The subiculum role on learning and memory tasks using rats and mice: A scoping review.

This scoping review aimed to systematically identify and summarize data related to subiculum involvement in learning and memory behavioral tasks in rats and mice. Following a systematic strategy based on PICO and PRISMA guidelines, we searched five indexed databases (PubMed, Web of Science, EMBASE, Scopus, and PsycInfo) using a standardized search strategy to identify peer-reviewed articles published in English (pre-registration: osf.io/hm5ea). We identified 31 articles investigating the role of the subiculum in spatial, working, and recognition memories (n = 11), memories related to addiction models (n = 9), aversive memories (n = 7), and memories related to appetitive learning (n = 5). We highlight a dissociation in the dorsoventral axis of the subiculum with many studies exploring the ventral subiculum (n = 21) but only a few exploring the dorsal one (n = 10). We also observe the necessity of more data including mice, female animals, genetic tools, and better statistical approaches for replication purposes and research refinement. These findings provide a broad framework of the subiculum involvement in learning and memory, showing essential questions that can be explored by further studies.

Transcriptomic analysis of dorsal and ventral subiculum after induction of acute seizures by electric stimulation of the perforant pathway in rats.

Preconditioning is a mechanism in which injuries induced by non-lethal hypoxia or seizures trigger cellular resistance to subsequent events. Norwood et al., in a 2010 study, showed that an 8-h-long period of electrical stimulation of the perforant pathway in rats is required for the induction of hippocampal sclerosis. However, in order to avoid generalized seizures, status epilepticus (SE), and death, a state of resistance to seizures must be induced in the hippocampus by a preconditioning paradigm consisting of two daily 30-min stimulation periods. Due to the importance of the subiculum in the hippocampal formation, this study aims to investigate differential gene expression patterns in the dorsal and ventral subiculum using RNA-sequencing, after induction of a preconditioning protocol by electrical stimulation of the perforant pathway. The dorsal (dSub) and ventral (vSub) subiculum regions were collected by laser-microdissection 24 h after preconditioning protocol induction in rats. RNA sequencing was performed in a Hiseq 4000 platform, reads were aligned using the STAR and DESEq2 statistics package was used to estimate gene expression. We identified 1176 differentially expressed genes comparing control to preconditioned subiculum regions, 204 genes were differentially expressed in dSub and 972 in vSub. The gene ontology enrichment analysis showed that the most significant common enrichment pathway considering up-regulated genes in dSub and vSub was steroid metabolism. In contrast, the most significant enrichment pathway considering down-regulated genes in vSub was axon guidance. Our results indicate that preconditioning induces changes in the expression of genes related to synaptic reorganization, increased cholesterol metabolism, and astrogliosis in both dSub and vSub. Both regions also presented a decrease in the expression of genes related to glutamatergic transmission and an increase in expression of genes related to complement system activation and GABAergic transmission. The down-regulation of proapoptotic and axon guidance genes in the ventral subiculum suggests that preconditioning may induce a neuroprotective environment in this region.

Deep Brain Stimulation for Refractory Temporal Lobe Epilepsy. Current Status and Future Trends.

A comparative analysis of the targets for deep brain stimulation (DBS) to treat refractory temporal lobe epilepsy and the rationale for its use is presented, with an emphasis on the latency to obtain the significant antiepileptic effect and the long-term seizure control. The analysis includes consideration of surgical techniques currently used to optimize antiseizure effects and decrease surgical risks. Seizure control is similar for programed DBS and DBS responsive to abnormal cortical or subcortical electroencephalogram (EEG) activity. There is no difference in the long-term seizure control between programmed and responsive and intermittent or continuous DBS. However, intermittent programed DBS may have a significant antiseizure effect starting in the first month when applied to a non-sclerotic tissue such as the parahippocampal cortex. DBS induces no neuropsychological deterioration.

Electrical Stimulation of Subiculum for the Treatment of Refractory Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis: A 2-Year Follow-Up Study.

