[New concepts in relation to generating and maintaining arousal]. / Nuevos conceptos sobre la generación y el mantenimiento de la vigilia.

INTRODUCTION: First conceived in 1949 by the research conducted by Moruzzi and Magoun, the concept of the ascending reticular activating system (ARAS) played a vital role in understanding the physiology of sleep and arousal, as well as in explaining the pathophysiological bases of diseases characterised by insomnia, hypersomnia or coma. Sixty years after this discovery, advances in our knowledge of the anatomy, electrophysiology and neurochemistry of the pathways involved in the generation and maintenance of arousal have made it necessary to reassess the original concept of ARAS. Nevertheless, in spite of the fact that the pathologies which, in some way or another, affect the state of arousal are common in the daily practice of different medical disciplines, the new physiological concepts in relation to the activating systems (generators of arousal) are not dealt with by a large number of medical practitioners. DEVELOPMENT: This work is a brief update on the activating systems, with special attention given to the concepts that can be applied most readily in order to gain an understanding of the pathophysiology of arousal. CONCLUSIONS: The new concepts about the activating systems are as follows: a) the activating systems are not only to be found in the reticular formation of the brain stem, but also include specific regions of the posterior hypothalamus and the anterior basal brain; b) the activating systems are made up of different neuronal groups that act by means of specific neurotransmitters or neuromodulators; and c) the activating systems generate arousal by direct modification of thalamic and cortical activity.

Effects of electrical stimulation of the vagus nerve on the development of visual habituation in the cat.

The vagus nerve participates in the control and regulation of important autonomous functions, emotional tasks, and neural activity. Electrical vagus nerve stimulation (VNS) is an approved procedure for the treatment of refractory epilepsy in humans. VNS has also been shown to improve mood complaints and cognitive function in both human patients and animals. Thus, the purpose of this study was to analyse and describe the effects of VNS on the development and establishment of sensory habituation and electrographic activity of the visual pathway in freely moving cats. Six cats had implants placed in the optic chiasm (OC), lateral geniculate body (LGB), mesencephalic reticular formation (MRF), primary visual cortex (VC) of the left hemisphere, and left vagus nerve. Immediately after surgery, all cats presented anisocoria and relaxation of the left nictitant membrane. Also showed vegetative-type responses such as myosis, licking, and swallowing during VNS. Animals were then subjected to repeated luminous stimuli at intervals of 1 and 3s to cause habituation. The effect of VNS on the frequency and latency of the habituation episodes and the electrographic changes in the registered brain structures were analysed. Latency analysis showed that VNS delayed the first habituation episode. VNS had transitory effects on the neural activity of the primary visual pathway structures, which caused a small but measurable delay in the establishment of habituation. In conclusion, VNS interferes with the development and establishment of visual habituation, an elementary form of non-associative learning, in freely moving cats.

Forebrain projections to brainstem nuclei involved in the control of mandibular movements in rats.

Mandibular movements occur through the triggering of trigeminal motoneurons. Aberrant movements by orofacial muscles are characteristic of orofacial motor disorders, such as nocturnal bruxism (clenching or grinding of the dentition during sleep). Previous studies have suggested that autonomic changes occur during bruxism episodes. Although it is known that emotional responses increase jaw movement, the brain pathways linking forebrain limbic nuclei and the trigeminal motor nucleus remain unclear. Here we show that neurons in the lateral hypothalamic area, in the central nucleus of the amygdala, and in the parasubthalamic nucleus, project to the trigeminal motor nucleus or to reticular regions around the motor nucleus (Regio h) and in the mesencephalic trigeminal nucleus. We observed orexin co-expression in neurons projecting from the lateral hypothalamic area to the trigeminal motor nucleus. In the central nucleus of the amygdala, neurons projecting to the trigeminal motor nucleus are innervated by corticotrophin-releasing factor immunoreactive fibers. We also observed that the mesencephalic trigeminal nucleus receives dense innervation from orexin and corticotrophin-releasing factor immunoreactive fibers. Therefore, forebrain nuclei related to autonomic control and stress responses might influence the activity of trigeminal motor neurons and consequently play a role in the physiopathology of nocturnal bruxism.

Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat.

We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation. Therefore, the depression of the PAN intraspinal fields produced by autogenetic stimulation described by Rudomin et al. (Exp Brain Res DOI 10.1007/s00221-006-0600-x, 2006) may be ascribed to other mechanisms besides a GABAa PAD. It is suggested that the small or no autogenetic PAD displayed by the examined joint afferents prevents presynaptic filtering of their synaptic actions and preserves the original information generated in the periphery. This could be important for proper adjustment of limb position.

Potential output pathways for agonistic-like responses resulting from the GABA(A) blockade of the torus semicircularis dorsalis in weakly electric fish, Gymnotus carapo.

The purpose of this study is to examine the pathways involved in the electromotor (electric organ discharge interruptions) and skeletomotor responses (defense-like) observed by blockade of GABAergic control of the torus semicircularis dorsalis (TSd) of the awake weakly electric fish Gymnotus carapo, described in a former study. Microinjection of NMDA (5 mM) into the pacemaker nucleus (PM) through a guide cannula previously implanted caused a prolonged interruption of the electric organ discharge (EOD) intermingled with reduction in frequency, similar to that described for TSd GABA(A) blockade, but without noticeable skeletomotor effects. The EOD alterations elicited by bicuculline microinjections (0.245 mM) into the TSd could be blocked or attenuated by a previous microinjection of AP-5 (0.5 mM), an NMDA antagonist, into the PM. Labeled terminals are found in the nucleus electrosensorius (nE) after injection of the biotinylated dextran amine (BDA) tracer into the TSd and into the sublemniscal prepacemaker nucleus (SPPn) subsequent to the tracer injection into the nE. Defense-like responses but not EOD interruptions are observed after microinjections of NMDA (5 mM) into the rhombencephalic reticular formation (RF), where labeled terminals are seen after BDA injection into the TSd and somata are filled after injection of the tracer into the spinal cord. In this last structure, marked fibers are seen subsequent to injection of BDA into the RF. These results suggest that two distinct pathways originate from the torus: one for EOD control, reaching PM through nE and SPPn, and the other one for skeletomotor control reaching premotor reticular neurons. Both paths could be activated by toral GABA(A) blockade.

Analysis of behavior-related excitatory inputs to a central pacemaker nucleus in a weakly electric fish.

Gymnotid electric fish explore their environment and communicate with conspecifics by means of rhythmic electric organ discharges. The neural command for each electric organ discharge arises from activity of a medullary pacemaker nucleus composed of two neuronal types: pacemaker and relay cells. During different behaviors as in courtship, exploration and agonistic interactions, these species display specific electric organ discharge frequency and/or waveform modulations. The neural bases of these modulations have been explained in terms of segregation of inputs to pacemaker or relay cells, as well as differential activation of the glutamate receptors of these cells. One of the most conspicuous electric organ discharge frequency modulations in Gymnotus carapo results from the activation of Mauthner cells, a pair of reticulospinal neurons that are involved in the organization of sensory-evoked escape responses in teleost fish. The activation of Mauthner cells in these animals produces a prolonged increase in electric organ discharge rate, whose neural mechanisms involves the activation of both N-methyl-D-aspartate (NMDA) and metabotropic glutamatergic receptors of pacemaker cells. Here we provide evidence which indicates that pacemaker cells are the only cellular target of the synaptic inputs responsible for the Mauthner cell initiated electric organ discharge modulation at the medullary pacemaker nucleus. Additionally, although pacemaker cells express both NMDA and non-NMDA ionotropic receptors, we found that non-NMDA receptors are not involved in this synaptic action which suggests that NMDA and non-NMDA receptor subtypes are not co-localized at the subsynaptic membrane. NMDA receptor activation of pacemaker cells seems to be an efficient neural strategy to produce long-lasting enhancements of the fish sampling capability during Mauthner cell-initiated motor behaviors.

