Neuronal Interactions Research Articles

Neuroplasticity and neuroimmune interactions in fatal asthma.

Alteration of airway neuronal function and density and bidirectional interaction between immune cells and sensory peripheral nerves have been proposed to trigger and perpetuate inflammation that contribute to asthma severity. To date, few studies analysed neuroplasticity and neuroinflammation in tissue of asthmatic individuals. We hypothesized that the presence of these phenomena would be a pathological feature in fatal asthma. We have quantified the expression of the pan-neuronal marker PGP9.5 and the neuronal sensory-derived neuropeptide calcitonin gene-related peptide (CGRP) in the large airways of 12 individuals deceased due to an asthma attack and compared to 10 control lung samples. The proximity between nerve bundles to eosinophils, mast cells and CADM1+ cells was also quantified. We have additionally developed a hPSC-derived sensory neuron/mast cell co-culture model, from where mast cells were purified and differences in gene expression profile assessed. Fatal asthma patients presented a higher PGP9.5 and CGRP positive area in the airways, indicating sensory neuroplasticity. Eosinophils, mast cells and CADM1+ cells were observed in close contact or touching the airway nerve bundles, and this was found to be statistically higher in fatal asthma samples. Invitro co-culture model showed that human mast cells adhere to sensory neurons and develop a distinct gene expression profile characterized by upregulated expression of genes related to heterophilic adhesion, activation and differentiation markers, such as CADM4, PTGS2, C-KIT, GATA2, HDC, CPA3, ATXN1 and VCAM1. Our results support a significant role for neuroplasticity and neuroimmune interactions in fatal asthma, that could be implicated in the severity of the fatal attack. Accordingly, the presence of physical neuron and mast cell interaction leads to differential gene expression profile in the later cell type.

Consciousness education: Why an enquiry into consciousness is an educational and spiritual imperative

ABSTRACT In this paper, we present a case for including consciousness studies within the educational curriculum from early years through to postcompulsory education. We contend that its current exclusion is due to the deep embeddedness in society of the materialist assumption that the brain produces consciousness. Hence, as a subject of study, consciousness is considered only of relevance to neuroscientists. Informed by this same assumption, notions of spirituality are also seen to be the product of neuronal interactions, and are ultimately illusory, rather than indicating the existence of a different kind of reality. However, there is no incontrovertible evidence to support this assumption, which is increasingly being questioned by leading-edge scientists, spiritual thinkers, and philosophers. Supported by findings from quantum physics, and from the wisdom of indigenous knowledges, there is a growing interest in alternative theories, such as the idea that consciousness may be primary, and matter may be an emergent property of consciousness. We examine arguments for these radically different perspectives, and how they inform, and are informed by, different worldviews. We argue that young people need to be made aware of those alternative worldviews so that they can make informed choices about who they are as spiritual beings.

Bilateral interactions of optic-flow sensitive neurons coordinate course control in flies

Animals rely on compensatory actions to maintain stability and navigate their environment efficiently. These actions depend on global visual motion cues known as optic-flow. While the optomotor response has been the traditional focus for studying optic-flow compensation in insects, its simplicity has been insufficient to determine the role of the intricate optic-flow processing network involved in visual course control. Here, we reveal a series of course control behaviours in Drosophila and link them to specific neural circuits. We show that bilateral electrical coupling of optic-flow-sensitive neurons in the fly’s lobula plate are required for a proper course control. This electrical interaction works alongside chemical synapses within the HS-H2 network to control the dynamics and direction of turning behaviours. Our findings reveal how insects use bilateral motion cues for navigation, assigning a new functional significance to the HS-H2 network and suggesting a previously unknown role for gap junctions in non-linear operations.

