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Experimental Neurology Mar 2017The habenula is activated in response to stressful and aversive events, resulting in exploratory inhibition. Although possible mechanisms for habenula activation have...
The habenula is activated in response to stressful and aversive events, resulting in exploratory inhibition. Although possible mechanisms for habenula activation have been proposed, the effects of chronic stress on the habenular structure have never been studied. Herein, we assessed changes in volume, cell density and dendritic structure of habenular cells after chronic stress exposure using stereological and 3D morphological analysis. This study shows for the first time that there is a hemispherical asymmetry in the medial habenula (MHb) of the adult rat, with the right MHb containing more neurons than its left counterpart. Additionally, it shows that chronic stress induces a bilateral atrophy of both the MHb and the lateral habenula (LHb). This atrophy was accompanied by a reduction of the number of neurons in the right MHb and the number of glial cells in the bilateral LHb, but not by changes in the dendritic arbors of multipolar neurons. Importantly, these structural changes were correlated with elevated levels of serum corticosterone and increased anxious-like behavior in stressed animals. To further assess the role of the habenula in stress-related anxiety, bilateral lesions of the LHb were performed; interestingly, in lesioned animals the chronic stress protocol did not trigger increases in circulating corticosterone or anxious-like behavior. This study highlights the role of the habenula in the stress responses and how its sub-regions are structurally impacted by chronic stress with physiological and behavioral consequences.
Topics: Animals; Anxiety; Chronic Disease; Corticosterone; Disease Models, Animal; Electrolysis; Habenula; Male; Maze Learning; Neuroglia; Neurons; Rats; Rats, Wistar; Silver Staining; Statistics, Nonparametric; Stress, Psychological
PubMed: 27940019
DOI: 10.1016/j.expneurol.2016.12.003 -
The Anatomical Record. Part A,... Apr 2006Multipolar cells in the ventral cochlear nucleus (VCN) are a structurally and functionally diverse group of projection neurons. Understanding their role in the ascending...
Multipolar cells in the ventral cochlear nucleus (VCN) are a structurally and functionally diverse group of projection neurons. Understanding their role in the ascending pathway involves partitioning multipolar cells into distinct populations and determining where in the brain each sends its coded messages. In this study, we used retrograde labeling techniques in rats to identify multipolar neurons that project their axons to the ipsilateral dorsal cochlear nucleus (DCN), the contralateral CN, or both structures. Three rats received injections of biotinylated dextran amine in the ipsilateral DCN and diamidino yellow in the contralateral CN. Several radiate multipolar neurons (defined by their axonal projections to the ipsilateral DCN and their dendrites that traverse VCN isofrequency sheets) were double-labeled but over 70% were not. This result suggests two distinct populations: (1) radiate-commissural (RC) multipolar cells that project to the ipsilateral DCN and the contralateral CN, and (2) radiate multipolar cells that project exclusively (in this context) to the ipsilateral DCN. In a different group of animals, we retrogradely labeled multipolar neurons that project their axons to the contralateral CN and measured the size of their cell bodies. The mean size of this population (266 +/- 156 microm2) was significantly smaller than those of RC-multipolar cells (418 +/- 140 microm2). We conclude that the CN commissural pathway is composed of at least two components: (1) RC multipolar cells and (2) commissural multipolar cells that are small- and medium-sized neurons that project exclusively (in this context) to the contralateral CN. These results identify separate structural groups of multipolar cells that may correspond to physiological unit types described in the literature. They also provide protocols for isolating and studying different populations of multipolar cells to determine the neural mechanisms that govern their responses to sound.
Topics: Amidines; Animals; Auditory Pathways; Axons; Cats; Cochlear Nucleus; Fluorescent Dyes; Guinea Pigs; Male; Neurons; Rats; Rats, Sprague-Dawley; Staining and Labeling
PubMed: 16550550
DOI: 10.1002/ar.a.20294 -
Nature Neuroscience Feb 2016Brain neural stem cells (radial glial progenitors, RGPs) undergo a mysterious form of cell cycle-entrained interkinetic nuclear migration (INM) that is driven apically...