Electrocortical and behavioral responses elicited by acute electrical stimulation of inferior thalamic peduncle and nucleus reticularis thalami in a patient with major depression disorder.

OBJECTIVE: Our aim was to study electrocortical and behavioral responses elicited by 6, 60 and 3/s stimulation of the inferior thalamic peduncle (ITP) and nucleus reticularis thalami (Re) in a patient with of major depression disorder resistant to psychotherapy, pharmacotherapy and electroconvulsive therapy and candidate to be treated by electrical stimulation of the ITP. METHODS: In this patient, two multicontact electrodes were implanted bilaterally through frontal coronal parasagittal burr-holes with oblique trajectories aiming ITP and Re. Stimulation was performed through externalized systems. Referential scalp electroencephalographic (EEG) recordings were performed and subjective sensations and clinical symptoms reported by patient and changes in responsiveness in single response tasks during stimulation trials were systematically recorded. RESULTS: Unilateral, low (6/s) and high (60/s) frequency stimulation of either ITP or Re produced identical recruiting-like responses or desynchronization-DC shift changes predominant at frontopolar region, bilaterally. Billateral, high intensity 3/s stimulation or either ITP or Re produced electrocortical responses that consisted in generalized 3/s spike-wave complexes predominant at frontopolar, frontocentral and frontotemporal regions. However, while ITP responses were accompanied by all symptoms described for a spontaneous absence attack, Re responses were behaviorly accompanied only by delayed reaction time. CONCLUSION: These data suggests that in humans as in cats, ITP and Re are both part of a non-specific thalamo-orbitofrontal system normally engaged in cortical synchronization, selective attention and sleep. SIGNIFICANCE: Under abnormal conditions, ITP and RE may play a role in the physiopathology of typical absence attacks and depression disorders.

Neuroanatomical approaches of the tectum-reticular pathways and immunohistochemical evidence for serotonin-positive perikarya on neuronal substrates of the superior colliculus and periaqueductal gray matter involved in the elaboration of the defensive behavior and fear-induced analgesia.

Deep layers of the superior colliculus, the dorsal periaqueductal gray matter and the inferior colliculus are midbrain structures involved in the generation of defensive behavior and fear-induced anti-nociception. Local injections of the GABA(A) antagonist bicuculline into these structures have been used to produce this defense reaction. Serotonin is thought to be the main neurotransmitter to modulate such defense reaction in mammals. This study is the first attempt to employ immunohistochemical techniques to locate serotonergic cells in the same midbrain sites from where defense reaction is evoked by chemical stimulation with bicuculline. The blockade of GABA(A) receptors in the neural substrates of the dorsal mesencephalon was followed by vigorous defensive reactions and increased nociceptive thresholds. Light microscopy immunocytochemistry with streptavidin method was used for the localization of the putative cells of defensive behavior with antibodies to serotonin in the rat's midbrain. Neurons positive to serotonin were found in the midbrain sites where defensive reactions were evoked by microinjection of bicuculline. Serotonin was localized to somata and projections of the neural networks of the mesencephalic tectum. Immunohistochemical studies showed that the sites in which neuronal perikarya positive to serotonin were identified in intermediate and deep layers of the superior colliculus, and in the dorsal and ventral columns of the periaqueductal gray matter are the same which were activated during the generation of defense behaviors, such as alertness, freezing, and escape reactions, induced by bicuculline. These findings support the contention that serotonin and GABAergic neurons may act in concert in the modulation of defense reaction in the midbrain tectum. Our neuroanatomical findings indicate a direct neural pathway connecting the dorsal midbrain and monoaminergic nuclei of the descending pain inhibitory system, with profuse synaptic terminals mainly in the pontine reticular formation, gigantocellularis nucleus, and nucleus raphe magnus. The midbrain tectum-gigantocellularis complex and midbrain tectum-nucleus raphe magnus neural pathways may provide an alternative output allowing the organization of the fear-induced anti-nociception by mesencephalic networks.

