bioRxiv Subject Collection: Neuroscience's Journal
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Thursday, September 26th, 2024
| Time |
Event |
| 4:41a |
Directional motion sensitivity in people with Visual Snow Syndrome is modulated by the presence of trailing-type palinopsia
Visual Snow Syndrome (VSS) is characterized by visual perceptual distortions, potentially linked to increased neural excitability. We hypothesized that this hyperexcitability might affect motion direction sensitivity in VSS, particularly in those with trailing-type palinopsia (TTP), an atypical perception of visual motion. Using a spatial suppression paradigm, we assessed motion duration discrimination thresholds for small (1 degrees), medium (2.5 degrees), and large (12 degrees) high-contrast gratings in 23 VSS and 27 control participants. Spatial Suppression Index (SSI) quantified size-dependent increases in duration thresholds. Visual Discomfort Questionnaire scores and VSS symptom ratings including TTP, afterimages, photophobia, etc. were also collected. VSS patients reported higher visual discomfort and perceptual disturbances. However, no group differences were found in duration thresholds or SSI. Notably, higher TTP scores were associated with lower duration thresholds, indicating a facilitatory effect of TTP on motion sensitivity. These findings suggest that 'visual snow,' the core symptom of VSS, is not linked to abnormal directional sensitivity or center-surround suppression associated with visual motion. However, the dependence of directional sensitivity on TTP emphasizes the heterogeneity of VSS, which should be considered in future neurophysiological and clinical models. | | 4:41a |
Disruption of the Social Visual Pathway in Autism Spectrum Disorder
The social visual pathway, which diverges from the dorsal pathway at the visual motion area (MT/V5) and runs from posterior down to anterior portions of the superior temporal sulcus (STS), specializes in processing dynamic social information. This study examined resting-state functional connectivity within this pathway in children with autism spectrum disorder (ASD) and typically developing (TD) children. Using data from the ABIDE (Autism Brain Imaging Data Exchange) repository, we found significant underconnectivity between the posterior and middle STS (pSTS-mSTS) in the right hemisphere in children with ASD compared to TD children. Weaker connectivity in this region of the pathway correlated with more severe social impairment symptoms in ASD and reduced social function across both ASD and TD groups. These findings suggest a specific disruption in the right hemisphere social visual pathway in ASD, potentially contributing to social deficits observed in the disorder. | | 11:34a |
The effects of P2Y12 loss on microglial gene expression, dynamics, and injury response in the cerebellum and cerebral cortex.
Despite the emerging consensus that microglia are critical to physiological and pathological brain function, it is unclear how microglial roles and their underlying mechanisms differ between brain regions. Microglia throughout the brain express common markers, such as the purinergic receptor P2Y12, that delineate them from peripheral macrophages. P2Y12 is a critical sensor of injury but also contributes to the sensing of neuronal activity and remodeling of synapses, with microglial loss of P2Y12 resulting in behavioral deficits. P2Y12 has largely been studied in cortical microglia, despite the fact that a growing body of evidence suggests that microglia exhibit a high degree of regional specialization. Cerebellar microglia, in particular, exhibit transcriptional, epigenetic, and functional profiles that set them apart from their better studied cortical and hippocampal counterparts. Here, we demonstrate that P2Y12 deficiency does not alter the morphology, distribution, or dynamics of microglia in the cerebellum. In fact, loss of P2Y12 does little to disturb the distinct transcriptomic profiles of cortical and cerebellar microglia. However, unlike in cortex, P2Y12 is not required for a full microglial response to focal injury, suggesting that cerebellar and cortical microglia use different cues to respond to injury. Finally, we show that P2Y12 deficiency impairs cerebellar learning in a delay eyeblink conditioning task, a common test of cerebellar plasticity and circuit function. Our findings suggest not only region-specific roles of microglial P2Y12 signaling in the focal injury response, but also indicate a conserved role for P2Y12 in microglial modulation of plasticity across regions. | | 11:35a |
Oxytocin receptor controls distinct components of pair bonding and development in prairie voles
Oxytocin receptor (Oxtr) signaling influences complex social behaviors in diverse species, including social monogamy in prairie voles. How Oxtr regulates specific components of social attachment behaviors and the neural mechanisms mediating them remains unknown. Here, we examine prairie voles lacking Oxtr and demonstrate that pair bonding comprises distinct behavioral modules: the preference for a bonded partner, and the rejection of novel potential mates. Our longitudinal study of social attachment shows that Oxtr sex-specifically influences early interactions between novel partners facilitating the formation of partner preference. Additionally, Oxtr suppresses promiscuity towards novel potential mates following pair bonding, contributing to rejection. Oxtr function regulates coordinated patterns of gene expression in regions implicated in attachment behaviors and regulates the expression of oxytocin in the paraventricular nucleus of the hypothalamus, a principal source of oxytocin. Thus, Oxtr controls genetically separable components of pair bonding behaviors and coordinates development of the neural substrates of attachment. | | 11:35a |
The capacity of the medial temporal lobe to represent memory items in their ordinal position in a sequence is domain-general
