Temperature-dependent RNA editing in octopus extensively recodes the neural proteome.

In poikilotherms, temperature changes challenge the integration of physiological function. Within the complex nervous systems of the behaviorally sophisticated coleoid cephalopods, these problems are substantial. RNA editing by adenosine deamination is a well-positioned mechanism for environmental acclimation. We report that the neural proteome of Octopus bimaculoides undergoes massive reconfigurations via RNA editing following a temperature challenge. Over 13,000 codons are affected, and many alter proteins that are vital for neural processes. For two highly temperature-sensitive examples, recoding tunes protein function. For synaptotagmin, a key component of Ca2+-dependent neurotransmitter release, crystal structures and supporting experiments show that editing alters Ca2+ binding. For kinesin-1, a motor protein driving axonal transport, editing regulates transport velocity down microtubules. Seasonal sampling of wild-caught specimens indicates that temperature-dependent editing occurs in the field as well. These data show that A-to-I editing tunes neurophysiological function in response to temperature in octopus and most likely other coleoids.

Integration of Parallel Opposing Memories Underlies Memory Extinction.

Accurately predicting an outcome requires that animals learn supporting and conflicting evidence from sequential experience. In mammals and invertebrates, learned fear responses can be suppressed by experiencing predictive cues without punishment, a process called memory extinction. Here, we show that extinction of aversive memories in Drosophila requires specific dopaminergic neurons, which indicate that omission of punishment is remembered as a positive experience. Functional imaging revealed co-existence of intracellular calcium traces in different places in the mushroom body output neuron network for both the original aversive memory and a new appetitive extinction memory. Light and ultrastructural anatomy are consistent with parallel competing memories being combined within mushroom body output neurons that direct avoidance. Indeed, extinction-evoked plasticity in a pair of these neurons neutralizes the potentiated odor response imposed in the network by aversive learning. Therefore, flies track the accuracy of learned expectations by accumulating and integrating memories of conflicting events.

Trade-off between Transcriptome Plasticity and Genome Evolution in Cephalopods.

RNA editing, a post-transcriptional process, allows the diversification of proteomes beyond the genomic blueprint; however it is infrequently used among animals for this purpose. Recent reports suggesting increased levels of RNA editing in squids thus raise the question of the nature and effects of these events. We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionarily conserved sites. Editing is enriched in the nervous system, affecting molecules pertinent for excitability and neuronal morphology. The genomic sequence flanking editing sites is highly conserved, suggesting that the process confers a selective advantage. Due to the large number of sites, the surrounding conservation greatly reduces the number of mutations and genomic polymorphisms in protein-coding regions. This trade-off between genome evolution and transcriptome plasticity highlights the importance of RNA recoding as a strategy for diversifying proteins, particularly those associated with neural function. PAPERCLIP.

Myelination of the nervous system: mechanisms and functions.

Myelination of axons in the nervous system of vertebrates enables fast, saltatory impulse propagation, one of the best-understood concepts in neurophysiology. However, it took a long while to recognize the mechanistic complexity both of myelination by oligodendrocytes and Schwann cells and of their cellular interactions. In this review, we highlight recent advances in our understanding of myelin biogenesis, its lifelong plasticity, and the reciprocal interactions of myelinating glia with the axons they ensheath. In the central nervous system, myelination is also stimulated by axonal activity and astrocytes, whereas myelin clearance involves microglia/macrophages. Once myelinated, the long-term integrity of axons depends on glial supply of metabolites and neurotrophic factors. The relevance of this axoglial symbiosis is illustrated in normal brain aging and human myelin diseases, which can be studied in corresponding mouse models. Thus, myelinating cells serve a key role in preserving the connectivity and functions of a healthy nervous system.

Training-Dependent Gradients of Timescales of Neural Dynamics in the Primate Prefrontal Cortex and Their Contributions to Working Memory.

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, for example, from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales are inherent properties of neurons and/or depend on training in a specific task and if the latter, how their modulations contribute to task performance. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition.

Brain Gene Regulatory Networks Coordinate Nest Construction in Birds.