Descending control of persistent pain: inhibitory or facilitatory?

The periaqueductal gray matter (PAG) and the nucleus raphe magnus and adjacent structures of the rostral ventromedial medulla (RVM), with their projections to the spinal dorsal horn, constitute the "efferent channel" of a pain-control system that "descends" from the brain onto the spinal cord. Considerable evidence has recently emerged regarding participation of this system in persistent pain conditions such as inflammation and neuropathy. Herein, this evidence is reviewed and organized to support the idea that persistent nociception simultaneously triggers descending facilitation and inhibition. In models of inflammation, descending inhibition predominates over facilitation in pain circuits with input from the inflamed tissue, and thus attenuates primary hyperalgesia, while descending facilitation predominates over inhibition in pain circuits with input from neighboring tissues, and thus facilitates secondary hyperalgesia. Both descending facilitation and inhibition mainly stem from RVM. The formalin-induced primary hyperalgesia, although considered a model for inflammation, is mainly facilitated from RVM. Also, formalin-induced secondary hyperalgesia is facilitated by RVM. Again, formalin triggers a concomitant but concealed descending inhibition. The (primary) hyperalgesia and allodynia of the neuropathic syndrome are also facilitated from RVM. Simultaneously, there is an inhibition of secondary neuronal pools that is partly supported from the PAG. Because in all these models of peripheral damage descending facilitation and inhibition are triggered simultaneously, it will be important to elucidate why inhibition predominates in some neuronal pools and facilitation in others. Therapies that enhance descending inhibition and/or attenuate descending facilitation are furthermore an important target for research in the future.

Diffusible signals and fasciculated growth in reticulospinal axon pathfinding in the hindbrain.

We have addressed the control of longitudinal axon pathfinding in the developing hindbrain, including the caudal projections of reticular and raphe neurons. To test potential sources of guidance signals, we assessed axon outgrowth from embryonic rat hindbrain explants cultured in collagen gels at a distance from explants of midbrain-hindbrain boundary (isthmus), caudal hindbrain, or cervical spinal cord. Our results showed that the isthmus inhibited caudally directed axon outgrowth by 80% relative to controls, whereas rostrally directed axon outgrowth was unaffected. Moreover, caudal hindbrain or cervical spinal cord explants did not inhibit caudal axons. Immunohistochemistry for reticular and raphe neuronal markers indicated that the caudal, but not the rostral projections of these neuronal subpopulations were inhibited by isthmic explants. Companion studies in chick embryos showed that, when the hindbrain was surgically separated from the isthmus, caudal reticulospinal axon projections failed to form and that descending pioneer axons of the medial longitudinal fasciculus (MLF) play an important role in the caudal reticulospinal projection. Taken together, these results suggest that diffusible chemorepellent or nonpermissive signals from the isthmus and substrate-anchored signals on the pioneer MLF axons are involved in the caudal direction of reticulospinal projections and might influence other longitudinal axon projections in the brainstem.

Bruxismo y dolor crónico orofacial / Bruxism and chronic orofacial pain

En el estado actual del conocimiento sobre los factores y mecanismos del bruxismo se han ido abandonando las posiciones de la relación causal estrecha entre oclusión y bruxismo, pero sin descartarla como factor a tener en cuenta por ser parte del complejo proceso perceptivo periférico. Crece la evidencia experimental del papel clave que juegan los mecanismos centrales excitadores e inhibidores de la actividad muscular y cuando se ha vuelto crónico de muy poca posibilidad de solución; salvo el efectgo placebo o la remisión espontánea. El dolor crónico orofacial no guarda una relación causal demostrable con el bruxismo pero, sin embargo, puede coexistir o no. No obstante, como factor irritativo crónico sobre las estructuras profundas perceptivas es muy probable que contribuya a establecer circuitos centrales por la acción neuroendócrina y de neuropéptidos vinculados a la acción neuromuscular y al dolor por el efecto de hiperalgesia central resultante de la estimulación repetitiva (wind up). Por ello, es muy importante el diagnósitoc multifactorial temprano y la terapia biaxial que es interactiva. La llamada vinculación del stress emocional con el dolor es parte de un fenómeno más complejo con los que se llaman fenómenos vivenciales como los culturales; estilo de enfrentamiento; rasgos de personalidad; ansiedad; angustia, miedo y la vinculación de la depresión con el dolor que interactúan con los neuroendócrinos. Dado que el dolor crónico (como otras enfermedades crónicas) es una condición para la cual usualmente la cura no es posible, el objetivo de la mayor parte de los casos de dolor crónico es un programa de tratamiento rehabilitativo más que curativo, para evitar la discapacitación y/o el padecimiento. Estos aspectos deben tratarse con una buena relación interpersonal, una serie de tests y una entrevista estructurada que permita la terapia cognitiva

