bioRxiv Subject Collection: Neuroscience's Journal
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Sunday, January 21st, 2024
| Time |
Event |
| 4:44a |
Mechanisms of gas sensing by internal sensory neurons in Drosophila larvae
Internal sensory neurons monitor the chemical and physical state of the body, providing critical information to the central nervous system for maintaining homeostasis and survival. A population of larval Drosophila sensory neurons, tracheal dendrite (td) neurons, elaborate dendrites along respiratory organs and may serve as a model for elucidating the cellular and molecular basis of chemosensation by internal neurons. We find that td neurons respond to decreases in O2 levels and increases in CO2 levels. We assessed the roles of atypical soluble guanylyl cyclases (Gycs) and a gustatory receptor (Gr) in mediating these responses. We found that Gyc88E/Gyc89Db were necessary for responses to hypoxia, and that Gr28b was necessary for responses to CO2. Targeted expression of Gr28b isoform c in td neurons rescued responses to CO2 in mutant larvae and also induced ectopic sensitivity to CO2 in the td network. Gas-sensitive td neurons were activated when larvae burrowed for a prolonged duration, demonstrating a natural-like feeding condition in which td neurons are activated. Together, our work identifies two gaseous stimuli that are detected by partially overlapping subsets of internal sensory neurons, and establishes roles for Gyc88E/Gyc89Db in the detection of hypoxia, and Gr28b in the detection of CO2. | | 6:19a |
Involvement of the cellular prion protein in seeding and spreading of sarkosyl-derived fractions of Alzheimer's disease in Prnp mutant mice and in the P301S transgenic tauopathy mice model
The natural cellular prion protein is known to play several roles during development and adult brain. Far from its pathological roles in prionopathies, the non-pathogenic cellular prion protein has been described as a receptor for several amyloid in oligomeric and prefibrillar forms. For some amyloids, specific domains of the protein play a crucial role in modulating amyloid's cellular uptake and seeding properties. In most studies, the functions and the role of putative amyloid receptors have been analyzed by using brain extracts derived from human neurodegenerative patients. Another strategy has been to modify the genetic dosage of the natural prion protein in genetic models of different diseases. In this study, we take advantage of both approaches to examine whether this protein plays a role in the seeding and spreading of pathogenic tau. Our results point to a role of the natural prion protein in the emergence of pathogenic tau in a mouse model overexpressing the mutation P301S of the human tau gene. In contrast, its role is minor when sarkosyl-derived brain samples of Alzheimer's disease are used. In fact, our results indicate that the use of this type of sample is not adequate to determine the role of a putative receptor in tau seeding and spreading. | | 11:16a |
Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development
Opioid receptors within the CNS regulate pain sensation and mood and are key targets for drugs of abuse. Within the adult rodent hippocampus (HPC), -opioid receptor agonists suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting the circuit. However, it is uncertain if this disinhibitory motif is conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition is robustly suppressed by opioids in HPC but not neocortex in mice and nonhuman primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif was established in early development when immature PV-INs and opioids already influence primordial network rhythmogenesis. Acute opioid-mediated modulation was partially occluded with morphine pretreatment, with implications for the effects of opioids on hippocampal network activity during circuit maturation as well as learning and memory. Together, these findings demonstrate that PV-INs exhibit a divergence in opioid sensitivity across brain regions that is remarkably conserved across evolution and highlights the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development. | | 11:16a |
Individual connectivity-based parcellations reflect functional properties of human auditory cortex
Neuroimaging studies of the functional organization of human auditory cortex have focused on group-level analyses to identify tendencies that represent the typical brain. Here, we mapped auditory areas of the human superior temporal cortex (STC) in 30 participants by combining functional network analysis and 1-mm isotropic resolution 7T functional magnetic resonance imaging (fMRI). Two resting-state fMRI sessions, and one or two auditory and audiovisual speech localizer sessions, were collected on 3-4 separate days. We generated a set of functional network-based parcellations from these data. Solutions with 4, 6, and 11 networks were selected for closer examination based on local maxima of Dice and Silhouette values. The resulting parcellation of auditory cortices showed high intraindividual reproducibility both between resting state sessions (Dice coefficient: 69-78%) and between