Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning.

According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidirectional plasticity appears crucial for learning, in which different microzones can undergo opposite changes of synaptic strength (e.g. downbound microzones-more likely depression, upbound microzones-more likely potentiation), and multiple forms of plasticity have been identified, distributed over different cerebellar circuit synapses. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding downbound and upbound modules that are subject to multiple plasticity rules. Simulations indicate that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity at the pf-PC synapses as well as at the synapses of the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both microzones contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC and/or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum can facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution.

Cardiorespiratory rhythm-contingent trace eyeblink conditioning in elderly adults.

Learning outcome is modified by the degree to which the subject responds and pays attention to specific stimuli. Our recent research suggests that presenting stimuli in contingency with a specific phase of the cardiorespiratory rhythm might expedite learning. Specifically, expiration-diastole (EXP-DIA) is beneficial for learning trace eyeblink conditioning (TEBC) compared with inspiration-systole (INS-SYS) in healthy young adults. The aim of this study was to investigate whether the same holds true in healthy elderly adults (n = 50, aged >70 yr). Participants were instructed to watch a silent nature film while TEBC trials were presented at either INS-SYS or EXP-DIA (separate groups). Learned responses were determined as eyeblinks occurring after the tone conditioned stimulus (CS), immediately preceding the air puff unconditioned stimulus (US). Participants were classified as learners if they made at least five conditioned responses (CRs). Brain responses to the stimuli were measured by electroencephalogram (EEG). Memory for the film and awareness of the CS-US contingency were evaluated with a questionnaire. As a result, participants showed robust brain responses to the CS, acquired CRs, and reported awareness of the CS-US relationship to a variable degree. There was no difference between the INS-SYS and EXP-DIA groups in any of the above. However, when only participants who learned were considered, those trained at EXP-DIA (n = 11) made more CRs than those trained at INS-SYS (n = 13). Thus, learned performance could be facilitated in those elderly who learned. However, training at a specific phase of cardiorespiratory rhythm did not increase the proportion of participants who learned.NEW & NOTEWORTHY We trained healthy elderly individuals in trace eyeblink conditioning, either at inspiration-systole or at expiration-diastole. Those who learned exhibited more conditioned responses when trained at expiration-diastole rather than inspiration-systole. However, there was no difference between the experimental groups in the proportion of individuals who learned or did not learn.

Central amygdala contributes to stimulus facilitation and pre-stimulus vigilance during cerebellar learning.

Our previous studies found that the central amygdala (CeA) modulates cerebellum-dependent eyeblink conditioning (EBC) using muscimol inactivation. We also found that CeA inactivation decreases cerebellar neuronal activity during the conditional stimulus (CS) from the start of training. Based on these findings, we hypothesized that the CeA facilitates CS input to the cerebellum. The current study tested the CS facilitation hypothesis using optogenetic inhibition with archaerhodopsin (Arch) and excitation with channelrhodopsin (ChR2) of the CeA during EBC in male rats. Optogenetic manipulations were administered during the 400 ms tone CS or during a 400 ms pre-CS period. As predicted by the CS facilitation hypothesis CeA inhibition during the CS impaired EBC and CeA excitation during the CS facilitated EBC. Unexpectedly, CeA inhibition just prior to the CS also impaired EBC, while CeA excitation during the pre-CS pathway did not facilitate EBC. The results suggest that the CeA contributes to CS facilitation and vigilance during the pre-CS period. These putative functions of the CeA may be mediated through separate output pathways from the CeA to the cerebellum.

Distinct Hippocampal Oscillation Dynamics in Trace Eyeblink Conditioning Task for Retrieval and Consolidation of Associations.

Trace eyeblink conditioning (TEBC) has been widely used to study associative learning in both animals and humans. In this paradigm, conditioned responses (CRs) to conditioned stimuli (CS) serve as a measure for retrieving learned associations between the CS and the unconditioned stimuli (US) within a trial. Memory consolidation, that is, learning over time, can be quantified as an increase in the proportion of CRs across training sessions. However, how hippocampal oscillations differentiate between successful memory retrieval within a session and consolidation across TEBC training sessions remains unknown. To address this question, we recorded local field potentials (LFPs) from the rat dorsal hippocampus during TEBC and investigated hippocampal oscillation dynamics associated with these two functions. We show that transient broadband responses to the CS were correlated with memory consolidation, as indexed by an increase in CRs across TEBC sessions. In contrast, induced alpha (8-10 Hz) and beta (16-20 Hz) band responses were correlated with the successful retrieval of the CS-US association within a session, as indexed by the difference in trials with and without CR.

