Image Guided Interpedicular Screw Placement Simulation System for Training and Skill Evaluation. Proof of Concept.

BACKGROUND: The SpineST-01 system is an image-guided vertebrae cannulation training system. During task execution, the computer calculates performance-based metrics displaying different visual perspectives (lateral view, axial view, anteroposterior view) with the position of the instrument inside the vertebra. Finally, a report with the metrics is generated as performance feedback. METHODS: A training box holds a 3D printed spine section. The computer works with 2 orthogonally disposed cameras, tracking passive markers placed on the instrument. Eight metrics were proposed to evaluate the execution of the surgical task. A preliminary study with 25 participants divided into 3 groups (12 novices, 10 intermediates, and 3 expert) was conducted to determine the feasibility of the system and to evaluate and assess the performance differences of each group using Kruskal-Wallis analysis and Mann-Whitney U analysis. In both analyses, a P value ≤ 0.05 was considered statistically significant. RESULTS: When comparing experts versus novices and all 3 groups, statistical analysis showed significant differences in 6 of the 8 metrics: axial angle error (°), lateral angle error (°), average speed (mm/second), progress between shots (mm), Time (seconds), and shots. The metrics that did not show any statistically significant difference were time between shots (seconds), and speed between shots (mm/second). Also, the average result comparison placed the experts as the best performance group. CONCLUSIONS: Initial testing of the SpineST-01 demonstrated potential for the system to practice image-guided cannulation tasks on lumbar vertebrae. Results showed objective differences between experts, intermediates, and novices in the proposed metrics, making this system a feasible option for developing basic navigation system skills without the risk of radiation exposure and objectively evaluating task performance.

The Transcriptomic Landscape of Pediatric Astrocytoma.

Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are classified into four categories. However, an additional layer of molecular classification considering the DNA sequence of the tumorigenesis-associated genes IDH1/2 and H3F3A has recently been incorporated into the classification guidelines. Although mutations in H3F3A are found exclusively in a subtype of grade IV pediatric astrocytoma, mutations in IDH1/2 genes are very rare in children under 14 years of age. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied. However, there is scarce information on these profiles in pediatric populations considering the status of tumorigenesis-associated genes. Therefore, here we report the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing. We found several well-documented biological functions associated with the misregulated genes in the four grades of astrocytoma, as well as additional biological pathways. Among the four grades of astrocytoma, we found shared misregulated genes that could have implications in tumorigenesis. Finally, we identified a transcriptional signature for almost all grades of astrocytoma that could be used as a transcription-based identification method.

Single sagittal craniosynostosis surgical treatment with the "Peau d́ours" technique. Single-center experience in Mexico.

Scaphocephaly (SC) is defined as an elongation of the anteroposterior axis of the skull resulting from the abnormal fusion of the sagittal suture. This study describes the "Peau d'ours" technique and results for correcting SC. We conducted a consecutive and retrospective analysis of patients treated from 2011 to 2016. We evaluated the gender, age, and surgical outcomes. A total of 53 patients were enrolled with a mean age of 19 months old. The advantages of this technique are healthy coronal and lambdoid suture preservation and symmetrical parietal bone flap opening. This technique is safe and simple to reproduce, allowing good surgical outcomes with a low incidence of secondary craniosynostosis. This technique is ideal for patients older than six months old.

Functional outcome after cord detethering in fecally incontinent patients with anorectal malformations.

PURPOSE: Tethered cord (TC) occurs in 36% of patients with anorectal malformations (ARMs), for whom the benefit of detethering surgery remains unclear regarding bowel and/or bladder function. This study aimed to examine whether cord detethering could improve fecal and urinary incontinence in these patients. METHODS: This was a retrospective study of TC patients (>3 years old) with fecal incontinence and ARMs, who underwent detethering surgery between 2016 and 2020 and were followed up for at least 6 months. RESULTS: Of the 27 included patients, 55% had sacral ratios between 0.4 and 0.7, and in 37% it was < 0.4; the remaining 8% was over 0.7; 52% suffered from colonic hypermotility. After detethering surgery, partial fecal continence was achieved in five patients (18%); total fecal continence, in ten patients (37%); 12 (44%) remained fecally incontinent. Partial urinary continence was obtained in four cases (14%), and the number of patients with total urinary continence rose from 7 (25%) to 15 (55%). Lower extremity symptoms were also improved in 72% of the cases. Patients with colonic hypomotility were found to have a better functional outcome than those with colonic hypermotility (69% vs. 43%, respectively). CONCLUSION: Our study demonstrated that detethering surgery led to remarkably improved bowel and bladder control in ARM patients with fecal incontinence, which, surprisingly, was not associated with sacral ratio.

