Hypothalamic hypocretinergic/orexinergic neurons projecting to the oral pontine rapid eye movement sleep inducing site in the cat.

The cat ventral oral pontine reticular nucleus (vRPO) is responsible for the generation and maintenance of rapid eye movement (REM) sleep. Hypothalamic neurons containing the peptide hypocretin-1 (also called orexin-A) which will be herewith defined as orexinergic (Orx) neurons, occupy a pre-eminent place in the integration and stabilization of arousal networks as well as in the physiopathology of narcolepsy/cataplexy. In the previous investigations, low-volume and dose microinjections of hypocretin-1 in cat vRPO produced a specific and significant suppression of REM sleep.

Functional Anatomy of Non-REM Sleep.

The state of non-REM sleep (NREM), or slow wave sleep, is associated with a synchronized EEG pattern in which sleep spindles and/or K complexes and high-voltage slow wave activity (SWA) can be recorded over the entire cortical surface. In humans, NREM is subdivided into stages 2 and 3-4 (presently named N3) depending on the proportions of each of these polygraphic events. NREM is necessary for normal physical and intellectual performance and behavior.

[The "thalamus-cerebral cortex" anatomofunctinal unit in the waking state].

The "thalamus-cerebral cortex unit" is awakened by the "ascending reticular activating system", which originates from neuronal groups located within the brainstem, hypothalamus and basal forebrain, all of which use known neurotransmitters and whose neurons are more active during wakefulness than during the other behavioral states. Synergies among several of these neurotransmitters are necessary to generate the cortical and thalamic activation that is characteristic of wakefulness. During the wakefulness the complex interrelated structures of the "thalamus-cerebral cortex unit" provide the pathway that interconnects cortex and thalamus and allow the modulation, and organization of the mechanisms producing the adequate activity of the different thalamic and cortical formations and the organization of cognitive processes and performance of appropriate behavioral responses.

Functional anatomy of the sleep-wakefulness cycle: wakefulness.

Sleep is a necessary, diverse, periodic, and an active condition circadian and homeostatically regulated and precisely meshed with waking time into the sleep-wakefulness cycle (SWC). Photic retinal stimulation modulates the suprachiasmatic nucleus, which acts as the pacemaker for SWC rhythmicity. Both the light period and social cues adjust the internal clock, making the SWC a circadian, 24-h period in the adult human.

[REM sleep modulation by non-GABAergic neurons of the hypothalamus and basal forebrain].

The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. The aim of the present revision is to map, using the results described in previous publications of our group, the local origin of the basal forebrain and hypothalamus non-GABAergic projections to the vRPO, and specially the contribution of the hypothalamic neurons positive to hypocretin/orexin (H/O) peptides.

Ultrastructural characterization of relationship between serotonergic and GABAergic structures in the ventral part of the oral pontine reticular nucleus.

The ventral part of the oral pontine reticular nucleus (vRPO) is involved in the generation and maintenance of rapid eye movement (REM) sleep. Both GABAergic and serotonergic neurotransmission have been implicated in the control of the sleep-wakefulness cycle. Nevertheless, the synaptic organization of serotonergic terminals in the vRPO has not yet been characterized.

Kainic acid intraocular injections during the postnatal critical period induce plastic changes in the visual system.

Changes in the retino-collicular projection and in the number of optic nerve (ON) axons in adult rats were analyzed after partial loss of retinal ganglion cells (RGCs), induced by intravitreal injections of kainic acid (KA) on postnatal days 2-3 (P2-P3) or 10-12 (P10-P12). KA injected at P2-P3 decreased the volume of the adult contralateral superior colliculus (SC) and the density of the retino-collicular contralateral projection, but maintained the neonatal pattern in the ipsilateral projection from the un-injected eye. ON axon number was significantly increased in the un-injected eye but decreased in the KA-injected eye.

[Vegetative condition (state) and conscious thought. Reflections scientific neuro and ethics].

Thirty years ago, the study of the brain lesions of a patient who had remained in a coma for eight years, together with my experience on the degree of wakefulness of animals with similar lesions, compelled me to reflecting on the level of consciousness that our patient had. Recent findings from functional magnetic resonance image, that have shown aspects of speech perception, emotional processing, language comprehension and even conscious awareness might be retained in patients who behaviourally meet all of the criteria that define the vegetative state, have allowed me to make new neuroscientists and ethical reflections.

[Origins and first steps of the Spanish Society for Neuroscience].

I recall the background, the environment, the people and the events that led to the birth of the Spanish Society for Neuroscience (SENC) and remember how and why the multidisciplinary Neurobiology teachers at the Medical School of the Universidad Autónoma de Madrid decided to organize the First Meeting of Spanish Neurobiologists in 1979. Our principal aim was to promote Neuroscience research in Spain. For this was necessary: to know each other, support each other and organize and set up a modern and solid framework for training young researchers in Neuroscience.

Sleep-wakefulness effects after microinjections of hypocretin 1 (orexin A) in cholinoceptive areas of the cat oral pontine tegmentum.

Hypocretinergic/orexinergic neurons, which are known to be implicated in narcolepsy, project to the pontine tegmentum areas involved in the control of rapid eye movement (REM) sleep. Here, we report the effects on sleep-wakefulness produced by low-volume microinjections of hypocretin (Hcrt)1 (20-30 nL, 100, 500 and 1000 microm) and carbachol (20-30 nL, 0.1 m) delivered in two areas of the oral pontine tegmentum of free-moving cats with electrodes for chronic sleep recordings: in the dorsal oral pontine tegmentum (DOPT) and in the ventral part of the oral pontine reticular nucleus (vRPO).