Brain neural stem cells (radial glial progenitors, RGPs) undergo a mysterious form of cell cycle-entrained interkinetic nuclear migration (INM) that is driven apically by cytoplasmic dynein and basally by the kinesin KIF1A, which has recently been implicated in human brain developmental disease. To understand the consequences of altered basal INM and the roles of KIF1A in disease, we performed constitutive and conditional RNAi and expressed mutant KIF1A in E16 to P7 rat RGPs and neurons. RGPs inhibited in basal INM still showed normal cell cycle progression, although neurogenic divisions were severely reduced. Postmitotic neuronal migration was independently disrupted at the multipolar stage and accompanied by premature ectopic expression of neuronal differentiation markers. Similar effects were unexpectedly observed throughout the layer of surrounding control cells, mimicked by Bdnf (brain-derived neurotrophic factor) or Dcx RNAi, and rescued by BDNF application. These results identify sequential and independent roles for KIF1A and provide an important new approach for reversing the effects of human disease.
Topics: Animals; Antigens, Differentiation; Brain-Derived Neurotrophic Factor; Cell Cycle; Cell Movement; Doublecortin Protein; Female; Humans; Kinesins; Mitosis; Neural Stem Cells; Neurons; Pregnancy; RNA Interference; Rats; Rats, Sprague-Dawley; Transfection
PubMed: 26752160
DOI: 10.1038/nn.4213 -
Frontiers in Neural Circuits 2018Previous avian thalamic studies have shown that the medial ventral thalamus is composed of several nuclei located close to the lateral wall of the third ventricle....
Previous avian thalamic studies have shown that the medial ventral thalamus is composed of several nuclei located close to the lateral wall of the third ventricle. Although the general connectivity is known, detailed morphology and connectivity pattern in some regions are still elusive. Here, using the intracellular filling technique in the chicken, we focused on two neural structures, namely, the retinorecipient neuropil of the n. geniculatus lateralis pars ventralis (GLv), and the adjacent n. intercalatus thalami (ICT). We found that the GLv-ne cells showed two different neuronal types: projection cells and horizontal interneurons. The projection cells showed variable morphologies and dendritic arborizations with axons that targeted the n. lentiformis mesencephali (LM), griseum tectale (GT), ICT, n. principalis precommissuralis (PPC), and optic tectum (TeO). The horizontal cells showed a widespread mediolateral neural process throughout the retinorecipient GLv-ne. The ICT cells, on the other hand, had multipolar somata with wide dendritic fields that extended toward the lamina interna of the GLv, and a projection pattern that targeted the n. laminaris precommissuralis (LPC). Together, these results elucidate the rich complexity of the connectivity pattern so far described between the GLv, ICT, pretectum, and tectum. Interestingly, the implication of some of these neural structures in visuomotor and somatosensory roles strongly suggests that the GLv and ICT are part of a bimodal circuit that may be involved in the generation/modulation of saccades, gaze control, and space perception.
Topics: Animals; Chickens; Neurons; Thalamic Nuclei
PubMed: 29479309
DOI: 10.3389/fncir.2018.00009 -
ELife Nov 2020Auditory processing depends upon inhibitory signaling by interneurons, even at its earliest stages in the ventral cochlear nucleus (VCN). Remarkably, to date only a...
