Reticular Formation Research Articles

Oxytocin moderates fMRI connectivity and response to implicit threat processing in cocaine use disorder

Stressful social experiences play an important role in increasing vulnerability to substance use, including cocaine. Oxytocin (OXT), known for its anxiolytic properties and involvement in social functioning, has been suggested as a potential therapeutic for cocaine use disorder (CUD). However, limited research has explored OXT’s influence on social stress in CUD, and no study has examined its effects on neural response to subconscious (implicit) social threat cues in this population. To address this gap, the present study administered intranasal OXT (24 IU) or placebo (PBO) to participants with CUD (CUD+, N = 76) or without CUD (CUD-, N = 61) in a randomized parallel design. Participants then completed a functional magnetic resonance imaging (fMRI) task involving briefly presented facial fear and anger (i.e., threat) cues, followed by neutral face stimuli. Whole-brain activation and amygdala functional connectivity (using psychophysiological interaction modeling) were examined in response to the facial threat cues. OXT reduced activation in the thalamus and pontine reticular formation in response to fear cues, and in the supplementary motor area for both fear and anger cues, regardless of CUD status. Additionally, under PBO, amygdala-medial prefrontal cortex connectivity to fear stimuli was negative for the CUD+ group, but under OXT, this coupling was positive, similar to the positive coupling observed for the CUD- group under both PBO and OXT administration. The finding of OXT-mediated reversal of amygdala-prefrontal coupling was specific to CUD+ and suggests that OXT alters circuitry related to threat surveillance and implicit emotion regulation in CUD. However, additional research is needed to determine whether these alterations due to OXT have clinical significance in CUD.

Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations.

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.

The autophagy process and oxidized LDL independently modulate the invasion and differentiation of extravillous trophoblastic cells to an endothelial-like phenotype in normoxia

IntroductionThe mechanisms leading to proper placentation are not fully understood. Extravillous trophoblasts (EVTs) are crucial for placentation through invasion and vascular remodeling, which, when impaired, promote a poor placentation. How autophagy could regulate EVTs function and the study of regulators of these processes, such as oxidized low-density lipoproteins (ox-LDL), could contribute to better understand events associated with pregnancy complications related to abnormal placental development, such as preeclampsia (PE). AimTo investigate the role of autophagy and oxidized LDL (ox-LDL) in invasion and endothelial-like phenotype acquisition of a model of EVTs, as well as to determine the levels of autophagy flux markers in control and PE placentas. MethodsInvasion and endothelial-like phenotype acquisition assays were performed in a cell line model of first trimester EVTs: HTR-8/SVneo cultured in normoxia (oxygen concentration of 20%), in the absence or the presence of the autophagy inhibitor bafilomycin or/and ox-LDL. Markers of autophagic flux were evaluated in human term placentas. ResultsAutophagy is essential for EVTs to acquire an endothelial-like phenotype but does not affect invasion. Conversely, ox-LDL decreases invasion and reticular structures formation, independent of autophagy. At pregnancy term, the levels of the autophagy markers LC3 and p62 are deregulated in the trophoblast cells of PE placentas. ConclusionAutophagy is necessary for proper endothelial-like phenotype acquisition in HTR-8/SVneo cultured in normoxia, and ox-LDL impairs this process as well as the invasion of EVTs by a mechanism independent of autophagy. Changes in autophagy and/or in the concentration of ox-LDL could affect placental vascular remodeling.

Shared subcortical arousal systems across sensory modalities during transient modulation of attention.

Subcortical arousal systems are known to play a key role in controlling sustained changes in attention and conscious awareness. Recent studies indicate that these systems have a major influence on short-term dynamic modulation of visual attention, but their role across sensory modalities is not fully understood. In this study, we investigated shared subcortical arousal systems across sensory modalities during transient changes in attention using block and event-related fMRI paradigms. We analyzed massive publicly available fMRI datasets collected while 1,561 participants performed visual, auditory, tactile, and taste perception tasks. Our analyses revealed a shared circuit of subcortical arousal systems exhibiting early transient increases in activity in midbrain reticular formation and central thalamus across perceptual modalities, as well as less consistent increases in pons, hypothalamus, basal forebrain, and basal ganglia. Identifying these networks is critical for understanding mechanisms of normal attention and consciousness and may help facilitate subcortical targeting for therapeutic neuromodulation.