Bruxismo y dolor crónico orofacial / Bruxism and chronic orofacial pain

En el estado actual del conocimiento sobre los factores y mecanismos del bruxismo se han ido abandonando las posiciones de la relación causal estrecha entre oclusión y bruxismo, pero sin descartarla como factor a tener en cuenta por ser parte del complejo proceso perceptivo periférico. Crece la evidencia experimental del papel clave que juegan los mecanismos centrales excitadores e inhibidores de la actividad muscular y cuando se ha vuelto crónico de muy poca posibilidad de solución; salvo el efectgo placebo o la remisión espontánea. El dolor crónico orofacial no guarda una relación causal demostrable con el bruxismo pero, sin embargo, puede coexistir o no. No obstante, como factor irritativo crónico sobre las estructuras profundas perceptivas es muy probable que contribuya a establecer circuitos centrales por la acción neuroendócrina y de neuropéptidos vinculados a la acción neuromuscular y al dolor por el efecto de hiperalgesia central resultante de la estimulación repetitiva (wind up). Por ello, es muy importante el diagnósitoc multifactorial temprano y la terapia biaxial que es interactiva. La llamada vinculación del stress emocional con el dolor es parte de un fenómeno más complejo con los que se llaman fenómenos vivenciales como los culturales; estilo de enfrentamiento; rasgos de personalidad; ansiedad; angustia, miedo y la vinculación de la depresión con el dolor que interactúan con los neuroendócrinos. Dado que el dolor crónico (como otras enfermedades crónicas) es una condición para la cual usualmente la cura no es posible, el objetivo de la mayor parte de los casos de dolor crónico es un programa de tratamiento rehabilitativo más que curativo, para evitar la discapacitación y/o el padecimiento. Estos aspectos deben tratarse con una buena relación interpersonal, una serie de tests y una entrevista estructurada que permita la terapia cognitiva (AU)

Role of dorsal raphe nucleus serotonin 5-HT1A receptor in the regulation of REM sleep.

Cholinergic neurons in the laterodorsal (LDT) and the pedunculopontine (PPT) tegmental nuclei act to promote REM sleep (REMS). The predominantly glutamatergic neurons of the REMS-induction region of the medial pontine reticular formation are in turn activated by cholinergic cells, which results in the occurrence of tonic and phasic components of REMS. All these neurons are inhibited by serotonergic (5-HT), noradrenergic, and presumably histaminergic (H2 receptor) and dopaminergic (D2 and D3 receptor) cells. 5-Hydroxytryptamine-containing neurons in the dorsal raphe nucleus (DRN) virtually cease firing when an animal starts REMS, consequently decreasing the release of 5-HT during this state. The activation of GABA(A) receptors is apparently responsible for this phenomenon. Systemic administration of the selective 5-HT1A receptor agonist 8-OHDPAT induces dose-dependent effects; i.e. low doses increase slow wave sleep and reduce waking, whereas large doses increase waking and reduce slow wave sleep and REM sleep. Direct injection of 8-OHDPAT or flesinoxan, another 5-HT1A agonist into the DRN, or microdialysis perfusion of 8-OHDPAT into the DRN significantly increases REMS. On the other hand, infusion of 8-OHDPAT into the LDT selectively inhibits REMS, as does direct administration into the DRN of the 5-HT1A receptor antagonists pindolol or WAY 100635. Thus, presently available evidence indicates that selective activation of the somatodendritic 5-HT1A receptor in the DRN induces an increase of REMS. On the other hand, activation of the postsynaptic 5-HT1A receptor at the level of the PPT/LDT nuclei decreases REMS occurrence.