INTRODUCTION: Evidence has been provided that the subiculum may play an important role in the generation of seizures. Electrical stimulation at this target has been reported to have anticonvulsive effects in kindling and pilocarpine rat models, while in a clinical study of hippocampal deep brain stimulation (DBS), contacts closest to the subiculum were associated with a better anticonvulsive effect. OBJECTIVES: To evaluate the effect of electrical stimulation of the subiculum in patients with refractory mesial temporal lobe epilepsy (MTLE) who have hippocampal sclerosis (HS). METHODS: Six patients with refractory MTLE and HS, who had focal impaired awareness seizures (FIAS) and focal to bilateral tonic-clonic seizures (FBTCS), had DBS electrodes implanted in the subiculum. During the first month after implantation, all patients were OFF stimulation, then they all completed an open-label follow-up of 24 months ON stimulation. DBS parameters were set at 3 V, 450 µs, 130 Hz, cycling stimulation 1 min ON, 4 min OFF. RESULTS: There was a mean reduction of 49.16% (±SD 41.65) in total seizure number (FIAS + FBTCS) and a mean reduction of 67.93% (±SD 33.33) in FBTCS at 24 months. FBTCS decreased significantly with respect to baseline, starting from month 2 ON stimulation. CONCLUSIONS: Subiculum stimulation is effective for FBTCS reduction in patients with MTLE and HS, suggesting that the subiculum mediates the generalization rather than the genesis of mesial temporal lobe seizures. Better results are observed at longer follow-up times.

Increased oxidative stress, hyperphosphorylation of tau, and dystrophic microglia in the hippocampus of aged Tupaia belangeri.

Aging is a major risk factor for the development of neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases are characterized by abnormal and prominent protein aggregation in the brain, partially due to deficiency in protein clearance. It has been proposed that alterations in microglia phagocytosis and debris clearance hasten the onset of neurodegeneration. Dystrophic microglia are abundant in aged humans, and it has been associated with the onset of disease. Furthermore, alterations in microglia containing ferritin are associated with neurodegenerative conditions. To further understand the process of microglia dysfunction during the aging process, we used hippocampal sections from Tupaia belangeri (tree shrews). Adult (mean age 3.8 years), old (mean age 6 years), and aged (mean age 7.5 years) tree shrews were used for histochemical and immunostaining techniques to determine ferritin and Iba1 positive microglia, iron tissue content, tau hyperphosphorylation and oxidized-RNA in dentate gyrus, subiculum, and CA1-CA3 hippocampal regions. Our results indicated that aged tree shrews presented an increased number of activated microglia containing ferritin, but microglia labeled with Iba1 with a dystrophic phenotype was more abundant in aged individuals. With aging, oxidative damage to RNA (8OHG) increased significantly in all hippocampal regions, while tau hyperphosphorylation (AT100) was enhanced in DG, CA3, and SUB in aged animals. Phagocytic inclusions of 8OHG- and AT100-damaged cells were observed in activated M2 microglia in old and aged animals. These data indicate that aged tree shrew may be a suitable model for translational research to study brain and microglia alterations during the aging process.

Endoscopic evaluation of middle ear anatomic variations in autopsy series: analyses of 204 ears / Avaliação endoscópica das variações anatômicas da orelha média em uma série de autópsias: análise de 204 orelhas

Abstract Introduction Microsurgery of the ear requires complete evaluation of middle ear surgical anatomy, especially the posterior tympanic cavity anatomy. Preoperative assessment of the middle ear cavity is limited by the permeability of eardrum and temporal bone density. Therefore, middle ear exploration is an extremely useful method to identify structural abnormalities and anatomical variations. Objective The aim of this study is to determine anatomic variations of the middle ear in an autopsy series. Methods All evaluations were performed in the Forensic Medicine Institute Morgue Department. The cases over 18 years of age, with no temporal bone trauma and history of otologic surgery included in this study. Results One hundred and two cadavers were included in the study. The mean age was 49.08 ± 17.76 years. Anterior wall prominence of the external auditory canal was present in 27 of all cadavers (26.4%). The tympanic membrane was normal in 192 ears (94%) while several eardrum pathologies were detected in 12 ears (6%). Agenesis of the pyramidal eminence and stapedial tendon was found in 3 ears. While the ponticulus was bony ridge-shaped in 156 of 204 ears (76.4%), it was bridge-shaped in 25 ears (12.3%). The ponticulus was absent in 23 ears (11.3%). While complete subiculum was present in 136 of all ears (66.7%), incomplete subiculum was present in 21 ears (10.3%). Subiculum was absent in 47 ears (23%). Facial dehiscence was found in 32 ears and the round window niche was covered by a pseudomembrane in 85 ears (41.6%). A fixed footplate was present in 7.4% of all ears, and no persistent stapedial artery was seen in any cases. Conclusion The pseudomembrane frequency covering the round window niche was found different from reports in the literature. In addition, the frequency of the external auditory canal wall prominence has been reported for the first time.

