OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Objective:To compare the changes of morphology of pharynx in patients with obstructive sleep apnea hypopnea syndrome （OSAHS） and healthy individuals during oral or nasal breathing, and explore the relevant influencing factors. Methods:Twenty-nine adult patients with OSAHS and 20 non-snoring controls underwent MRI to obtain upper airway structural measurements while the subjects were awake and during mouth breathing with a nasal clip.The following were analyzed. ①The changes of upper airway structure of oral and nasal respiration in non-snoring control/OSAHS patients were observed; ②The differences and influencing factors of upper airway structure changes between OSAHS patients and controls were compared during breathing. Results:The control group consisted of 15 males and 5 females, with an apnea-hypopnea index （AHI）<5 events/h, while the OSAHS group comprised 26 males and 3 females with an AHI of 40.4±23.1 events/h and the mean lowest arterial oxygen saturation （LSaO2） was 79.5% ±10.0%. In the both groups, the vertical distance between the mandible and the posterior pharyngeal wall decreased （P<0.05）; The long axis of tongue body decreased （P<0.05）, and the contact area between tongue and palate decreased. There was no significant change in the total volume of the retropalatine（RP） and retroglossal（RG） airway in the control group （P>0.05）. However, the minimum cross-sectional area and volume of the RP airway in OSAHS decreased （P<0.001）. The lateral diameters of uvula plane in OSAHS decreased during mouth breathing, which was contrary to the trend in the control group （P=0.017）. The AHI of patients was positively correlated with the reduction of the volume of the RP airway during oral breathing （P=0.001）; The reduction of the distance between the mandible and the posterior pharyngeal wall was positively correlated with the length of the airway （P<0.001）. Conclusion:Mouth breathing leads to the shortening of the long axis of the tongue, the reduction of the contact area between the soft palate and the tongue, vertical distance between the mandible and the posterior pharyngeal wall, and the cross-sectional area of the epiglottis plane. These changes vary between OSAHS patients and controls. During mouth breathing, the diameters, areas and volumes of the RP area decreased, and were more significant in severe cases.
Male ; Adult ; Female ; Humans ; Mouth Breathing ; Sleep Apnea, Obstructive/surgery* ; Pharynx/surgery* ; Palate, Soft ; Uvula/surgery* ; Syndrome