Autism spectrum disorder-like behaviors induced by hyper-glutamatergic NMDA receptor signaling through hypo-serotonergic 5-HT1A receptor signaling in the prefrontal cortex in mice exposed to prenatal valproic acid.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, social deficits, and cognitive impairments. Maternal use of valproic acid (VPA) during pregnancy is associated with an increased risk of ASD in offspring. The prevailing pathophysiological hypothesis for ASD involves excitation/inhibition (E/I) imbalances and serotonergic dysfunction. Here, we investigated the association between glutamatergic-serotonergic neuronal interactions and ASD-like behaviors in mice exposed to prenatal VPA. Prenatal VPA exposure induced excessive repetitive self-grooming behavior and impaired social behavior and object recognition memory in young adult period. Prenatal VPA mice showed hyper-glutamatergic function (increase in basal extracellular glutamate levels and CaMKII phosphorylation) and hypo-serotonergic function (decrease in 5-hydroxyindoleacetic acid and stimulation-induced serotonin [5-HT] release, but an increase in 5-HT transporter expression) in the prefrontal cortex. Treatment with a low-affinity NMDA receptor antagonist (memantine), a selective 5-HT reuptake inhibitor (fluoxetine), and a 5-HT1A receptor agonist (tandospirone) attenuated both the increase in CaMKII phosphorylation and ASD-like behavior of prenatal VPA mice. Opto-genetic activation of the serotonergic neuronal system attenuated impairments in social behavior and object recognition memory in prenatal VPA mice. WAY-100635-a 5-HT1A receptor antagonist-antagonized the effect of fluoxetine on impaired social behavior and object recognition memory. These results suggest that E/I imbalance and ASD-like behavior are associated with hypo-serotonergic receptor signaling through 5-HT1A receptors in prenatal VPA mice.

Computational Fuzzy Modelling Approach to Analyze Neuronal Calcium Dynamics With Intracellular Fluxes.

Mathematical neuroscience investigates how calcium distribution in nerve cells affects the neurological system. The interaction of numerous systems is necessary for the operation of several cellular processes in neuron cells, such as calcium, buffer, ER etc. The dynamics of interacting parameters give useful information on neural cell function. This work uses a mathematical model to analyze the dynamic interactions of buffer and ER inside neurons, considering their spatial properties. While buffers bind to calcium ions and lower their concentration, the endoplasmic reticulum (ER) serves as a reservoir, holding a significant number of free calcium ions. The uncertainty of initial values of calcium concentration poses challenges for researchers to develop calcium signaling models. In this article, we examined the exact solution and approximate solution of the mathematical model that was analyzed using the fuzzy undetermined coefficient approach. MATLAB is being used to perform the simulation. Endoplasmic reticulum and buffer have been found to have a substantial impact on calcium signaling. Fuzzy differential equation Provides a useful tool for evaluating complicated processes with imprecise values when ordinary differential equations perform not precisely. They allow for the examination of dynamic processes under fuzzy settings, which contributes to advances research.

Spontaneous Brain Activity Emerges from Pairwise Interactions in the Larval Zebrafish Brain

Brain activity is characterized by brainwide spatiotemporal patterns that emerge from synapse-mediated interactions between individual neurons. Calcium imaging provides access to recordings of whole-brain activity at single-neuron resolution and, therefore, allows the study of how large-scale brain dynamics emerge from local activity. In this study, we use a statistical mechanics approach—the pairwise maximum entropy model—to infer microscopic network features from collective patterns of activity in the larval zebrafish brain and relate these features to the emergence of observed whole-brain dynamics. Our findings indicate that the pairwise interactions between neural populations and their intrinsic activity states are sufficient to explain observed whole-brain dynamics. In fact, the pairwise relationships between neuronal populations estimated with the maximum entropy model strongly correspond to observed structural connectivity patterns. Model simulations also demonstrated how tuning pairwise neuronal interactions drives transitions between observed physiological regimes and pathologically hyperexcitable whole-brain regimes. Finally, we use virtual resection to identify the brain structures that are important for maintaining the brain in a physiological dynamic regime. Together, our results indicate that whole-brain activity emerges from a complex dynamical system that transitions between basins of attraction whose strength and topology depend on the connectivity between brain areas. Published by the American Physical Society 2024

