In vivo synaptic transmission in the zebra finch high vocal center and robust nucleus of the arcopallium after different stimulus patterns

BACKGROUND： Electrophysiological studies using brain slices have revealed that the developmental regulation of synaptic plasticity in vocal learning pathway is essential for song learning in zebra finches. Publications reporting in vivo electrophysiological investigation are scarce. Many aspects of neural mechanisms underlying song learning and production still remain uncertain. OBJECTIVE： To observe the efficacy of paired pulses and the effect on synaptic transmission induced by low-frequency stimulations, high-frequency stimulations, and theta-burst stimulations. DESIGN, TIME AND SETTING： A comparative observation. The experiment was conducted from October 2006 to October 2007 in the Neurophysiology Laboratory of South-China Normal University. MATERIALS： Twenty-four adult male zebra finches were supplied by the Department of Animal Experiment of College of Life Sciences, South China Normal University. A SEN-7203 stimulator （NIHON KOHDEN）, as well as a DSJ-731WF microelectrode amplifier and DSJ-F amplifier （provided by South-China Normal University）, were used to stimulate and record, respectively. METHODS： Animals were randomly divided into low-frequency, high-frequency, and theta-burst frequency stimulation groups. After recording evoked potentials, an input-output curve was evaluated. Subsequently, the efficacy of paired pulses with different stimulus intensity （1/3, 1/2, 2/3, or 3/4 of the value that induced the largest synaptic response）, as well as interpulse intervals （50, 75, and 100 ms）, was measured in each group. The test stimulus intensity was set to a level that evoked 1/2 or 1/3 amplitude of the maximum response. MAIN OUTCOME MEASURES： Changes in amplitude, slope, and area of evoked potentials elicited by different stimulus patterns. RESULTS： （1） Efficacy of paired pulses： there was significant paired-pulse facilitation in the high vocal center and robust nucleus of the arcopallium （HVC-RA） synapse. Efficacy decreased when paired-pulse intervals or stimulus intensities were increased. （2） Low-frequency stimulations at 1 Hz had a negligible effect on efficacy of synaptic transmission, while 5 Hz depressed synaptic transmission for only 5 minutes. （3） High-frequency stimulations at 50 Hz or 100 Hz induced synaptic depression that lasted for up to 30 minutes. （4） Theta-burst stimulation depressed synaptic transmission efficiency significantly for about 10 minutes. However, in contrast to low-frequency or high-frequency stimulations, theta-burst stimulations also induced slight potentiation of synaptic transmission for up to 60 minutes following depression phase, although the slope or area did not change. CONCLUSION： Paired pulses induced a remarkable efficacy of paired pulses in the high vocal center and robust nucleus of the arcopallium pathway. Low-frequency, high-frequency, or theta-burst frequency stimulation did not induce long-lasting changes in synaptic transmission.

Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture

The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.

Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury

The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after lfuid percussion injury. Diazepam can inhibit the hy-perexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment signiifcantly increased the slope of input-output curves in rat neurons after lfuid per-cussion injury. Diazepam signiifcantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the lfuid per-cussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.

Insulin Age-Dependently Modulates Synaptic Transmission and AMPA Receptor Trafficking in Region CA1 of the Rat Hippocampus

Insulin induces long-term depression (insulin-LTD) in the CA1 region of the rat juvenile hippocampus. This insulin-LTD may be due in part to internalization of the GluA2 subunit of the AMPA receptor (AMPAR) events that haven’t been studied in the mature rat hippocampus. In our studies, we used hippocampal preparations from juvenile (14 - 25 days) and mature (60 - 90 days) rats to assess insulin modulation of CA1 synaptic transmission and AMPAR trafficking and phosphorylation. Using field potential electrophysiology, we observed that insulin induced LTD in the juvenile hippocampus (as previously reported) in the presence and absence of phosphoinositide 3-kinase (PI3K) activity, but produced no significant long-term changes in the mature hippocampus in the presence of PI3K activity. Interestingly, during PI3K inhibition, insulin did produce LTD in the mature hippocampus. Additionally, insulin induced a long-term decrease in plasma membrane expression of the GluA2 and GluA1 subunits of the AMPAR in the juvenile, but not mature hippocampus. Furthermore, there was a long-term decrease in GluA1 phosphorylation at Serine 845 in the juvenile, but not mature hippocampus. These data reveal that insulin modulation of synaptic plasticity and AMPAR modulation within the hippocampus is age-dependent, suggesting that insulin-regulated behaviors may also show age-dependence. These findings are important largely due to the increased use of insulin as a therapeutic throughout the lifespan. Our data suggest that additional work should be done to determine how this use of insulin throughout different stages of life might affect synaptic function and development.

