Modulation Of Neuronal Activity Research Articles

Physiological Role of Orexin/Hypocretin in the Human Body in Motivated Behavior: A Comprehensive Review.

Neurohormones are neurosecretory materials released by neurosecretory cells that serve both as neuromodulators in the brain and spinal cord and as circulating regulatory hormones. They serve a wide range of functions, including homeostasis,development, and modulation of neuronal and muscle activity. In the hypothalamus, neurohormones called hypocretins are created that were discoveredin the late nineties. Orexin receptors (OXRs) have been shown to enhance synaptic signaling in the central nervous system at the cellular level.The orexins improve stimulated neural activity in the hippocampus, which, in turn, aids with spatial memory, learning, and mood. They presentthemselves as mediators for the hypothalamic functions. They have been shown to regulate sleep-wake cycles, arousal mechanisms, addiction, sympathetic nerve activity (SNA), blood pressure, and thermogenesis. Its role in storing brown adipose tissue has implications for thermal homeostasis. The significant role of orexins is seen in tumorigenesis when orexin A (OrxA) and orexin B (OrxB) induce apoptosis in fast-growing tumor cells. Orexin-null subjects show clinical narcolepsy, indicating that orexins were responsible for keeping them awake. Orexin microinjections in mice brains stimulated increased physical activity, thus possibly countering diet-induced obesity. Physical activity significantly increased plasma orexin-A levels, which facilitated the process of energy homeostasis. The amount of adrenocorticotropic hormone (ACTH) increases in stress conditions, which further facilitates the release of the stress hormone cortisol. No increase in the ACTH hormone is seen in stressed mice administered with orexin receptor 2 (OX2R) antagonists thus showing orexin's role in stress reaction. As a result of linking hypocretin/orexin to various physiological procedures, increased research into the medicinal potential of drugs targeting these receptors is emerging. We summed up in this review the recent advances in our understanding of how orexin and its receptor system play an essential role in clinical and pathological functions. This research summarizes a new area for research in human medicine, providing the possibility of controlling a vast array of physiological functions through intra-cerebroventricular injections of a single neuropeptide.

Magnetic Nanomaterials Mediate Electromagnetic Stimulations of Nerves for Applications in Stem Cell and Cancer Treatments.

Although some progress has been made in the treatment of cancer, challenges remain. In recent years, advancements in nanotechnology and stem cell therapy have provided new approaches for use in regenerative medicine and cancer treatment. Among them, magnetic nanomaterials have attracted widespread attention in the field of regenerative medicine and cancer; this is because they have high levels of safety and low levels of invasibility, promote stem cell differentiation, and affect biological nerve signals. In contrast to pure magnetic stimulation, magnetic nanomaterials can act as amplifiers of an applied electromagnetic field in vivo, and by generating different effects (thermal, electrical, magnetic, mechanical, etc.), the corresponding ion channels are activated, thus enabling the modulation of neuronal activity with higher levels of precision and local modulation. In this review, first, we focused on the relationship between biological nerve signals and stem cell differentiation, and tumor development. In addition, the effects of magnetic nanomaterials on biological neural signals and the tumor environment were discussed. Finally, we introduced the application of magnetic-nanomaterial-mediated electromagnetic stimulation in regenerative medicine and its potential in the field of cancer therapy.

Learning-Induced Odor Modulation of Neuronal Activity in Auditory Cortex.