Seizures induced by penicillin microinjections in the mesencephalic tegmentum.

The location and extension of a convulsive area in the brain stem in cats was determined through penicillin microinjections (0.5-1.0 microl) of a concentrated sodium penicillin solution (500 IU/microl), stereotactically oriented to multiple structures, in fully awake animals, partially restrained through a rod fixation system that avoided pain, allowed the observation of clinical seizures and simultaneous recording of EEG, EMG and multiple unit activity (MUA) from the injected site and the motor cortex (Cx). Clinical and EEG seizure patterns in relation to the injected sites and penicillin doses were studied in another group of animals using doses from 12.5 IU/0.1 microl to 125 IU/1.0 microl. The time relationship between muscular clonus, EEG spikes and MUA at the injected site and Cx were analyzed. The only area in which penicillin induced seizures was the mesencephalic tegmentum (MT). The amount of penicillin but not the stereotactic coordinates determined the seizure type. MT EEG and MUA paroxysms anticipated clinical seizure and Cx EEG spikes. When Cx EEG appeared, they were accompanied by an increase in MUA beginning in the Cx and EMG, followed by significant increase in MT MUA. The sequence of events suggest that MT seizure activity propagates via alternative pathways not involving direct reticulospinal or pyramidal tract pathways.

Correlation between concomitant theta waves in nucleus reticularis pontis oralis and in hippocampus, thalamus and neocortex during dreaming in rats.

Theta waves, which are the main electrophysiological expression of dreaming activity in many brain structures of rats, often undergo specific changes in voltage and frequency according to the oniric patterns. Much is known about their mechanisms but little is known regarding their origin, which has been ascribed to a specific activation of either the reticular formation or the septal nuclei or nucleus reticularis pontis oralis. In the present study, rats were prepared for chronic recording of the electro-oscillograms of cortical areas 10, 3 and 17, of hippocampal CA1 and CA3 fields, of nucleus reticularis thalami, nucleus reticularis pontis oralis and occasionally of nucleus reticularis caudalis. Head, rostrum, eye and forelimb movements were also recorded, so that the oniric behaviors could be precisely identified. The scatter diagrams and the corresponding correlation coefficients (r) of the voltage of concomitant waves were determined for each possible pair of leads. The potentials were analyzed at a frequency of 256 Hz over a period of 1 to 3 sec. A very high degree of correlation was observed between theta waves in nucleus reticularis pontis oralis, hippocampal fields and nucleus reticularis pontis caudalis; sometimes r approached unity. Although these data cannot be taken as proof of nucleus reticularis pontis oralis being the source of theta waves, they are at least compatible with this hypothesis.

Correlation between concomitant theta waves in nucleus reticularis pontis oralis and in hippocampus, thalamus and neocortex during dreaming in rats

Theta waves, which are the main electrophysiological expression of dreaming activity in many brain structures of rats, often undergo specific changes in voltage and frequency according to the oniric patterns. Much is known about their mechanisms but little is known regarding their origin, which has been ascribed to a specific activation of either the reticular formation or the septal nuclei or nucleus reticularis pontis oralis. In the present study, rats were prepared for chronic recording of the electro-oscillograms of cortical areas 10, 3 and 17, of hippocampal CA1 and CA3 fields, of nucleus reticularis thalami, nucleus reticularis pontis oralis and occasionally of nucleus reticularis caudalis. Head, rostrum, eye and forelimb movements were also recorded, so that the oniric behaviors could be precisely identified. The scatter diagrams and the corresponding correlation coefficients (r) of the voltage of concomitant waves were determined for each possible pair of leads. The potentials were analyzed at a frequency of 256 Hz over a period of 1 to 3 sec. A very high degree of correlation was observed between theta waves in nucleus reticularis pontis oralis, hippocampal fields and nucleus reticularis pontis caudalis; sometimes r approached unity. Although these data cannot be taken as proof of nucleus reticularis pontis oralis being the source of theta waves, they are at least compatible with this hypothesis.