Association of medullary reticular formation ventral part with spasticity in mice suffering from photothrombotic stroke

Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions.Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy‑5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase.

Understanding subcortical projections to the lateral posterior thalamic nucleus and its subregions using retrograde neural tracing.

The rat lateral posterior thalamic nucleus (LP) is composed of the rostromedial (LPrm), lateral (LPl), and caudomedial parts, with LPrm and LPl being areas involved in information processing within the visual cortex. Nevertheless, the specific differences in the subcortical projections to the LPrm and LPl remain elusive. In this study, we aimed to reveal the subcortical regions that project axon fibers to the LPl and LPrm using a retrograde neural tracer, Fluorogold (FG). After FG injection into the LPrm or LPl, the area was visualized immunohistochemically. Retrogradely labeled neurons from the LPrm were distributed in the retina and the region from the diencephalon to the medulla oblongata. Diencephalic labeling was found in the reticular thalamic nucleus (Rt), zona incerta (ZI), ventral lateral geniculate nucleus (LGv), intergeniculate leaflet (IGL), and hypothalamus. In the midbrain, prominent labeling was found in the periaqueductal gray (PAG) and deep layers of the superior colliculus. Additionally, retrograde labeling was observed in the cerebellar and trigeminal nuclei. When injected into the LPl, several cell bodies were labeled in the visual-related regions, including the retina, LGv, IGL, and olivary pretectal nucleus (OPT), as well as in the Rt and anterior pretectal nucleus (APT). Less labeling was found in the cerebellum and medulla oblongata. When the number of retrogradely labeled neurons from the LPrm or LPl was compared as a percentage of total subcortical labeling, a larger percentage of subcortical inputs to the LPl included projections from the APT, OPT, and Rt, whereas a large proportion of subcortical inputs to the LPrm originated from the ZI, reticular formation, and PAG. These results suggest that LPrm not only has visual but also multiple sensory-and motor-related functions, whereas the LPl takes part in a more visual-specific role. This study enhances our understanding of subcortical neural circuits in the thalamus and may contribute to our exploration of the mechanisms and disorders related to sensory perception and sensory-motor integration.

Comprehensive Morphometric Analysis of the Rhomboid Fossa: Implications for Safe Entry Zones in Brainstem Surgery

The rhomboid fossa (RF) is a crucial anatomical region in brainstem surgery, as it contains essential structures like the reticular formation and cranial nerve nuclei. This study aims to provide a detailed understanding of the RF's complex microsurgical anatomy, which is vital for the safe execution of neurosurgical procedures. Morphometric analysis was conducted on 45 adult human brainstems preserved in 10% formalin. Thirteen linear measurements were performed under 20x magnification, using a millimeter graph to identify key anatomical landmarks. The study provided precise measurements of the rhomboid fossa, with a length of 34.65 mm and a width of 22.61 mm. The facial colliculus (FC) measured 4.26 mm in length on the left and 4.45 mm on the right, with corresponding widths of 3.77 mm and 3.50 mm. The distance between the sulcus limitans incisures was 9.52 mm, while the distance from the upper border of the medullary striae to obex was 11.53 mm. The proximity of the FC to the median sulcus was measured at 0.86 mm on the right and 0.96 mm on the left. Additionally, two safe entry zones-the suprafacial and infrafacial triangles-were identified, offering pathways to reach dorsal pons lesions through the RF. This comprehensive morphometric analysis of the RF enhances the understanding of its intricate anatomy. By describing safe entry zones, the suprafacial and infrafacial triangles, and providing precise measurements of key anatomical features, this research serves as a valuable resource for neurosurgeons in planning and executing brainstem surgeries.

Self-organizing recruitment of compensatory areas maximizes residual motor performance post-stroke.