Sensory cortices, even of primary regions, are not purely unisensory. Rather, cortical neurons in sensory cortex show various forms of multisensory interactions. While some multisensory interactions naturally co-occur, the combination of others will co-occur through experience. In real life, learning and experience will result in conjunction with seemingly disparate sensory information that ultimately becomes behaviorally relevant, impacting perception, cognition, and action. Here we describe a novel auditory discrimination task in mice, designed to manipulate the expectation of upcoming trials using olfactory cues. We show that, after learning, female mice display a transient period of several days during which they exploit odor-mediated expectations for making correct decisions. Using two-photon calcium imaging of single neurons in auditory cortex (ACx) during behavior, we found that the behavioral effects of odor-mediated expectations are accompanied by an odor-induced modulation of neuronal activity. Further, we find that these effects are manifested differentially, based on the response preference of individual cells. A significant portion of effects, but not all, are consistent with a predictive coding framework. Our data show that learning novel odor-sound associations evoke changes in ACx. We suggest that behaviorally relevant multisensory environments mediate contextual effects as early as ACx.SIGNIFICANCE STATEMENT Natural environments are composed of multisensory objects. It remains unclear whether and how animals learn the regularities of congruent multisensory associations and how these may impact behavior and neural activity. We tested how learned odor-sound associations affected single-neuron responses in auditory cortex. We introduce a novel auditory discrimination task for mice in which odors set different contexts of expectation to upcoming trials. We show that, although the task can be solved purely by sounds, odor-mediated expectation impacts performance. We further show that odors cause a modulation of neuronal activity in auditory cortex, which is correlated with behavior. These results suggest that learning prompts an interaction of odor and sound information as early as sensory cortex.

Situation-Based Neuromorphic Memory in Spiking Neuron-Astrocyte Network.

Mammalian brains operate in very special surroundings: to survive they have to react quickly and effectively to the pool of stimuli patterns previously recognized as danger. Many learning tasks often encountered by living organisms involve a specific set-up centered around a relatively small set of patterns presented in a particular environment. For example, at a party, people recognize friends immediately, without deep analysis, just by seeing a fragment of their clothes. This set-up with reduced "ontology" is referred to as a "situation." Situations are usually local in space and time. In this work, we propose that neuron-astrocyte networks provide a network topology that is effectively adapted to accommodate situation-based memory. In order to illustrate this, we numerically simulate and analyze a well-established model of a neuron-astrocyte network, which is subjected to stimuli conforming to the situation-driven environment. Three pools of stimuli patterns are considered: external patterns, patterns from the situation associative pool regularly presented to the network and learned by the network, and patterns already learned and remembered by astrocytes. Patterns from the external world are added to and removed from the associative pool. Then, we show that astrocytes are structurally necessary for an effective function in such a learning and testing set-up. To demonstrate this we present a novel neuromorphic computational model for short-term memory implemented by a two-net spiking neural-astrocytic network. Our results show that such a system tested on synthesized data with selective astrocyte-induced modulation of neuronal activity provides an enhancement of retrieval quality in comparison to standard spiking neural networks trained via Hebbian plasticity only. We argue that the proposed set-up may offer a new way to analyze, model, and understand neuromorphic artificial intelligence systems.

Electrodeposited NaYF4:Yb3+, Er3+ up-conversion films for flexible neural device construction and near-infrared optogenetics.

Near-infrared optogenetics based on up-conversion materials provides a promising tool for the dissection of neural circuit functions in deep brain regions. However, it remains a challenge to combine near-infrared up-conversion optogenetic stimulation with high-density electrophysiological recording in a minimally invasive manner. Here, we develop a flexible device for simultaneous electrophysiological recording and near-infrared optogenetics. The flexible device is constructed by integrating polymer-based flexible recording microelectrodes with electrodeposited NaYF4:Yb3+, Er3+ up-conversion films that can convert deep-tissue-penetrating near-infrared light into visible light for optogenetic activation of C1V1-expressing neurons. The emission properties of the up-conversion films are optimized for green light emission to stimulate C1V1 opsins. Owing to their minimized surgical footprint and high mechanical compliance, chronically implanted devices enable simultaneous electrophysiological recording and near-infrared optogenetic modulation of neuronal activities in the brain.

Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and the leading monogenic cause of autism spectrum disorder (ASD). Serotonergic neurotransmission has a key role in the modulation of neuronal activity during development, and therefore, it has been hypothesized to be involved in ASD and co-occurring conditions including FXS. As serotonin is involved in synaptic remodeling and maturation, serotonergic insufficiency during childhood may have a compounding effect on brain patterning in neurodevelopmental disorders, manifesting as behavioral and emotional symptoms. Thus, compounds that stimulate serotonergic signaling such as psilocybin may offer promise as effective early interventions for developmental disorders such as ASD and FXS. The aim of the present study was to test whether different protocols of psilocybin administration mitigate cognitive deficits displayed by the recently validated Fmr1-Δexon 8 rat model of ASD, which is also a model of FXS. Our results revealed that systemic and oral administration of psilocybin microdoses normalizes the aberrant cognitive performance displayed by adolescent Fmr1-Δexon 8 rats in the short-term version of the novel object recognition test-a measure of exploratory behavior, perception, and recognition. These data support the hypothesis that serotonin-modulating drugs such as psilocybin may be useful to ameliorate ASD-related cognitive deficits. Overall, this study provides evidence of the beneficial effects of different schedules of psilocybin treatment in mitigating the short-term cognitive deficit observed in a rat model of FXS.

Development and use of a high-throughput screen to identify novel modulators of the corticotropin releasing factor binding protein.

Stress responses are believed to involve corticotropin releasing factor (CRF), its two cognate receptors (CRF1 and CRF2), and the CRF-binding protein (CRFBP). Whereas decades of research has focused on CRF1, the role of CRF2 in the central nervous system (CNS) has not been thoroughly investigated. We have previously reported that CRF2, interacting with a C terminal fragment of CRFBP, CRFBP(10kD), may have a role in the modulation of neuronal activity. However, the mechanism by which CRF interacts with CRFBP(10kD) and CRF2 has not been fully elucidated due to the lack of useful chemical tools to probe CRFBP. We miniaturized a cell-based assay, where CRFBP(10kD) is fused as a chimera with CRF2, and performed a high-throughput screen (HTS) of 350,000 small molecules to find negative allosteric modulators (NAMs) of the CRFBP(10kD)-CRF2 complex. Hits were confirmed by evaluating activity toward parental HEK293 cells, toward CRF2 in the absence of CRFBP(10kD), and toward CRF1 in vitro. Hits were further characterized in ex vivo electrophysiology assays that target: 1) the CRF1+ neurons in the central nucleus of the amygdala (CeA) of CRF1:GFP mice that express GFP under the CRF1 promoter, and 2) the CRF-induced potentiation of N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic transmission in dopamine neurons in the ventral tegmental area (VTA). We found that CRFBP(10kD) potentiates CRF-intracellular Ca2+release specifically via CRF2, indicating that CRFBP may possess excitatory roles in addition to the inhibitory role established by the N-terminal fragment of CRFBP, CRFBP(27kD). We identified novel small molecule CRFBP-CRF2 NAMs that do not alter the CRF1-mediated effects of exogenous CRF but blunt CRF-induced potentiation of NMDAR-mediated synaptic transmission in dopamine neurons in the VTA, an effect mediated by CRF2 and CRFBP. These results provide the first evidence of specific roles for CRF2 and CRFBP(10kD) in the modulation of neuronal activity and suggest that CRFBP(10kD)-CRF2 NAMs can be further developed for the treatment of stress-related disorders including alcohol and substance use disorders.

Low intensity repetitive transcranial magnetic stimulation modulates brain-wide functional connectivity to promote anti-correlated c-Fos expression

Repetitive transcranial magnetic stimulation (rTMS) induces action potentials to induce plastic changes in the brain with increasing evidence for the therapeutic importance of brain-wide functional network effects of rTMS; however, the influence of sub-action potential threshold (low-intensity; LI-) rTMS on neuronal activity is largely unknown. We investigated whether LI-rTMS modulates neuronal activity and functional connectivity and also specifically assessed modulation of parvalbumin interneuron activity. We conducted a brain-wide analysis of c-Fos, a marker for neuronal activity, in mice that received LI-rTMS to visual cortex. Mice received single or multiple sessions of excitatory 10 Hz LI-rTMS with custom rodent coils or were sham controls. We assessed changes to c-Fos positive cell densities and c-Fos/parvalbumin co-expression. Peak c-Fos expression corresponded with activity during rTMS. We also assessed functional connectivity changes using brain-wide c-Fos-based network analysis. LI-rTMS modulated c-Fos expression in cortical and subcortical regions. c-Fos density changes were most prevalent with acute stimulation, however chronic stimulation decreased parvalbumin interneuron activity, most prominently in the amygdala and striatum. LI-rTMS also increased anti-correlated functional connectivity, with the most prominent effects also in the amygdala and striatum following chronic stimulation. LI-rTMS induces changes in c-Fos expression that suggest modulation of neuronal activity and functional connectivity throughout the brain. Our results suggest that LI-rTMS promotes anticorrelated functional connectivity, possibly due to decreased parvalbumin interneuron activation induced by chronic stimulation. These changes may underpin therapeutic rTMS effects, therefore modulation of subcortical activity supports rTMS for treatment of disorders involving subcortical dysregulation.