SIRT1 activation by Ligustrazine ameliorates migraine via the paracrine interaction of microglia and neurons

BackgroundNeuroinflammation with associated oxidative stress aggravates the pathogenesis and progression of migraine. Ligustrazine (LGZ) is a key component from traditional edible-medicinal herb Ligusticum chuanxiong Hort., and has the effects of anti-platelet aggregation, expanding small arteries, improving microcirculation and promoting blood circulation and removing blood stasis in clinic. Hypothesis/PurposeThis study aims to investigate the pharmacological effect and mechanism of LGZ in migraine. Study Design/MethodsA mouse model of migraine was induced by nitroglycerin (NTG), and LPS/IFN-γ stimulated microglial cell model was conducted to investigate neuroinflammation, the paracrine interactions between microglia and neurons were determined by the co-culture system, and the effect of LGZ on stability of SIRT1 protein was measured by cellular thermal shift assay (CETSA). Whilst, the SIRT1 inhibitor EX527 was used alone or co-treatment with LGZ in vitro or in vivo. ResultsLGZ significantly attenuated migraine-like behaviors in NTG-induced mice, and ameliorated neuroinflammation and related oxidative damage in brain tissue, but co-treatment with SIRT1 inhibitor EX527 abolished the protective effects of LGZ. Mechanistically, LGZ mitigated neuroinflammation by upregulating SIRT1 expression and subsequently inhibiting the activation of NF-κB pathway in microglia. CETSA indicated that LGZ significantly maintained the stability of SIRT1 protein in microglia. While, in the co-culture system, culture medium from LPS/IFN-γ-treated microglia exacerbated neuronal damage and oxidative stress, which was suppressed by treating LPS/IFN-γ-induced microglia with LGZ, this effect might be related to the activation of Nrf2 signals in neurons. Notably, SIRT1 inhibitor EX527 abrogated the effects of LGZ both in vitro and in vivo. ConclusionConsequently, SIRT1 might be an important pharmacological target of LGZ, which attenuates migraine associated neuroinflammation and oxidative stress by interfering the crosstalk between microglia and neurons, thereby relieving migraine.

Exploring the Association Between Clinical Characteristics and Etiopathogenesis of Tinnitus: A Cross-Sectional Study.

Background Tinnitus is the perception of internal noises like ringing or hissing, which can greatly affect quality of life. It involves increased neuronal synchrony and interactions with non-auditory brain structures. There's no universal classification system due to its varied origins and mechanisms, and current protocols often overlook physiotherapy, especially for non-otologic causes such as Cervicogenic and Temporomandibular disorders. This study seeks to link clinical features with tinnitus characteristics to better identify underlying causes and improve diagnostic protocols. Methods A prospective observational cross-sectional study was conducted from June 2022 to March 2024 in a rural hospital in Central India, involving 75 patients with tinnitus. The study included comprehensive history, clinical examination, and physiotherapy assessments to categorize tinnitus into otologic, non-otologic, or central types. Each type was analyzed to correlate its characteristics with underlying causes. The findings aim to improve diagnostic protocols and deepen understanding of tinnitus origins. Results The otologic origin of tinnitus was found in 53 (70.7%) patients. Out of 16 (21.3%) patients in the non-otologic category, three (4%) of patients had a somatosensory origin, seven (9.3%) of patients were found to have a somatosensory cervicogenic origin of tinnitus, and six (8%) of patients had a central origin of tinnitus. The remaining six (8%) were found to have mixed origins. Conclusion Otologic tinnitus was the commonest cause of tinnitus, followed by cervicogenic tinnitus. Ours is probably the first study that classifies tinnitus based on otologic and non-otologic origin, with special emphasis on cervicogenic origin tinnitus. Further research could study tinnitus chronicity, causes, and treatments using objective measures and advanced diagnostics.

Inference on the Macroscopic Dynamics of Spiking Neurons.

