Altered norepinephrine transmission after spatial learning impairs sleep-mediated memory consolidation in rats.

The therapeutic use of noradrenergic drugs makes the evaluation of their effects on cognition of high priority. Norepinephrine (NE) is an important neuromodulator for a variety of cognitive processes and may importantly contribute to sleep-mediated memory consolidation. The NE transmission fluctuates with the behavioral and/or brain state and influences associated neural activity. Here, we assessed the effects of altered NE transmission after learning of a hippocampal-dependent task on neural activity and spatial memory in adult male rats. We administered clonidine (0.05 mg/kg, i.p.; n = 12 rats) or propranolol (10 mg/kg, i.p.; n = 11) after each of seven daily learning sessions on an 8-arm radial maze. Compared to the saline group (n = 9), the drug-treated rats showed lower learning rates. To assess the effects of drugs on cortical and hippocampal activity, we recorded prefrontal EEG and local field potentials from the CA1 subfield of the dorsal hippocampus for 2 h after each learning session or drug administration. Both drugs significantly reduced the number of hippocampal ripples for at least 2 h. An EEG-based sleep scoring revealed that clonidine made the sleep onset faster while prolonging quiet wakefulness. Propranolol increased active wakefulness at the expense of non-rapid eye movement (NREM) sleep. Clonidine reduced the occurrence of slow oscillations (SO) and sleep spindles during NREM sleep and altered the temporal coupling between SO and sleep spindles. Thus, pharmacological alteration of NE transmission produced a suboptimal brain state for memory consolidation. Our results suggest that the post-learning NE contributes to the efficiency of hippocampal-cortical communication underlying memory consolidation.

Modulation of Prefrontal Cortex Slow Oscillations by Phasic Activation of the Locus Coeruleus.

Cortical slow rhythmic activity, a hallmark of deep sleep, is observed under urethane anesthesia. Synchronized fluctuations of the membrane excitability of a large neuronal population are reflected in the extracellular Local Field Potential (LFP), as high-amplitude slow (∼1 Hz) oscillations (SO). The SO-phase indicates the presence (Up) or absence (Down) of neuronal spiking. The cortical state is controlled by the input from thalamic and neuromodulatory centers, including the brainstem noradrenergic nucleus Locus Coeruleus (LC). The bidirectional modulation of neuronal excitability by noradrenaline (NA) is well known. We have previously shown that LC phasic activation caused transient excitability increase in the medial prefrontal cortex (mPFC). In the present study, we characterized the effect of LC phasic activation on the prefrontal population dynamics at a temporal scale of a single SO cycle. We applied short (0.2 s) trains of electric pulses (0.02-0.05 mA at 20-50 Hz) to the LC cell bodies and monitored a broadband (0.1 Hz-8 kHz) mPFC LFP in urethane-anesthetized rats. The direct electrical stimulation of LC (LC-DES), applied during the Up-phase, enhanced the firing probability in the mPFC by ∼20% and substantially prolonged Up-states in 56% of trials. The LC-DES applied during Down-phase caused a rapid Down-to-Up transition in 81.5% of trials. The LC-DES was more effective at a higher frequency, but not at a higher current. Our results suggest that transient NA release, coupled to SO, may promote synaptic plasticity and memory consolidation by sustaining a depolarized state in the mPFC neurons.

Derechos de Niños, Niñas y Adolescentes en el contexto de la pandemia de COVID-19 / Rights of Children and Adolescents in the context of the COVID-19 pandemic

Webinar N° 35, realizado el 19 de noviembre de 2020 por el ORAS-CONHU en coordinación con Voces Ciudadanas - Perú. Se logró establecer un dialogo intergeneracional con actores diversos, relevantes desde el rol que desempeñan en el enfrentamiento de la pandemia producida por COVID-19 con el objetivo de analizar sobre los avances y desafíos que enfrenta la región en cuanto a los derechos de niños, niñas y adolescentes establecidos en la Convención sobre los Derechos del Niño. El encuentro contó con la representación de jóvenes de Ecuador y Perú, el Presidente del Comité por los Derechos del Niño de las Naciones Unidas y el Coordinador de Derechos de la Asociación Latinoamericana de Pediatría.