Effect of electroacupuncture on synaptic transmission in dentate gyrus of the hippocampus in cerebral ischemic injured rats

BACKGROUND： Some studies suggest that the long-term potentiation （LTP） of synaptic transmission may be the basis for the neural synaptic plasticity of hippocampus, but can be evoked by various factors including electroacupuncture. OBJECTIVE： To observe the effect of electroacupuncture on the activities of basic synaptic transmission in dentate gyrus of hippocampus and the changes of high frequency stimulation （HFS） induced activity of synaptic transmission in cerebral ischemic injured rats. DESIGN： A randomized control trial.SETTING： Shenzhen Hospital of Traditional Chinese Medicine affiliated to Guangzhou University of Traditional Chinese Medicine. MATERIALS： Sixty healthy male Wistar rats, weighing 150-250 g, were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. The experiment began after adaptation of environment for 1 week under standard experimental environment. The main experimental instruments included the programming electrical acupuncture apparatus （PCEA, product of the Institute of Acupuncture and Meridians, Anhui College of Traditional Chinese Medicine） and multichannel physiologic recorder （RM-86, Nihon Konden）. METHODS： The experiment was carried out in Guangzhou University of Traditional Chinese Medicine between July 2003 and July 2004. ①Embedding of brain electrodes： In reference of the Pellegrino＇s rat brain atlas, the bipolar electrode stimulator was embedded into the perforant path （PP） anterior to the entorhinal area with location coordinates of AP 7.5 mm, L 4.2 mm and H 3.0 mm, that is, 7.5 mm posterior to the anterior fontanelle, 4.2 mm laterally on the right side and 3.0 mm under the subcortex. The subcortex recorder electrode coordinates are AP 3.8 mm, L 2.5 mm and H 3.5 mm, located in the granular cell layer of the unilateral dentate gyrus （DG） of hippocampus, at the site of which an opening with the diameter of 1.5 mm was drilled for the purpose of embedding of the stimulating and recording electrodes, and at the site by mild adjusting the positions of these electrodes where maximal population spike （PS） was recorded, fastened the electrodes at last. ② The 60 rats were randomized into two major groups, namely, fundamental stimulation （FS） group （basic group） and high frequency stimulation （HFS） group. Each group was further divided into three subgroups respectively： Sham-operated subgroup （n=10）： only exposed bilateral common carotid arteries without blocking their blood flow; Cerebral ischemia model subgroup （n=10）： exposing bilateral common carotid arteries and blocking their blood flow; Ischemia plus electroacupuncture subgroup （n=10）： blocked blood flow of bilateral common carotid arteries and received electroacupuncture. The electroacupuncture acupoints were the points of Du meridian, including Baihui （GV20）, Dazhui （GV14）, and points of Pen meridian, including Qihai （CV6） and Guanyuan （CV4）. ③ Process of electroacupuncture： All the rats underwent testing stimulation （1/30 Hz frequency and 0.1 ms breadth） at 30 minutes before modeling, PS values were recorded as the indexes of the excitation of DG granular cell population, and the data were input to computer for data analysis. During the experiment, the intensity of stimulation was kept stable by adopting 1/2 the value of stimulation intensity that could induce maximal PS amplitude. In the basic group, PS were recorded for 120 