-019-41661-9

Cited by 100 publications

(99 citation statements)

References 65 publications

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“…Rapid increase of the OTR expression in P14-21 corresponds with the peak time of synaptic formation and maturation in rodent brains 56,57 . Synaptic maturation patterns differ in cortical layers during early postnatal periods 58,59 . For example, tactile stimulus specific activity pattern emerges in the superficial layers of the barrel cortex that is subsequently followed by deep layer maturation in mice 59 .…”

Section: Discussionmentioning

confidence: 99%

Quantitative cellular-resolution map of the oxytocin receptor in postnatally developing mouse brains

et al. 2020

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The oxytocin receptor (OTR) plays critical roles in social behavior development. Despite its significance, brain-wide quantitative understanding of OTR expression remains limited in postnatally developing brains. Here, we develop postnatal 3D template brains to register whole brain images with cellular resolution to systematically quantify OTR cell densities. We utilize fluorescent reporter mice (Otr venus/+) and find that cortical regions show temporally and spatially heterogeneous patterns with transient postnatal OTR expression without cell death. Cortical OTR cells are largely glutamatergic neurons with the exception of cells in layer 6b. Subcortical regions show similar temporal regulation except the hypothalamus and two hypothalamic nuclei display sexually dimorphic OTR expression. Lack of OTR expression correlates with reduced dendritic spine densities in selected cortical regions of developing brains. Lastly, we create a website to visualize our high-resolution imaging data. In summary, our research provides a comprehensive resource for postnatal OTR expression in the mouse brain.

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Section: Discussionmentioning

confidence: 99%

Quantitative cellular-resolution map of the oxytocin receptor in postnatally developing mouse brains

et al. 2020

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“…In addition, this period corresponds to an important stage in the initiation of neural circuit formation, which includes dendritic outgrowth and synaptic production in the mPFC. In fact, it has been reported that a developmental peak in prefrontal cortex volume occurs from the first to the second week after birth [36], and dendritic arborization and length in the mPFC rapidly increase during this period [37,38]. In addition, during the first postnatal week, mediodorsal thalamic projections precede neural circuit formation in the prefrontal cortex [39].…”

Section: Discussionmentioning

confidence: 99%

Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development

Tenkumo

Ohta

Suzuki

et al. 2020

Heliyon

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It is widely accepted that maternal separation (MS) induces stress in children and disrupts neural circuit formation during early brain development. Even though such disruption occurs transiently early in life, its influence persists after maturation, and could lead to various neurodevelopmental disorders. Our recent study revealed that repeated MS reduces the number of inhibitory neurons and synapses in the medial prefrontal cortex (mPFC) and causes mPFC-related social deficits after maturation. However, how MS impedes mPFC development during early brain development remains poorly understood. Here, we focused on brain-derived neurotrophic factor (BDNF) involved in the development of inhibitory neurons, and examined time-dependent BDNF expression in the mPFC during the pre-weaning period in male rats exposed to MS. Our results show that MS attenuates BDNF expression only around the end of the first postnatal week. Likewise, mRNA expression of activity-regulated cytoskeletonassociated protein (Arc), an immediate-early gene whose expression is partly regulated by BDNF, also decreased in the MS group along with the reduction in BDNF expression. On the contrary, mRNA expression of tropomyosinrelated kinase B (TrkB), which is a BDNF receptor, was scarcely altered, while its protein expression decreased in the MS group only during the weaning period. In addition, MS reduced mRNA levels of glutamic acid decarboxylase (GAD) 65, a GABA synthesizing enzyme, only during the weaning period. Our results suggest that repeated MS temporarily attenuates BDNF signaling in the mPFC during early brain development. BDNF plays a crucial role in the development of inhibitory neurons; therefore, transient attenuation of BDNF signaling may cause delays in GABAergic neuron development in the mPFC.

