Analog Modeling of Human Cognitive Functions with Tripartite Synapses

Searching for an understanding of how the brain supports conscious processes, cognitive scientists have proposed two main classes of theory: Global Workspace and Information Integration theories. These theories seem to be complementary, but both still lack grounding in terms of brain mechanisms responsible for the production of coherent and unitary conscious states. Here we propose following James Robertson's "Astrocentric Hypothesis" - that conscious processing is based on analog computing in astrocytes. The "hardware" for these computations is calcium waves mediated by adenosine triphosphate signaling. Besides presenting our version of this hypothesis, we also review recent findings on astrocyte morphology that lend support to their functioning as Local Hubs (composed of protoplasmic astrocytes) that integrate synaptic activity, and as a Master Hub (composed, in the human brain, by a combination of interlaminar, fibrous, polarized and varicose projection astrocytes) that integrates whole-brain activity.

5-HT1A, but not 5-HT2 and 5-HT7, receptors in the nucleus raphe magnus modulate hypoxia-induced hyperpnoea

Aim: In the present study, we assessed the role of 5-hydroxytryptamine (5-HT) receptors (5-HT1A, 5-HT2 and 5-HT7) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia.Methods: To this end, pulmonary ventilation (V-E) and body temperature (T-b) of male Wistar rats were measured in conscious rats, before and after a 0.1 mu L microinjection of WAY-100635 (5-HT1A receptor antagonist, 3 mu g 0.1 mu L-1, 56 mM), ketanserin (5-HT2 receptor antagonist, 2 mu g 0.1 mu L-1, 36 mM) and SB269970 (5-HT7 receptor antagonist, 4 mu g 0.1 mu L-1, 103 mM) into the NRM, followed by 60 min of severe hypoxia exposure (7% O-2).Results: Intra-NMR microinjection of vehicle (control rats) or 5-HT antagonists did not affect V-E or T-b during normoxic conditions. Exposure of rats to 7% O-2 evoked a typical hypoxia-induced anapyrexia after vehicle microinjections, which was not affected by microinjection of WAY-100635, SB269970 or ketanserin. The hypoxia-induced hyperpnoea was not affected by SB269970 and ketanserin intra-NMR. However, the treatment with WAY-100635 intra-NRM attenuated the hypoxia-induced hyperpnoea.Conclusion: These data suggest that 5-HT acting on 5-HT1A receptors in the NRM increases the hypoxic ventilatory response.

Perceptual Information Integration: Hypothetical Role of Astrocytes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

What is Consciousness? Towards a Preliminary Definition

There is little or no general agreement about what researchers should focus on when studying consciousness. The most active scientific studies often use the methods of Cognitive Neuroscience and focus mainly on vision. Other aspects and contents of consciousness, namely thoughts and emotions, are much less studied, possibly leading to a biased view of what consciousness is and how it works. In this essay we describe what we call a referential nucleus, implicit in much of consciousness research. In this context, 'consciousness' refers to (partially) reportable content experienced by living individuals. We then discuss the philosophical concept of a phenomenal world and another contemporary view that conscious experience involves, besides integration of information in the brain, participation in action-perception cycles in a natural, social and cultural environment. These views imply a need to reconceptualize 'qualia' as the conscious aspect of subjective experiences, thus stating properties of consciousness that pose serious challenges to an exclusive approach via Cognitive Neuroscience, because experimental settings oversimplify conscious experiences, narrowing them to fragments correlated with measured brain activity and behaviour In conclusion we argue that a science of consciousness requires a broad interdisciplinary range of research, including qualitative methods from the Human Sciences.

On a dual role for clonidine stimulation of the ventromedial nucleus of the hypothalamus in sodium and potassium renal excretions of rats

The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an α 1-adrenergic receptor antagonist) and yohimbine (an α 2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of α 1-adrenoceptors and that inhibitory effects require α(2A)-adrenoceptors.

