Total sleep deprivation impairs fear memory retrieval by decreasing the basolateral amygdala activity.

It is well known that sleep deprivation impairs fear memory processes, but little is known about the underlying mechanisms or circuits. The aim of this study was to evaluate the effects of total sleep deprivation (24 h) on contextual fear memory acquisition, consolidation, and retrieval, as well as c-Fos activity in the hippocampus and amygdala. Fear memory recall was associated with an increase in the number of c-Fos-positive cells in the hippocampal CA1 and CA3 regions and the basolateral amygdala (BLA). Total sleep deprivation before to the acquisition and during consolidation of memory impaired retrieval and blocked the associated c-Fos activity in the hippocampus and amygdala. In contrast, total sleep deprivation before memory recall also impaired retrieval, but selectively prevented the increase of c-Fos activity in the amygdala (but not in the hippocampus). Our data indicate that sleep is essential not only for acquisition and consolidation but also for the retrieval of fear memories. They also suggest a differential susceptibility of specific memory-related neural circuits (hippocampus and BLA) to the absence of sleep.

Cannabinoid type-1 receptors in the paraventricular nucleus of the hypothalamus inhibit stimulated food intake.

Cannabinoid receptor type 1 (CB1)-dependent signaling in the brain is known to modulate food intake. Recent evidence has actually shown that CB1 can both inhibit and stimulate food intake in fasting/refeeding conditions, depending on the specific neuronal circuits involved. However, the exact brain sites where this bimodal control is exerted and the underlying neurobiological mechanisms are not fully understood yet. Using pharmacological and electrophysiological approaches, we show that local CB1 blockade in the paraventricular nucleus of the hypothalamus (PVN) increases fasting-induced hyperphagia in rats. Furthermore, local CB1 blockade in the PVN also increases the orexigenic effect of the gut hormone ghrelin in animals fed ad libitum. At the electrophysiological level, CB1 blockade in slices containing the PVN potentiates the decrease of the activity of PVN neurons induced by long-term application of ghrelin. Hence, the PVN is (one of) the site(s) where signals associated with the body's energy status determine the direction of the effects of endocannabinoid signaling on food intake.

Pharmacological enhancement of the endocannabinoid system in the nucleus accumbens shell stimulates food intake and increases c-Fos expression in the hypothalamus.

BACKGROUND AND PURPOSE: Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei. EXPERIMENTAL APPROACH: Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections. KEY RESULTS: Our results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB(1) antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT. CONCLUSIONS AND IMPLICATIONS: These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.

De la restauración neuronal a la reorganización de los circuitos neuronales: una aproximación a las funciones del sueño / From neuronal recovery to the reorganisation of neuronal circuits: a review of the functions of sleep

Objetivo. Analizar datos y conceptos que se han generadoen torno a una de las funciones propuestas para el sueño: la restauraciónneuronal. Desarrollo. El sueño es un estado de concienciadiferente de la vigilia. Los mamíferos invierten una buena partede su vida en dormir; por ejemplo, los humanos dormimos una terceraparte de nuestra vida, pero ¿para qué invertir tanto tiempo enun estado donde perdemos contacto con el entorno?, ¿qué pasaríasi no durmiéramos? La privación de sueño total altera procesoscognitivos, como la memoria o la atención; si esta privación seprolonga, el sujeto se deteriora y muere. Se ha propuesto que elsueño sirve para restaurar a los organismos del desgaste ocurridodurante la vigilia y, dado que los primeros efectos de la ausenciade sueño se observan en procesos que dependen directamente delcerebro, se ha sugerido que la restauración neuronal es su principalobjetivo. En este trabajo se analizan algunos estudios sobre losefectos de la privación de sueño total en humanos y ratas, así comola relación entre el sueño y el sistema de las neurotrofinas, el cualpromueve la supervivencia y la restauración neuronal. Finalmente,se discuten teorías recientes sobre la función del sueño. Conclusiones.La restauración de las neuronas no es el fin último del sueño,sino mantener y reorganizar los circuitos neuronales, incluyendo laneoformación de sinapsis, que permiten modificar redes neuronalesexistentes, por efecto de la experiencia, y todo esto para el adecuadofuncionamiento del cerebro y su adaptación al ambiente

Aim. To analyse the data and concepts that have been produced in relation to one of the functions that have beensuggested for sleep, namely, neuronal recovery. Development. Sleep is a state of consciousness that is different to that ofarousal. Mammals devote an important part of their lives to sleeping; for example, as humans, we sleep for a third of our lives,but why do we spend so much time in a state where we lose contact with our surroundings? What would happen if we didn’tsleep? Total sleep deprivation alters cognitive processes such as memory or attention, and if this deprivation is prolonged, theindividual deteriorates and dies. It has been suggested that sleep provides the organism with time to recover from the wear andtear that occurs during the waking state and, given that the first effects of the absence of sleep are seen to affect processes thatare directly dependent on the brain, it has been claimed that its main purpose is to allow neuronal recovery. In this work weanalyse some of the studies on the effects of total sleep deprivation in humans and rats, as well as the relationship betweensleep and the neurotrophin system, which promotes neuronal survival and recovery. Finally, the latest theories about thefunction of sleep are discussed. Conclusions. Neuron recovery is not the ultimate purpose of sleep; rather it is to allow formaintenance and reorganisation of neuronal circuits, including new synapse formation, which enables existing neuronalnetworks to be modified by the effect of experience, and all this makes it possible for the brain to work properly and to adaptitself to the environment

[From neuronal recovery to the reorganisation of neuronal circuits: a review of the functions of sleep]. / De la restauración neuronal a la reorganización de los circuitos neuronales: una aproximación a las funciones del sueño.

AIM: To analyse the data and concepts that have been produced in relation to one of the functions that have been suggested for sleep, namely, neuronal recovery. DEVELOPMENT: Sleep is a state of consciousness that is different to that of arousal. Mammals devote an important part of their lives to sleeping; for example, as humans, we sleep for a third of our lives, but why do we spend so much time in a state where we lose contact with our surroundings? What would happen if we didn't sleep? Total sleep deprivation alters cognitive processes such as memory or attention, and if this deprivation is prolonged, the individual deteriorates and dies. It has been suggested that sleep provides the organism with time to recover from the wear and tear that occurs during the waking state and, given that the first effects of the absence of sleep are seen to affect processes that are directly dependent on the brain, it has been claimed that its main purpose is to allow neuronal recovery. In this work we analyse some of the studies on the effects of total sleep deprivation in humans and rats, as well as the relationship between sleep and the neurotrophin system, which promotes neuronal survival and recovery. Finally, the latest theories about the function of sleep are discussed. CONCLUSIONS: Neuron recovery is not the ultimate purpose of sleep; rather it is to allow for maintenance and reorganisation of neuronal circuits, including new synapse formation, which enables existing neuronal networks to be modified by the effect of experience, and all this makes it possible for the brain to work properly and to adapt itself to the environment.