minutes after modeling, and among the rats in the electroacupuncture group, PS was recorded at 10 minutes before and 60 minutes after blocking blood flow in the carotid artery during continuous electrical acupuncture. In the HFS group, HFS was given immediately after modeling, PS were recorded for 180 minutes at 10 minutes after HFS was given in the sham-operated group and model group, rats in the electroacupuncture group were treated with electroacupuncture for 60 minutes at 30 minutes after HFS was given, and PS was recorded for 180 minutes after 10 minutes. LTP was triggered by HFS and PS values were determined and recorded through measuring stimulations respectively 0, 10, 30, 60, 120 and 180 minutes after the evokes.④ Methods for expressing the level of synaptic transmission： Each testing stimulus provoked one PS, and 10 successive amplitude values （V/mV） were averaged relevant to a certain time cut. The averaged PS of 6 time cuts at 30 minutes before modeling was made as basal synaptic transmission level as control. Synaptic transmission at each time cut was expressed as： p=（ Vdifferentime cut / Vbasal） × 100%. MAIN OUTCOME MEASURES： The differences of synaptic transmission level were compared among the subgroups in the basic group after models also among the subgroups in the HFS group after HFS.RESULTS： All the 60 rats were involved in the analysis of results. ① Comparison of synaptic transmission level at different time cut after modeling and the effect of electroacupuncture in the subgroups of the basic group： The synaptic transmission level in the sham-operated subgroup had no significant change within 120 minutes （P 〉 0.05）. The synaptic transmission levels at 10, 30 and 60 minutes in the model subgroup were obviously lower than those in the sham-operated group [（60±7）%, （90±3）%, （93±4）%; （100±5）%, （102±6）%, （105±7）%, P 〈 0.05-0.01]. With the prolongation of time for ischemia/reperfusion, the synaptic transmission level gradually ascended to the normal level, and those at 90 and 120 minutes were close to those in the sham-operated group （P 〉 0.05）. In the subgroup of electroacupuncture, the synaptic transmission levels at 10, 30, 60, 90 and 120 minutes were obviously higher than those in the model subgroup [（93±5）%, （106±10）%, （123±16）%, （145±20）%, （168±25）%; （96±7）%, （98±8）%, P 〈 0.05-0.01].② Comparison of synaptic transmission level at different time cut after HFS and the effect of electroacupuncture in the groups： In the sham-operated group, the synaptic transmission level after HFS increased significantly, and maintained without decrease within 180 minutes. In the model group, the synaptic transmission level at 0, 10, 30, 60, 120 and 180 minutes after HFS were obviously lower than those in the sham-operated group [（60±7）%, （95±9）%, （138±11）%, （141±13）%, （140±13）%, （138±15）%; （100±6）%, （182±21）%, （179±18）%, （177±18）%, （175±23）%, （178±24）%, P 〈 0.01]. The synaptic transmission level at 60, 120 and 180 minutes after HFS in the electroacupuncture group were close to those in the sham-operated group （P 〉 0.05）, those at 120 and 180 minutes after HFS in the electroacupuncture group were obviously higher than those in the model group [（171±22）%, （181±25）%, P 〈 0.05-0.01]. CONCLUSION： Electroacupuncture could enhance the basic activity of synaptic transmission in the dentate gyros of hippocampus in cerebral ischemic injury in rats. Electroacupuncture has obvious LTP effect on the activity of synaptic transmission induced by HFS.