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“…Brains were harvested and mCherry+, BFP+ and GFP puncta+ neurons were analyzed at P30 (Fig. 9C), when pyramidal cortical neurons are morphologically and synaptically mature (50). Adnp deficient dendrites had significantly more puncta compared to Scramble shRNA dendrites (Fig.…”

Section: Resultsmentioning

confidence: 99%

14-3-3 shuttles Activity-dependent neuroprotective protein to the cytoplasm to promote appropriate neuronal morphogenesis, cortical connectivity and calcium signaling

Bennison

Blazejewski

Liu

et al. 2020

Preprint

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30Neurite formation is the earliest stage of neuronal morphogenesis, where primitive 31 dendrites and the primitive axon emerge from a spherical neuron and begin to elongate. Defective 32 neuritogenesis is a contributing pathogenic mechanism behind a variety of neurodevelopmental 33 disorders. Activity-dependent neuroprotective protein (Adnp) is essential to embryonic and 34 postnatal brain development, and mutations in ADNP are among the most frequent underlying 35 autism spectrum disorder (ASD). We found that knockdown of Adnp in vitro and in vivo in mouse 36 layer 2/3 pyramidal neurons leads to increased neurite initiation and defective neurite elongation, 37suggesting that Adnp has distinct roles in each. In vivo analysis revealed that deficits begin at P0 38 and are sustained throughout development, the most notable of which include increased neurite 39 stabilization, disrupted angle of the apical dendrite, increased basal dendrite number, and increased 40 axon length. Because small changes in neuronal morphology can have large-scale effects on 41 neuronal function and connectivity, we performed ex vivo calcium imaging to assess spontaneous 42 function of layer 2/3 pyramidal neurons deficient in Adnp. This revealed that Adnp deficient 43 neurons had a greater spontaneous calcium influx and a higher proportion of cells firing action 44 potentials. Next, we utilized GRAPHIC, a novel synaptic tracing technology, to assess 45 interhemispheric cortical connectivity. We found increased interhemispheric excitatory 46 connectivity between Adnp deficient layer 2/3 pyramidal neurons. Because Adnp is a 47 57Neuritogenesis is a fundamental step of cortical development essential for establishing 58 correct neuronal morphology, connectivity, and function (1, 2). Immature neurons have a spherical 59 morphology that upon maturation develops to extend a single axon and multiple dendrites (3)(4)(5)(6). 60This complex feat is driven by neuronal polarization which causes an initial break in symmetry 61 within an immature neuron, seamlessly followed by the two stages of neuritogenesis: neurite 62 initiation followed by neurite elongation (4, 7, 8). Following neuronal polarization, actin 63 aggregates form the sites of primitive neurites, precursors to the axon and dendrites (4, 9, 10). At 64 these sites, actin rich filopodia and lamellipodia rapidly extend and retract before being stabilized 65 by microtubule invasion. Microtubules then drive neurite elongation as primitive neurites are lead 66 to their appropriate destinations where they differentiate into a single axon and multiple dendrites 67 (8,(11)(12)(13)(14). It is of current interest which proteins are key players in this early developmental 68 process, particularly those which are causatively mutated in neurodevelopmental disorders. 69Following neurite formation, dendrites mature and develop intricately branched, complex 70 structures that form synaptic contacts with neighboring neurons that, when formed correctly, lead 71 to functional connectivity (1, 2, 15). The sit...

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Early postnatal development of pyramidal neurons across layers of the mouse medial prefrontal cortex

Cited by 100 publications

References 65 publications

Quantitative cellular-resolution map of the oxytocin receptor in postnatally developing mouse brains

Quantitative cellular-resolution map of the oxytocin receptor in postnatally developing mouse brains

Repeated maternal separation causes transient reduction in BDNF expression in the medial prefrontal cortex during early brain development, affecting inhibitory neuron development

14-3-3 shuttles Activity-dependent neuroprotective protein to the cytoplasm to promote appropriate neuronal morphogenesis, cortical connectivity and calcium signaling

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