Whereas the orderly recruitment of compensatory motor cortical areas after stroke depends on the size of the motor cortex lesion affecting arm and hand movements, the mechanisms underlying this reorganization are unknown. Here, we hypothesized that the recruitment of compensatory areas results from the motor system's goal to optimize performance given the anatomical constraints before and after the lesion. This optimization is achieved through two complementary plastic processes: a homeostatic regulation process, which maximizes information transfer in sensory-motor networks, and a reinforcement learning process, which minimizes movement error and effort. To test this hypothesis, we developed a neuro-musculoskeletal model that controls a 7-muscle planar arm via a cortical network that includes a primary motor cortex and a premotor cortex that directly project to spinal motor neurons, and a contra-lesional primary motor cortex that projects to spinal motor neurons via the reticular formation. Synapses in the cortical areas are updated via reinforcement learning and the activity of spinal motor neurons is adjusted through homeostatic regulation. The model replicated neural, muscular, and behavioral outcomes in both non-lesioned and lesioned brains. With increasing lesion sizes, the model demonstrated systematic recruitment of the remaining primary motor cortex, premotor cortex, and contra-lesional cortex. The premotor cortex acted as a reserve area for fine motor control recovery, while the contra-lesional cortex helped avoid paralysis at the cost of poor joint control. Plasticity in spinal motor neurons enabled force generation after large cortical lesions despite weak corticospinal inputs. Compensatory activity in the premotor and contra-lesional motor cortex was more prominent in the early recovery period, gradually decreasing as the network minimized effort. Thus, the orderly recruitment of compensatory areas following strokes of varying sizes results from biologically plausible local plastic processes that maximize performance, whether the brain is intact or lesioned.

Celastrol alleviates atopic dermatitis by regulating Ezrin-mediated mitochondrial fission and fusion.

Celastrol, a bioactive molecule extracted from the plant Tripterygium wilfordii Hook F., possesses anti-inflammatory, anti-obesity and anti-tumour properties. Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF-α-stimulated HaCaT cells and DNCB-induced Balb/c mice as invitro and invivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL-4, IL-13, TNF-α, IL-5, IL-31, IL-33, IgE, TSLP, IL-17, IL-23, IL-1β, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF-α-induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi-1 (a mitochondrial fission inhibitor) and Ezrin-specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co-immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin-mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD.

New Step in Understanding the Pathogenetic Mechanism of Sudden Infant Death Syndrome: Involvement of the Pontine Reticular Gigantocellular Nucleus.

This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep-wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy.

Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.

Optogenetic stimulation of Phox2b-expressing neurons in the respiratory parafacial region rescue fentanyl-induced respiratory depression

The primary cause of death from opioid overdose is opioid-induced respiratory depression (OIRD), which results in substantial suppression of respiratory rate, destabilization of breathing patterns, severe hypercapnia, and a heightened risk for life-threatening apnea. A crucial chemosensitive brainstem region, located in the rostral ventrolateral medullary reticular formation, contains a bilateral cluster of approximately 800 non-opioid receptor-expressing glutamatergic, non-catecholaminergic, Phox2b+ propriobulbar neurons. These neurons are stimulated by CO2 and acidification and play a vital role in regulating breathing to prevent respiratory acidosis. Under normal circumstances, opioid induced hypercapnia should stimulate these cells to restore ventilation and prevent disturbances in arterial blood gases. However, during OIRD, it remains unclear whether these neurons can effectively rescue breathing in the response to opioid induced hypercapnia. The present study aims to address this question by investigating whether the ability of these neurons to stimulate breathing is significantly altered during opioid-induced respiratory depression. Using optogenetic stimulation, we stimulated these Phox2b+ cells before and after fentanyl to test for whether their ability to stimulate ventilation is reduced during OIRD. As expected, fentanyl (500 μg/kg, ip) resulted in respiratory rate suppression and destabilization of breathing pattern. Before fentanyl administration optogenetic stimulation of Phox2b+ cells increased breathing activity in a pulse stimulation frequency dependent (5-20Hz) manner. Unexpectedly, following fentanyl administration, similar optogenetic stimulation of Phox2b+ cells resulted in a significantly greater frequency dependent (5-20Hz) increase in breathing activity compared to pre-fentanyl levels. Additionally, both hypercapnia (FiCO2 = 0.1) or hypoxia (FiO2 = = 0.1) produced an increase breathing activity in a similar manner in pre- and post-fentanyl conditions. The results suggest that fentanyl paradoxically increases the ability of Phox2b+ cells to stimulate breathing but shifts the steady-state relationship between ventilation and arterial blood gases, such that resting ventilation is reduced. FAPESP, NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Parotid hypersalivation after inferior salivatory nucleus glutamate/NMDA receptor excitation in the rat