Evaluation of the melting temperature of TaqMan probes as a genotyping method for IDH1, IDH2, and H3F3A in pediatric astrocytomas / Evaluación del método de temperatura de disociación de sondas TaqMan para la genotipificación de IDH1, IDH2 y H3F3A en astrocitomas pediátricos

Abstract Background: Astrocytomas are cancer tumors of the central nervous system and represent the most common type of solid tumors during human childhood. In 2016, the World Health Organization established a molecular classification system to regroup tumor entities to achieve a more accurate diagnosis and a better clinical decision-making and selection of treatment in patients with these types of tumors. Methods: We evaluated a genotyping assay for rapid and cost-effective mutation detection in astrocytomas using TaqMan probes in an asymmetric polymerase chain reaction (PCR) assay. Results: Four diffuse astrocytomas (Grade II), three anaplastic astrocytomas (Grade III), and four glioblastomas (Grade IV) were sequenced, and all of them displayed the wild-type (WT) sequence. We tried to set up this melting analysis for the genotyping of pediatric astrocytomas by identifying the specific melting temperatures of the TaqMan probes due to the presence of the WT sequences in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and H3.3 histone A genes (H3F3A). We used an IDH1-TaqMan probe to identify the WT status of IDH1 in two different WT deoxyribonucleic acid (DNA) templates (pilocytic and diffuse astrocytoma) and obtained four melting temperature values ranged from 65.6 to 92.2°C. Furthermore, only four out of 29 reactions displayed amplification of the DNA template. Sanger sequencing was faster and more reliable to detect the gene status in all the sequenced samples. Conclusions: We conclude that conventional Sanger sequencing remains the gold standard for the genotyping of pediatric astrocytomas.

Resumen Introducción: Los astrocitomas son un tipo de cáncer que afecta al sistema nervioso central y representan el tumor sólido más común durante la infancia. En el año 2016, la Organización Mundial de la Salud estableció un sistema de clasificación molecular para reagrupar tumores con identidades genéticas similares y lograr un diagnóstico más preciso, lo que lleva a tomar las decisiones clínicas idóneas al elegir el tratamiento de pacientes con este tipo de tumores. Métodos: Se evaluó un protocolo que involucra el uso de sondas TaqMan en un ensayo de reacción en cadena de la polimerasa asimétrica para la detección de mutaciones en astrocitomas. Se secuenciaron cuatro astrocitomas difusos (Grado II), tres astrocitomas anaplásicos (Grado III) y cuatro glioblastomas (Grado IV). Se intentó establecer las condiciones del análisis para la genotipificación de los astrocitomas pediátricos mediante la identificación de las temperaturas de disociación específicas de las sondas TaqMan producidas por la prescencia de las secuancias WT en los genes isocitrato deshidrogenasa 1 y 2 (IDH1, IDH2) y H3.3 histona A (H3F3A). Resultados: Los astrocitomas mostraron la secuencia wild type (WT) (silvestre) de los genes. Se utilizó una sonda TaqMan IDH1 para identificar el estado de este gen en dos templados WT de DNA (astrocitoma pilocítico y difuso) y se obtuvieron cuatro valores de temperatura de disociación (65.6-92.2 °C). Solo cuatro de las 29 reacciones mostraron amplificación de DNA. La secuenciación de Sanger fue más rápida y confiable para detectar el estado de los genes en todas las muestras. Conclusiones: La secuenciación de Sanger sigue siendo la técnica más práctica para la genotipificación de astrocitomas pediátricos.

The Role of Time as a Prognostic Factor in Pediatric Brain Tumors: a Multivariate Survival Analysis.

