scholarly journals Intrinsic neuronal activity during migration controls the recruitment of specific interneuron subtypes in the postnatal mouse olfactory bulb

2020 ◽  
Author(s):  
Bugeon Stéphane ◽  
Haubold Clara ◽  
Ryzynski Alexandre ◽  
Cremer Harold ◽  
Platel Jean-Claude

AbstractNeuronal activity has been identified as a key regulator of neuronal network development, but the impact of activity on migration and terminal positioning of interneuron subtypes is poorly understood. The absence of early subpopulation markers and the presence of intermingled migratory and post-migratory neurons makes the developing cerebral cortex a difficult model to answer these questions. Postnatal neurogenesis in the subventricular zone offers a more accessible and compartmentalized model. Neural stem cells regionalized along the border of the lateral ventricle produce two main subtypes of neural progenitors, granule cells and periglomerular neurons that migrate tangentially in the rostral migratory stream before migrating radially in the OB layers. Here we take advantage of targeted postnatal electroporation to compare the migration of these two population. We do not observe any obvious differences regarding the mode of tangential or radial migration between these two subtypes. However, we find a very striking increase of intrinsic calcium activity only in granule cell precursors when they switch from tangential to radial migration. By decreasing neuronal excitability in granule cell precursors, we find that neuronal activity is critical for normal migratory speed at the end of tangential migration. Importantly, we also find that activity is required for normal positioning and survival of granule cell precursors in the OB layers. Strikingly, decreasing activity of periglomerular neuron precursors did not impact their positioning or survival. Altogether these findings suggest that neuronal excitability plays a subtype specific role during the late stage of migration of postnatally born olfactory bulb interneurons.Significance StatementWhile neuronal activity is a critical factor regulating different aspects of neurogenesis, it has been challenging to study its role during the migration of different neuronal subpopulations. Here, we use postnatal targeted electroporation to label and manipulate the two main olfactory bulb interneuron subpopulations during their migration: granule cell and periglomerular neuron precursors. We find a very striking increase of calcium activity only in granule cell precursors when they switch from tangential to radial migration. Interestingly, blocking activity in granule cell precursors affected their migration, positioning and survival while periglomerular neuron precursors are not affected. These results suggest that neuronal activity is required specifically for the recruitment of granule cell precursors in the olfactory bulb layers.

2017 ◽  
Author(s):  
Jeremy T. Chang ◽  
Michael J. Higley

AbstractGABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.Significance StatementGABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 183-184
Author(s):  
Shannon L Dierking ◽  
Harold J Monegue ◽  
Merlin D Lindemann

Abstract Piglet weaning weight is a critical factor that influences post-weaning growth and performance. Weaning weight is a function of birth weight and the amount and nutrient density of the milk consumed during lactation. Milk production is influenced by sow mammary gland development and diet consumption but may also be a biological function of teat location along the udder line. The objective of this study was then to determine the effects of piglet nursing location along the udder on overall piglet gain and weaning weight. A total of 1,078 individual piglets were observed during the nursing period at three time points during lactation. The teat pairs along the udder line were labeled from anterior to posterior (1-7, respectively) to define nursing location. At the end of the lactation period, the observed piglet nursing location was evaluated for both actual weaning weight and overall piglet weight gain during lactation. Data were evaluated by analysis of variance with the statistical model utilizing litter size as a covariate. As expected, when litter size was utilized as a covariate, there was a significant effect on piglet weaning weight (P < 0.0001), and there was both a linear and quadratic effect of location (L, P < 0.0001; Q, P = 0.0009) on both weaning weight and lactation piglet gain. Heavier piglets were weaned from more anterior teats (teat pairs 1-4), with the numerically heaviest piglets weaned from teat pair 4 (6.12 kg), with the lowest weight piglets being weaned from teat pair 7 (5.17 kg). Piglet weight gain during lactation was impacted by litter size (P < 0.0001), but nursing location did not affect lactation weight gain (P = 0.57). Due to the differences in piglet weights at weaning, it can be concluded that piglet nursing location influences overall piglet weaning weight.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3909
Author(s):  
Melissa S. Totten ◽  
Derek M. Pierce ◽  
Keith M. Erikson

The aim of this study was to determine the impact of diet-induced obesity (DIO) on trace element homeostasis and gene expression in the olfactory bulb and to identify potential interaction effects between diet, sex, and strain. Our study is based on evidence that obesity and olfactory bulb impairments are linked to neurodegenerative processes. Briefly, C57BL/6J (B6J) and DBA/2J (D2J) male and female mice were fed either a low-fat diet or a high-fat diet for 16 weeks. Brain tissue was then evaluated for iron, manganese, copper, and zinc concentrations and mRNA gene expression. There was a statistically significant diet-by-sex interaction for iron and a three-way interaction between diet, sex, and strain for zinc in the olfactory bulb. Obese male B6J mice had a striking 75% increase in iron and a 50% increase in manganese compared with the control. There was an increase in zinc due to DIO in B6J males and D2J females, but a decrease in zinc in B6J females and D2J males. Obese male D2J mice had significantly upregulated mRNA gene expression for divalent metal transporter 1, alpha-synuclein, amyloid precursor protein, dopamine receptor D2, and tyrosine hydroxylase. B6J females with DIO had significantly upregulated brain-derived neurotrophic factor expression. Our results demonstrate that DIO has the potential to disrupt trace element homeostasis and mRNA gene expression in the olfactory bulb, with effects that depend on sex and genetics. We found that DIO led to alterations in iron and manganese predominantly in male B6J mice, and gene expression dysregulation mainly in male D2J mice. These results have important implications for health outcomes related to obesity with possible connections to neurodegenerative disease.


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