Spatial Distribution of Parvalbumin-Positive Fibers in the Mouse Brain and Their Alterations in Mouse Models of Temporal Lobe Epilepsy and Parkinson's Disease / 神经科学通报·英文版

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.

Functional Autapses Form in Striatal Parvalbumin Interneurons but not Medium Spiny Projection Neurons / 神经科学通报·英文版

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr2+. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABAA receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.

Immunohistochemical distribution of calcium binding proteins in the cochlear nuclear complex of circling mice / Distribución inmunohistoquímica de proteínas de unión a calcio en el complejo nuclear coclear de ratones circulantes

SUMMARY: The term "circling mouse" refers to an animal model of deafness, in which the mouse exhibits circling, head tossing, and hyperactivity, with pathological features including degenerated spiral ganglion cells in the cochlea, and the loss of the organ of Corti. The cochlear nuclear (CN) complex, a part of the auditory brain circuit, is essential to process both ascending and descending auditory information. Considering calcium's (Ca2+) importance in homeostasis of numerous biological processes, hearing loss by cochlear damage, either by ablation or genetic defect, could cause changes in the Ca2+ concentration that might trigger functional and structural alterations in the auditory circuit. However, little is known about the correlation of the central nervous system (CNS) pathology in circling mice, especially of the auditory pathway circuit and Ca2+ changes. This present study investigates the distribution of Ca2+- binding proteins (CaBPs), calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR) by using a free floating immunohistochemical method inthe CN of the wild-type mouse (+/+), the heterozygous mouse (+/cir), and the homozygous (cir/cir) mouse. CaBPs are well known to be an important factor that regulates Ca2+ concentrations. Compared with the dorsal and ventral cochlear nuclei of +/+ and +/ cirmice, prominent decreases of CaBPs' immunoreactivity (IR) in cir/cirmice were observed in the somas, as well as in the neuropil. The present study reportson the overall distribution and changes in the immunoreactivity of CaBPs in the CN of cir/cirmice because ofa hearing defect. This data might be helpful to morphologically elucidate CNS disorders and their relation to CaBPs immunoreactivity related to hearing defects.

RESUMEN: El término "ratón circulante" se refiere a un modelo animal con sordera, en el que el ratón exhibe hiperactividad, movimientos circulares y movimientos de la cabeza, con características patológicas que incluyen células ganglionares espirales degeneradas en la cóclea, un canal de Rosenthal vacío y la pérdida del órgano de Corti. El complejo nuclear coclear (CN), una parte del circuito cerebral auditivo, es esencial para procesar la información auditiva tanto ascendente como descendente. Considerando la importancia del calcio (Ca2+) en la homeostasis de numerosos procesos biológicos, la hipoacusia por daño coclear, por ablación o por defecto genético, podría provocar cambios en la concentración de Ca2+que pueden desencadenar alteraciones funcionales y estructurales en el circuitoauditivo. Sin embargo, existe poca información de la correlación de la patología del sistema nervioso central (SNC) en ratones circulantes, especialmente del circuito de la víaauditiva y los cambios de Ca2+. Este estudio nvestiga la distribución de proteínas de unión a Ca2+ (CaBP), calbindina D-28k (CB), parvalbúmina (PV) y calretinina (CR) mediante el uso de un método inmunohistoquímico de flotaciónlibre en el CN del ratón de tiposalvaje (+/+), el ratón heterocigoto (+/cir) y el ratón homocigoto (cir/cir). Se sabe que los CaBP son un factor importante que regula las concentraciones de Ca2+. En comparación con los núcleos cocleares dorsal y ventral de los ratones +/+ y +/ cir, se observaron disminuciones prominentes de la inmunorreactividad (IR) de CaBPs en los ratonescir/cir en los somas, asícomo en el neuropilo. El presente estudio informa sobre la distribución general y los cambios en la inmunorreactividad de CaBP en el CN de ratones cir/cir debido a un defecto auditivo. Estos datos podrían ser útiles para dilucidar morfológicamente los trastornos del SNC y su relación con la inmunorreactividad de CaBP relacionada con los defectosauditivos.

Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice / 神经科学通报·英文版

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N

Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice / 神经科学通报·英文版

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N

Seafood Allergy: Causes, Prevention Modalities, and Treatment Guidelines in the Indian Scenario

Seafood allergy is a hypersensitivity disorder with growing prevalence. Allergy to shellfish is among the leading cause of food allergyin adults, and the most common cause of food allergic emergency department visits. Seafood allergy is immunologic response toproteins in these foods and include IgE antibody-mediated allergy. Allergies can occur at any age but are common in adults andadolescents than in children. While figures vary from country to country, approximately 1–2% of the adult population and <1% ofchildren are affected. In most patients tolerance develops to food antigens, however, when tolerance fails to develop, hypersensitivityreaction occurs. Food allergy affects up to 8% of the children below 5 years of age and approximately 3.5% in the general population.Adults with shellfish allergies should be aware of how to use this on themselves or their child if child is suspected shellfish allergy.It is also recommended for such individuals to wear medical alert bracelet necklace or carry USB drive so that health care workercan be aware of their condition in emergency. Effective and accurate diagnostic workup is essential for clinicians and patients. Thisarticle summarizes about seafood allergy cause, diagnostic approaches, and management in case of life-threatening emergencies.

The role of parvalbumin interneuron-mediated disinhibition in the antidepressant effects of ketamine / 医学研究生学报

ObjectiveTo observe the role of parvalbumin interneuron-mediated disinhibition in the antidepressant effects of ketamine.MethodsForty-eight adult male C57BL/6 mice were randomly divided into the following four groups (n=12): group Saline + Saline (group SS), group LPS + Saline (group LS), group Saline + Ketamine (group SK) and group LPS + Ketamine (group LK). The depression model was established by intraperitoneal injection of LPS (1 mg/kg), and ketamine (10 mg/kg) or physiological saline (equal volume) intraperitoneally injected 20 hours later. Four hours after ketamine administration, the open field test and the forced swimming test were performed. The hippocampus was harvested after the behavioral test. PCR and Western blot were used to detect the expressions of PV and GAD67. Electrophysiology were used to detect the change of miniExcitatory post-synaptic current of pyramidal neurons in hippocampus CA1 region.ResultsCompared with the group SS, the time spent in the center zone of the arena was significantly decreased, the immobility time was significantly increased, the mRNA and protein content of PV were significantly increased, the amplitude and frequency of miniEPSC were significantly decreased in the group LS (P0.05).ConclusionKetamine can exert rapid antidepressant effects by down-regulating the expression of PV and then exerting disinhibition regulation on pyramidal neurons.

Temporomandibular inflammation mobilizes parvalbumin and FosB/deltaFosB neurons of amygdala and dorsal raphe

Pathophysiological mechanisms involved in orofacial pain and their relationship with emotional disorders have emerged as an important research area for multidisciplinary studies. In particular, temporomandibular disorders (TMD) have been evaluated clinically from both physiological and psychological perspectives. We hypothesized that an altered neuronal activity occurs in the amygdala and the dorsal raphe nucleus (DR), encephalic regions involved in the modulation of painful and emotional information. Adult male Wistar rats were used in an experimental complete Freund's adjuvant (CFA)-induced temporomandibular joint (TMJ) inflammation model. CFA was applied for 1 or 10 days, and the animals were euthanized for brain samples dissection for FosB/ΔFosB and parvalbumin (PV) immunostaining. Our results were consistent in showing that the amygdala and DR were activated in the persistent inflammatory phase (10 days) and that the expression of PV+ interneurons in the amygdala was decreased. In contrast, in the DR, the expression of PV+ interneurons was increased in persistent states of CFA-induced TMJ inflammation. Moreover, at 10 days of inflammation, there was an increased co-localization of PV+ and FosB/ΔFosB+ neurons in the basolateral and central nucleus of the amygdala. Different nuclei of the amygdala, as well as portions of the DR, were activated in the persistent phase (10 days) of TMJ inflammation. In conclusion, altered activity of the amygdala and DR was detected during persistent inflammatory nociception in the temporomandibular joint. These regions may be essential for both sensory and affective dimensions of orofacial pain.