The process of inference on networks of spiking neurons is essential to decipher the underlying mechanisms of brain computation and function. In this study, we conduct inference on parameters and dynamics of a mean-field approximation, simplifying the interactions of neurons. Estimating parameters of this class of generative model allows one to predict the system's dynamics and responses under changing inputs and, indeed, changing parameters. We first assume a set of known state-space equationsand address the problem of inferring the lumped parameters from observed time series. Crucially, we consider this problem in the setting of bistability, random fluctuations in system dynamics, and partial observations, in which some states are hidden. To identify the most efficient estimation or inversion scheme in this particular system identification, we benchmark against state-of-the-art optimization and Bayesian estimation algorithms, highlighting their strengths and weaknesses. Additionally, we explore how well the statistical relationships between parameters are maintained across different scales. We found that deep neural density estimators outperform other algorithms in the inversion scheme, despite potentially resulting in overestimated uncertainty and correlation between parameters. Nevertheless, this issue can be improved by incorporating time-delay embedding. We then eschew the mean-field approximation and employ deep neural ODEs on spiking neurons, illustrating prediction of system dynamics and vector fields from microscopic states. Overall, this study affords an opportunity to predict brain dynamics and responses to various perturbations or pharmacological interventions using deep neural networks.

Resection of the adipose fin from rainbow trout acutely alters the cerebral transcriptome and respiratory frequency

As many as 100 million salmonid fish are tagged annually by removing the adipose fin, usually for recovery statistics and the fishing industry. In a multi-parametrical approach, we evaluated the response to resection of the adipose fin in rainbow trout Oncorhynchus mykiss over the course of 72 h. Both the concentrations of lactate and the cerebral transcriptomes differed in rainbow trout early after adipose fin clipping compared to the matching intact controls. The number of differentially expressed genes significantly increased, first in the midbrain and later in the forebrain, in fin-clipped compared to intact trout. Several of these genes were predicted to be involved in pain-induced and synaptogenesis-related pathways, suggesting that adipose fin resection may affect the architecture of neuronal networks. In an experimental setup applying swimming tunnels, we tested whether removal of the adipose fin had any consequences on the behavior of fin-clipped versus intact trout exposed to a regularly recurring water flow. Concomitant with increased and prevailing breath frequencies after repeated exposure to water flows, we observed a marked transcriptional response in the forebrain of fin-clipped trout compared with intact unchallenged controls at later time points after the resection. The resulting list of differentially expressed genes was assigned to a broad range of signaling pathways involved in trans-synaptic signaling, neuronal interaction dynamics, and neuroplasticity. Taken together, our findings suggest that resection of the potentially flow-sensory adipose fin alters pathways related to pain perception and likely enhances the physiological response to the current, probably indicating increased physical effort. We also deduce from the transcriptomic data that amputation of the adipose fin leads to reorganization of the high-level integration system in the brain. The short-term effects observed in the present study require further validation to estimate the prevailing stress for the organism. Nevertheless, we propose considering alternative tagging methods for salmonid fish that do not conflict with fish welfare, as the amputation of the adipose fin may have more far-reaching physiological effects than previously assumed.

Fasting induces metabolic switches and spatial redistributions of lipid processing and neuronal interactions in tanycytes

The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus plays a crucial role in energy balance and glucose homeostasis. It is characterized by a high functional heterogeneity and plasticity, but the underlying molecular mechanisms governing its features are not fully understood. Here, 5481 hypothalamic ependymocytes were cataloged using FACS-assisted scRNAseq from fed, 12h-fasted, and 24h-fasted adult male mice. With standard clustering analysis, typical ependymal cells and β2-tanycytes appear sharply defined, but other subpopulations, β1- and α-tanycytes, display fuzzy boundaries with few or no specific markers. Pseudospatial approaches, based on the 3V neuroanatomical distribution, enable the identification of specific versus shared tanycyte markers and subgroup-specific versus general tanycyte functions. We show that fasting dynamically shifts gene expression patterns along the 3V, leading to a spatial redistribution of cell type-specific responses. Altogether, we show that changes in energy status induce metabolic and functional switches in tanycyte subpopulations, providing insights into molecular and functional diversity and plasticity within the tanycyte population.

