Expression of N-methyl-D-aspartic acid 2A-B and 2B receptors in anterior thalamic nucleus and subiculum complex of rats

BACKGROUND：Glutamate acid ionotropic receptor N-methyl-D-aspartic acid （NMDA） takes part in long-term potentiation, thereby influencing the process of learning and memory. OBJECTIVE： To verify expression of NMDA 2A/B and 2B receptors in the anterior thalamic nucleus and subiculum complex of rats. DESIGN, TIME AND SETTING： A single-sample observation was performed at Department of Anatomy in Dalian Medical University （Dalian, Liaoning, China） from April to September in 2007. MATERIALS： Ten adult Wistar rats were used for this study, as well as rabbit anti-NMDA 2A/B and 2B antibodies. METHODS： The rats were anesthetized and perfused, followed by brain resection and coronal sectioning of the brain tissue. A 1：3 series was selected for immunohistochemistry, using antibodies specific to NMDA 2A/B and 2B receptors. Photos were taken using the Nikon image analysis system. MAIN OUTCOME MEASURES： Expression and distribution of immunohistochemistry staining of NMDA 2A/B and 2B receptor subunits. RESULTS： There were a large number of NMDA 2A/B and 2B receptor-positive neurons distributed throughout the anterior dorsal thalamic nucleus. In the anterior ventral thalamic nucleus, distribution of positive neurons was rare, staining intensity was lighter, and cell bodies were smaller compared with the anterior dorsal thalamic nucleus. In the subiculum complex, staining intensity of NMDA 2A/B and 2B-positive neurons was weakest in the molecular layer and stronger in the pyramidal layer, in particular the region with large cell bodies adjacent to the molecular layer. In the multiform layer, more positive neurons of various sizes were detected. CONCLUSION： NMDA 2A/B and 2B receptor subunits were richly distributed in the anterior thalamic nucleus, with a small difference existing between the anterior dorsal nucleus and anterior ventral nucleus. These neurons were also differentially distributed within the three layers of the subiculum complex.

Mechanisms of secondary damage to the thalamic nucleus and substantia nigra in an adult hypertensive rat model following middle cerebral artery occlusion

BACKGROUND： Following ischemia, apoptosis is observed at the ipsilateral ventropostenor thalamic nucleus and substantia nigra, which are distant from, but connected to, the ischemic cerebral cortex, in animals with normotension. However, secondary brain damage in hypertension has not been clearly investigated. OBJECTIVE： The present study determined whether neuronal apoptosis is associated with neuronal loss in the ipsilateral ventroposterior thalamic nucleus and substantia nigra following cortical ischemia in adult hypertensive rats. Results should provide options for determining a time window for anti-apoptotic therapy. DESIGN, TIME AND SETTING： All experimental procedures in this randomized, controlled trial were conducted at the Neurological Laboratory of the First Affiliated Hospital of Sun Yat-sen University of China between October 2006 and July 2008. MATERIALS： Monoclonal primary antibodies specific to mouse anti-rat microtubule-associated protein 2 and glial fibrillary acidic protein were respectively purchased from Sigma Chemical, USA and BD Pharmingen, USA. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling （TUNEL） detection kits were purchased from Roche Applied Science, Switzerland and Upstate, USA, respectively. METHODS： A total of 64 male, Sprague Dawiey rats, aged 60-90 days, were equally and randomly divided into middle cerebral artery occlusion and sham surgery groups. Renovascular hypertension was established in both groups by renal artery occlusion. Right distal middle cerebral artery occlusion was performed by electrocoagulation in the middle cerebral artery occlusion group. MAIN OUTCOME MEASURES： Microtubule-associated protein 2 and glial fibrillary acidic protein were detected by immunohistochemistry, and apoptotic cells were observed by TUNEL assay. The stainings were separately detected in the ipsilateral ventroposterior thalamic nucleus and substantia nigra. RESULTS： During the 4 weeks following distal middle cerebral artery occlusion in renovascular hypertensive rats, microtubule-associated protein 2 expression gradually, but significantly, decreased （P 〈 0.05）. Expression of glial fibrillary acidic protein increased significantly in the ipsilateral ventroposterior thalamic nucleus and substantia nigra （P 〈 0.05） and reached a peak at 4 weeks. In addition, number of apoptotic cells was significantly increased in both areas compared with the sham controls （P 〈 0.05）, with a peak at 2 weeks. CONCLUSION： Results suggested that neuronal loss in the ipsilateral ventroposterior thalamic nucleus and substantia nigra following distal middle cerebral artery occlusion in hypertensive rats could be a secondary event resulting from apoptosis. The temporal apoptosis profile provides options for determining a time window for anti-apoptotic therapy at 2 weeks after stroke.