Climbing fibers provide essential instructive signals for associative learning.

Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber (CF) inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. In the present study we used cell-type-specific perturbations of various cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning in mice. Our findings reveal that, although optogenetic stimulation of either CFs or Purkinje cells can drive learning under some conditions, even subtle reductions in CF signaling completely block learning to natural stimuli. We conclude that CFs and corresponding Purkinje cell complex spike events provide essential instructive signals for associative cerebellar learning.

Retracción palpebral en ojo contralateral: poscirugía de ptosis palpebral / Eyelid retraction in contralateral eye: eyelid ptosis postsurgery

Se presenta a una paciente con antecedentes de tratamiento quirúrgico hace dos años para la elevación del párpado superior por ptosis palpebral derecha, quien exhibía retracción palpebral izquierda, aparentemente secundaria a la cirugía de ptosis, que dejaba expuesta ampolla de filtración por trabeculectomía previa, la cual le causaba molestias permanentes y la limitaba a realizar sus actividades diarias, cuadro clínico que se constató a las 24 horas en el posoperatorio. Se remitió a nuestro Centro y se discutió en colectivo. Se decidió realizar nueva cirugía de la ptosis derecha y tarsorrafia izquierda, con lo que se logró corrección de la ptosis derecha y recubrimiento de la bula de filtración del ojo izquierdo. Se mantuvo asintomática hasta los 3 meses del posoperatorio en que apareció con retracción palpebral izquierda recurrente. Se evaluó nuevamente y se decidió, por la edad de la paciente y los antecedentes de reintervenciones en ambos ojos así como el riesgo de complicación de cirugía filtrante, aplicar toxina botulínica en el párpado superior, 3 cc equivalente a 7 U. Con la aplicación de la toxina botulínica se logró la caída del párpado superior izquierdo, lo que permitió cubrir la bula de filtración, y desapareció la sintomatología. La toxina botulínica, a pesar de tener un efecto transitorio, constituye una buena opción en los pacientes con retracción palpebral en quienes otros tratamientos no han sido satisfactorios(AU)

A female patient with a history of surgical treatment for eyelid ptosis is reported. Two years before, she was operated on for correction of upper eyelid due to right eyelid ptosis, but now she presented left eyelid retraction, apparently secondary to ptosis surgery, which exposed a filtering bleb caused by previous traveculectomy. This condition caused permanent disturbances and restricted her daily activities, a clinical picture that was confirmed 24 hours after the surgery. She was sent to our center and the case was collectively discussed. It was decided to perform a new surgery to correct right ptosis and left tarsoraphy. The result was correction of right ptosis and coating of the filtering bleb in the left eye. She remained asymptomatic for three months in the postoperative period, but recurrent left eyelid retraction occurred. She was re-evaluated and it was decided, due to the patient´s age and the history of resurgeries in both eyes in addition to the risk of filtering surgery complications, to apply botulinum toxin in the upper eyelid at a dose of 3cc equal to 7 U. The administration of botulinum toxin allows fall of the left upper eyelid and covering of the filtering bleb, thus symptoms disappeared. Despite its transient effect, botulinum toxic is a good option for patients with eyelid retraction who had not achieved satisfactory results with other types of treatment(AU)

Reinstatement of short-latency responses after asymptotic Pavlovian conditioning training by the presentation of an extraneous stimulus

The purpose of this study was to examine whether the progressive disappearance of short-latency conditioned responses, or inhibition of delay, observed in Pavlovian conditioning with long inter-stimulus intervals, could be reverted by the presentation of a novel stimulus. In one experiment, two groups of rabbits received extensive training with a short (250 ms) or a long (1500 ms) tone that overlapped and terminated with a periorbital shock unconditioned stimulus. After training, the presentation of an extraneous stimulus prior to tone onset produced a reinstatement of short latency CRs in the group trained with the long CS, but did not affect CR latency in the group trained with the short CS. This finding is consistent with Pavlov's (1927) view that conditioning with long conditioned stimuli involves the acquisition of response tendencies in the early portion of the stimulus that are subsequently suppressed by the development of an inhibitory process.