A Whole-brain Map of Long-range Inputs to GABAergic Interneurons in the Mouse Caudal Forelimb Area / 神经科学通报·英文版

The caudal forelimb area (CFA) of the mouse cortex is essential in many forelimb movements, and diverse types of GABAergic interneuron in the CFA are distinct in the mediation of cortical inhibition in motor information processing. However, their long-range inputs remain unclear. In the present study, we combined the monosynaptic rabies virus system with Cre driver mouse lines to generate a whole-brain map of the inputs to three major inhibitory interneuron types in the CFA. We discovered that each type was innervated by the same upstream areas, but there were quantitative differences in the inputs from the cortex, thalamus, and pallidum. Comparing the locations of the interneurons in two sub-regions of the CFA, we discovered that their long-range inputs were remarkably different in distribution and proportion. This whole-brain mapping indicates the existence of parallel pathway organization in the forelimb subnetwork and provides insight into the inhibitory processes in forelimb movement to reveal the structural architecture underlying the functions of the CFA.

Entry of rabies virus in the olfactory bulb of mice and effect of infection on cell markers of neurons and astrocytes / Ingreso del virus de la rabia en el bulbo olfatorio de ratones y efecto de la infección en marcadores celulares de neuronas y astrocitos

There are few studies of infection by rabies virus in the olfactory bulb (OB). This work was carried out with the purpose of establishing the time required to detect rabies antigens in the OB of mouse, after the intramuscular inoculation of the virus and to evaluate the effect of the infection on the expression of three proteins: calbindin (CB), parvalbumin (PV) and the glial fibrillary acidic protein (GFAP). Mice were inoculated with rabies virus intramuscularly in the hind limbs. Every 8 hours, after 72 hours postinoculation (p.i.), animals were sacrificed by perfusion with paraformaldehyde and coronal sections of OB were obtained for immunohistochemical study. These cuts were used to reveal the entry and spread of viral antigens. Tissue sections obtained in the terminal phase of the disease (144 hours p.i.), and controls of the same age were also processed for immunohistochemistry of CB, PV and GFAP. Rabies virus antigens were initially detected at 80 hours p.i. in a few mitral cells. At 88 hours p.i. the antigens had spread through most of these neurons but until the terminal phase of the disease there was little dispersion of the virus towards other cellular layers of the OB. The CB protein was expressed in cells of the glomerular stratum, the PV in cells of the outer plexiform layer and the GFAP was expressed in all the layers of the OB. Viral infection generated loss of CB expression and increase of PV expression. Immunoreactivity to GFAP was increased in the outer plexiform layer of the OB as a response to infection.

Son escasos los estudios de la infección por virus de la rabia en el bulbo olfatorio (OB). Este trabajo se realizó con el objetivo de establecer el tiempo requerido para detectar antígenos de rabia en el OB del ratón, luego de la inoculación intramuscular del virus y evaluar el efecto de la infección en la expresión de tres proteínas: calbindina (CB), parvoalbúmina (PV) y la proteína ácida fibrilar glial (GFAP). Los ratones fueron inoculados con virus de la rabia por vía intramuscular en las extremidades posteriores. Cada 8 horas, después de 72 horas de inoculación (p.i.), los animales se sacrificaron por perfusión con paraformaldehído y se obtuvieron secciones coronales de OB para el estudio inmunohistoquímico. Estos cortes se usaron para revelar la entrada y propagación de antígenos virales. Las secciones de tejido obtenidas en la fase terminal de la enfermedad (144 horas p.i.), y los controles de la misma edad también se procesaron para inmunohistoquímica de CB, PV y GFAP. Los antígenos del virus de la rabia se detectaron inicialmente a las 80 horas p.i. en unas pocas células mitrales. A las 88 horas p.i. los antígenos se habían diseminado a través de la mayoría de estas neuronas, pero hasta la fase terminal de la enfermedad había poca dispersión del virus hacia otras capas celulares del OB. La proteína CB se expresó en las células del estrato glomerular, la PV en células de la capa plexiforme externa y la GFAP se expresó en todas las capas del OB. La infección viral generó pérdida de expresión de CB y aumento en la expresión de PV. La inmunorreactividad a GFAP aumentó en la capa plexiforme externa del OB como respuesta a la infección.

Laminar Distribution of Neurochemically-Identified Interneurons and Cellular Co-expression of Molecular Markers in Epileptic Human Cortex / 神经科学通报·英文版

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.