Abnormal synaptic plasticity and impaired cognition in schizophrenia

Schizophrenia(SCZ)is a severe mental illness that affects several brain domains with relation to cognition and behaviour.SCZ symptoms are typically classified into three categories,namely,positive,negative,and cognitive.The etiology of SCZ is thought to be multifactorial and poorly understood.Accumulating evidence has indicated abnormal synaptic plasticity and cognitive impairments in SCZ.Synaptic plasticity is thought to be induced at appropriate synapses during memory formation and has a critical role in the cognitive symptoms of SCZ.Many factors,including synaptic structure changes,aberrant expression of plasticityrelated genes,and abnormal synaptic transmission,may influence synaptic plasticity and play vital roles in SCZ.In this article,we briefly summarize the morphology of the synapse,the neurobiology of synaptic plasticity,and the role of synaptic plasticity,and review potential mechanisms underlying abnormal synaptic plasticity in SCZ.These abnormalities involve dendritic spines,postsynaptic density,and long-term potentiation-like plasticity.We also focus on cognitive dysfunction,which reflects impaired connectivity in SCZ.Additionally,the potential targets for the treatment of SCZ are discussed in this article.Therefore,understanding abnormal synaptic plasticity and impaired cognition in SCZ has an essential role in drug therapy.

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson’s disease

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.

Genetic mechanisms underlying synaptic pathology in Autism Spectrum Disorder (ASD)

Autism spectrum disorder(ASD)is a neuronal developmental disorder that is characterized by de⁃fects both in social interaction and verbal communication,and is often accompanied by restricted interest,and repeti⁃tive and stereotyped behaviors.The prevalence of ASD is approximately 0.8%~1.2%in China.Although its etiology remains unclear in most cases,over 1000 genes or genomic loci have been linked to its pathogenic origin,indicating a strong genetic influence,as well as complicated pathogenic mechanisms.Here,we reviewed recent findings in the possible genetic effects on synaptic pathophysiology of ASD,and a particular focus was put on variants in genes that are related to synaptic morphology or functions,such as FMR1,NRXN,NLGN,SHANK and MeCP2.The synaptic pathology caused by these genetic defects may substantially contribute to the pathogenesis of ASD.This review out⁃lines several lines of evidence that have been recently reported to support the hypothesis that a genetic defect may lead to a synaptic pathology that may underlie the pathogenesis of ASD.

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.

Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.

Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.

Rac1 Modulates Excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells

Ras-related C3 botulinum toxin substrate 1(Racl),a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity,is a key regulator of cytoskeletal reorganization in dendrites and spines.Here,we investigated whether and how Racl modulates synaptic transmission in mouse retinal ganglion cells(RGCs)using selective conditional knockout of Racl(Racl-cKO).Racl-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents,while glycine/GABA_A receptor-mediated miniature inhibitory postsynaptic currents were not affected.Although the total GluA1 protein level was increased in Racl-cKO mice,its expression in the membrane component was unchanged.RaclcKO did not affect spine-like branch density in single dendrites,but significantly reduced the dendritic complexity,which resulted in a decrease in the total number of dendritic spine-like branches.These results suggest that Racl selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.

Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

Objective Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer＇s disease （AD）. Although amyloid-β （Aβ） aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons （PNs） in the olfactory lobe of the fruit fly. Methods Cholinergic spontaneous and miniature excitatory postsynaptic current （mEPSC） were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue. Results In fly pupae （2 days before eclosion）, overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc. Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.

Amyotrophic lateral sclerosis as a synaptopathy

The synapse is an incredibly specialized structure that allows for the coordinated communication of information from one neuron to another. When assembled into circuits, steady streams of excitatory and inhibitory synaptic activity shape neural outputs. At the organismal level, ensembles of neural networks underlie behavior, emotion and memory. Disorder or dysfunctions of synapses, a synaptopathy, may underlie a host of developmental and degenerative neurological conditions. There is a possibility that amyotrophic lateral sclerosis may be a result of a synaptopathy within the neuromotor system. To this end, particular attention has been trained on the excitatory glutamatergic synapses and their morphological proxy, the dendritic spine. The extensive detailing of these dysfunctions in vulnerable neuronal populations, including corticospinal neurons and motor neurons, has recently been the subject of original research in rodents and humans. If amyotrophic lateral sclerosis is indeed a synaptopathy, it is entirely consistent with other proposed pathogenic mechanisms – including glutamate excitotoxicity, accumulation of misfolded proteins and mitochondrial dysfunction at distal axon terminals(cortico-motor neuron and neuromuscular). Further, although the exact mechanism of disease spread from region to region is unknown, the synaptopathy hypothesis is consistent with emerging die-forward evidence and the prion-like propagation of misfolded protein aggregates to distant neuronal populations. Here in this mini-review, we focus on the timeline of synaptic observations in both cortical and spinal neurons from different rodent models, and provide a conceptual framework for assessing the synaptopathy hypothesis in amyotrophic lateral sclerosis.