Memory systems in humans are less segregated than initially thought as learning tasks from different memory domains (e.g., declarative vs. procedural) can recruit similar brain areas. However, it remains unclear whether the functional role of these overlapping brain regions and the hippocampus in particular is domain-general. Here, we test the hypothesis that the hippocampus encodes and preserves the temporal order of sequential information irrespective of the nature of that information. We used multivariate pattern analyses (MVPA) of functional magnetic resonance imaging (fMRI) data acquired in young healthy individuals during the execution of learned sequences of movements and objects to test whether the hippocampus represents information about the temporal order of items in a learned sequence irrespective of their nature. We also examined such coding in brain regions involved in both motor (primary and premotor cortices) and object (perirhinal cortex and parahippocampus) sequence learning. Our results suggest that hippocampal and perirhinal multivoxel activation patterns do not carry information about specific items or temporal position in a random series of objects or movements. Rather, these regions code for the representation of items in their learned temporal position in sequences irrespective of their nature (i.e., item-position coding). In contrast, although all other ROIs showed evidence of item-position coding, this representation could at least partially be attributed to the coding of other information such as position information. Altogether, our findings indicate that the capacity of regions in the medial temporal lobe to represent the temporal order of sequential information is domain-general. Our data suggest that these regions contribute to the development of item-position maps that might provide a cognitive framework to order sequential behaviors irrespective of their nature. | | 11:35a |
An in vivo and in vitro spatiotemporal atlas of human midbrain development
The dopaminergic system has key roles in human physiology and is implicated in a broad range of neurological and neuropsychiatric conditions that are increasingly investigated using induced pluripotent stem cell-derived midbrain models. To determine the similarity of such models to human systems, we undertook single cell and spatial profiling of first and second trimester fetal midbrain and compared it to in vitro midbrain models. Our initial histological analysis of second trimester fetal midbrain revealed structural complexity already similar to that of adult tissue, although this similarity did not fully extend to transcriptional activity. Moreover, we show that in vitro models recapitulate the transcriptional activity of late first trimester fetal midbrain, while 3D models replicate the spatial organization and cellular microenvironments of first and second trimester fetal midbrain. Understanding the extent of human tissue recapitulation in midbrain laboratory models is essential to justify their use as biological proxies. | | 12:48p |
Multi-omics identification of extracellular components of the fetal monkey and human neocortex.
During development, precursor cells are continuously and intimately interacting with their extracellular environment, which guides their ability to generate functional tissues and organs. Much is known about the development of the neocortex in mammals. This information has largely been derived from histological analyses, heterochronic cell transplants, and genetic manipulations in mice, and to a lesser extent from transcriptomic and histological analyses in humans. However, these approaches have not led to a characterization of the extracellular composition of the developing neocortex in any species. Here, using a combination of single-cell transcriptomic analyses from published datasets, and our proteomics and immunohistofluorescence analyses, we provide a more comprehensive and unbiased picture of the early developing fetal neocortex in humans and non-human primates. Our findings provide a starting point for further hypothesis-driven studies on structural and signaling components in the developing cortex that had previously not been identified. | | 12:48p |
Spatial transcriptomics reveals modulation of transcriptional networks across brain regions after auditory threat conditioning
Prior research has demonstrated genome-wide transcriptional changes related to fear and anxiety across species, often focusing on individual brain regions or cell types. However, the extent of gene expression differences across brain regions and how these changes interact at the level of transcriptional connectivity remains unclear. To address this, we performed spatial transcriptomics RNAseq analyses in an auditory threat conditioning paradigm in mice. We generated a spatial transcriptomic atlas of a coronal mouse brain section covering cortical and subcortical regions, corresponding to histologically defined regions. Our finding revealed widespread transcriptional responses across all brain regions examined, particularly in the medial and lateral habenula, and the choroid plexus. Network analyses highlighted altered transcriptional connectivity between cortical and subcortical regions, emphasizing the role of steroidogenic factor 1. These results provide new insights into the transcriptional networks involved in auditory threat conditioning, enhancing our understanding of molecular and neural mechanisms underlying fear and anxiety disorders. | | 7:16p |
Effect of Acute Alcohol Consumption in a Novel Rodent Model of Decision Making