Nest building is a vital behavior exhibited during breeding in birds, and is possibly induced by environmental and social cues. Although such behavioral plasticity has been hypothesized to be controlled by adult neuronal plasticity, empirical evidence, especially at the neurogenomic level, remains limited. Here, we aim to uncover the gene regulatory networks that govern avian nest construction and examine whether they are associated with circuit rewiring. We designed an experiment to dissect this complex behavior into components in response to pair bonding and nest material acquisition by manipulating the presence of mates and nest materials in 30 pairs of zebra finches. Whole-transcriptome analysis of 300 samples from five brain regions linked to avian nesting behaviors revealed nesting-associated gene expression enriched with neural rewiring functions, including neurogenesis and neuron projection. The enriched expression was observed in the motor/sensorimotor and social behavior networks of female finches, and in the dopaminergic reward system of males. Female birds exhibited predominant neurotranscriptomic changes to initiate the nesting stage, while males showed major changes after entering this stage, underscoring sex-specific roles in nesting behavior. Notably, major neurotranscriptomic changes occurred during pair bonding, with minor changes during nest material acquisition, emphasizing social interactions in nest construction. We also revealed gene expression associated with reproductive behaviors and tactile sensing for nesting behavior. This study presents novel neurogenomic evidence supporting the hypothesis of adult neural plasticity underlying avian nest-construction behavior. By uncovering the genetic toolkits involved, we offer novel insights into the evolution of animals' innate ability to construct nests.

Brain local stability and network flexibility of table tennis players: a 7T MRI study.

Table tennis players have adaptive visual and sensorimotor networks, which are the key brain regions to acquire environmental information and generate motor output. This study examined 20 table tennis players and 21 control subjects through ultrahigh field 7 Tesla magnetic resonance imaging. First, we measured percentage amplitude of fluctuation across five different frequency bands and found that table tennis players had significantly lower percentage amplitude of fluctuation values than control subjects in 18 brain regions, suggesting enhanced stability of spontaneous brain fluctuation amplitudes in visual and sensorimotor networks. Functional connectional analyses revealed increased static functional connectivity between two sensorimotor nodes and other frontal-parietal regions among table tennis players. Additionally, these players displayed enhanced dynamic functional connectivity coupled with reduced static connectivity between five nodes processing visual and sensory information input, and other large-scale cross-regional areas. These findings highlight that table tennis players undergo neural adaptability through a dual mechanism, characterized by global stability in spontaneous brain fluctuation amplitudes and heightened flexibility in visual sensory networks. Our study offers novel insights into the mechanisms of neural adaptability in athletes, providing a foundation for future efforts to enhance cognitive functions in diverse populations, such as athletes, older adults, and individuals with cognitive impairments.

The evolution of synaptic and cognitive capacity: Insights from the nervous system transcriptome of Aplysia.

The gastropod mollusk Aplysia is an important model for cellular and molecular neurobiological studies, particularly for investigations of molecular mechanisms of learning and memory. We developed an optimized assembly pipeline to generate an improved Aplysia nervous system transcriptome. This improved transcriptome enabled us to explore the evolution of cognitive capacity at the molecular level. Were there evolutionary expansions of neuronal genes between this relatively simple gastropod Aplysia (20,000 neurons) and Octopus (500 million neurons), the invertebrate with the most elaborate neuronal circuitry and greatest behavioral complexity? Are the tremendous advances in cognitive power in vertebrates explained by expansion of the synaptic proteome that resulted from multiple rounds of whole genome duplication in this clade? Overall, the complement of genes linked to neuronal function is similar between Octopus and Aplysia. As expected, a number of synaptic scaffold proteins have more isoforms in humans than in Aplysia or Octopus. However, several scaffold families present in mollusks and other protostomes are absent in vertebrates, including the Fifes, Lev10s, SOLs, and a NETO family. Thus, whereas vertebrates have more scaffold isoforms from select families, invertebrates have additional scaffold protein families not found in vertebrates. This analysis provides insights into the evolution of the synaptic proteome. Both synaptic proteins and synaptic plasticity evolved gradually, yet the last deuterostome-protostome common ancestor already possessed an elaborate suite of genes associated with synaptic function, and critical for synaptic plasticity.

Gaming expertise induces meso­scale brain plasticity and efficiency mechanisms as revealed by whole-brain modeling.