Physiological Roles of β-amyloid in Regulating Synaptic Function:Implications for AD Pathophysiology

The physiological functions of endogenous amyloid-β(Aβ),which plays important role in the pathology of Alzheimer's disease(AD),have not been paid enough attention.Here,we review the multiple physiological effects of Aβ,particularly in regulating synaptic transmission,and the possible mechanisms,in order to decipher the real characters of Aβunder both physiological and pathological conditions.Some worthy studies have shown that the deprivation of endogenous Aβgives rise to synaptic dysfunction and cognitive deficiency,while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal hyperexcitability.In this review,we provide a new view for understanding the role of Aβin AD pathophysiology from the perspective of physiological meaning.

Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons.Here we explored how gestational exposure to dexamethasone,a synthetic glucocorticoid commonly used in clinical practice,has lasting effects on offspring's learning and memory.Adult offspring rats of prenatal dexamethasone exposure(PDE)displayed significant impairments in novelty recognition and spatial learning memory,with some phenotypes maintained transgenerationally.PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations,and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory,but these changes failed to carry over to offspring of F5 and F7 generations.Mechanistically,altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission,which might be related to oocyte-specific high expression and transmission of miR-133a-3p.Together,PDE affects hippocampal excitatory synaptic transmission,with lasting consequences across generations,and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Inventory of the Thermo-Physiological Behavior of Fabrics—A Review

A comprehensive literature review was performed to create an inventory of thermal-physiological quantities for fabrics from different fiber materials, material blends, and fabric structures. The goal was to derive over-arching concepts that cannot be seen by the individual studies alone. Equations of best fits suggest non-linear changes for fabric thickness, thermal and water-vapor resistance with changes in material blend ratio. Air permeability decreases with increasing fabric density and fabric weight wherein the degree of decrease differs among fabric materials, blend ratio, and fabric structure. Water-vapor transmission rates strongly depend on fabric thickness, material, and blend, but marginally depend on fabric structure as long as the fabric and material thickness remain the same.

Resident immune responses to spinal cord injury:role of astrocytes and microglia

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

反复禁锢应激对小鼠mPFC脑区神经元突触活动影响

目的探讨反复禁锢应激对野生型C57BL6/J小鼠内侧前额叶皮质(mPFC)锥体神经元突触活动的影响。方法将12~20周龄雄性小鼠随机分为对照组和禁锢组。禁锢组给予反复禁锢应激刺激,每天1 h,连续4 d。采用高架十字迷宫实验评估小鼠的焦虑样行为,采用全细胞膜片钳技术记录小鼠mPFC脑区锥体神经元的兴奋性和抑制性突触后电流。结果禁锢组的小鼠焦虑样行为明显增加(t=3.069,P<0.01);mPFC脑区锥体神经元微小兴奋性突触后电流的频率增加(t=4.009,P<0.01),微小抑制性突触后电流的幅度增加(t=2.172,P<0.05)。结论反复禁锢应激能够增强小鼠mPFC脑区锥体神经元的兴奋性和抑制性突触传递。这些mPFC脑区锥体神经元突触传递的可塑性改变可能与反复禁锢应激导致的焦虑相关行为改变密切相关。

太赫兹辐射调控神经元突触传递的动力学特征提取方法

突触后电位是神经元传递信息的重要载体,该信号的动力学分析是神经科学研究中的常用方法。但目前传统的分析方法中多采用手工提取动力学特征值,分析数据量有限。针对此缺陷,本文提出了一种神经元突触传递的动力学特征提取方法。在该方法中,采用低通滤波器提取有效数据,降低了数据计算量和复杂性;采用中值滤波算法去除了信号中随机噪声、刺激伪迹,并校正基线漂移,利用曲线拟合提取了突触后电位信号波形斜率特征值,实现突触后电位信号变化趋势的可视化。该特征提取方法的平均绝对百分比误差一般在5%左右,幅度特征值的平均绝对百分比误差一般在3%左右。同时取95%的置信区间,降低波形的测量误差,使得有效数据正检率指标高达98%。结果表明该特征提取方法可提取信号中的有效数据,并能保证特征值提取的精度,减小了人工提取存在的误差。通过神经元响应数据,验证了该方法的可行性,提出了太赫兹调控神经元突触传递的猜想。