Changes of Auditory Brainstem Response and Expression of Parvalbumin , Calretinin and Calbindin D-28K in the Inferior Colliculus in Rats Following Noise Exposure / 听力学及言语疾病杂志

Objective To study the possible mechanism of hearing impairment after noise exposure .Methods Adult SD rats (n=14) were monaurally exposed to a loud noise (16 kHz ,one octave band pass (116 dB SPL)) for 1-hour ,or left as non-exposed controls (n=8) .The ABR was measured before and on the 7th day following unilateral noise exposure .All the Animals were euthanased at 7th day following acoustic trauma .We used Western blots to quantify protein levels of PV ,CR and CB in the inferior colliculus .Results The auditory thresholds in 8 , 12 ,16 ,20 ,24 ,and 32 kHz of all the ears exposed to noise showed a significant increase (P<0 .001) .Compared to the sham -exposed controls ,noise-exposed animals had significantly higher levels of PV and CR and lower levels of CB in both the ipsilateral and contralateral IC than controls (P<0 .05) .Respectively ,all the noise-exposed ani-mals had higher levels of PV and CR in the ipsilateral IC than ipsilateral side (P<0 .05) .Conclusion These studies display a significant threshold shift and changes on the expressions of PV ,CR and CB in IC following acoustic trau-ma ,which may be related to noise deafness ,tinnitus and other series of auditory dysfunction .

Effects of resveratrol on cognitive dysfunction and the expression of parvalbumin in depression model mice / 中华行为医学与脑科学杂志

Objective To examine the antidepressant effects of resveratrol (RSV),and its possible mechanism specialized on improving cognitive function.Methods Thirty-two C57BL/6J mice were randomly divided into four groups:Control,Model,Model+RSV and Model+NA+RSV groups.The mice were subjected corticosterone (20 mg/(kg · d)) intraperitoneal injection for 21 consecutive days except the control mice.From the 22nd to 42nd day,the mice in different groups received further treatment with vehicle/ RSV (400 mg/(kg · d),op)/NA (100 mg/(kg · d),ip)+RSV (400 mg/(kg · d),op).The sugar preference test,novel object recognition test,novel location recognition test and water maze test were applied to evaluate the cognitive effects of RSV on mice.Subsequently,the silence information regulation factor 1 (SIRT1),peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α),parvalbumin (PV) transcription and translation level were evaluated by RT-PCR and Western blotting.Results The sugar preference test showed that the depression model mediated by CORT injection was successfully established(F（1,30） =6,P=0.038).In in the novel object learning test,resveratrol significantly increased the proration on the frequency ((-0.20±0.37) vs (0.16±0.29))and duration((0.10±0.45) vs (0.62±0.29)) and decreased the proration on the distance((0.09±0.36) vs (0.55±0.27)).In the water maze test,resveratrol reduced the time((41±9)s;(26± 8) s) and distance ((295± 70) cm;(224±43) cm) to find the platform.All the results were accompanied with the increased expression of protein SIRT1 (F(3,29) =15.60,P＜0.01),PGC-1α(F(3,29)=7.51,P=0.0006) and PV (F(3,29) =17.87,P=0.0004).While pretreatment with nicotinamide,resveratrol could not rescue the cognitive impairment and could not reverse the iecreased expression level of protein SIRT1,PGC-1 α and PV.Conelusion Resveratrol can reverse the cognitive dysfunction of depressant mice,which may be achieved by activating the SIRT1/PGC-1α signaling pathway and increasing the transcription and protein expression of PV.

Effects of Ketamine on Basal Gamma Band Oscillation and Sensory Gating in Prefrontal Cortex of Awake Rats / 神经科学通报·英文版

Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.

Atlas of the Striatum and Globus Pallidus in the Tree Shrew: Comparison with Rat and Mouse / 神经科学通报·英文版

The striatum and globus pallidus are principal nuclei of the basal ganglia. Nissl- and acetylcholinesterase-stained sections of the tree shrew brain showed the neuroanatomical features of the caudate nucleus (Cd), internal capsule (ic), putamen (Pu), accumbens, internal globus pallidus, and external globus pallidus. The ic separated the dorsal striatum into the Cd and Pu in the tree shrew, but not in rats and mice. In addition, computer-based 3D images allowed a better understanding of the position and orientation of these structures. These data provided a large-scale atlas of the striatum and globus pallidus in the coronal, sagittal, and horizontal planes, the first detailed distribution of parvalbumin-immunoreactive cells in the tree shrew, and the differences in morphological characteristics and density of parvalbumin-immunoreactive neurons between tree shrew and rat. Our findings support the tree shrew as a potential model for human striatal disorders.