Thalamic Nucleus Reuniens Glutamatergic Neurons Mediate Colorectal Visceral Pain in Mice via 5-HT2B Receptors

Irritable bowel syndrome(IBS)is a common functional bowel disorder characterized by abdominal pain and visceral hypersensitivity.Reducing visceral hypersensitivity is the key to effectively relieving abdominal pain in IBS.Increasing evidence has confirmed that the thalamic nucleus reuniens(Re)and 5-hydroxytryptamine(5-HT)neurotransmitter system play an important role in the development of colorectal visceral pain,whereas the exact mechanisms remain largely unclear.In this study,we found that high expression of the 5-HT2B receptors in the Re glutamatergic neurons promoted colorectal visceral pain.Specifically,we found that neonatal maternal deprivation(NMD)mice exhibited visceral hyperalgesia and enhanced spontaneous synaptic transmission in the Re brain region.Colorectal distension(CRD)stimulation induced a large amount of c-Fos expression in the Re brain region of NMD mice,predominantly in glutamatergic neurons.Furthermore,optogenetic manipulation of glutamatergic neuronal activity in the Re altered colorectal visceral pain responses in CON and NMD mice.In addition,we demonstrated that 5-HT2B receptor expression on the Re glutamatergic neurons was upregulated and ultimately promoted colorectal visceral pain in NMD mice.These findings suggest a critical role of the 5HT2B receptors on the Re glutamatergic neurons in the regulation of colorectal visceral pain.

Regulation of Cued Fear Expression via Corticotropin-ReleasingFactor Neurons in the Ventral Anteromedial Thalamic Nucleus

The ventral part of the anteromedial thalamic nucleus(AMv)is in a position to convey information to the cortico-hippocampal-amygdalar circuit involved in the processing of fear memory.Corticotropin-releasing-factor(CRF)neurons are closely associated with the regulation of stress and fear.However,few studies have focused on the role of thalamic CRF neurons in fear memory.In the present study,using a conditioned fear paradigm in CRF transgenic mice,we found that the c-Fos protein in the AMv CRF neurons was significantly increased after cued fear expression.Chemogenetic activation of AMv CRF neurons enhanced cued fear expression,whereas inhibition had the opposite effect on the cued fear response.Moreover,chemogenetic manipulation of AMv CRF neurons did not affect fear acquisition or contextual fear expression.In addition,anterograde tracing of projections revealed that AMv CRF neurons project to wide areas of the cerebral cortex and the limbic system.These results uncover a critical role of AMv CRF neurons in the regulation of conditioned fear memory.

Research progress in the efficacy of deep brain stimulation with different targets in Parkinson's disease

Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic nucleus(STN),globus pallidus(GPi),meso-ventral thalamic nucleus(VIM),pontine peduncle nucleus(PPN),posterior subthalamic region(PSA)and zonation of undetermined zone(ZI).This paper summarizes the efficacy of each target in the treatment of PD with DBS,not only makes a systematic analysis and comparison of motor symptoms,but also makes a detailed description of the efficacy of non-motor symptoms,so as to provide a personalized treatment basis for PD patients to select appropriate target targets in DBS.

The role of microglia in thalamic reticular nucleus in acupuncture regulating cognitive deficits in insomnia rats