Sensory feedback and central neuronal interactions in mouse locomotion.

Locomotion is a complex process involving specific interactions between the central neural controller and the mechanical components of the system. The basic rhythmic activity generated by locomotor circuits in the spinal cord defines rhythmic limb movements and their central coordination. The operation of these circuits is modulated by sensory feedback from the limbs providing information about the state of the limbs and the body. However, the specific role and contribution of central interactions and sensory feedback in the control of locomotor gait and posture remain poorly understood. We use biomechanical data on quadrupedal locomotion in mice and recent findings on the organization of neural interactions within the spinal locomotor circuitry to create and analyse a tractable mathematical model of mouse locomotion. The model includes a simplified mechanical model of the mouse body with four limbs and a central controller composed of four rhythm generators, each operating as a state machine controlling the state of one limb. Feedback signals characterize the load and extension of each limb as well as postural stability (balance). We systematically investigate and compare several model versions and compare their behaviour to existing experimental data on mouse locomotion. Our results highlight the specific roles of sensory feedback and some central propriospinal interactions between circuits controlling fore and hind limbs for speed-dependent gait expression. Our models suggest that postural imbalance feedback may be critically involved in the control of swing-to-stance transitions in each limb and the stabilization of walking direction.

Distinct olfactory mucosal macrophage populations mediate neuronal maintenance and pathogen defense

The olfactory mucosa is important for both the sense of smell and as a mucosal immune barrier to the upper airway and brain. However, little is known about how the immune system mediates the conflicting goals of neuronal maintenance and inflammation in this tissue. A number of immune cell populations reside within the olfactory mucosa and yet we have little understanding of how these resident olfactory immune cells functionally interact with the chemosensory environment. Identifying these interactions will allow therapeutic manipulations that treat disorders such as post-viral olfactory dysfunction. Macrophages are the most prevalent immune cell type in the uninflamed olfactory mucosa and here, we identify two distinct tissue macrophage populations in murine olfactory mucosa. P2ry12hi macrophages are transcriptionally specialized for neuron interactions, closely associated with olfactory neuron cell bodies, long-term tissue residents, and functionally specialized to phagocytose cells and debris, including olfactory neurons. Conversely, MHC Class IIhi macrophages are transcriptionally dedicated to cytokine production and antigen presentation, localized primarily within the olfactory lamina propria, more rapidly replaced by blood monocytes, and rapidly produce chemokines in response to viral infection. We further show that these macrophage signatures are present in human olfactory biopsies, and P2ry12-like olfactory macrophages are reduced in patients with long-term smell loss following COVID-19. Together, these data show that two olfactory macrophage populations regulate neurons and initiate the immune response, contributing to our understanding of both olfactory immunity and tissue-resident macrophage biology.

Interaction of Cortricotropin-Releasing Hormone and Capsaicin-Sensitive Afferent Neurons in Gastroprotection

Interaction of Cortricotropin-Releasing Hormone and Capsaicin-Sensitive Afferent Neurons in Gastroprotection

Higher-order interactions between hippocampal CA1 neurons are disrupted in amnestic mice.

Across systems, higher-order interactions between components govern emergent dynamics. Here we tested whether contextual threat memory retrieval in mice relies on higher-order interactions between dorsal CA1 hippocampal neurons requiring learning-induced dendritic spine plasticity. We compared population-level Ca2+ transients as wild-type mice (with intact learning-induced spine plasticity and memory) and amnestic mice (TgCRND8 mice with high levels of amyloid-β and deficits in learning-induced spine plasticity and memory) were tested for memory. Using machine-learning classifiers with different capacities to use input data with complex interactions, our findings indicate complex neuronal interactions in the memory representation of wild-type, but not amnestic, mice. Moreover, a peptide that partially restored learning-induced spine plasticity also restored the statistical complexity of the memory representation and memory behavior in Tg mice. These findings provide a previously missing bridge between levels of analysis in memory research, linking receptors, spines, higher-order neuronal dynamics and behavior.