Effects of Exhausted Treadmill Running on the Expression of Parvalbumin Positive Neurons and GluN2B-containing NMDA Receptors in the Prefrontal Cortex of Rats / 中国运动医学杂志

Objective To explore the effects of excise-induced fatigue on the microloop plasticity of prefrontal cortex through observing the expression of parvalbumin positive neurons in prefrontal cortexes of rats induced by exhaustive exercise,so as to find out the possible mechanism of the central regulation of exercise-induced fatigue by measuring the expression of NMDAR2B receptors.Methods Thirty-six Wistar rats were randomly divided into an exhausted group (E),a repeated exhaustion group (RE) and a control group (CG),each of 12.For group E,the adjusted Bedford incremental load of treadmill exercise program was employed:the initial treadmill speed was 8.2 m/min,lasting for 15 minutes,then increased to 15 m/min for another 15 minutes,and finally increased to 20 m/min till exhaustion.For RE group,they were given continuous treadmill exercises to exhaustion for consecutive 7 days.The immunofluorescence technique was used to observe the expression of PV+ interneurons after exhausted treadmill running.The Western blotting technique was used to determine the expression of NMDAR2B in the tissue of the prefrontal cortex.Results After the exhausted treadmill running,the expression of PV+ interneurons in the prefrontal cortexes of both E and RE groups increased significantly compared with the control group(P＜0.01).The immunofluorescence results indicated that NMDAR2B positive neurons were seen in group E,but not obviously in group CG and RE.The Western blotting showed that compared with CG group the protein expression of NMDAR2B in prefrontal cortexes of group E was relatively high,and that of group RE was relatively low,but without significant difference (P＞0.05).The running distance and prefrontal cortex NMDAR2B expression were found negatively correlated (P＜ 0.01).Conclusions Exhaustive exercises have an impact on the plasticity in rats' prefrontal cortex neural network through regulating the local loop of PV positive neurons.This plasticity of the prefrontal cortex is involved in the regulation of central fatigue.The present study might provide morphological basis for the research of central mechanism of the exercise-induced fatigue.

Neuronal Expression and Cell-Type-Specific Gene-Silencing of Best1 in Thalamic Reticular Nucleus Neurons Using pSico-Red System

Assessing the cell-type expression pattern of a certain gene can be achieved by using cell-type-specific gene manipulation. Recently, cre-recombinase-dependent gene-silencing tool, pSico has become popular in neuroscientific research. However, pSico has a critical limitation that gene-silenced cell cannot be identified by fluorescence, due to an excision of the reporter gene for green fluorescence protein (GFP). To overcome this limitation, we newly developed pSico-Red, with mCherry gene as a reporter outside two loxP sites, so that red mCherry signal is detected in all transfected cells. When a cell expresses cre, GFP is excised and shRNA is enabled, resulting in disappearance of GFP. This feature of pSico-Red provides not only cell-type-specific gene-silencing but also identification of cre expressing cells. Using this system, we demonstrated for the first time the neuronal expression of the Bestrophin-1 (Best1) in thalamic reticular nucleus (TRN) and TRN-neuron-specific gene-silencing of Best1. We combined adeno-associated virus (AAV) carrying Best1-shRNA in pSico-Red vector and transgenic mouse expressing cre under the promoter of distal-less homeobox 5/6 (DLX5/6), a marker for inhibitory neurons. Firstly, we found that almost all of inhibitory neurons in TRN express Best1 by immunohistochemistry. Using pSico-Red virus, we found that 80% of infected TRN neurons were DLX5/6-cre positive but parvalbumin negative. Finally, we found that Best1 in DLX5/6-cre positive neurons were significantly reduced by Best1-shRNA. Our study demonstrates that TRN neurons strongly express Best1 and that pSico-Red is a valuable tool for cell-type-specific gene manipulation and identification of specific cell population.