Video games are a valuable tool for studying the effects of training and neural plasticity on the brain. However, the underlying mechanisms related to plasticity-associated brain structural changes and their impact on brain dynamics are unknown. Here, we used a semi-empirical whole-brain model to study structural neural plasticity mechanisms linked to video game expertise. We hypothesized that video game expertise is associated with neural plasticity-mediated changes in structural connectivity that manifest at the meso­scale level, resulting in a more segregated functional network topology. To test this hypothesis, we combined structural connectivity data of StarCraft II video game players (VGPs, n = 31) and non-players (NVGPs, n = 31), with generic fMRI data from the Human Connectome Project and computational models, to generate simulated fMRI recordings. Graph theory analysis on simulated data was performed during both resting-state conditions and external stimulation. VGPs' simulated functional connectivity was characterized by a meso­scale integration, with increased local connectivity in frontal, parietal, and occipital brain regions. The same analyses at the level of structural connectivity showed no differences between VGPs and NVGPs. Regions that increased their connectivity strength in VGPs are known to be involved in cognitive processes crucial for task performance such as attention, reasoning, and inference. In-silico stimulation suggested that differences in FC between VGPs and NVGPs emerge in noisy contexts, specifically when the noisy level of stimulation is increased. This indicates that the connectomes of VGPs may facilitate the filtering of noise from stimuli. These structural alterations drive the meso­scale functional changes observed in individuals with gaming expertise. Overall, our work sheds light on the mechanisms underlying structural neural plasticity triggered by video game experiences.

Ischemia-reperfusion myocardial infarction induces remodeling of left cardiac-projecting stellate ganglia neurons.

Neurons in the stellate ganglion (SG) provide sympathetic innervation to the heart, brown adipose tissue (BAT), and other organs. Sympathetic innervation to the heart becomes hyperactive following myocardial infarction (MI). The impact of MI on the morphology of cardiac sympathetic neurons is not known, but we hypothesized that MI would stimulate increased cell and dendritic tree size in cardiac neurons. In this study, we examined the effects of ischemia-reperfusion MI on sympathetic neurons using dual retrograde tracing methods to allow detailed characterization of cardiac- and BAT-projecting neurons. Different fluorescently conjugated cholera toxin subunit B (CTb) tracers were injected into the pericardium and the interscapular BAT pads, respectively. Experimental animals received a 45-min occlusion of the left anterior descending coronary artery and controls received sham surgery. One week later, hearts were collected for assessment of MI infarct and SGs were collected for morphological or electrophysiological analysis. Cardiac-projecting SG neurons from MI mice had smaller cell bodies and shorter dendritic trees compared with sham animals, specifically on the left side ipsilateral to the MI. BAT-projecting neurons were not altered by MI, demonstrating the subpopulation specificity of the response. The normal size and distribution differences between BAT- and cardiac-projecting stellate ganglion neurons were not altered by MI. Patch-clamp recordings from cardiac-projecting left SG neurons revealed increased spontaneous excitatory postsynaptic currents despite the decrease in cell and dendritic tree size. Thus, increased dendritic tree size does not contribute to the enhanced sympathetic neural activity seen after MI.NEW & NOTEWORTHY Myocardial infarction (MI) causes structural and functional changes specifically in stellate ganglion neurons that project to the heart, but not in cells that project to brown adipose fat tissue.

Evaluating the daily modulation of FADD and related molecular markers in different brain regions in male rats.

Fas-Associated protein with Death Domain (FADD), a key molecule controlling cell fate by balancing apoptotic versus non-apoptotic functions, is dysregulated in post-mortem brains of subjects with psychopathologies, in animal models capturing certain aspects of these disorders, and by several pharmacological agents. Since persistent disruptions in normal functioning of daily rhythms are linked with these conditions, oscillations over time of key biomarkers, such as FADD, could play a crucial role in balancing the clinical outcome. Therefore, we characterized the 24-h regulation of FADD (and linked molecular partners: p-ERK/t-ERK ratio, Cdk-5, p35/p25, cell proliferation) in key brain regions for FADD regulation (prefrontal cortex, striatum, hippocampus). Samples were collected during Zeitgeber time (ZT) 2, ZT5, ZT8, ZT11, ZT14, ZT17, ZT20, and ZT23 (ZT0, lights-on or inactive period; ZT12, lights-off or active period). FADD showed similar daily fluctuations in all regions analyzed, with higher values during lights off, and opposite to p-ERK/t-ERK ratios regulation. Both Cdk-5 and p35 remained stable and did not change across ZT. However, p25 increased during lights off, but exclusively in striatum. Finally, no 24-h modulation was observed for hippocampal cell proliferation, although higher values were present during lights off. These results demonstrated a clear daily modulation of FADD in several key brain regions, with a more prominent regulation during the active time of rats, and suggested a key role for FADD, and molecular partners, in the normal physiological functioning of the brain's daily rhythmicity, which if disrupted might participate in the development of certain pathologies.