Objective:To explore the mechanism of acupuncture in regulating cognitive deficits in insomnia rats by observing the effect of acupuncture on microglia in thalamic reticular nucleus(TRN).Methods:Thirty rats were randomly divided into a control group,a model group and an acupuncture group,with 10 rats in each group.The insomnia model was established by intraperitoneal injection of para-chlorophenylalanine(PCPA)once a day for 2 d.Rats in the control group were intraperitoneally injected with the same amount of normal saline.Rats in the acupuncture group received acupuncture at Neiguan(PC 6)and Zusanli(ST 36)for 5 consecutive days.The CLOCKLAB 2 data acquisition system was used to dynamically observe the sleep of the rats throughout the experiment.The cognition of rats was evaluated by event-related potentials(ERPs).After intervention,brain tissue was extracted.Immunofluorescence was used to test the fluorescence expression in TRN region.The concentrations of interleukin(IL)-1βand tumor necrosis factor(TNF)-αwere detected by enzyme-linked immunosorbent assay.Results:After intraperitoneal injection of PCPA suspension,the spontaneous activity in light period of rats in the model group and acupuncture group increased significantly compared with the control group(both P<0.01).After acupuncture treatment,the rats in the acupuncture group had much less spontaneous activity during the light period than those in the model group(P<0.01),and the results indicated that acupuncture could effectively improve the sleep quality of insomnia rats.Compared with the control group,rats in the model group showed that the P3 latency,the average optical density of microglia,and the concentrations of IL-1βand TNF-αincreased significantly(all P<0.05),and the P3 amplitude decreased significantly(P<0.01).Compared with the model group,rats in the acupuncture group presented that the P3 latency,the average optical density of microglia,and the concentrations of IL-1βand TNF-αwere significantly decreased(all P<0.05),and the amplitude of P3 was significantly increased(P<0.05).Conclusion:Acupuncture possesses an ability to improve the cognitive state in insomnia rats.The mechanism may be related to inhibiting the microglial activation,diminishing the levels of pro-inflammatory mediators like IL-1βand TNF-α,and promoting the recovery of central nervous system function.

Cross-Modal Interaction and Integration Through Stimulus-Specific Adaptation in the Thalamic Reticular Nucleus of Rats

Stimulus-specific adaptation(SSA),defined as a decrease in responses to a common stimulus that only partially generalizes to other rare stimuli,is a widespread phenomenon in the brain that is believed to be related to novelty detection.Although cross-modal sensory processing is also a widespread phenomenon,the interaction between the two phenomena is not well understood.In this study,the thalamic reticular nucleus(TRN),which is regarded as a hub of the attentional system that contains multi-modal neurons,was investigated.The results showed that SSA existed in an interactive oddball stimulation,which mimics stimulation changes from one modality to another.In the bimodal integration,SSA to bimodal stimulation was stronger than to visual stimulation alone but similar to auditory stimulation alone,which indicated a limited integrative effect.Collectively,the present results provide evidence for independent cross-modal processing in bimodal TRN neurons.

Neuronal firing in the ventrolateral thalamus of patients with Parkinson＇s disease differs from that with essential tremor

Background Although thalamotomy could dramatically improve both parkinsonian resting tremor and essential tremor （ET）, the mechanisms are obviously different. This study aimed to investigate the neuronal activities in the ventrolateral thalamus of Parkinson＇s disease （PD） and ET. Methods Thirty-six patients （PD： 20, ET： 16） were studied. Microelectrode recordings in the ventral oral posterior （Vop）and the ventral intermediate nucleus （Vim） of thalamus was performed on these patients who underwent thalamotomy.Electromyography （EMG） was recorded simultaneously on the contralateral limbs to surgery. Single unit analysis and the interspike intervals （ISIs） were measured for each neuronal type. ISI histogram and auto-correlograms were constructed to estimate the pattern of neuronal firing. Mann-Whitney test and Kruskal-Wallis （K-W） test were used to compare the mean spontaneous firing rate （MSFR） of neurons of PD and ET patients. Results Three hundred and twenty-three neurons were obtained from 20 PD trajectories, including 151 （46.7%） tremor related neuronal activity, 74 neurons （22.9%） with tonic firing, and 98 （30.4%） neurons with irregular discharge. One hundred and eighty-seven neurons were identified from 16 ET trajectories including 46 （24.6%） tremor-related neuronal activity, 77 （41.2%） neurons with tonic firing, and 64 neurons （34.2%） with irregular discharge. The analysis of MSFR of neurons with tonic firing was 26.7 （3.4-68.3） Hz （n=74） and that of neurons with irregular discharge （n=98） was 13.9 （3.0-58.1） Hz in PD; whereas MSFR of neurons with tonic firing （n=77） was 48.8 （19.0-135.5） Hz and that of neurons with irregular discharge （n=64） was 26.3 （8.7-84.7） Hz in ET. There were significant differences in the MSFR of two types of neuron for PD and ET （K-W test, both P〈0.05）. Significant differences in the MSFR of neuron were also obtained from Vop and Vim of PD and ET （16.3 Hz vs. 34.8 Hz, 28.0 Hz vs. 49.9 Hz） （K-W test, both P 〈0.05）, respectively. Conclusion In consistent with recent findings, the decreased MSFR of neurons observed in the Vop is likely to be involved in PD whereas the increased MSFR of neurons seen in the Vim may be a cause of ET.