Effects of enriched environment on sevoflurane-induced PV interneuronsphenotypic loss and long-term cognitive dysfunction in neonatal rats / 临床麻醉学杂志

Objective To investigate the expression of parvalbumin (PV)in the cognitive im-pairment mice induced by sevoflurane anesthesia,and to explore whether enriched environment could reverse it.Methods One hundred and forty-four Six-day-old C57BL/6 male mice at postnatal day 6 were randomly divided into the following four groups (n =36):control+standard environment group (group CS),control+enriched environment group(group CE),sevoflurane anesthesia+standard en-vironment group(group SS)and sevoflurane anesthesia+enriched environment group(group SE).An-imals were exposed to 3% sevoflurane plus 30% O 2 or 30% O 2 2 h daily for 3 days from postnatal day 6 (P6)to P8.The exposed pups were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or to a standard environment.Western blotting were used for determining PV ex-pression in the prefrontal cortex and hippocampus at P9,P14,P42,P60 and P90.Cognitive functions were assessed by performing the open field (P41 ),and fear conditioning tests (P42-43 and P89-90, respectively).Results In the open field test,there was no significant difference in the total travel dis-tance and the time spent in the center of the arena among groups.In the contextual fear condition test, compared with group CS,the group SS only exhibited a reduced freezing response in the contextual test at P43,but not at P90.In the cued fear conditioning test,no difference was observed in the freez-ing time among the four groups.The PV expression in the prefrontal cortex and hippocampus of group SS were significantly lower than that of group CS at P9 and P14 (P <0.001),while recovered at P60 and P90.The PV expression in the prefrontal cortex and hippocampus of group SE were significantly higher than that of group SS at P42 (P <0.05).Linear regression analysis demonstrated a positive correlation between the PV expression in the prefrontal cortex and the freezing time induced by envi-ronment (r =0.670 7,P =0.000 1),and there was a positive correlation between the PV expression in hippocampus and the freezing time induced by environment (r = 0.509 6,P = 0.001 9 ). Conclusion The cognitive impairment induced by sevoflurane anesthesia may be associated with the reduction of PV in the prefrontal cortex and hippocampus.Placement of the sevoflurane-exposed mice in an enriched environment prevented the development of these abnormalities.

New use of old drug:introductiono f the antidepressant effects of ketamine and the underlying mechanisms / 医学研究生学报

Ketamine, a nons-elective N -methyl-D-aspartate (NMDA ) receptor antagonist , is widely used as a general anesthetic in clinical practice. Recent studies have shown that ketamine can produce rapid , effective, and long-lasting antidepressant effects , and the strength of synaptic plasticity induced by inhibitory interneurons , excitatory transmitters , AMPA receptors , and postsynaptic signal pathways may be involved in this procedure .The antidepressant effects of ketamine and the underlying mechanisms are concisely intro -duced in this paper .

Unilateral olfactory functional deprivation model in the left peripheral nostrils by electric cautery injury:olfactory bulb neurogenesis and transformation / 中国组织工程研究

BACKGROUND:Olfactory bulb neurogenesis, transformation and maturation have been considered the hot topic. Olfactory bulb experience and nervous activity can influence olfactory bulb neurogenesis. However, no study reports that olfactory bulb functions can affect olfactory bulb neurogenesis in guinea pigs. OBJECTIVE:To investigate the effect of unilateral olfactory functional deprivation on doublecortin, calbindin and parvalbumin expression in olfactory bulb of juvenile guinea pigs. METHODS:Total y 24 guinea pigs were randomly divided into two groups, which were kil ed after establishing olfactory functional deprivation model through electric cautery injury at the left peripheral nostrils. At 3 and 6 weeks after modeling, the specimens were harvested. The expression change of doublecortin, calbindin and parvalbumin in two sides’ olfactory bulb of juvenile guinea pigs was detected by immunohistochemistry. RESULTS AND CONCLUSION:The number of doublecortin, calbindin and parvalbumin positive cells in olfactory bulb at the un-deprived side was significantly higher than that at the deprived side at 3 and 6 weeks (P<0.05). This finding indicates that olfactory neural activities can affect neurogenesis and transformation in guinea pigs.