Temporal associations between sleep slow oscillations, spindles and ripples.

The systems consolidation of memory during slow-wave sleep (SWS) is thought to rely on a dialogue between hippocampus and neocortex that is regulated by an interaction between neocortical slow oscillations (SOs), thalamic spindles and hippocampal ripples. Here, we examined the occurrence rates of and the temporal relationships between these oscillatory events in rats, to identify the possible direction of interaction between these events under natural conditions. To facilitate comparisons with findings in humans, we combined frontal and parietal surface EEG with local field potential (LFP) recordings in medial prefrontal cortex (mPFC) and dorsal hippocampus (dHC). Consistent with a top-down driving influence, EEG SO upstates were associated with an increase in spindles and hippocampal ripples. This increase was missing in SO upstates identified in mPFC recordings. Ripples in dHC recordings always followed the onset of spindles consistent with spindles timing ripple occurrence. Comparing ripple activity during co-occurring SO-spindle events with that during isolated SOs or spindles, suggested that ripple dynamics during SO-spindle events are mainly determined by the spindle, with only the SO downstate providing a global inhibitory signal to both thalamus and hippocampus. As to bottom-up influences, we found an increase in hippocampal ripples ~200 ms before the SO downstate, but no similar increase of spindles preceding SO downstates. Overall, the temporal pattern is consistent with a loop-like scenario where, top-down, SOs can trigger thalamic spindles which, in turn, regulate the occurrence of hippocampal ripples. Ripples, bottom-up, and independent from thalamic spindles, can contribute to the emergence of neocortical SOs.

Parallel organization of the avian sensorimotor arcopallium: Tectofugal visual pathway in the pigeon (Columba livia).

The sensory-motor division of the avian arcopallium receives parallel inputs from primary and high-order pallial areas of sensory and vocal control pathways, and sends a prominent descending projection to ascending and premotor, subpallial stages of these pathways. While this organization is well established for the auditory and trigeminal systems, the arcopallial subdivision related to the tectofugal visual system and its descending projection to the optic tectum (TeO) has been less investigated. In this study, we charted the arcopallial area displaying tectofugal visual responses and by injecting neural tracers, we traced its connectional anatomy. We found visual motion-sensitive responses in a central region of the dorsal (AD) and intermediate (AI) arcopallium, in between previously described auditory and trigeminal zones. Blocking the ascending tectofugal sensory output, canceled these visual responses in the arcopallium, verifying their tectofugal origin. Injecting PHA-L into the visual, but not into the auditory AI, revealed a massive projection to tectal layer 13 and other tectal related areas, sparing auditory, and trigeminal ones. Conversely, CTB injections restricted to TeO retrogradely labeled neurons confined to the visual AI. These results show that the AI zone receiving tectofugal inputs sends top-down modulations specifically directed to tectal targets, just like the auditory and trigeminal AI zones project back to their respective subpallial sensory and premotor areas, as found by previous studies. Therefore, the arcopallium seems to be organized in a parallel fashion, such that in spite of expected cross-modal integration, the different sensory-motor loops run through separate subdivisions of this structure.

Sleep stage dynamics in neocortex and hippocampus.

Mammalian sleep comprises the stages of slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Additionally, a transition state is often discriminated which in rodents is termed intermediate stage (IS). Although these sleep stages are thought of as unitary phenomena affecting the whole brain in a congruent fashion, recent findings have suggested that sleep stages can also appear locally restricted to specific networks and regions. Here, we compared in rats sleep stages and their transitions between neocortex and hippocampus. We simultaneously recorded the electroencephalogram (EEG) from skull electrodes over frontal and parietal cortex and the local field potential (LFP) from the medial prefrontal cortex and dorsal hippocampus. Results indicate a high congruence in the occurrence of sleep and SWS (>96.5%) at the different recording sites. Congruence was lower for REM sleep (>87%) and lowest for IS (<36.5%). Incongruences occurring at sleep stage transitions were most pronounced for REM sleep which in 36.6 per cent of all epochs started earlier in hippocampal LFP recordings than in the other recordings, with an average interval of 17.2 ± 1.1 s between REM onset in the hippocampal LFP and the parietal EEG (p < 0.001). Earlier REM onset in the hippocampus was paralleled by a decrease in muscle tone, another hallmark of REM sleep. These findings indicate a region-specific regulation of REM sleep which has clear implications not only for our understanding of the organization of sleep, but possibly also for the functions, e.g. in memory formation, that have been associated with REM sleep.