A computational model for the neurobiological substrates of visual attention.

Two interesting and complex tasks are performed by the brain in the process of perception: the integration of characteristics leading to an easier recognition of a pattern as a whole (binding), and the extraction of properties that need to be detailed and analyzed (attention). Attention seems to have a reciprocal relation with binding, inasmuch as the latter promotes the composition of features and their dependencies, while the former selects a single characteristic independently of the remainder. Classically, binding is viewed as a process whereby sets of properties are gathered in representative entities, which are themselves linked to form higher level structures, in a sequence that culminates in the total integration of the pattern features in a localized construct. The convergent axonal projections from one cortical area to another would be the neurobiological mechanism through which binding is achieved. Attention comprises the selective excitation of neuronal networks or pathways that stand for specific pattern properties. The thalamus and its reticular nucleus would then be the anatomical substrate of the attentional focus. In this paper we propose a computational model aiming at bringing together the main (and apparently diverging) ideas about binding and attention. Based on experimental data, a neuronal network representing cortical pyramidal cells is assembled, and its structure and function are related to the binding and attention phenomena. Actually, the convergent projections that enlarge the visual receptive field are associated to binding, while a specific change in the pyramidal cell behavior is responsible for attention. Computer simulations are shown which reproduce the electrophysiology of pyramidal cells and mimic some interesting experimental results in visual attention. We conclude by conjecturing that attention is a driven interruption in the regular process of binding.

Behavioral responses induced by electrical stimulation of the caudate nucleus in freely moving cats.

The caudate nucleus and adjacent structures of 26 freely moving cats were stimulated through multiwire electrodes chronically implanted. Two main effects here observed with trains of pulses of high frequency (100 Hz) and short duration (1 s): (1) contralateral head turning and (2) arrest reaction, which was associated with crouching and escape behavior. The responses follow a certain topographic distribution. Head turning was elicited with the lowest mean threshold in sites located in the internal two-thirds and caudal region of the caudate nucleus, while the arrest reaction was elicited from the ventromedial region of the caudate and adjacent nucleus accumbens. Stimulation of the corpus callosum and internal capsule produces postural instability, ventral flexion of the head and flexion of the contralateral limb. The extra-caudate responses were accompanied by contralateral head turning when the stimulated points were near of the caudate border. Experimental evidence suggested that striatal responses were not due to current spread to adjacent structures or to activation of corticofugal fibers. The head rotation was suppressed following interruption of the ipsilateral striatal outflow by electrolytic lesion of the globus pallidus and adjacent internal capsule. The chemical lesion of the substantia nigra and the ventral pallidum produced a significant increase in the stimulation threshold for head turning and arrest reaction, respectively. These results suggest a topographic arrangement of the responses evoked by electrical stimulation of the caudate nucleus in the cat, which are mediated by the substantia nigra pars reticulata and the ventral pallidum.

Enhancement of water intake in rats after lidocaine injection in the zona incerta.

Physiological evidence indicates that the zona incerta (ZI) may be an important region for convergence of signals mediating drinking. It is known that the ZI receives neural influences from brain osmoreceptive zones. Also there are wide-spread projections from the ZI to the neocortex. In the present experiments, lidocaine (1 microliter, 20 ng/microliters) was injected into the rostral aspect of the ZI. The animals were previously stimulated for water drinking by: a) overnight water deprivation; b) 2 M NaCl IP; c) AII (50 ng) in the anteroventral wall of the third ventricle (AV3V). In every case, lidocaine administration significantly enhanced the volume of water drank. The results support the idea that ZI exerts an inhibitory influence upon the expression of drinking behavior.