Corrección funcional y estética de blefaroptosis y telecanto traumático unilateral / Functional and aesthetic correction of traumatic unilateral blepharoptosis and telecant

La reconstrucción funcional y estética del párpado traumático requiere el conocimiento anatómico y funcional de sus partes. El análisis semiológico previo permite reconocer la causa de la ptosis y poder planificar el acto quirúrgico...La reconstrucción palpebral traumática con alteración de todas las unidades requiere la individualización de cada unidad anatómica. La exploración minuciosa, permite detectar la causa y poder restablecer con diferentes procedimientos la función natural palpebral. El caso clínico-quirúrgico presentado demuestra que restableciendo los parámetros anátomos-funcionales de la región se puede ofrecer un tratamiento tanto reparador como estético.

The functional and aesthetic reconstruction of the traumatic eyelid requires the precise knowledge of the periorbital anatomy. A previous complete semiologic exam helps to clarify the ethiology of ptosis and planning the surgical procedure...The patient recovers the eyelid function and presents a very good post op evolution with a good functional and aesthetic result. The surgical aproach detects the etiology and with different techniques provides a natural eyelid function. This clincal case shows that we can offer a direct repair and aesthetic solution by restablishing the anatomic-functional periorbital units.

Triquiasis palpebral como secuela de algunas enfermedades dermatológicas y oftalmológicas: resolución ambulatoria con criocirugía: nuestra experiencia / Palpebral trichiasis as sequelae of some dermatological and oftalmological diseases: ambuatory procedure with cryosurgery: our experience

La triquiasis es una orientación anómala interna adquirida de una o más pestañas, que puede producir, en casos severos, úlceras de córnea. A menudo se le asocia con tracoma y blefaritis crónica estafilocóccica o posterior a cirugías oftalmológicas. El tratamiento de la enfermedad es difícil, pero existen varias opciones disponibles: la cirugía convencional (blefaroplastia) o la depilación simple o por diferentes métodos: electrodepilación, radiofrecuencia, Láser Argón y criocirugía. Presentamos un trabajo donde se utilizó la criocirugía como tratamiento para diez casos de triquiasis, con excelentes resultados

Holoprosencefalia asociada a displasia fronto nasal: a propósito de un caso de diagnóstico prenatal / Holoprosencephaly associate to fronto nasal dysolasia: case of antenatal diagnosis

Presentamos un caso de diagnóstico prenatal por ultrasonido, de holoprosencefalia sublobar con displasia fronto nasal. La existencia de 2 proboscis con narina única cada una simuló una etmocefalia. El diagnóstico diferencial definitivo es por hipertelorismo, narinas separadas, junto con las imágenes de monoventrículo en ultrasonido y en tomografía axial computarizada. El veruna sola proboscis sin buscar la opuesta simuló una holoprosencefalia sublobar. El requerimiento de autopsia fue negado. Esta asociación de holoprosencefalia con displasia fronto nasal no había sido descrita en la literatura venezolana

Colgajo miocutáneo de dorso nasal para reconstrucción del canto interno palpebral / Mycutaneous dorsal nasal flap for medial eyelid canthal repair

El área cantal interna palpebral es una zona de dificil resolución ante un defecto de continuidad. La resección con bordes oncológicos de las lesiones, y la realización de un procedimiento quirúrgico que brinde buenos resultados funcionales y estéticos es primordial. Se presenta una nueva técnica para la resolución de los defectos de continuidad en el área del canto interno palpebral para lesiones menores de 4 cm2 que no afecten al tendón del canto interno o al sistema de drenaje lagrimal. Dicho procedimiento está basado en el principio del colgajo miocutáneo con diseño V-Y de dorso nasal. Las ventajas de dicha técnica están determinadas por el cierre inmediato en un sólo acto quirúrgico, aporte de piel de similar textura y calidad, bajo índice de complicaciones, cierre sin tensión y excelente resultado estético

Reconstrucción funcional del párpado inferior / Functional reconstruction of lower eyelid

Este trabajo presenta una nueva técnica, descrita por Hinderer, mediante la cual recuperamos la función palpebral inferior. Nuestras exigencias, abarcan 13 pacientes, en todos ellos llenamos las espectativas que nos propusimos. Consideramos que la función del párpado inferior, no solo es de importancia para la visión, sino tambien cumple un papel estético en la expresión humana de ahí que desde hace muchos años atrás, su estudio fue encausado por numerosos autores.

Contribución a la operación de las bolsas palpebrales. Variante técnica de Rafael de la Plaza y José M. Arroyo / De la Plaza and Arroyo's blepharoplasty technique variant

El autor hace un aporte de su experiencia con la técnica de R. de la Plaza y Arroyo en la blefaroplastía, creando un muro de contención al sufurar la FCP con el periostio orbitario luego de reintroducir lagrasa periocular