Resumo Introdução A otomicrocirurgia requer avaliação completa da anatomia cirúrgica da orelha média, especialmente da anatomia da cavidade timpânica posterior. A avaliação pré-operatória da cavidade timpânica é limitada pela permeabilidade do tímpano e densidade do osso temporal. Portanto, a exploração da orelha média é um método extremamente útil para identificar anormalidades estruturais e variações anatômicas. Objetivo Determinar as variações anatômicas da orelha média em uma série de autópsias. Método Todas as avaliações foram realizadas no necrotério do Instituto Médico-Legal. Os casos com mais de 18 anos, sem trauma do osso temporal e história de cirurgia otológica foram incluídos neste estudo. Resultados Cento e dois cadáveres foram incluídos no estudo. A média de idade foi de 49,08 ± 17,76 anos. A proeminência da parede anterior do conduto auditivo externo estava presente em 27 de todos os cadáveres (26,4%). A membrana timpânica era normal em 192 orelhas (94%), enquanto várias alterações do tímpano foram detectadas em 12 orelhas (6%). Agenesia da eminência piramidal e do tendão do estapédio foi encontrada em 3 orelhas. Enquanto o pontículo tinha formato de crista óssea em 156 das 204 orelhas (76,4%), tinha o formato de ponte em 25 orelhas (12,3%). O pontículo estava ausente em 23 orelhas (11,3%). Enquanto o subículo completo estava presente em 136 de todas as orelhas (66,7%), encontrava-se incompleto em 21 orelhas (10,3%). O subículo estava ausente em 47 orelhas (23%). Deiscência facial foi encontrada em 32 orelhas e o nicho da janela redonda estava coberto por uma pseudomembrana em 85 orelhas (41,6%). A platina fixa foi observada em 7,4% de todas as orelhas e a artéria estapediana persistente não foi vista. Conclusão A frequência da pseudomembrana que cobre o nicho da janela redonda foi diferente daquela encontrada na literatura. Além disso, a frequência da proeminência da parede do canal auditivo externo foi relatada pela primeira vez.

Endoscopic evaluation of middle ear anatomic variations in autopsy series: analyses of 204 ears.

INTRODUCTION: Microsurgery of the ear requires complete evaluation of middle ear surgical anatomy, especially the posterior tympanic cavity anatomy. Preoperative assessment of the middle ear cavity is limited by the permeability of eardrum and temporal bone density. Therefore, middle ear exploration is an extremely useful method to identify structural abnormalities and anatomical variations. OBJECTIVE: The aim of this study is to determine anatomic variations of the middle ear in an autopsy series. METHODS: All evaluations were performed in the Forensic Medicine Institute Morgue Department. The cases over 18 years of age, with no temporal bone trauma and history of otologic surgery included in this study. RESULTS: One hundred and two cadavers were included in the study. The mean age was 49.08±17.76 years. Anterior wall prominence of the external auditory canal was present in 27 of all cadavers (26.4%). The tympanic membrane was normal in 192 ears (94%) while several eardrum pathologies were detected in 12 ears (6%). Agenesis of the pyramidal eminence and stapedial tendon was found in 3 ears. While the ponticulus was bony ridge-shaped in 156 of 204 ears (76.4%), it was bridge-shaped in 25 ears (12.3%). The ponticulus was absent in 23 ears (11.3%). While complete subiculum was present in 136 of all ears (66.7%), incomplete subiculum was present in 21 ears (10.3%). Subiculum was absent in 47 ears (23%). Facial dehiscence was found in 32 ears and the round window niche was covered by a pseudomembrane in 85 ears (41.6%). A fixed footplate was present in 7.4% of all ears, and no persistent stapedial artery was seen in any cases. CONCLUSION: The pseudomembrane frequency covering the round window niche was found different from reports in the literature. In addition, the frequency of the external auditory canal wall prominence has been reported for the first time.