There is no evidence that prolonged pre diagnostic symptomatic intervals (PSI) increases the risk of death in pediatric brain tumors. When investigating the role of time previous research had not controlled for confounding variables or measured the pretreatment interval (PTI). We use the term global delay interval (GDI) to describe the sum of PSI and PTI. The aim of this research was to evaluate whether there was a decrease in the probability of survival in children with brain tumors due to a prolonged PSI, PTI and GDI, using a multivariate survival analysis. We retrospective review 127 clinical records labeled with the diagnosis of CNS tumors attended at a specialized pediatric center in Mexico City from January 2008 to December 2012. Patients with PSI and GDI diagnosed between 3 and 6 months showed statistical lower probability of surviving that those with intervals <3 months even when adjusting for age, sex, localization and tumor grade. When stratified for the place of residency and adjusted for sex, age, localization, grade of tumor, type of surgery and coadjuvant therapy, a GDI between 3 and 6 months showed to be a risk factor for the overall survival of brain tumors compared with an interval < 3 months. When analyzing the interaction, high grade tumors are at more risk of dying when GDI was between 3 and 6 months compared to <3 months. Prolonged PSI and GDI showed to be a potential prognostic factor for survival in CNS tumors, especially in high grade tumors. Future prospective research should measure the PSI, PTI and GDI and adjust for covariates in order to properly infer the effect of time in pediatric brain tumors.

Phrenic nerve neurotization utilizing half of the spinal accessory nerve to the functional restoration of the paralyzed diaphragm in high spinal cord injury secondary to brain tumor resection.

The authors present a case of functional improvement of diaphragmatic paralysis in high spinal cord injury, performing a neurotization of the phrenic nerve with accessory spinal nerve hemisection. A C1-C2 injury of the spinal cord was diagnosed in a 12-year-old male, secondary to resection of a brainstem glioma. The patient did not have diaphragmatic motility at the moment that the mechanical ventilation was removed; however, he presented apnea. The patient underwent neurotization of the right phrenic nerve with the right spinal accessory nerve, 5 months after the injury and 6 months after nerve transfer; he had complete mobilization of the right hemidiaphragm, nevertheless persisted with paralysis of the left hemidiaphragm. This achievement reduced the use of mechanical ventilation during the day.

Endoscopic ventriculo-cisterno-ventricular approach in the treatment of bilateral trapped temporal horn related to fungal infection in a child: case report and review of the literature.

INTRODUCTION: Focal hydrocephalus including trapped temporal horn (TTH), isolated lateral and fourth ventricles, is caused by obstruction and/or adhesion related to various etiologies. With the advent of the neuroendoscope, endoscopic procedures have become an alternative in selected cases. CASE REPORT: A 2-year-old male from a rural town in México was referred to our institution because of multiple supra- and infra-tentorial abscesses and hydrocephalus. The patient had progressive deterioration and developed bilateral trapped temporal horn related to multi-septated hydrocephalus, so we performed an endoscopic ventricular-cistern-ventriculostomy through a single right temporal burr hole. POSTOPERATIVE COURSE: Bilateral TTH and multi-septated hydrocephalus were effectively treated with a single external ventricular drainage (EVD) catheter, from the right temporal horn to the left temporal horn through the interpeduncular cistern; after clamping the EVD for 3 days with no evidence of hydrocephalus, the EVD was removed. The size of the ventricles remained stable afterwards, and no clinical or radiological evidence of hydrocephalus was observed after 3 months of follow-up. DISCUSSION: Endoscopic ventriculocisternostomy is effective in selected cases of TTH. We know that dilatation of the temporal horn widens the window between the anterior choroidal artery and optic tract superiorly, and the posterior communicating and CN III inferiorly, making the described procedure feasible, even in the approach to the contralateral side. Even though this is a rare condition, we believe it is a safe and effective option to eliminate multiple shunts and/or to reduce the number of catheters needed to treat bilateral THH related to multi-septated hydrocephalus.

Expression of microRNAs in tumors of the central nervous system in pediatric patients in México.