Contribution of inwardly rectifying K+ channel 4.1 of supraoptic astrocytes to the regulation of vasopressin neuronal activity by hypotonicity.

Astrocytic morphological plasticity and its modulation of adjacent neuronal activity are largely determined by astrocytic volume regulation, in which glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and potassium channels including inwardly rectifying K+ channel 4.1 (Kir4.1) are essential. However, associations of astrocyte-dominant Kir4.1 with other molecules in astrocytic volume regulation and the subsequent influence on neuronal activity remain unclear. Here, we report our study on these issues using primary cultures of rat pups' hypothalamic astrocytes and male adult rat brain slices. In astrocyte culture, hyposmotic challenge (HOC) significantly decreased GFAP monomer expression and astrocytic volume at 1.5 min and increased Kir4.1 expression and inwardly rectifying currents (IRCs) at 10 min. BaCl2 (100 μmol/l) suppressed the HOC-increased IRCs, which was simulated by VU0134992 (2μmol/l), a Kir4.1 blocker. Preincubation of the astrocyte culture with TGN-020 (10μmol/l, a specific AQP4 blocker) made the HOC-increased Kir4.1 currents insignificant. In hypothalamic brain slices, HOC initially decreased and then increased the firing rate of vasopressin (VP) neurons in the supraoptic nucleus. In the presence of BaCl2 or VU0134992, HOC-elicited rebound increase in VP neuronal activity was blocked. GFAP was molecularly associated with Kir4.1, which was increased by HOC at 20 min; this increase was blocked by BaCl2 . These results suggest that HOC-evoked astrocytic retraction or decrease in the volume and length of its processes is associated with increased Kir4.1 activity. Kir4.1 involvement in HOC-elicited astrocytic retraction is associated with AQP4 activity and GFAP plasticity, which together determines the rebound excitation of VP neurons.

Nigrostriatal dopamine pathway regulates auditory discrimination behavior

The auditory striatum, the tail portion of dorsal striatum in basal ganglia, is implicated in perceptual decision-making, transforming auditory stimuli to action outcomes. Despite its known connections to diverse neurological conditions, the dopaminergic modulation of sensory striatal neuronal activity and its behavioral influences remain unknown. We demonstrated that the optogenetic inhibition of dopaminergic projections from the substantia nigra pars compacta to the auditory striatum specifically impairs mouse choice performance but not movement in an auditory frequency discrimination task. In vivo dopamine and calcium imaging in freely behaving mice revealed that this dopaminergic projection modulates striatal tone representations, and tone-evoked striatal dopamine release inversely correlated with the evidence strength of tones. Optogenetic inhibition of D1-receptor expressing neurons and pharmacological inhibition of D1 receptors in the auditory striatum dampened choice performance accuracy. Our study uncovers a phasic mechanism within the nigrostriatal system that regulates auditory decisions by modulating ongoing auditory perception.

A universal model of electrochemical safety limits in vivo for electrophysiological stimulation.