Although salivation is essential during eating behavior, little is known about the brainstem centers that directly control the salivary glands. With regard to the inferior salivatory nucleus (ISN), the site of origin of the parasympathetic preganglionic cell bodies that innervate the parotid glands, previous anatomical studies have located it within the rostrodorsal medullary reticular formation. However, to date there is no functional data that shows the secretory nature of the somas grouped in this region. To activate only the somas and rule out the activation of the efferent fibers from and the afferent fibers to the ISN, in exp. 1, NMDA neurotoxin was administered to the rostrodorsal medullary region and the secretion of saliva was recorded during the following hour. Results showed an increased secretion of parotid saliva but a total absence of submandibular-sublingual secretion. In exp. 2, results showed that the hypersecretion of parotid saliva after NMDA microinjection was completely blocked by the administration of atropine (a cholinergic blocker) but not after administration of dihydroergotamine plus propranolol (α and β-adrenergic blockers, respectively). These findings suggest that the somata of the rostrodorsal medulla are secretory in nature, controlling parotid secretion via a cholinergic pathway. The data thus functionally supports the idea that these cells constitute the ISN.

Altered functional connectivity of brainstem nuclei in new daily persistent headache: Evidence from resting-state functional magnetic resonance imaging.

The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed-based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well-matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations. Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus-central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area-parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016). Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions.

Multi-dimensional assembly of ZnO nanodots in the reticular carbon nanofibers for high-performance lithium-ion batteries

Due to the high theoretical specific capacity, abundant resources, easy availability, and environmental amicability, zinc oxide (ZnO) has been regarded as a promising alternative for lithium-ion battery anode. However, the further application of ZnO anode is still faced with great challenges such as huge volume transformation and intrinsic low conductivity. Herein, we propose a simple strategy for the preparation of ZnO/carbon clusters (∼50 nm) which are assembled with uniformly distributed ZnO nanodots (∼5 nm) in the three-dimensional carbon nanofibers (ZnO/CNFs) through an electrospinning and subsequent carbonization process using gallic acid-zinc coordination polymer (GAZ) as precursor. The multi-dimensional assembly of ZnO nanodots and reticular formation of conductive carbon network can effectively alleviate the volume change of ZnO anode during long-term cycling process and promote the fast transfer of electrolyte ions/electrons, greatly improving the rate and cycle performance. As a result, the ZnO/CNFs electrode exhibits excellent rate performance of 375.3 mAh g−1 at 2 A g−1 and long cycling stability with capacity retention of 92% over 600 cycles at 1 A g−1. These features indicate that the systematic combination of electrospinning and metal-organic coordination polymers have significant promise for the construction of high-performance metal derivative anodes.

Functional plasticity of glutamatergic neurons of medullary reticular nuclei after spinal cord injury in mice

Spinal cord injury disrupts the descending command from the brain and causes a range of motor deficits. Here, we use optogenetic tools to investigate the functional plasticity of the glutamatergic reticulospinal drive of the medullary reticular formation after a lateral thoracic hemisection in female mice. Sites evoking stronger excitatory descending drive in intact conditions are the most impaired after injury, whereas those associated with a weaker drive are potentiated. After lesion, pro- and anti-locomotor activities (that is, initiation/acceleration versus stop/deceleration) are overall preserved. Activating the descending reticulospinal drive improves stepping ability on a flat surface of chronically impaired injured mice, and its priming enhances recovery of skilled locomotion on a horizontal ladder. This study highlights the resilience and capacity for reorganization of the glutamatergic reticulospinal command after injury, along with its suitability as a therapeutical target to promote functional recovery.

High-Frequency Local Field Potential Oscillations for Pigeons in Effective Turning

Flexible turning behavior endows Homing Pigeons (Columba livia domestica) with high adaptability and intelligence in long-distance flight, foraging, hazard avoidance, and social interactions. The present study recorded the activity pattern of their local field potential (LFP) oscillations and explored the relationship between different bands of oscillations and turning behaviors in the formatio reticularis medialis mesencephali (FRM). The results showed that the C (13–60 Hz) and D (61–130 Hz) bands derived from FRM nuclei oscillated significantly in active turning, while the D and E (131–200 Hz) bands oscillated significantly in passive turning. Additionally, compared with lower-frequency stimulation (40 Hz and 60 Hz), 80 Hz stimulation can effectively activate the turning function of FRM nuclei. Electrical stimulation elicited stronger oscillations of neural activity, which strengthened the pigeons’ turning locomotion willingness, showing an enhanced neural activation effect. These findings suggest that different band oscillations play different roles in the turning behavior; in particular, higher-frequency oscillations (D and E bands) enhance the turning behavior. These findings will help us decode the complex relationship between bird brains and behaviors and are expected to facilitate the development of neuromodulation techniques for animal robotics.