PURPOSE: MicroRNAs were identified as molecules that participate in gene regulation; alterations in their expression characterize central nervous system (CNS). Information in pediatrics is scarce, so the objective of this work was to determine and then compare the patterns of expression of microRNAs in astrocytomas, ependymomas, and medulloblastomas, as well as in non-neoplastic brain. METHODS: Low-density arrays were utilized to evaluate 756 microRNAs in three samples of each type of tumor and non-neoplastic brain. The relative expression was calculated in order to identify the three microRNAs whose expression was modified notably. This was verified using RT-qPCR in more number of tumor samples. RESULTS: The microRNAs selected for testing were miR-100-5p, miR-195-5p, and miR-770-5p. A higher expression of miR-100-5p was observed in the astrocytomas and ependymomas compared to the medulloblastomas: on average 3.8 times (p < 0.05). MiR-770-5p was expressed less in medulloblastomas compared to astrocytomas four times (p = 0.0162). MiR-195-5p had a low expression in medulloblastomas compared to non-neoplastic cerebellum (p = 0.049). In all three tumor types, expression of miR-770-5p was lower than in non-neoplastic brain (p < 0.001). CONCLUSIONS: These microRNAs may represent potential markers in these tumors.

Reductions in the expression of miR-124-3p, miR-128-1, and miR-221-3p in pediatric astrocytomas are related to high-grade supratentorial, and recurrent tumors in Mexican children.

PURPOSE: Astrocytomas are the most frequent type of tumor of the central nervous system in children. Hence, it is important to describe markers that may improve our understanding of their behavior. Mature microRNAs (miRNAs) may be such biological markers. They are small molecules of RNA that regulate gene expression post-transcriptionally. Due to their importance in cancer, the objective of the present study was to determine the profile of expression of precursor and mature forms of miR-124-3p, miR-128-1, and miR-221-3p using RT-qPCR in pediatric samples. METHODS: A total of 57 astrocytomas embedded in paraffin were selected. As controls, the study included 13 samples of normal brain tissue. RESULTS: Three of eight miRNAs were selected after a preliminary screening. All the miRNAs showed higher levels of expression in normal brain tissue. The expression of miR-124-3p and miR-128-1 decreased in astrocytomas than in normal brain tissue in all grades (p < 0.05 in both cases), and this reduction was most evident in GIV (407- and 1,469-fold, respectively); however, the expression of the precursor forms pre-miR-128-1 and pre-miR-221 was higher in GIV (3.5-fold) than in GI. The levels of miR-128-1 were higher in infratentorial tumors than in supratentorial cases (p = 0.006). Finally, the expression of miR-221-3p was higher in non-recurrent tumors and live patients (p = 0.0185 and p = 0.0004, respectively). CONCLUSIONS: The low expression of these miRNAs may constitute a potential marker of astrocytomas that correlates with localization, possibly due to alterations in the maturation processes of these miRNAs that produced low mature forms in patients with recurrent pediatric astrocytomas.

Epigenetic modifications in cell lines of human astrocytoma differentially regulate expression of apoptotic genes.

OBJECTS: Epigenetic alterations, known as epimutations, act by deregulating gene expression. These epimutations are reversible through the action of chromatin modifiers such as DNA methylation (DNA-met) and histone deacetylases (HDAC) inhibitors. The present study evaluated the effect of 5-azacitidine (5-aza) and sodium butyrate (NaBu) as inhibitors of DNA-met and HDAC, respectively, in the expression of genes involved in apoptosis. METHODS: D54-MG, U373-MG, and T98G cell lines were exposed to 8 mM of NaBu and 12 µM of 5-aza, as well as a combination of both, for 24 h. The expression of the Bcl-2, Bak-1, Bax, Caspase-3, and Caspase-9 genes was assessed by RT-PCR. RESULTS: They show that the Bcl-2, Caspase-3, and Caspase-9 genes were not expressed by the U373-MG and T98G lines, and that the D54-MG line did not express Bak-1. After treatment, however, these cell lines expressed all of the genes due to the effect of 5-aza on Bak-1 in D54-MG and Caspase-9 in T98G, which suggests repression by DNA-met. Meanwhile, Bcl-2, Caspase-3, and Caspase-9 were in the U373-MG and T98G lines expressed after NaBu treatment. The effect of 5-aza induced an increase in the expression of Bax and Bcl-2, while NaBu produced a similar effect on the Bak-1 and Bax genes. CONCLUSIONS: Results reveal that histone deacetylation is the principle mechanism for repressing these genes and that their basal expression is regulated primarily by this form of histone modification.