Learning induces EPO/EPOr expression in memory relevant brain areas, whereas exogenously applied EPO promotes remote memory consolidation.

Memory and learning allow animals to appropriate certain properties of nature with which they can navigate in it successfully. Memory is acquired slowly and consists of two major phases, a fragile early phase (short-term memory, <4 h) and a more robust and long-lasting late one (long-term memory, >4 h). Erythropoietin (EPO) prolongs memory from 24 to 72 h when animals are trained for 5 min in a place recognition task but not when training lasted 3 min (short-term memory). It is not known whether it promotes the formation of remote memory (≥21 days). We address whether the systemic administration of EPO can convert a short-term memory into a long-term remote memory, and the neural plasticity mechanisms involved. We evaluated the effect of training duration (3 or 5 min) on the expression of endogenous EPO and its receptor to shed light on the role of EPO in coordinating mechanisms of neural plasticity using a single-trial spatial learning test. We administered EPO 10 min post-training and evaluated memory after 24 h, 96 h, 15 days, or 21 days. We also determined the effect of EPO administered 10 min after training on the expression of arc and bdnf during retrieval at 24 h and 21 days. Data show that learning induces EPO/EPOr expression increase linked to memory extent, exogenous EPO prolongs memory up to 21 days; and prefrontal cortex bdnf expression at 24 h and in the hippocampus at 21 days, whereas arc expression increases at 21 days in the hippocampus and prefrontal cortex.

Increased functional connectivity between the auditory cortex and the frontoparietal network compensates for impaired visuomotor transformation after early auditory deprivation.

Early auditory deprivation leads to a reorganization of large-scale brain networks involving and extending beyond the auditory system. It has been documented that visuomotor transformation is impaired after early deafness, associated with a hyper-crosstalk between the task-critical frontoparietal network and the default-mode network. However, it remains unknown whether and how the reorganized large-scale brain networks involving the auditory cortex contribute to impaired visuomotor transformation after early deafness. Here, we asked deaf and early hard of hearing participants and normal hearing controls to judge the spatial location of a visual target. Compared with normal hearing controls, the superior temporal gyrus showed significantly increased functional connectivity with the frontoparietal network and the default-mode network in deaf and early hard of hearing participants, specifically during egocentric judgments. However, increased superior temporal gyrus-frontoparietal network and superior temporal gyrus-default-mode network coupling showed antagonistic effects on egocentric judgments. In deaf and early hard of hearing participants, increased superior temporal gyrus-frontoparietal network connectivity was associated with improved egocentric judgments, whereas increased superior temporal gyrus-default-mode network connectivity was associated with deteriorated performance in the egocentric task. Therefore, the data suggest that the auditory cortex exhibits compensatory neuroplasticity (i.e. increased functional connectivity with the task-critical frontoparietal network) to mitigate impaired visuomotor transformation after early auditory deprivation.

Phantom limb syndrome: from pathogenesis to treatment. A narrative review.

Phantom Limb Syndrome (PLS) can be defined as the disabling or painful sensation of the presence of a body part that is no longer present after its amputation. Anatomical changes involved in Phantom Limb Syndrome, occurring at peripheral, spinal and brain levels and include the formation of neuromas and scars, dorsal horn sensitization and plasticity, short-term and long-term modifications at molecular and topographical levels. The molecular reorganization processes of Phantom Limb Syndrome include NMDA receptors hyperactivation in the dorsal horn of the spinal column leading to inflammatory mechanisms both at a peripheral and central level. At the brain level, a central role has been recognized for sodium channels, BDNF and adenosine triphosphate receptors. In the paper we discuss current available pharmacological options with a final overview on non-pharmacological options in the pipeline.

Chemogenetic inhibition of TrkB signalling reduces phrenic motor neuron survival and size.