Elp1 function in placode-derived neurons is critical for proper trigeminal ganglion development.

The trigeminal nerve is the largest cranial nerve and functions in somatosensation. Cell bodies of this nerve are positioned in the trigeminal ganglion, which arises from the coalescence of neural crest and placode cells. While this dual cellular origin has been known for decades, the molecular mechanisms controlling trigeminal ganglion development remain obscure. We performed RNAsequencing on the forming chick trigeminal ganglion and identified Elongator acetyltransferase complex subunit 1 ( Elp1 ) for further study. Mutations in ELP1 cause familial dysautonomia (FD), a fatal disorder characterized by the presence of smaller trigeminal nerves and sensory deficits. While Elp1 has established roles in neurogenesis, its functions in placode cells during trigeminal gangliogenesis have not been investigated. To this end, we used morpholinos to deplete Elp1 from chick trigeminal placode cells. Elp1 knockdown decreased trigeminal ganglion size and led to aberrant innervation of the eye by placode-derived neurons. Trigeminal nerve branches exhibited fewer axons, and abnormal interactions between placode-derived neurons and neural crest cells were observed. These findings reveal a new role for Elp1 in chick placode-derived neurons during trigeminal ganglion development. These results have potential high significance to provide new insights into trigeminal ganglion development and the etiology of FD. Elp1 is expressed in undifferentiated neural crest cells and placode-derived neurons contributing to the trigeminal ganglion.Elp1 knockdown in trigeminal placode cells reduces trigeminal ganglion size.Elp1 depletion from trigeminal placode cells leads to aberrant target tissue innervation and disrupts proper neural crest-placodal neuron interactions in the trigeminal ganglion. NIH R01DE024217 and NIH R03HD108480.

Dynamics of non–identical coupled Chialvo neuron maps

We study numerically the dynamics of low–dimensional ensembles of discrete neuron models - Chialvo maps. We are focused on choosing the autonomous map parameters corresponding to the invariant curve. We consider two cases of coupling organization: (i) via a nonlinear function of models; (ii) linear coupling, which is an analog of electrical neuron interaction. For the first case, the possibility of invariant curve doublings and the emergence of quasi-periodicity within Arnold tongues as a result of the secondary Neimark-Sacker bifurcation are found. For the second case, we discover an area of three-frequency quasi-periodicity for the case of two neurons. It arises softly as a result of quasi-periodic Hopf bifurcation. We demonstrate a set of resonant two-frequency regimes tongues embedded in this area and bounded by lines of saddle-node bifurcations of invariant curves. For ensemble of three linearly coupled maps, four-frequency quasi-periodicity becomes possible with a built-in system of tongues of three-frequency regimes (tori). We discuss the effect of noise and the evolution of “noise quasi-periodic” regimes, resonant regimes of this type and bifurcations of invariant tori with increasing of noise intensity.

Neuroprotective effect of omidenepag on excitotoxic retinal ganglion cell death regulating COX-2–EP2–cAMP–PKA/Epac pathway via Neuron–Glia interaction

Glutamate excitotoxicity is involved in retinal ganglion cell (RGC) death in various retinal degenerative diseases, including ischemia–reperfusion injury and glaucoma. Excitotoxic RGC death is caused by both direct damage to RGCs and indirect damage through neuroinflammation of retinal glial cells. Omidenepag (OMD), a novel E prostanoid receptor 2 (EP2) agonist, is a recently approved intraocular pressure-lowering drug. The second messenger of EP2 is cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). In this study, we investigated the neuroprotective effects of OMD on excitotoxic RGC death by focusing on differences in cAMP downstream signaling from the perspective of glia–neuron interactions.We established a glutamate excitotoxicity model in vitro and NMDA intravitreal injection model in vivo. In vitro, rat primary RGCs were used in an RGC survival rate assay. MG5 cells (mouse microglial cell line) and A1 cells (astrocyte cell line) were used for immunocytochemistry and Western blotting to evaluate the expressions of COX-1/2, PKA, Epac1/2, pCREB, cleaved caspase-3, inflammatory cytokines, and neurotrophic factors. Mouse retinal specimens underwent hematoxylin and eosin staining, flat-mounted retina examination, and immunohistochemistry.OMD significantly suppressed excitotoxic RGC death, cleaved caspase-3 expression, and activated glia both in vitro and in vivo. Moreover, it inhibited Epac1 and inflammatory cytokine expression and promoted COX-2, pCREB, and neurotrophic factor expression.OMD may have neuroprotective effects through inhibition of the Epac pathway and promotion of the COX-2–EP2–cAMP–PKA pathway by modulating glia–neuron interaction.