Midline thalamic neurons are differentially engaged during hippocampus network oscillations.

The midline thalamus is reciprocally connected with the medial temporal lobe, where neural circuitry essential for spatial navigation and memory formation resides. Yet, little information is available on the dynamic relationship between activity patterns in the midline thalamus and medial temporal lobe. Here, we report on the functional heterogeneity of anatomically-identified thalamic neurons and the differential modulation of their activity with respect to dorsal hippocampal rhythms in the anesthetized mouse. Midline thalamic neurons expressing the calcium-binding protein calretinin, irrespective of their selective co-expression of calbindin, discharged at overall low levels, did not increase their activity during hippocampal theta oscillations, and their firing rates were inhibited during hippocampal sharp wave-ripples. Conversely, thalamic neurons lacking calretinin discharged at higher rates, increased their activity during hippocampal theta waves, but remained unaffected during sharp wave-ripples. Our results indicate that the midline thalamic system comprises at least two different classes of thalamic projection neuron, which can be partly defined by their differential engagement by hippocampal pathways during specific network oscillations that accompany distinct behavioral contexts. Thus, different midline thalamic neuronal populations might be selectively recruited to support distinct stages of memory processing, consistent with the thalamus being pivotal in the dialogue of cortical circuits.

Attentional capture? Synchronized feedback signals from the isthmi boost retinal signals to higher visual areas.

When a salient object in the visual field captures attention, the neural representation of that object is enhanced at the expense of competing stimuli. How neural activity evoked by a salient stimulus evolves to take precedence over the neural activity evoked by other stimuli is a matter of intensive investigation. Here, we describe in pigeons (Columba livia) how retinal inputs to the optic tectum (TeO, superior colliculus in mammals), triggered by moving stimuli, are selectively relayed on to the rotundus (Rt, caudal pulvinar) in the thalamus, and to its pallial target, the entopallium (E, extrastriate cortex). We show that two satellite nuclei of the TeO, the nucleus isthmi parvocelullaris (Ipc) and isthmi semilunaris (SLu), send synchronized feedback signals across tectal layers. Preventing the feedback from Ipc but not from SLu to a tectal location suppresses visual responses to moving stimuli from the corresponding region of visual space in all Rt subdivisions. In addition, the bursting feedback from the Ipc imprints a bursting rhythm on the visual signals, such that the visual responses of the Rt and the E acquire a bursting modulation significantly synchronized to the feedback from Ipc. As the Ipc feedback signals are selected by competitive interactions, the visual responses within the receptive fields in the Rt tend to synchronize with the tectal location receiving the "winning" feedback from Ipc. We propose that this selective transmission of afferent activity combined with the cross-regional synchronization of the areas involved represents a bottom-up mechanism by which salient stimuli capture attention.

Lack of efficacy of curcumin on neurodegeneration in the mouse model of Niemann-Pick C1.

In order to determine the efficacy of curcumin in ameliorating symptoms of neurodegeneration in the mouse model of Niemann-Pick C1, a variety of formulations and dosages of curcumin, one comparable to one previously reported as efficacious, were provided orally to Npc1(-/-)mice. Plasma levels of curcumin, survival, tests of motor performance, and memory (in some cases) were performed. We found variable, but mild, increases in survival (1.5% to 18%). The greatest increased survival occurred with the highest dose (which was unformulated) while the control for the lipidated formulation (containing phosphatidylcholine and stearic acid) had an equivalent impact and other formulations, while not significantly increased, are also not statistically different in effect from the highest dose. We conclude that curcumin is not a highly efficacious treatment for neurodegeneration in Npc1(-/-) mice. Phosphatidylcholine and stearic acid should be studied further.