Electrophysiological stimulation has been widely adopted for clinical diagnostic and therapeutic treatments for modulation of neuronal activity. Safety is a primary concern in an interventional design leveraging the effects of electrical charge injection into tissue in the proximity of target neurons. While modalities of tissue damage during stimulation have been extensively investigated for specific electrode geometries and stimulation paradigms, a comprehensive model that can predict the electrochemical safety limits in vivo doesn’t yet exist. Here we develop a model that accounts for the electrode geometry, inter-electrode separation, material, and stimulation paradigm in predicting safe current injection limits. We performed a parametric investigation of the stimulation limits in both benchtop and in vivo setups for flexible microelectrode arrays with low impedance, high geometric surface area platinum nanorods and PEDOT:PSS, and higher impedance, planar platinum contacts. We benchmark our findings against standard clinical electrocorticography and depth electrodes. Using four, three and two contact electrochemical impedance measurements and comprehensive circuit models derived from these measurements, we developed a more accurate, clinically relevant and predictive model for the electrochemical interface potential. For each electrode configuration, we experimentally determined the geometric correction factors that dictate geometry-enforced current spreading effects. We also determined the electrolysis window from cyclic-voltammetry measurements which allowed us to calculate stimulation current safety limits from voltage transient measurements. From parametric benchtop electrochemical measurements and analyses for different electrode types, we created a predictive equation for the cathodal excitation measured at the electrode interface as a function of the electrode dimensions, geometric factor, material and stimulation paradigm. We validated the accuracy of our equation in vivo and compared the experimentally determined safety limits to clinically used stimulation protocols. Our new model overcomes the design limitations of Shannon’s equation and applies to macro- and micro-electrodes at different density or separation of contacts, captures the breakdown of charge-density based approaches at long stimulation pulse widths, and invokes appropriate power exponents to current, pulse width, and material/electrode-dependent impedance.

Effect of nootropic dipeptide noopept on CA1 pyramidal neurons involves α7AChRs on interneurons in hippocampal slices from rat

Noopept (NP) is a proline-containing dipeptide with nootropic and neuroprotective properties. We have previously shown that NP significantly increased the frequency of spontaneous IPSCs in hippocampal CA1 pyramidal cells mediated by the activation of inhibitory interneurons in stratum radiatum. The cholinergic system plays an important role in the performance of cognitive functions, furthermore multiple behavioral and clinical facts link NP with the cholinergic system. The present study was undertaken to reveal the possible interaction of NP with neuronal nicotinic acetylcholine receptors (nAChRs). Currents were recorded from rat hippocampal neurons using the whole-cell, patch-clamp technique. NP (5 µM) increased the action potential firing frequency recorded from GABAergic interneurons in the stratum radiatum (SR) of CA1 region. This effect was almost completely abolished by the application of the α7 nAChR-selective antagonists α-bungarotoxin (α-BGT; 6 nM) and methyllycaconitine (MLA; 20 nM). The increase in the frequency of spontaneous IPSCs in CA1 pyramidal cells induced by NP was also eliminated by α7 nAChRs antagonists. These results imply the involvement of α7 nAChRs in the modulation of hippocampal neuronal activity caused by NP and indicate that a7 nAChRs are an important site of action of NP.

Thermal effects on neurons during stimulation of the brain

All electric and magnetic stimulation of the brain deposits thermal energy in the brain. This occurs through either Joule heating of the conductors carrying current through electrodes and magnetic coils, or through dissipation of energy in the conductive brain. Objective. Although electrical interaction with brain tissue is inseparable from thermal effects when electrodes are used, magnetic induction enables us to separate Joule heating from induction effects by contrasting AC and DC driving of magnetic coils using the same energy deposition within the conductors. Since mammalian cortical neurons have no known sensitivity to static magnetic fields, and if there is no evidence of effect on spike timing to oscillating magnetic fields, we can presume that the induced electrical currents within the brain are below the molecular shot noise where any interaction with tissue is purely thermal. Approach. In this study, we examined a range of frequencies produced from micromagnetic coils operating below the molecular shot noise threshold for electrical interaction with single neurons. Main results. We found that small temperature increases and decreases of 1 ∘C caused consistent transient suppression and excitation of neurons during temperature change. Numerical modeling of the biophysics demonstrated that the Na-K pump, and to a lesser extent the Nernst potential, could account for these transient effects. Such effects are dependent upon compartmental ion fluxes and the rate of temperature change. Significance. A new bifurcation is described in the model dynamics that accounts for the transient suppression and excitation; in addition, we note the remarkable similarity of this bifurcation’s rate dependency with other thermal rate-dependent tipping points in planetary warming dynamics. These experimental and theoretical findings demonstrate that stimulation of the brain must take into account small thermal effects that are ubiquitously present in electrical and magnetic stimulation. More sophisticated models of electrical current interaction with neurons combined with thermal effects will lead to more accurate modulation of neuronal activity.