GABAergic and non-GABAergic thalamic, hypothalamic and basal forebrain projections to the ventral oral pontine reticular nucleus: their implication in REM sleep modulation.

The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. Some of these connections utilize the inhibitory neurotransmitter GABA.

[Modulation by the GABA of the ventro-oral-pontine reticular REM sleep-inducing neurons].

From a multidisciplinary study in our laboratory we have compiled numerous findings on the role played by the inhibitory neurotransmitter GABA in the ventral part of the oral pontine reticular nucleus (vRPO), REM sleep induction and maintenance brainstem structure. Functional GABA in the vRPO is located in a few small and scattered neuronal bodies, and in an abundant number of synaptic terminals: 30% of all synaptic terminals in vRPO are GABAergic. These terminals form inhibitory, symmetric synapses on the soma and different segments of the dendritic tree of the vRPO neurons, mainly in those of large diameter.

GABAergic structures in the ventral part of the oral pontine reticular nucleus: An ultrastructural immunogold analysis.

GABA mediates inhibitory effects in neurons of the ventral part of the oral pontine reticular nucleus (vRPO). Evidence increasingly suggests that GABA plays an important role in the modulation of rapid eye movement (REM) sleep generation in the cat vRPO. Here, we investigate the anatomical substrate of this modulation using GABA immunocytochemistry.

[The biography of a neuron].

A summary review of current concepts regarding the major events in the long life cycle (the "biography") of a typical human brain neuron, and the main cellular and molecular mechanisms involved, is provided. Once born in the embryo, neurons never undergo cell division: Their differentiated phenotype, which includes the multiple neuronal networks that each cell establishes, is the cumulative result, over years of development, if many cell-autonomous (intrinsic) and intercellular (extrinsic) signaling events that regulate gene expression. The effect of such signals is not just qualitative, but dependent on their precise timing and dosage.

[The orbitofrotal cortex I: anatomy and memory procesing].

The orbitofrontal cortex has extensive tight connections with the medial temporal tobe and medial thalamic structures, which are responsible for memory processing and consolidation. What is more, this cortex is constantly activated in the memory encoding processes. This makes the orbitofrontal cortex a critical region for memory formation.

A quantitative study of the brainstem cholinergic projections to the ventral part of the oral pontine reticular nucleus (REM sleep induction site) in the cat.

The ventral part of the cat oral pontine reticular nucleus (vRPO) is the site in which microinjections of small dose and volume of cholinergic agonists produce long-lasting rapid eye movement sleep with short latency. The present study determined the precise location and proportions of the cholinergic brainstem neuronal population that projects to the vRPO using a double-labeling method that combines the neuronal tracer horseradish peroxidase-wheat germ agglutinin with choline acetyltransferase immunocytochemistry in cats. Our results show that 88.

Projections from the cat posterior lateral hypothalamus to the ventral part of the oral pontine reticular nucleus contain a GABAergic component.

The posterior lateral hypothalamus (PLH) has long been considered crucial to normal wakefulness while the ventral part of the oral pontine reticular nucleus (vRPO) is involved in the generation and maintenance of rapid eye movement (REM) sleep. However, to date, there is no information on the ultrastructure or neurotransmitter content of the hypothalamo-reticular projection. In the present study, we examined the morphology and synaptic organization of PLH terminals in the vRPO using PLH injections of biotinylated dextran amine (BDA) as well as of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP).

[Sleep, learning and memory].

As a subject, "Sleep, Learning and Memory" is quite lively. Many papers have been published on this subject in the last 20 years. However, these papers present major contradictions.

[Adult neurogenesis and stem cells. Functional capacity].

The ability of stem cells to give rise to new neurons in the adult central nervous system is a phenomenon that has raised many hopes. The possible doors opened by the potentiality of these cells in benefit of neurological patients are numerous. But we need more research and facts to avoid raising false expectations.

Brain structures and mechanisms involved in the generation of REM sleep.

This article reviews the central nervous mechanisms involved in the broad network that generates and maintains REM sleep. Experimental investigations have identified the pontine tegmentum as the critical substrate for REM sleep mechanisms. Several pontine structures are involved in the generation of each particular polygraphic event that characterizes REM sleep: desynchronization in the electroencephalogram, theta rhythm in the hippocampus, muscle atonia, pontogeniculooccipital waves and rapid eye movements.

Firing activity and postsynaptic properties of morphologically identified neurons of ventral oral pontine reticular nucleus.

The ventral part of the oral pontine reticular nucleus (vRPO) is an important region for the generation and maintenance of REM sleep. Firing activity and synaptic response properties of morphologically identified vRPO neurons have been investigated in urethane-anaesthetized cats. Extracellular recordings were performed through recording micropipettes and neurons were extracellularly stained with biocytin.

[A new history of basal ganglia and physiopathology of Parkinson's disease].

The author analyzes basic and clinical experimental works of the last forty years and reaches the following conclusions: The motor system is an indivisible entity in which the basal ganglia are a key part. An important link in the history of the basal ganglia is the description by Llamas and Reinoso-Suárez in 1965 of connections from the substantia nigra compacta to the globus pallidus medialis and lateralis, and striatum through extremely thin, diffusely distributed fibers. They also described connections from the ventral tegmental area to the basal forebrain and the cerebral cortex.

[Cajal and neuroscience in the eve of the third millenium].

This is a brief history of the birth of Neuroscience as an independent branch of knowledge. The importance of Cajal's contribution to the structuralization of modern Neuroscience is described. Outstanding contributions to Neuroscience of the last century, particularly the Decade of the Brain, are summarized.