Brain derived neurotrophic factor (BDNF) signalling through its high-affinity tropomyosin receptor kinase B (TrkB) is known to have potent effects on motor neuron survival and morphology during development and in neurodegenerative diseases. Here, we employed a novel 1NMPP1 sensitive TrkBF616 rat model to evaluate the effect of 14 days inhibition of TrkB signalling on phrenic motor neurons (PhMNs). Adult female and male TrkBF616 rats were divided into 1NMPP1 or vehicle treated groups. Three days prior to treatment, PhMNs in both groups were initially labeled via intrapleural injection of Alexa-Fluor-647 cholera toxin B (CTB). After 11 days of treatment, retrograde axonal uptake/transport was assessed by secondary labeling of PhMNs by intrapleural injection of Alexa-Fluor-488 CTB. After 14 days of treatment, the spinal cord was excised 100 µm thick spinal sections containing PhMNs were imaged using two-channel confocal microscopy. TrkB inhibition reduced the total number of PhMNs by ∼16 %, reduced the mean PhMN somal surface areas by ∼25 %, impaired CTB uptake 2.5-fold and reduced the estimated PhMN dendritic surface area by ∼38 %. We conclude that inhibition of TrkB signalling alone in adult TrkBF616 rats is sufficient to lead to PhMN loss, morphological degeneration and deficits in retrograde axonal uptake/transport.

Reimagining neuroscientific and andragogical principles for dementia care education.

This article aims to explore the integration of Louis Cozolino's (2013) andragogical strategies with the tenets of person-centered dementia care practices to enhance dementia care education. The article examines the multiple dimensions of learning in adulthood, highlighting the role of neural plasticity and lifelong brain adaptation in shaping learning and experiential strategies. This in-depth evaluation underscores the significance of tailoring andragogical approaches to the needs of adult learners, who, in this context, are care providers for persons with dementia. This is done through proper understanding of the neurobiological realities and the unique learning needs of adults. Such tailored approaches can be aligned with the brain's adaptive nature by recognizing the intricate interplay of cognitive, emotional, and social dimensions. Highlighting the need for including lessons on the person-centered approach in dementia care education, the paper argues that adult learners - who are essentially part of the dementia care workforce - first need to learn, appreciate, and embrace the approach before applying it in their caregiving practices. This article presents an overarching argument that integration of Cozolino's principles of adult learning with tenets of person-centered dementia care could provide a robust framework for dementia care education.

Pairing-Dependent Plasticity in a Dissected Fly Brain Is Input-Specific and Requires Synaptic CaMKII Enrichment and Nighttime Sleep.

In Drosophila, in vivo functional imaging studies revealed that associative memory formation is coupled to a cascade of neural plasticity events in distinct compartments of the mushroom body (MB). In-depth investigation of the circuit dynamics, however, will require an ex vivo model that faithfully mirrors these events to allow direct manipulations of circuit elements that are inaccessible in the intact fly. The current ex vivo models have been able to reproduce the fundamental plasticity of aversive short-term memory, a potentiation of the MB intrinsic neuron (Kenyon cells [KCs]) responses after artificial learning ex vivo However, this potentiation showed different localization and encoding properties from those reported in vivo and failed to generate the previously reported suppression plasticity in the MB output neurons (MBONs). Here, we develop an ex vivo model using the female Drosophila brain that recapitulates behaviorally evoked plasticity in the KCs and MBONs. We demonstrate that this plasticity accurately localizes to the MB α'3 compartment and is encoded by a coincidence between KC activation and dopaminergic input. The formed plasticity is input-specific, requiring pairing of the conditioned stimulus and unconditioned stimulus pathways; hence, we name it pairing-dependent plasticity. Pairing-dependent plasticity formation requires an intact CaMKII gene and is blocked by previous-night sleep deprivation but is rescued by rebound sleep. In conclusion, we show that our ex vivo preparation recapitulates behavioral and imaging results from intact animals and can provide new insights into mechanisms of memory formation at the level of molecules, circuits, and brain state.SIGNIFICANCE STATEMENT The mammalian ex vivo LTP model enabled in-depth investigation of the hippocampal memory circuit. We develop a parallel model to study the Drosophila mushroom body (MB) memory circuit. Pairing activation of the conditioned stimulus and unconditioned stimulus pathways in dissected brains induces a potentiation pairing-dependent plasticity (PDP) in the axons of α'ß' Kenyon cells and a suppression PDP in the dendrites of their postsynaptic MB output neurons, localized in the MB α'3 compartment. This PDP is input-specific and requires the 3' untranslated region of CaMKII Interestingly, ex vivo PDP carries information about the animal's experience before dissection; brains from sleep-deprived animals fail to form PDP, whereas those from animals who recovered 2 h of their lost sleep form PDP.

Crossmodal plasticity following short-term monocular deprivation.

