scholarly journals Disruption of Transient SERT Expression in Thalamic Glutamatergic Neurons Alters Trajectory of Postnatal Interneuron Development in the Mouse Cortex

2019 ◽  
Vol 30 (3) ◽  
pp. 1623-1636 ◽  
Author(s):  
Roberto De Gregorio ◽  
Xiaoning Chen ◽  
Emilie I Petit ◽  
Kostantin Dobrenis ◽  
Ji Ying Sze

Abstract In mice, terminal differentiation of subpopulations of interneurons occurs in late postnatal stages, paralleling the emergence of the adult cortical architecture. Here, we investigated the effects of altered initial cortical architecture on later interneuron development. We identified that a class of somatostatin (SOM)-expressing GABAergic interneurons undergoes terminal differentiation between 2nd and 3rd postnatal week in the mouse somatosensory barrel cortex and upregulates Reelin expression during neurite outgrowth. Our previous work demonstrated that transient expression (E15-P10) of serotonin uptake transporter (SERT) in thalamocortical projection neurons regulates barrel elaboration during cortical map establishment. We show here that in thalamic neuron SERT knockout mice, these SOM-expressing interneurons develop at the right time, reach correct positions and express correct neurochemical markers, but only 70% of the neurons remain in the adult barrel cortex. Moreover, those neurons that remain display altered dendritic patterning. Our data indicate that a precise architecture at the cortical destination is not essential for specifying late-developing interneuron identities, their cortical deposition, and spatial organization, but dictates their number and dendritic structure ultimately integrated into the cortex. Our study illuminates how disruption of temporal-specific SERT function and related key regulators during cortical map establishment can alter interneuron development trajectory that persists to adult central nervous system.

2021 ◽  
pp. 1-14
Author(s):  
Fangmei He ◽  
Yuchen Zhang ◽  
Xiaofeng Wu ◽  
Youjun Li ◽  
Jie Zhao ◽  
...  

Background: Amnestic mild cognitive impairment (aMCI) is the transitional stage between normal aging and Alzheimer’s disease (AD). Some aMCI patients will progress into AD eventually, whereas others will not. If the trajectory of aMCI can be predicted, it would enable early diagnosis and early therapy of AD. Objective: To explore the development trajectory of aMCI patients, we used diffusion tensor imaging to analyze the white matter microstructure changes of patients with different trajectories of aMCI. Methods: We included three groups of subjects:1) aMCI patients who convert to AD (MCI-P); 2) aMCI patients who remain in MCI status (MCI-S); 3) normal controls (NC). We analyzed the fractional anisotropy and mean diffusion rate of brain regions, and we adopted logistic binomial regression model to predicate the development trajectory of aMCI. Results: The fraction anisotropy value is significantly reduced, the mean diffusivity value is significantly increased in the two aMCI patient groups, and the MCI-P patients presented greater changes. Significant changes are mainly located in the cingulum, fornix, hippocampus, and uncinate fasciculus. These changed brain regions significantly correlated with the patient’s Mini-Mental State Examination scores. Conclusion: The study predicted the disease trajectory of different types of aMCI patients based on the characteristic values of the above-mentioned brain regions. The prediction accuracy rate can reach 90.2%, and the microstructure characteristics of the right cingulate band and the right hippocampus may have potential clinical application value to predict the disease trajectory.


2019 ◽  
Vol 13 ◽  
pp. 117906951982605
Author(s):  
Chi-Jen Yang ◽  
Kuo-Ting Tsai ◽  
Nan-Fu Liou ◽  
Ya-Hui Chou

The Drosophila olfactory system is an attractive model for exploring the wiring logic of complex neural circuits. Remarkably, olfactory local interneurons exhibit high diversity and variability in their morphologies and intrinsic properties. Although olfactory sensory and projection neurons have been extensively studied of development and wiring; the development, mechanisms for establishing diversity, and integration of olfactory local interneurons into the developing circuit remain largely undescribed. In this review, we discuss some challenges and recent advances in the study of Drosophila olfactory interneurons.


2020 ◽  
Vol 40 (40) ◽  
pp. 7637-7650 ◽  
Author(s):  
Shingo Nakazawa ◽  
Yumiko Yoshimura ◽  
Masahiro Takagi ◽  
Hidenobu Mizuno ◽  
Takuji Iwasato

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anamika Agrawal ◽  
Gulcin Pekkurnaz ◽  
Elena F Koslover

Eukaryotic cells modulate their metabolism by organizing metabolic components in response to varying nutrient availability and energy demands. In rat axons, mitochondria respond to glucose levels by halting active transport in high glucose regions. We employ quantitative modeling to explore physical limits on spatial organization of mitochondria and localized metabolic enhancement through regulated stopping of processive motion. We delineate the role of key parameters, including cellular glucose uptake and consumption rates, that are expected to modulate mitochondrial distribution and metabolic response in spatially varying glucose conditions. Our estimates indicate that physiological brain glucose levels fall within the limited range necessary for metabolic enhancement. Hence mitochondrial localization is shown to be a plausible regulatory mechanism for neuronal metabolic flexibility in the presence of spatially heterogeneous glucose, as may occur in long processes of projection neurons. These findings provide a framework for the control of cellular bioenergetics through organelle trafficking.


2020 ◽  
Author(s):  
Georg Hafner ◽  
Julien Guy ◽  
Mirko Witte ◽  
Pavel Truschow ◽  
Alina Rüppel ◽  
...  