Commissural NTS lesions and cardiovascular responses in aortic baroreceptor-denervated rats

Both acute (1 day) lesions of the commissural nucleus of the solitary tract (commNTS) and aortic baroreceptor denervation increase pressor responses to bilateral common carotid occlusion (BCO) during a 60-second period in conscious rats. In this study, we investigated the following: (1) the effects of commNTS lesions on basal mean arterial pressure (MAP) and heart rate (HR) of aortic denervated (ADNx) rats; (2) the effects of acute commNTS lesions on pressor responses to BCO in ADNx rats; and (3) the effects of chronic (10 days) commNTS lesions on the pressor response to BCO. ADNx increased basal MAP and HR in sham-lesioned rats. Acute commNTS lesions abolished the MAP and HR increases observed in ADNx rats. Acute commNTS lesions increased the pressor responses to BCO in rats with intact- baroreceptor innervation but produced no additional change in the pressor response to BCO in ADNx rats. Chronic commNTS lesions did not change the pressor responses to BCO in rats with intact-baroreceptor innervation. The data show that acute commNTS lesions abolish the MAP increase produced by aortic baroreceptor denervation. They also suggest that acute commNTS lesions enhance the pressor response to BCO by partial withdrawal of aortic baroreceptor inputs into the NTS. Chronically, reorganization in the remaining aortic baroreceptor or in the baroreflex function as a whole might produce normalization of the cardiovascular responses to BCO.

N-methyl-D-aspartate channel and consciousness: From signal coincidence detection to quantum computing

Research on Blindsight, Neglect/Extinction and Phantom limb syndromes, as well as electrical measurements of mammalian brain activity, have suggested the dependence of vivid perception on both incoming sensory information at primary sensory cortex and reentrant information from associative cortex. Coherence between incoming and reentrant signals seems to be a necessary condition for (conscious) perception. General reticular activating system and local electrical synchronization are some of the tools used by the brain to establish coarse coherence at the sensory cortex, upon which biochemical processes are coordinated. Besides electrical synchrony and chemical modulation at the synapse, a central mechanism supporting such a coherence is the N-methyl-D-aspartate channel, working as a 'coincidence detector' for an incoming signal causing the depolarization necessary to remove Mg 2+, and reentrant information releasing the glutamate that finally prompts Ca 2+ entry. We propose that a signal transduction pathway activated by Ca 2+ entry into cortical neurons is in charge of triggering a quantum computational process that accelerates inter-neuronal communication, thus solving systemic conflict and supporting the unity of consciousness. © 2001 Elsevier Science Ltd.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

Objective - We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. Methods - Holtzman rats were used. Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-μl volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. Results - Losartan (40 nmol) and [Sar1, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar1, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. Conclusion - MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Toward an Explanation of the Genesis of Ketamine-Induced Perceptual Distortions and Hallucinatory States

The NMDA receptor (NMDAR) channel has been proposed to function as a coincidence-detection mechanism for afferent and reentrant signals, supporting conscious perception, learning, and memory formation. In this paper we discuss the genesis of distorted perceptual states induced by subanesthetic doses of ketamine, a well-known NMDA antagonist. NMDAR blockage has been suggested to perturb perceptual processing in sensory cortex, and also to decrease GABAergic inhibition in limbic areas (leading to an increase in dopamine excitability). We propose that perceptual distortions and hallucinations induced by ketamine blocking of NMDARs are generated by alternative signaling pathways, which include increase of excitability in frontal areas, and glutamate binding to AMPA in sensory cortex prompting Ca++ entry through voltage-dependent calcium channels (VDCCs). This mechanism supports the thesis that glutamate binding to AMPA and NMDARs at sensory cortex mediates most normal perception, while binding to AMPA and activating VDCCs mediates some types of altered perceptual states. We suggest that Ca++ metabolic activity in neurons at associative and sensory cortices is an important factor in the generation of both kinds of perceptual consciousness.