Live Imaging of Mitochondria in the Intact Fly Wing.

Detailed mechanisms governing the transport of mitochondria in neurons have recently emerged, although it is still poorly understood how the regulation of transport is coordinated in space and time within the physiological context of an organism. Here, we provide a protocol to study the intracellular dynamics of mitochondria in the wing neurons of adult Drosophila in situ. The mounting and imaging procedures that we describe are suitable for use on most microscopes, and they can be easily implemented in any laboratory. Our noninvasive mounting procedures, combined with the translucency of the wing cuticle in adult animals, makes the wing nervous system accessible to advanced microscopy studies in a physiological environment. Combining the powerful genetics of Drosophila with time-lapse live imaging, users of this protocol will be able to analyze mitochondrial dynamics over time in a subset of sensory neurons in the wing. These cells extend long axons with a stereotypical plus-end-out microtubule orientation that represents a unique model to understand the logic of neuronal cargo transport, including the mitochondria. Finally, the neurons in this tissue respond to mechanical and chemical stimulation of the sensory organs of the wing, opening up the possibility of coupling the study of mitochondrial dynamics with the modulation of neuronal activity in aging Drosophila We anticipate that the unique characteristics of this in vivo system will contribute to the discovery of novel mechanisms that regulate mitochondrial dynamics within an organismal context with relevant implications for the pathogenesis of age-dependent neurological disorders.

Optical control of neuronal activities with photoswitchable nanovesicles.

Precise modulation of neuronal activity by neuroactive molecules is essential for understanding brain circuits and behavior. However, tools for highly controllable molecular release are lacking. Here, we developed a photoswitchable nanovesicle with azobenzene-containing phosphatidylcholine (azo-PC), coined 'azosome', for neuromodulation. Irradiation with 365 nm light triggers the trans-to-cis isomerization of azo-PC, resulting in a disordered lipid bilayer with decreased thickness and cargo release. Irradiation with 455 nm light induces reverse isomerization and switches the release off. Real-time fluorescence imaging shows controllable and repeatable cargo release within seconds (< 3 s). Importantly, we demonstrate that SKF-81297, a dopamine D1-receptor agonist, can be repeatedly released from the azosome to activate cultures of primary striatal neurons. Azosome shows promise for precise optical control over the molecular release and can be a valuable tool for molecular neuroscience studies.

Modulating effects of FGF12 variants on NaV1.2 and NaV1.6 being associated with developmental and epileptic encephalopathy and Autism spectrum disorder: A case series.

SummaryObjectiveFibroblast Growth Factor 12 (FGF12) may represent an important modulator of neuronal network activity and has been associated with developmental and epileptic encephalopathy (DEE). We sought to identify the underlying pathomechanism of FGF12-related disorders.MethodsPatients with pathogenic variants in FGF12 were identified through published case reports, GeneMatcher and whole exome sequencing of own case collections. The functional consequences of two missense and two copy number variants (CNVs) were studied by co-expression of wildtype and mutant FGF12 in neuronal-like cells (ND7/23) with the sodium channels NaV1.2 or NaV1.6, including their beta-1 and beta-2 sodium channel subunits (SCN1B and SCN2B).ResultsFour variants in FGF12 were identified for functional analysis: one novel FGF12 variant in a patient with autism spectrum disorder and three variants from previously published patients affected by DEE. We demonstrate the differential regulating effects of wildtype and mutant FGF12 on NaV1.2 and NaV1.6 channels. Here, FGF12 variants lead to a complex kinetic influence on NaV1.2 and NaV1.6, including loss- as well as gain-of function changes in fast and slow inactivation.InterpretationWe could demonstrate the detailed regulating effect of FGF12 on NaV1.2 and NaV1.6 and confirmed the complex effect of FGF12 on neuronal network activity. Our findings expand the phenotypic spectrum related to FGF12 variants and elucidate the underlying pathomechanism. Specific variants in FGF12-associated disorders may be amenable to precision treatment with sodium channel blockers.FundingDFG, BMBF, Hartwell Foundation, National Institute for Neurological Disorders and Stroke, IDDRC, ENGIN, NIH, ITMAT, ILAE, RES and GRIN