Abstract Background Alcohol use, especially at high consumption levels, can lead to irrational decision-making. In humans, this can lead to harmful outcomes often seen in the context of driving under the influence and or aggressive behavior. To date, the field is lacking comprehensive animal models to examine the impact of alcohol use on decision making in rodents, particularly to examine sex differences in choice behavior. To address this issue, the present study examined the effects of acute alcohol consumption during a behavioral approach-avoidance task that captures momentary changes in decision-making behavior and choice selection in female and male rats. Methods Our team has developed a novel behavioral protocol involving a concurrent choice to consume four different concentrations of alcohol and sucrose combinations. During the task, female or male rats can approach or avoid drinking solutions in four distinct corners of our test apparatus. The solutions were prepared in inverse concentrations (higher sucrose was paired with lower alcohol and vice versa) so that the rodents pursue minimal alcohol use by consuming the higher sucrose concentrations or higher concentrations of alcohol by drinking the lower sucrose concentrations. The animals also have the option to avoid drinking alcohol by not approaching any of the drinking cups. Behavior and choice were tracked during task performance involving different solution concentrations of alcohol and sucrose. Results The choice of consuming different concentrations of alcohol or sucrose resulted in sex-dependent differences in an approach-avoid trade-off pattern of behavior that was sensitive to different concentrations of alcohol/sucrose combinations. Notably, males were greatly affected by the introduction of alcohol into the task environment, approaching higher alcohol concentrations significantly more often than the non-alcohol containing options. In contrast, females choice patterns and task performance were largely unchanged during alcohol and non-alcohol containing tasks. Regardless of sex, we identify a novel method for identifying individual subject decision-making abnormalities during and after alcohol consumption. Conclusions This research reveals a novel approach for examining the effects of acute alcohol exposure during a trade-off task, with decision patterns being more impacted by alcohol use in males as compared to females. We also offer the field a novel approach for identifying individual abnormalities in decision making behavior with the presentation of alcohol. Future research can explore these abnormal patterns in both acute and chronic alcohol conditions to develop methods for identifying subjects at-risk for developing an alcohol use disorder and the deleterious impact of alcohol on rational decision making. | | 7:16p |
GPR30 in spinal cholecystokinin-positive neurons modulates neuropathic pain via mediating descending facilitation
Neuropathic pain, a major health problem affecting 7 - 10% of the global population, lacks effective treatment due to its elusive mechanisms. Cholecystokinin-positive (CCK+) neurons in the spinal dorsal horn (SDH) are critical for neuropathic pain, yet the underlying molecular mechanisms remain unclear. Here we showed that the membrane estrogen receptor G-protein coupled estrogen receptor (GPER/GPR30) in spinal was significantly upregulated in chronic constriction injury (CCI) mice and that inhibition of GPR30 in CCK+ neurons reversed CCI-induced neuropathic pain. Besides, GPR30 in spinal CCK+ neurons was essential for the enhancement of AMPA-mediated excitatory synaptic transmission in CCI mice. Furthermore, GPR30 was expressed in the spinal CCK+ neurons receiving direct projection from the primary sensory cortex (S1-SDH). Chemogenetic inhibition of S1-SDH post-synaptic neurons alleviated CCI-induced neuropathic pain. Conversely, chemogenetic activation of these neurons mimicked neuropathic pain symptoms, which were attenuated by spinal inhibition of GPR30. Finally, we confirmed that GPR30 in S1-SDH post-synaptic neurons is required for CCI-induced neuropathic pain. Taken together, our findings suggest that GPR30 in spinal CCK+ neurons is pivotal for neuropathic pain and mediates descending facilitation by corticospinal direct projections, thereby representing a promising therapeutic target for neuropathic pain. | | 7:16p |
Differential participation of the corticospinal and corticorubral neurons during motor execution in the rat
The sensorimotor cortex is crucial for learning and executing new movements with precision (Nudo & Frost, 2007). It selectively modulates sensory information flow and represents motor information in a spatially organized manner (Canedo, 1997; Chen et al., 2017). The pyramidal system is made up layer 5 pyramidal tract neurons (PTNs), which are organized into populations with distinct morphological, genetic and functional properties. These subpopulations project to different subcortical structures in a segregated manner (Nudo & Frost, 2007). To understand whether PTNs projecting to different structures play distinct functional roles in motor control, we characterized two types of layer 5 neurons in the motor cortex: corticorubral (CR) neurons, which project to the red nucleus, and corticospinal (CS) neurons, which project to the spinal cord. To analyze movement performance in rats, we compared the selective optogenetic inhibition of motor cortex CS or CR neurons during lever movement execution in response to a light stimulus. As the animals progressed through the training sessions, the variability of lever trajectories decreased, and the movements became more stereotyped. Photoinhibition of CS or CR neurons increased the performance variability of learned movements but differentially affected kinematic parameters. CR neuron inhibition affected amplitude, duration, reaction times, speed, and acceleration of the movement. In contrast, inhibition of CS neurons mainly altered the duration, speed, and acceleration of the movement. We conclude that CS and CR are complementary pathways for transmitting information rather than copies of the same motor command. |
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