A brief period of monocular deprivation (MD) induces short-term plasticity of the adult visual system. Whether MD elicits neural changes beyond visual processing is yet unclear. Here, we assessed the specific impact of MD on neural correlates of multisensory processes. Neural oscillations associated with visual and audio-visual processing were measured for both the deprived and the non-deprived eye. Results revealed that MD changed neural activities associated with visual and multisensory processes in an eye-specific manner. Selectively for the deprived eye, alpha synchronization was reduced within the first 150 ms of visual processing. Conversely, gamma activity was enhanced in response to audio-visual events only for the non-deprived eye within 100-300 ms after stimulus onset. The analysis of gamma responses to unisensory auditory events revealed that MD elicited a crossmodal upweight for the non-deprived eye. Distributed source modeling suggested that the right parietal cortex played a major role in neural effects induced by MD. Finally, visual and audio-visual processing alterations emerged for the induced component of the neural oscillations, indicating a prominent role of feedback connectivity. Results reveal the causal impact of MD on both unisensory (visual and auditory) and multisensory (audio-visual) processes and, their frequency-specific profiles. These findings support a model in which MD increases excitability to visual events for the deprived eye and audio-visual and auditory input for the non-deprived eye.

Plasticity and genetic effects contribute to different axes of neural divergence in a community of mimetic Heliconius butterflies.

Changes in ecological preference, often driven by spatial and temporal variation in resource distribution, can expose populations to environments with divergent information content. This can lead to adaptive changes in the degree to which individuals invest in sensory systems and downstream processes, to optimize behavioural performance in different contexts. At the same time, environmental conditions can produce plastic responses in nervous system development and maturation, providing an alternative route to integrating neural and ecological variation. Here, we explore how these two processes play out across a community of Heliconius butterflies. Heliconius communities exhibit multiple Mullerian mimicry rings, associated with habitat partitioning across environmental gradients. These environmental differences have previously been linked to heritable divergence in brain morphology in parapatric species pairs. They also exhibit a unique dietary adaptation, known as pollen feeding, that relies heavily on learning foraging routes, or trap-lines, between resources, which implies an important environmental influence on behavioural development. By comparing brain morphology across 133 wild-caught and insectary-reared individuals from seven Heliconius species, we find strong evidence for interspecific variation in patterns of neural investment. These largely fall into two distinct patterns of variation; first, we find consistent patterns of divergence in the size of visual brain components across both wild and insectary-reared individuals, suggesting genetically encoded divergence in the visual pathway. Second, we find interspecific differences in mushroom body size, a central component of learning and memory systems, but only among wild caught individuals. The lack of this effect in common-garden individuals suggests an extensive role for developmental plasticity in interspecific variation in the wild. Finally, we illustrate the impact of relatively small-scale spatial effects on mushroom body plasticity by performing experiments altering the cage size and structure experienced by individual H. hecale. Our data provide a comprehensive survey of community level variation in brain structure, and demonstrate that genetic effects and developmental plasticity contribute to different axes of interspecific neural variation.

Dental Pulp-Derived Stem Cells Preserve Astrocyte Health During Induced Gliosis by Modulating Mitochondrial Activity and Functions.

Astrocytes have been implicated in the onset and complication of various central nervous system (CNS) injuries and disorders. Uncontrolled astrogliosis (gliosis), while a necessary process for recovery after CNS trauma, also causes impairments in CNS performance and functions. The ability to preserve astrocyte health and better regulate the gliosis process could play a major role in controlling damage in the aftermath of acute insults and during chronic dysfunction. Here in, we demonstrate the ability of dental pulp-derived stem cells (DPSCs) in protecting the health of astrocytes during induced gliosis. First of all, we have characterized the expression of genes in primary astrocytes that are relevant to the pathological conditions of CNS by inducing gliosis. Subsequently, we found that astrocytes co-cultured with DPSCs reduced ROS production, NRF2 and GCLM expressions, mitochondrial membrane potential, and mitochondrial functions compared to the astrocytes that were not co-cultured with DPSCs in gliosis condition. In addition, hyperactive autophagy was also decreased in astrocytes that were co-cultured with DPSCs compared to the astrocytes that were not co-cultured with DPSCs during gliosis. This reversal and mitigation of gliosis in astrocytes were partly due to induction of neurogenesis in DPSCs through enhanced expressions of the neuronal genes like GFAP, NeuN, and Synapsin in DPSCs and by secretion of higher amounts of neurotropic factors, such as BDNF, GDNF, and TIMP-2. Protein-Protein docking analysis suggested that BDNF and GDNF can bind with CSPG4 and block the downstream signaling. Together these findings demonstrate novel functions of DPSCs to preserve astrocyte health during gliosis.