Craneoestenosis. II. Análisis de las craneoestenosis sindromáticas y diferentes tipos de tratamiento / Craneosynostosis. II. Analysis of syndromatic craniosynostosis and different types of treatment

En esta segunda parte del trabajo de revisión de las craneoestenosis se analizan los diferentes tipos de craneoestenosis sindromáticas, sus características clínicas, imagenológicas y, en los casos que se conocen, las alteraciones genéticas. También se describen los diferentes tipos de tratamientos para las craneoestenosis, tanto sindromáticas como no sindrómaticas, desde los tratamientos quirúrgicos clásicos para lograr la descompresión cerebral, la restauración de la anatomía y proporcionar el mayor grado de estética al menor. Por último, se incluye información acerca de los tratamientos de vanguardia como son las técnicas en ingeniería de tejidos, la utilización de sistemas bioabsorbibles, de sistemas de distracción ósea e, incluso, la cirugía endoscópica. Se espera que pronto exista un mayor número de publicaciones que reporten el éxito de estas nuevas técnicas.

In this second part of the Review Article on craniosynostosis, different types of syndromatic craniosynostosis are analyzed along with clinical and imaging aspects and, in known cases, embryogenetic alterations. Different types of treatments are also described for both syndromic and nonsyndromic craniosynostosis. These range from the classic surgical treatments for achieving brain decompression, restoring the anatomy and providing the highest degree of aesthetics for the child. Last, but not least, information on cutting-edge treatments such as techniques in tissue engineering, use of bioabsorbable bone distractors and even endoscopic surgical systems are included. It is expected that in the near future there should be a greater number of publications that report the success of these new techniques.

Craneoestenosis. I. Bases biológicas y análisis de las craneoestenosis no sindromáticas / Craniosynostosis. I. Biological basis and analysis of nonsyndromic craniosynostosis

Las craneoestenosis, definidas como el cierre, la osificación y la esclerosis de una o más suturas del cráneo, ocasionan diferentes grados de compresión cerebral, hipertensión intracraneana y deterioro del cociente intelectual y la visión del niño. En esta primera parte de la revisión se presenta un panorama histórico de este padecimiento desde la época prehistórica, atravesando por diferentes siglos y culminando con la experiencia francesa y mexicana. Se presenta el informe de la serie del Hospital Infantil de México Federico Gómez. Se presentan sucintamente las bases biológicas, abordando aspectos embriogénicos, epidemiológicos, etiológicos, así como fisiopatológicos, clínicos e imagenológicos. Finalmente, se analizan siete diferentes tipo de craneoestenosis simples o no sindromáticas, ya sea de una o más suturas.

Craniosynostoses are defined as closure, ossification and sclerosis of one or more cranial sutures. This condition causes different grades of brain compression, intracranial hypertension and detriment of intellectual coefficient and vision. In the first part of this review article, an overview of the history of craniosynostosis is presented from prehistorical times through the subsequent centuries, culminating with the French and Mexican experience. The Hospital Infantil de México Federico Gómez series are also presented. Following this, the biological bases are summarized including embryogenetic, epidemiological and etiological features, as well as pathophysiological, clinical and imaging aspects. Finally, seven different types of nonsyndromatic craniosynostoses are analyzed including those with one or more sutures.

Cerebral Anatomy of the Spider Monkey Ateles Geoffroyi Studied Using Magnetic Resonance Imaging. First Report: a Comparative Study with the Human Brain Homo Sapiens / Anatomía Cerebral del mono araña Ateles geoffroyi estudiada utilizando imágenes de resonancia magnética. Primer reporte: estudio comparativo con el cerebro humano Homo Sapiens

The objective of the present qualitative study was to analyze the morphological aspects of the inner cerebral anatomy of two species of primates, using magnetic resonance images (MRI): spider monkey (A. geoffroyi) and human (H. sapiens), on the basis of a comparative study of the cerebral structures of the two species, focusing upon the brain of the spider monkey and, primarily, its limbic system. In spite of being an endemic Western hemisphere species, a fact which is by its own right interesting for research due to this animal’s social organization and motor functions, the spider monkey (A. geoffroyi) has hardly been studied in regard to its neuroanatomy. MRI was carried out, in one spider monkey, employing a General Electric Signa 1.5 T scanner. This investigation was carried in accordance to international regulations for the protection of animals in captivity, taking into account all protective means utilized in experimental handling, and not leaving behind any residual effects, either physiological or behavioral. From a qualitative point of view, the brains of the spider monkey and the human were found to have similar structures. In reference to shape, the most similar structures were found in the limbic system; proportionally, however, cervi cal curvature, amygdala, hippocampus, anterior commissure and the colliculi, were larger in the spider monkey than in the human.