Auditory processing depends upon inhibitory signaling by interneurons, even at its earliest stages in the ventral cochlear nucleus (VCN). Remarkably, to date only a single subtype of inhibitory neuron has been documented in the VCN, a projection neuron termed the D-stellate cell. With the use of a transgenic mouse line, optical clearing, and imaging techniques, combined with electrophysiological tools, we revealed a population of glycinergic cells in the VCN distinct from the D-stellate cell. These multipolar glycinergic cells were smaller in soma size and dendritic area, but over ten-fold more numerous than D-stellate cells. They were activated by auditory nerve and T-stellate cells, and made local inhibitory synaptic contacts on principal cells of the VCN. Given their abundance, combined with their narrow dendritic fields and axonal projections, it is likely that these neurons, here termed L-stellate cells, play a significant role in frequency-specific processing of acoustic signals.
Topics: Animals; Auditory Perception; Cochlear Nucleus; Female; Interneurons; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic
PubMed: 33141020
DOI: 10.7554/eLife.54350 -
Frontiers in Cellular Neuroscience 2020A battery of genetically encoded calcium indicators (GECIs) with different binding kinetics and calcium affinities was developed over the recent years to permit...
A battery of genetically encoded calcium indicators (GECIs) with different binding kinetics and calcium affinities was developed over the recent years to permit long-term calcium imaging. GECIs are calcium buffers and therefore, expression of GECIs may interfere with calcium homeostasis and signaling pathways important for neuronal differentiation and survival. Our objective was to investigate if the biolistically induced expression of five commonly used GECIs at two postnatal time points (days 14 and 22-25) could affect the morphological maturation of cortical neurons in organotypic slice cultures of rat visual cortex. Expression of GCaMP3 in both time windows, and of GCaMP5G and TN-XXL in the later time window impaired apical and /or basal dendrite growth of pyramidal neurons. With time, the proportion of GECI transfectants with nuclear filling increased, but an only prolonged expression of TN-XXL caused higher levels of neurodegeneration. In multipolar interneurons, only GCaMP3 evoked a transient growth delay during the early time window. GCaMP6m and GCaMP6m-X were quite "neuron-friendly." Since growth-impaired neurons might not have the physiological responses typical of age-matched wildtype neurons the results obtained after prolonged developmental expression of certain GECIs might need to be interpreted with caution.
PubMed: 33192315
DOI: 10.3389/fncel.2020.570596 -
Scientific Reports Feb 2020In commercial flocks of laying hens, keel bone fractures (KBFs) are prevalent and associated with behavioural indicators of pain. However, whether their impact is severe...
In commercial flocks of laying hens, keel bone fractures (KBFs) are prevalent and associated with behavioural indicators of pain. However, whether their impact is severe enough to induce a depressive-like state of chronic stress is unknown. As chronic stress downregulates adult hippocampal neurogenesis (AHN) in mammals and birds, we employ this measure as a neural biomarker of subjective welfare state. Radiographs obtained longitudinally from Lohmann Brown laying hens housed in a commercial multi-tier aviary were used to score the severity of naturally-occurring KBFs between the ages of 21-62 weeks. Individual birds' transitions between aviary zones were also recorded. Focal hens with severe KBFs at 3-4 weeks prior to sampling (n = 15) had lower densities of immature doublecortin-positive (DCX) multipolar and bipolar neurons in the hippocampal formation than focal hens with minimal fractures (n = 9). KBF severity scores at this time also negatively predicted DCX cell numbers on an individual level, while hens that acquired fractures earlier in their lives had fewer DCX neurons in the caudal hippocampal formation. Activity levels 3-4 weeks prior to sampling were not associated with AHN. KBFs thus lead to a negative affective state lasting at least 3-4 weeks, and management steps to reduce their occurrence are likely to have significant welfare benefits.
Topics: Animal Husbandry; Animal Welfare; Animals; Avian Proteins; Chickens; Doublecortin Domain Proteins; Female; Fractures, Bone; Gene Expression; Hippocampus; Housing, Animal; Microtubule-Associated Proteins; Neurogenesis; Neurons; Neuropeptides; Poultry Diseases; Reproduction; Sternum; Stress, Psychological; Trauma Severity Indices
PubMed: 32080271
DOI: 10.1038/s41598-020-59940-1 -
IScience Mar 2018CNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report that conditional deletion of the Rho GTPase in...
CNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report that conditional deletion of the Rho GTPase in cerebellar granule cell precursors (GCPs) results in abnormalities in cerebellar foliation revealed by iDISCO clearing methodology, a loss of columnar organization of proliferating GCPs in the external germinal layer (EGL), disordered parallel fiber organization in the molecular layer (ML), and a failure to extend a leading process and form a neuron-glial junction during migration along Bergmann glia (BG). Notably, GCPs lacking had a multi-polar morphology and slowed migration rate. In addition, secondary defects occurred in BG development and organization, especially in the lateral cerebellar hemispheres. By phosphoproteomic analysis, affected Cdc42 targets included regulators of the cytoskeleton, cell adhesion and polarity. Thus, Cdc42 signaling pathways are critical regulators of GCP polarity and the formation of neuron-glial junctions during cerebellar development.
PubMed: 29888765
DOI: 10.1016/j.isci.2018.01.004 -
Acta Histochemica Et Cytochemica Dec 2022Bisphenol A (BPA) is an endocrine disrupting chemical. Human epidemiological studies have suggested that adverse neurobehavioral outcomes are induced by fetal exposure...
Bisphenol A (BPA) is an endocrine disrupting chemical. Human epidemiological studies have suggested that adverse neurobehavioral outcomes are induced by fetal exposure to BPA. The remarkable differences in the corticogenesis between human and agyrencephalic mammals are an increase in the intermediate progenitor cells (IPCs) and a following increase in the subplate thickness. It is uncertain whether low doses of BPA (low-BPA) affect human early corticogenesis when basal progenitor cells (BPs) produce IPCs resulting in amplified neurogenesis. In this study, human-derived neuronal stem/progenitor cells were exposed to low-BPA or the vehicle only, and the resultant cell type-specific molecular changes and morphology were analyzed. We focused on stem cells immunoreactive for SOX2, BPs for NHLH1, and immature neurons for DCX. SOX2-positive cells significantly decreased at day (DIV) 4 and 7, whereas NHLH1-positive cells tended to be higher, while DCX-positive cells significantly increased at DIV7 when exposed to 100 nM of BPA compared with the vehicle. Morphologically DCX-positive cells showed a decrease in unipolar cells and an increase in multipolar cells when exposed to 100 nM of BPA compared with the vehicle. These results provide insights into the effect of low-BPA on neuronal differentiation in the human fetal corticogenesis.
PubMed: 36688137
DOI: 10.1267/ahc.22-00090 -
Revista de NeurologiaIt is sought to expose in a simple but rigorous way the physical, neurobiological and methodological foundations of the magnetoencephalography (MEG). (Review)
Review
OBJECTIVE
It is sought to expose in a simple but rigorous way the physical, neurobiological and methodological foundations of the magnetoencephalography (MEG).
DEVELOPMENT
We start from the basic properties of the classical electromagnetism, analyzing in detail the concepts of electric and magnetic fields, the Maxwell s equations and the multipolar development of potentials. All these tools are very important to know the peculiarities of the MEG studies. Later on, they are reviewed very briefly the different types of potentials generated by the neurons and their implication in the MEG. Lastly, some necessary technical characteristics will be commented for detection of the very weak neuromagnetic fields. It is shortly exposed the concept of tunnel effect, in one that detection systems used at the present time are based (SQUID).
CONCLUSION
MEG is a very promising recent technique that is used in epilepsy studies, evoked potentials and other functional pathologies. Its utility in clinic continues being even controversial. However, it is fundamental to know the mechanisms that justify their use in order to know better their benefits and limitations.
Topics: Action Potentials; Biophysical Phenomena; Biophysics; Electricity; Humans; Magnetics; Magnetoencephalography; Mathematics; Models, Theoretical; Neurons
PubMed: 12134349
DOI: No ID Found