Role of autonomic, nociceptive, and limbic brainstem nuclei in core autism features.

Although multiple theories have speculated about the brainstem reticular formation's involvement in autistic behaviors, the in vivo imaging of brainstem nuclei needed to test these theories has proven technologically challenging. Using methods to improve brainstem imaging in children, this study set out to elucidate the role of the autonomic, nociceptive, and limbic brainstem nuclei in the autism features of 145 children (74 autistic children, 6.0-10.9 years). Participants completed an assessment of core autism features and diffusion- and T1-weighted imaging optimized to improve brainstem images. After data reduction via principal component analysis, correlational analyses examined associations among autism features and the microstructural properties of brainstem clusters. Independent replication was performed in 43 adolescents (24 autistic, 13.0-17.9 years). We found specific nuclei, most robustly the parvicellular reticular formation-alpha (PCRtA) and to a lesser degree the lateral parabrachial nucleus (LPB) and ventral tegmental parabrachial pigmented complex (VTA-PBP), to be associated with autism features. The PCRtA and some of the LPB associations were independently found in the replication sample, but the VTA-PBP associations were not. Consistent with theoretical perspectives, the findings suggest that individual differences in pontine reticular formation nuclei contribute to the prominence of autistic features. Specifically, the PCRtA, a nucleus involved in mastication, digestion, and cardio-respiration in animal models, was associated with social communication in children, while the LPB, a pain-network nucleus, was associated with repetitive behaviors. These findings highlight the contributions of key autonomic brainstem nuclei to the expression of core autism features.

Myelin lesion in the aspartoacylase (Aspa) knockout rat, an animal model for Canavan disease.

Canavan disease (CD) is a fatal hereditary neurological disorder caused by a mutation in the aspartoacylase (ASPA) gene and characterized by neurological signs and vacuolation in the central nervous system (CNS). The mutation inhibits the hydrolysis of N-acetyl-aspartate (NAA) resulting in accumulation of NAA in the CNS. A new Aspa-knockout rat was generated by transcription activator-like effector nuclease (TALEN) technology. Herein we describe the pathological and morphometrical findings in the brain and spinal cords of Aspa-knockout rats. Although Aspa-knockout rats did not show any neurological signs, vacuolation with swollen axons, hypomyelination, and activated swollen astrocytes were observed mainly in the brainstem reticular formation, ascending and descending motor neuron pathway, and in the olfactory tract. Morphometrical analysis revealed no obvious change in the number of neurons. These changes in the CNS are similar to human CD, suggesting that this animal model would be useful for further study of treatment and understanding the pathophysiology of human CD.

Synchronization analysis of time series obtained from anesthetized rats during painful action

The purpose of this work is to determine the possibility of detecting changes in the relationships between such physiological rhythms as the activity of neurons in the reticular formation of the medulla oblongata, fluctuations in the blood pressure and respiration in anesthetized rats before and during the development of a pathological state associated with painful colorectal distension. This stretch mimics the pain localized in the lower abdomen in patients with irritable bowel syndrome and it is accompanied by responses of the brain neurons, fluctuations in the blood pressure and respiration. The analysis of changes in the relationships of these rhythms consisted in identifying phase synchronization between the time series of the variability of neuronal activity intervals and the variability of blood pressure intervals at the respiratory rate before and during pain exposure. Methods. To solve this problem, the synchrosqueezed wavelet transform method was applied, which makes it possible to effectively calculate the instantaneous frequencies and phases of non-stationary signals. As indicators of synchronization, we used the values of the index and the duration of phase synchronization as a time interval during which the value of the synchronization index is close to 1. Results. It has been established that the pain effect provides an adjustment of the frequency of the neuronal activity variability and the occurrence of synchronization between this activity and the blood pressure variability at the respiratory rate or causes an adjustment of the frequency of the blood pressure variability and the occurrence of synchronization between the blood pressure variability and the respiratory rhythm. It was found that the pain effect increases the duration of phase synchronization between the variability of the blood pressure and the respiratory rhythm or reduces the duration of phase synchronization between the variability of neuronal activity and the respiratory rhythm. Conclusion. The effect of painful colorectal distension on changes in the parameters of phase synchronization between physiological rhythms in anesthetized rats was studied in detail.