Agouti-Induced Anxiety-Like Behavior Is Mediated by Central Serotonergic Pathways in Zebrafish.

Overexpression of the agouti-signaling protein (asip1), an endogenous melanocortin antagonist, under the control of a constitutive promoter in zebrafish [Tg(Xla.Eef1a1:Cau.Asip1]iim4] (asip1-Tg) increases food intake by reducing sensitivity of the central satiety systems and abolish circadian activity rhythms. The phenotype also shows increased linear growth and body weight, yet no enhanced aggressiveness in dyadic fights is observed. In fact, asip1-Tg animals choose to flee to safer areas rather than face a potential threat, thus suggesting a potential anxiety-like behavior (ALB). Standard behavioral tests, i.e., the open field test (OFT), the novel object test (NOT), and the novel tank dive test (NTDT), were used to investigate thigmotaxis and ALB in male and female zebrafish. Results showed that the asip1-Tg strain exhibited severe ALB in every test, mainly characterized by pronounced freezing behavior and increased linear and angular swimming velocities. asip1-Tg animals exhibited low central serotonin (5-HT) and dopamine (DA) levels and high turnover rates, thus suggesting that central monoaminergic pathways might mediate melanocortin antagonist-induced ALB. Accordingly, the treatment of asip1-Tg animals with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversed the ALB phenotype in NTDT as well as 5-HT turnover. Genomic and anatomical data further supported neuronal interaction between melanocortinergic and serotonergic systems. These results suggest that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonist has an anxiogenic effect mediated by serotonergic transmission.

The primate cortical LFP exhibits multiple spectral and temporal gradients and widespread task dependence during visual short-term memory.

Although cognitive functions are hypothesized to be mediated by synchronous neuronal interactions in multiple frequency bands among widely distributed cortical areas, we still lack a basic understanding of the distribution and task dependence of oscillatory activity across the cortical map. Here, we ask how the spectral and temporal properties of the local field potential (LFP) vary across the primate cerebral cortex, and how they are modulated during visual short-term memory. We measured the LFP from 55 cortical areas in two macaque monkeys while they performed a visual delayed match to sample task. Analysis of peak frequencies in the LFP power spectra reveals multiple discrete frequency bands between 3 and 80 Hz that differ between the two monkeys. The LFP power in each band, as well as the sample entropy, a measure of signal complexity, display distinct spatial gradients across the cortex, some of which correlate with reported spine counts in cortical pyramidal neurons. Cortical areas can be robustly decoded using a small number of spectral and temporal parameters, and significant task-dependent increases and decreases in spectral power occur in all cortical areas. These findings reveal pronounced, widespread, and spatially organized gradients in the spectral and temporal activity of cortical areas. Task-dependent changes in cortical activity are globally distributed, even for a simple cognitive task.NEW & NOTEWORTHY We recorded extracellular electrophysiological signals from roughly the breadth and depth of a cortical hemisphere in nonhuman primates (NHPs) performing a visual memory task. Analyses of the band-limited local field potential (LFP) power displayed widespread, frequency-dependent cortical gradients in spectral power. Using a machine learning classifier, these features allowed robust cortical area decoding. Further task dependence in LFP power were found to be widespread, indicating large-scale gradients of LFP activity, and task-related activity.