El objetivo del presente estudio cualitativo fue analizar los aspectos morfológicos de la anatomía cerebral interna utilizando imágenes de resonancia magnética (IRM) en dos especies de primates, El mono Araña (A. geoffroyi) y el humano (H. sapiens), tomando como base un estudio comparativo de las estructuras cerebrales de las dos especies, concentrándose primordialmente en el sistema límbico del cerebro del mono araña. Aunque es una especie común en el hemisferio occidental, es interesante para estudiar dada su organización social y funciones motoras, el mono araña (A. geoffroyi) ha sido poco estudiado en cuanto a su neuroanatomía. Las IRM fueron hechas a un mono araña utilizando un resonador General Electrics Signa 1.5 T. Esta investigación se llevo a cabo conforme a las leyes internacionales para la protección de animales en cautiverio y teniendo en cuenta todas las medidas de protección para el manejo experimental para evitar cualquier efecto residual de índole comportamental o fisiológico. Desde un punto de vista cualitativo, los cerebros del mono araña y el humano tenían estructuras similares. Con respecto a la forma, las estructuras más parecidas fueron encontradas en el sistema límbico, sin embargo la curvatura cervical, la amígdala, el hipocampo, la comisura anterior y el colículo fueron más grandes proporcionalmente en el mono araña que en el humano.

Glioblastoma multiforme in children: experience at Hospital Infantil de Mexico Federico Gomez.

OBJECTIVE: To evaluate clinical evolution of pediatric patients diagnosed with glioblastoma multiforme (GBM) at Hospital Infantil de México Federico Gómez. METHODS: Cases of patients treated from January to May, 2007, were included in this study. Variables analyzed were: age, diagnosis, size of tumor, histopathological description, degree of resection, time of stay in hospital, complications and outcome using Pearson's chi-squared test and logistic regression. CONCLUSION: Sixteen patients were identified. Mean age of presentation was 8.8. An increased frequency of complications was observed in younger patients and longer survival rates in patients with greater resections; main mode of presentation was directly related to intracranial hypertension; size of tumor was not related to evolution or outcome. Modern histological classifications especially designed for children are deemed necessary to accurately diagnose GBM.