Derechos de los niños hospitalizados en Santafé de Bogotá: situación y perspectivas / Hospitalized childrenïs rights in Santafe de Bogota: situation and perspectives

La hospitalización de los niños tiene efectos emocionales -muchas veces negativos- sobre éstos y sus familias, por lo que deben introducirse medidas especiales para humanizar la atención que se les brinda. Este libro presenta los resultados de una investigación que buscaba establecer hasta qué punto los derechos de los niños son tenidos en cuenta en las instituciones de salud y se reflejan en el trato a las niñas y niños, en la disposición de los espacios físicos, en las actitudes de los funcionarios y usuarios de los servicios, en los procesos de información y comunicación y, en general, en las iniciativas que se emprenden con el fin de mejorar la calidad de los servicios hospitalarios. Con el fin de contribuír a mejorar la atención prestada además de analizar la situación de los niños en los hospitales, este libro formula recomendaciones detalladas para que los funcionarios, el personal asistencia y los padres de familia contribuyan a que los hospitales se conviertan en instituciones amigas de los niños, donde se tengan en cuenta sus derechos

Análisis de la situación de los derechos de los niños hospitalizados / Analysis of the situation of the rights of hospitalized children

Investigación por demanda dentro de la línea de salud pública que tuvo como objetivo general, establecer hasta qué punto los derechos de los niños han penetrado realmente el ambiente hospitalario para reflejarse en la disposición y diseño de los espacios físicos, en el trato humano, en las actitudes de los funcionarios y usuarios de los servicios, en los procesos de comunicación e información y, en general, en las distintas iniciativas que se emprenden con el fin de mejorar la calidad de los servicios hospitalarios. Entre noviembre de 1997 y febrero de 1998, la Secretaría Distrital de Salud y "Defensa de los Niños Internacional, DNI- Colombia", estuvieron comprometidos en la realización de un estudio sobre la vigencia de los derechos de los niños en los departamentos de pediatría de los hospitales de segundo y tercer nivel adscritos a la Secretaría Distrital de Salud. El interés por realizar la investigación surgió del conocimiento sobre los electos emocionales negativos que la hospitalización puede tener en los niños y sus familias, si no se introducen medidas especiales para humanizar la atención que se les brinda. El marco de referencia de este trabajo fue la Convención internacional de los derechos del niño que es el tratado internacional más significativo que se haya elaborado con el objetivo de aunar esfuerzos en la búsqueda de mejores condiciones de vida y bienestar para los niños y las niñas del mundo. En ella se encuentra implícita toda una ética basada en el reconocimiento del niño como ser humano con necesidades propias determinadas por el momento específico de su desarrollo y como sujeto activo y participante en la realización de sus derechos.

The general objective of this public health research was to establish to what extent children's rights have really penetrated the hospital environment to be reflected in the layout and design of physical spaces, in human treatment, in the attitudes of officials and users of services, in communication and information processes and, in general, in the different initiatives undertaken to improve the quality of hospital services. Between November 1997 and February 1998, the District Health Secretariat and "Defensa de los Niños Internacional, DNI-Colombia" were engaged in conducting a study on the enforcement of children's rights in the pediatric departments of the second and third level hospitals attached to the District Health Secretariat. The interest in conducting the research arose from the knowledge of the negative emotional effects that hospitalization can have on children and their families, if special measures are not introduced to humanize the care provided to them. The frame of reference for this work was the International Convention on the Rights of the Child, which is the most significant international treaty ever drafted with the aim of joining efforts in the search for better living conditions and well-being for the world's children. Implicit in it is a whole ethic based on the recognition of the child as a human being with his or her own needs determined by the specific moment of his or her development and as an active subject and participant in the realization of his or her rights.