Abstract The neocortex is composed of layers. Whether layers constitute an essential framework for the formation of functional circuits is not well understood. We investigated the brain-wide input connectivity of vasoactive intestinal polypeptide (VIP) expressing neurons in the reeler mouse. This mutant is characterized by a migration deficit of cortical neurons so that no layers are formed. Still, neurons retain their properties and reeler mice show little cognitive impairment. We focused on VIP neurons because they are known to receive strong long-range inputs and have a typical laminar bias toward upper layers. In reeler, these neurons are more dispersed across the cortex. We mapped the brain-wide inputs of VIP neurons in barrel cortex of wild-type and reeler mice with rabies virus tracing. Innervation by subcortical inputs was not altered in reeler, in contrast to the cortical circuitry. Numbers of long-range ipsilateral cortical inputs were reduced in reeler, while contralateral inputs were strongly increased. Reeler mice had more callosal projection neurons. Hence, the corpus callosum was larger in reeler as shown by structural imaging. We argue that, in the absence of cortical layers, circuits with subcortical structures are maintained but cortical neurons establish a different network that largely preserves cognitive functions.


1996 ◽  
Vol 16 (6) ◽  
pp. 1300-1306 ◽  
Author(s):  
Johannes Vogel ◽  
Wolfgang Kuschinsky

The pattern of capillary plasma perfusion was investigated in the rat brain during functional activation. Functional hyperemia was induced in the left whisker-barrel cortex by deflection of the right mystacial vibrissae for 2 min at frequencies of 1–7 Hz. Rats were decapitated under anesthesia 3 s after i.v. bolus injection of Evans blue dye. The steep increase of the arterial dye concentration ensures that divergent capillary plasma transit times result in unequal intracapillary dye concentrations. Plasma perfusion heterogeneity was determined from the coefficient of variation (CV) of Evans blue concentrations measured in numerous single capillaries of the whisker-barrel cortex. Functional hyperemia was quantified from measurements of CBF using the [14C]-iodoantipyrine technique in a second experimental group. CBF in the left whisker-barrel cortex increased with the stimulation frequency and was maximal at 5 Hz compared to the right side. Conversely, plasma perfusion heterogeneity decreased with stimulation frequency in a reciprocal way, being minimal at 5 Hz. Results indicate a decrease in the microcirculatory flow heterogeneity during functional hyperemia in the brain.


1975 ◽  
Vol 37 (1) ◽  
pp. 159-166 ◽  
Author(s):  
Henry I. Stukuls

The two studies extended the principles of clustering to nonverbal stimuli. College Ss were asked to learn and recall random objects under varied conditions of exposure time and spatial organization. Increments in exposure time produced increments in total recall and clustering. Also the spatial organization of stimuli facilitated total recall and the organizational process in memory. The greatest amount of recall and clustering occurred with objects from the left as opposed to the right side of the visual display and increased spatial organization of relatively random display produced increased amounts of clustering in free recall. These data for 72 students were interpreted in terms of the associationistic (Jenkins, 1952) and the mediational (Bousfield, 1953) views of clustering.


2003 ◽  
Vol 90 (5) ◽  
pp. 2987-3000 ◽  
Author(s):  
Michael Beierlein ◽  
Jay R. Gibson ◽  
Barry W. Connors

Normal operations of the neocortex depend critically on several types of inhibitory interneurons, but the specific function of each type is unknown. One possibility is that interneurons are differentially engaged by patterns of activity that vary in frequency and timing. To explore this, we studied the strength and short-term dynamics of chemical synapses interconnecting local excitatory neurons (regular-spiking, or RS, cells) with two types of inhibitory interneurons: fast-spiking (FS) cells, and low-threshold spiking (LTS) cells of layer 4 in the rat barrel cortex. We also tested two other pathways onto the interneurons: thalamocortical connections and recurrent collaterals from corticothalamic projection neurons of layer 6. The excitatory and inhibitory synapses interconnecting RS cells and FS cells were highly reliable in response to single stimuli and displayed strong short-term depression. In contrast, excitatory and inhibitory synapses interconnecting the RS and LTS cells were less reliable when initially activated. Excitatory synapses from RS cells onto LTS cells showed dramatic short-term facilitation, whereas inhibitory synapses made by LTS cells onto RS cells facilitated modestly or slightly depressed. Thalamocortical inputs strongly excited both RS and FS cells but rarely and only weakly contacted LTS cells. Both types of interneurons were strongly excited by facilitating synapses from axon collaterals of corticothalamic neurons. We conclude that there are two parallel but dynamically distinct systems of synaptic inhibition in layer 4 of neocortex, each defined by its intrinsic spiking properties, the short-term plasticity of its chemical synapses, and (as shown previously) an exclusive set of electrical synapses. Because of their unique dynamic properties, each inhibitory network will be recruited by different temporal patterns of cortical activity.


2017 ◽  
Author(s):  
Myrto Denaxa ◽  
Guilherme Neves ◽  
Adam Rabinowitz ◽  
Sarah Kemlo ◽  
Petros Liodis ◽  
...  

AbstractCortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs) is established in the mammalian forebrain. CIs are generated in excess from basal forebrain progenitors and their final numbers are adjusted via an intrinsically determined program of apoptosis that takes place during an early postnatal window. Here, we provide evidence that the extent of CI apoptosis during this critical period is plastic, cell type specific and can be reduced in a cell autonomous manner by acute increases in neuronal activity. We propose that the physiological state of the emerging neural network controls the activity levels of local CIs to modulate their numbers in a homeostatic manner.


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