O óxido nítrico (NO) no controle neural da pressão arterial: Modulação da transmissão glutamatérgica no NTS

The neuromodulatory effect of nitric oxide (NO) on glutamatergic transmission within the NTS related to cardiovascular regulation has been widely investigated. Activation of glutamatergic receptors in the NTS stimulates the production and release of NO and other nitrosyl substances with neurotransmitter/neuromodulator properties. The presence of NOS, including the protein nNOS and its mRNA in vagal afferent terminals in the NTS and nodose ganglion cells suggest that NO can act on glutamatergic transmission. We previously reported that iontophoresis of L-NAME on NTS neurons receiving vagal afferent inputs significantly decreased the number of action potentials evoked by iontophoretic application of AMPA. In addition, iontophoresis of the NO donor papaNONOate enhanced spontaneous discharge and the number of action potentials elicited by AMPA, suggesting that NO could be facilitating AMPA-mediated neuronal transmission within the NTS. Furthermore, the changes in renal sympathetic discharge during activation of baroreceptors and cardiopulmonary receptors involve activation of AMPA and NMDA receptors in the NTS and these responses are attenuated by microinjection of L-NAME in the NTS of conscious and anesthetized rats. Cardiovascular responses elicited by application of NO in the NTS are closely similar to those obtained after activation of vagal afferent inputs, and L-glutamate is the main neurotransmitter of vagal afferent fibers. In this review we discuss the possible neuromodulatory mechanisms of central produced/released NO on glutamatergic transmission within the NTS.

Estudo comparativo de vias de acesso cirúrgico na contracepção cirúrgica feminina: Microlaparoscopia versus minilaparotomia

Purpose: to compare in a retrospective way, 51 women who underwent tubal ligation, 30 through microlaparoascopy (Gmicrol) and 21 through minilaparotomy (Gminil). Methods: the analyzed parameters were: total time for accomplishment of the procedure and the surgical technique, time of hospital stay and return to the habitual activities after the surgery, postoperative pain, morbidity, satisfaction degree and esthetic effect, considering values of p<0,05 as significant, and also standard cost. Results: Gmicrol took less time to accomplish the surgery than the Gminil (43 against 57 minutes respectively, p<0,05), less time to accomplish the surgical technique (6.48 against 30.32 minutes respectively, p<0,05), and lower hospital stay (9,90 hours as against 41,7 hours respectively, p <0,05). There was no significant difference between the two groups regarding time to return to the habitual activities after surgery. To evaluate postoperative pain, a scale of 0-10 it was applied. Gmicrol present a lower pain score on the 1st and 2nd postoperative days (1.13 and 0.26 to Gmicrol and 4.52 and 1.14 to Gminil, respectively, p<0,05). There was no significant difference between immediate postoperative the most common complaint being pain at the site of pain and that on the 3rd postoperative day. Gminil presented a higher morbidity rate incision. To evaluate the satisfaction degree and esthetic effect, numeric values were attributed to as good, regular, poor and very bad as answered by the patiets. Gmicrol presented a higher satisfaction degree (p<0,05) and better esthetic effect as compared to Gminil (p <0,05). The microlaparoscopy standard cost was R$ 109.30 being lower than that of minilaparotomy. Conclusions: tubal ligation by microlaparoscopy, under local anesthesia and conscious sedation presented some advantages compared to minilaparotomy.

Biomolecular information, brain activity and cognitive functions

Molecular neurobiology has provided an explanation of mechanisms supporting mental functions as learning, memory, emotion and consciousness. However, an explanatory gap remains between two levels of description: molecular mechanisms determining cellular and tissue functions, and cognitive functions. In this paper we review molecular and cellular mechanisms that determine brain activity, and then hypothetize about their relation with cognition and consciousness. The brain is conceived of as a dynamic system that exchanges information with the whole body and the environment. Three explanatory hypotheses are presented, stating that: a) brain tissue function is coordinated by macromolecules controlling ion movements, b) structured (amplitude, frequency and phase-modulated) local field potentials generated by organized ionic movement embody cognitive information patterns, and c) conscious episodes are constructed by a large-scale mechanism that uses oscillatory synchrony to integrate local field patterns. © by São Paulo State University.

Some considerations on the possible effects of the failure of the United States Congress to renew the ATPDEA

Includes bibliography

¿A Chilean wine cluster? governance and upgrading in the phase of internationalization

Includes bibliography