Genetic control of neuronal activity enhances axonal growth only on permissive substrates

BackgroundNeural tissue has limited regenerative ability. To cope with that, in recent years a diverse set of novel tools has been used to tailor neurostimulation therapies and promote functional regeneration after axonal injuries.MethodIn this report, we explore cell-specific methods to modulate neuronal activity, including opto- and chemogenetics to assess the effect of specific neuronal stimulation in the promotion of axonal regeneration after injury.ResultsOpto- and chemogenetic stimulations of neuronal activity elicited increased in vitro neurite outgrowth in both sensory and cortical neurons, as well as in vivo regeneration in the sciatic nerve, but not after spinal cord injury. Mechanistically, inhibitory substrates such as chondroitin sulfate proteoglycans block the activity induced increase in axonal growth.ConclusionsWe found that genetic modulations of neuronal activity on both dorsal root ganglia and corticospinal motor neurons increase their axonal growth capacity but only on permissive environments.

Spinal cord injury and repetitive magnetic stimulation

Spinal cord injuries induce motor and sensory deficits. The development of therapies aimed to improve these functions after spinal cord injury is therefore necessary. Repeated magnetic stimulation (rMS) is an innovative and non-invasive technique which has been used to modulate the activity of neuronal networks in various diseases such as bipolar disorder or Parkinson's disease. rMS could therefore display beneficial functional effects in people with spinal cord injury. Studies carried out in vitro, in vivo and ex vivo have made it possible to partly understand the mechanisms underlying the modulation of neuronal activity induced by rMS protocols. Its use in preclinical models of spinal cord injury has also shown beneficial functional effects. Thus, rMS seems to be a promising therapy in the recovery of lost functions after spinal cord injury.

Neuroimmune crosstalk in the gut and liver.

It has long been assumed that the nervous system exerts distinct effects on immune functions, given the large number of immune disorders that are affected by mental stress. In fact, many different immune cells have been shown to possess a wide variety of neurotransmitter receptors and receive signals from various neurotransmitters, including acetylcholine and noradrenaline. Compared with the findings on local neuroimmune interactions, limited experimental techniques have so far failed to capture a comprehensive overview of neuroimmune interactions between distant organs and the autonomic nervous system in vivo, and the molecular mechanisms underlying local immune regulation of the nervous system have long remained unclear. However, the recent rapid progress in genetic recombination, microscopy and single-cell analysis has deepened our understanding of the anatomical and physiological functions of peripheral nerves at each organ to which they belong. Furthermore, the development of optogenetic and chemogenetic methods has enabled the artificial modulation of specific neuronal activities, and there has been remarkable progress in elucidation of the interaction between nerves and immune cells in vivo, particularly in barrier organs such as the gastrointestinal tract, respiratory tract and skin. This review focuses on the immunoregulatory mechanisms governed by the autonomic nervous system and outlines the latest findings in the regulation of enteric and hepatic immunity by the nervous system.

Serotonergic regulation of bipolar cell survival in the developing cerebral cortex.

One key factor underlying the functional balance of cortical networks is the ratio of excitatory and inhibitory neurons. The mechanisms controlling the ultimate number of interneurons are beginning to be elucidated, but to what extent similar principles govern the survival of the large diversity of cortical inhibitory cells remains to be investigated. Here, we investigate the mechanisms regulating developmental cell death in neurogliaform cells, bipolar cells, and basket cells, the three main populations of interneurons originating from the caudal ganglionic eminence and the preoptic region. We found that all three subclasses of interneurons undergo activity-dependent programmed cell death. However, while neurogliaform cells and basket cells require glutamatergic transmission to survive, the final number of bipolar cells is instead modulated by serotonergic signaling. Together, our results demonstrate that input-specific modulation of neuronal activity controls the survival of cortical interneurons during the critical period of programmed cell death.