resting state and task sessions (Dice coefficient: 62-73%). This demonstrates that auditory areas in STC can be reliably segmented into functional subareas. The interindividual variability was significantly larger than intraindividual variability (Dice coefficient: 57%-68%, p<0.001), indicating that the parcellations also captured meaningful interindividual variability. The individual-specific parcellations yielded the highest alignment with task response topographies, suggesting that individual variability in parcellations reflects individual variability in auditory function. Furthermore, connectional homogeneity within networks was highest for the individual-specific parcellations. Our findings suggest that individual-level parcellations capture meaningful idiosyncrasies in auditory cortex organization. | | 11:45a |
Activational and organizational effects of sex hormones on hippocampal inhibition
Peripheral and brain-produced sex hormones exert sex-specific regulation of hippocampal cognitive function. Estrogen produced by neuronal aromatase regulates inhibitory neurons (INs) and hippocampal-dependent memory in adult females but not in male mice. How and when this sex effect is stablished and how peripheral and brain sources of estrogen interact in the control of hippocampal INs is currently unknown. Using ex-vivo electrophysiology, molecular analysis, estrous cycle monitoring and neonatal hormonal manipulations, we show evidences that suggest that neuron-derived estrogen and peripheral hormones independently exert activational effects on CA1 synaptic inhibition and perineuronal nets (PNNs) surrounding parvalbumin (PV)-expressing INs. Before puberty, aromatase is expressed in PV INs and regulates synaptic inhibition in female but not in male mice. Neonatal testosterone abolished the effect of brain-derived estrogen on adult female synaptic inhibition and disrupted brain-derived estrogen regulation of PV IN PNNs. Our results suggest that sex differences in brain-derived estrogen effects on CA1 inhibition are established by organizational effects of neonatal gonadal hormones and highlight the role of INs as mediators of the sexual differentiation of the hippocampus. | | 11:45a |
The FinnBrain Multimodal Neonatal Template and Atlas Collection: T1, T2, and DTI brain templates, and accompanying cortical and subcortical atlases
The accurate processing of neonatal and infant brain MRI data is crucially important for developmental neuroscience, but presents challenges that child and adult data do not. Tissue segmentation and image coregistration accuracy can be improved by optimizing template images and / or related segmentation procedures. Here, we describe the construction of the FinnBrain Neonate (FBN-125) template; a multi-contrast template with T1- and T2-weighted as well as diffusion tensor imaging derived fractional anisotropy and mean diffusivity images. The template is symmetric and aligned to the Talairach-like MNI 152 template and has high spatial resolution (0.5 mm3). In addition, we provide atlas labels, constructed from manual segmentations, for cortical grey matter, white matter, cerebrospinal fluid, brainstem, and cerebellum as well as the bilateral hippocampi, amygdalae, caudate nuclei, putamina, globi pallidi, and thalami. We provide this multi-contrast template along with the labelled atlases for the use of the neuroscience community in the hope that it will prove useful in advancing developmental neuroscience, for example, by helping to achieve reliable means for spatial normalization and measures of neonate brain structure via automated computational methods. Additionally, we provide standard co-registration files that will enable investigators to reliably transform their statistical maps to the adult MNI space, which has the potential to improve the consistency and comparability of neonatal studies or the use of adult MNI space atlases in neonatal neuroimaging. | | 5:31p |
Context dependent contributions of the direct and indirect pathways in the associative and sensorimotor striatum
To determine whether the contributions of striatal projection neurons from the direct (dSPNs) and indirect (iSPNs) pathways of the basal ganglia to action selection and locomotion can be generalized across the associative (DMS) and sensorimotor (DLS) striatum we compared the optogenetic activation or inhibition of these pathways on different tests. We show that self-modulation of dSPNs or iSPNs in either compartment has opposite contributions to real-time place preference, and to selecting an action in the DMS but not in the DLS. During reward seeking displacements, activation of either pathway in both compartments, or inhibition of dSPNs in the DMS slows movement. During spontaneous displacements, dSPNs activation showed opposing effects depending on the compartment modulated. Remarkably, inhibition of either pathway in the DLS decreases while only iSPNs inhibition in the DMS facilitates these displacements. These findings support a model of opposite, complementary and undescribed contributions of the striatal pathways depending on the compartment and context. |
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