Neurotransmisores del sistema límbico. Hipocampo. GABA y memoria. Segunda parte

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Summary: Action of GABA agonists and antagonists on memory. The θ rhythm. Muscimol may directly alter memory. Recently, a modified matching to position (MTP) paradigm was employed aimed at influencing the type of associations a rat may use to solve the task. The main behavioral manipulation was the application of a differential outcomes procedure (DOP). DOP implies correlating each event to be remembered with a different reward condition. This procedure will result in the development of specific reward expectations which will in turn increase and guide choice behavior. Such different reward expectations will not be present when the reward assignation used is either common or random (non-differential outcomes procedure, NOP). Intraventricular infusion of muscimol or CSF in rats carrying out a delayed MTP using either a MOP or an NOP protocol will affect both groups of rats, but the nature of the deficit will differ depending on the reinforcement contingencies. Rats trained in DOP will show general non-mnemonic damage independent of delay, i.e., performance will be affected at all delay intervals employed. On the contrary, rats trained in NOP will show delay-dependent damage. This appears to demonstrate that muscimol may also have untoward memory effects, which further indicates that activation of GABA receptors will affect a set of memory associations and functions. Difficulties experienced in the past regarding LTP induction at the level of the CA3-CA1 synapse using time-based spike presentation protocols have been disconcerting given the preeminence of these synapses as a model system for the study of synaptic plasticity. Results previously discussed in experiments using picrotoxin as a GABA inhibitor have suggested that such difficulties arise from the requirement that, for LTP to be induced, CA1 dendrites must be persistently and totally activated. Doublets used in this case represent a minimal burst, or level of post-synaptic stimulation for LTP induction that subsumes greater depolarizations. In vitro, synaptically induced bursts would correspond to regenerative electrical events in apical dendrites of pyramidal neurons. The same requirements for dendritic activation would be satisfied in vivo during the θ rhythm, which is present during active exploration. Therefore, GABA might serve as an engram modulator through the activation of the hippocampal θ rhythm. Effect of μ-opioid receptors on hippocampal memory activity. Hippocampal μ-opioid receptors (MOR) have been involved in the formation of memory associated with the abuse of opioid drugs. When chronically activated, and during programmed drug abstinence, MORs acutely modulate hippocampal synaptic plasticity At the level of neuronal networks, MORs increase excitability of area CA1 by means of a disinhibition of pyramidal cells. The specific inhibitory interneuronal subtypes which become affected by activation of MORs are not known. Nevertheless, not all subtypes are inhibited and some subtypes preferentially express these receptors. In one study, the effect of activation of MORs on inhibitory patterns and propagation of excitatory activity in CA1 of rat hippocampus was investigated through cortical images created using voltage-sensitive dyes. MOR activation increased excitatory activity originated by the increased stimulating input to stratum oriens (i.e., Schäffer collateral and commissural [SCC] fibers, as well as the retrograde pathway), to stratum radiatum (i.e., SCC fibers) and to stratum lacunosum-moleculare (i.e., the perforant pathway and the thalamus). Increased excitatory activity was additionally facilitated by propagation through the neural network of area CA1. This was observed as a proportionally greater increment of amplitudes of excitatory activity in sites distant from the originally evoked activity. Such facilitation was noted in excitatory activity propagating from three sites of stimulation. The increment and facilitation were prevented with GABAA receptor antagonists (bicuculline, 30 μM), but not with GABAB receptor antagonists (CGP, 10 μM). Besides, MOR activation inhibited inhibitory post-synaptic potentials (IPSPs) in every layer of area CA1. These findings suggest that MOR-originated suppression of GABA release to GABAA receptors increases every type of input to pyramidal CA1 neurons and facilitates propagation of excitatory activity through the neural network of area CA1. Cannabis indica and memory. Cannabinoids (derived from Cannabis indica, or marihuana) disturb memory processes in mammalians. In spite of the fact that the neuronal cannabinoid CB1 receptor was identified several years ago, the neuronal network mechanisms mediating these effects are still controversial. Tritium-labeled GABA-releasing experiments have been used to test for the localization of this receptor at a cellular and subcellular level in the human hippocampus. CB1 expression detected with this technique is limited to hippocampal interneurons, most of which, it could be determined, are cholecystokinin-containing basket neurons. The CB1-positive neuronal somata show immune staining of their cytoplasm, but not of their somatodendritic plasma membrane. CB1-immunoreactive axonic terminals densely cover the entire hippocampus and form symmetrical synapses, characteristic of GABAergic neuronal boutons. It could thus be observed that WIN 55,212-2, a CB1-receptor agonist, considerably reduces the release of tritium-labeled GABA, and that this effect is preventable using the receptor antagonist, SR 141716A. This single pattern of expression and pre-synaptic modulation of GABA release suggests the existence of a preserved role of CB1 receptors in the control of inhibitory hippocampal networks responsible for the generation and maintenance of fast and slow oscillation patterns. Therefore, a probable mechanism whereby cannabinoids could affect associational processes in memory might be a disturbance of synchrony of rhythmical events in distinct neuronal populations. GABA effects against aging. Certain components which stimulate GABAergic neurotransmission might prevent the hippocampal and striatal degeneration which typically appears with old age and causes memory deterioration. On using a 4-vessel occlusion model in animals to study the effect of ischemia on expression of GABAA receptor subunits, which are vulnerable in region CA1 and resistant in region CA3 of Amnion's horn, an increment in expression of GABAA2, GABA B2, GABA G2 units and a decrement in expression of GABA A1 and GABA A3 subunits in region CA3 were obtained. On the contrary, there was no change in region CA1 or the dentate gyrus under the same conditions. These data speak in favor of the stimulation of type 2 receptor GABAergic subunits which might protect certain hippocampal areas against a harmful neurodegenerative effect, for example, of memory activities during old age.