scholarly journals Active control of arousal by a locus coeruleus GABAergic circuit

2018 ◽  
Author(s):  
Vincent Breton-Provencher ◽  
Mriganka Sur

AbstractArousal and novelty responses linked to locus coeruleus noradrenergic (LC-NA) activity affect cognitive performance. However, the mechanisms that control modes of LC-NA activity remain unknown. Here, we reveal a local population of GABAergic neurons (LC-GABA) capable of modulating LC-NA activity and arousal. Monosynaptic retrograde virus tracing shows that inputs to LC-GABA and LC-NA neurons arise from similar regions, though a few regions provide differential inputs to one subtype over the other. Recordings in the LC demonstrate two modes of LC-GABA responses whereby spiking is either correlated or broadly anti-correlated with LC-NA responses, reflecting anatomically similar and functionally coincident inputs, or differential and non-coincident inputs, to LC-NA and LC-GABA neurons. Coincident inputs control the gain of phasic LC-NA mediated novelty responses, while non-coincident inputs, such as from the prefrontal cortex to LC, alter overall levels of LC-NA responses without affecting response gain. These findings demonstrate distinct modes by which an inhibitory LC circuit regulates the gain and tone of arousal in the brain.

Author(s):  
David McNeill

This paper outlines an argument for how development in child speech and gesture could shed light on language evolution: child acquisition can be thought of as two types of acquisition, one of which goes extinct (gesture-first, Acquisition 1) and is replaced by another (gesture–speech unity, Acquisition 2). For ontogenesis, this implies that children acquire two languages, one of which is extinct, and which again goes extinct in ontogenesis (it continues as “gestures of silence” rather than as gestures of speech). There is no way to get from Acquisition 1 to Acquisition 2. They are on different tracks. Even when they converge in the same sentence, as they sometimes do, they alternate and do not combine. I propose that the 3~4 year timing of Acquisition 2 relates to the natural selection of a kind of gestural self–response I call “Mead’s Loop”, which took place in a certain psychological milieu at the origin of language. This milieu emerges now in ontogenesis at 3~4 years and with it Mead’s Loop. It is self-aware agency, on which a self-response depends. Other developments, such as theory of mind and shared intentionality, likewise depend on it and also emerge around the same time. The prefrontal cortex, anchoring a ring of language centers in the brain, matures at that point as well, another factor influencing the late timing. On the other hand, a third acquisition, speech evoking adult attachment, begins at (or even before) birth, as shown by a number of studies, and provides continuity through the two acquisitions and extinction.


2011 ◽  
Vol 106 (3) ◽  
pp. 1558-1569 ◽  
Author(s):  
Klaus Wunderlich ◽  
Ulrik R. Beierholm ◽  
Peter Bossaerts ◽  
John P. O'Doherty

Prefrontal cortex has long been implicated in tasks involving higher order inference in which decisions must be rendered, not only about which stimulus is currently rewarded, but also which stimulus dimensions are currently relevant. However, the precise computational mechanisms used to solve such tasks have remained unclear. We scanned human participants with functional MRI, while they performed a hierarchical intradimensional/extradimensional shift task to investigate what strategy subjects use while solving higher order decision problems. By using a computational model-based analysis, we found behavioral and neural evidence that humans solve such problems not by occasionally shifting focus from one to the other dimension, but by considering multiple explanations simultaneously. Activity in human prefrontal cortex was better accounted for by a model that integrates over all available evidences than by a model in which attention is selectively gated. Importantly, our model provides an explanation for how the brain determines integration weights, according to which it could distribute its attention. Our results demonstrate that, at the point of choice, the human brain and the prefrontal cortex in particular are capable of a weighted integration of information across multiple evidences.


2017 ◽  
Vol 63 (6) ◽  
pp. 565-569
Author(s):  
E.A. Ivanova ◽  
N.N. Zolotov ◽  
I.G. Kapitsa ◽  
V.F. Pozdnev ◽  
E.A. Valdman ◽  
...  

Rats with experimental Parkinson’s syndrome induced by seven-day intraperitoneal administration of rotenone at a dose of 2.75 mg/kg have an increased activity of prolylendopeptidase (EC 3.4.21.26, PREP) in blood serum and a decreased activity of adenosine deaminase (EC 3.5.4.4, ADA) in serum and in the prefrontal cortex. PREP and ADA activity in other brain structures (in the striatum, hypothalamus and hippocampus) did not change; dipeptidyl peptidase IV activity (EC 3.4.14.5, DPP-4, CD26) also remained constant in serum and in all the brain structures investigated. Afobazole and levodopa, which exhibit antiparkinsonian activity in this model of Parkinson’s syndrome, decrease elevated PREP activity in serum and increase reduced ADA activity in the prefrontal cortex of rats with the experimental pathology. Meanwhile, treatment with the study drugs was associated with a decrease of ADA activity in the other brain structures.


1968 ◽  
Vol 59 (3) ◽  
pp. 479-486 ◽  
Author(s):  
Lars-Ake Idahl ◽  
Bo Hellman

ABSTRACT The combination of enzymatic cycling and fluorometry was used for measuring glucose and glucose-6-phosphate in pancreatic β-cells from obese-hyperglycaemic mice. The glucose level of the β-cells corresponded to that of serum over a wide concentration range. In the exocrine pancreas, on the other hand, a significant barrier to glucose diffusion across the cell membranes was demonstrated. During 5 min of ischaemia, the glucose level remained practically unchanged in the β-cells while it increased in the liver and decreased in the brain. The observation that the pancreatic β-cells are characterized by a relatively low ratio of glucose-6-phosphate to glucose may be attributed to the presence of a specific glucose-6-phosphatase.


Author(s):  
Burbaeva G.Sh. ◽  
Androsova L.V. ◽  
Vorobyeva E.A. ◽  
Savushkina O.K.

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.


2020 ◽  
Vol 25 (45) ◽  
pp. 4799-4805 ◽  
Author(s):  
Osvaldo Flores-Bastías ◽  
Gonzalo I. Gómez ◽  
Juan A. Orellana ◽  
Eduardo Karahanian

Background: High ethanol intake induces a neuroinflammatory response resulting in the subsequent maintenance of chronic alcohol consumption. The melanocortin system plays a pivotal role in the modulation of alcohol consumption. Interestingly, it has been shown that the activation of melanocortin-4 receptor (MC4R) in the brain decreases the neuroinflammatory response in models of brain damage other than alcohol consumption, such as LPS-induced neuroinflammation, cerebral ischemia, glutamate excitotoxicity, and spinal cord injury. Objectives: In this work, we aimed to study whether MC4R activation by a synthetic MC4R-agonist peptide prevents ethanol-induced neuroinflammation, and if alcohol consumption produces changes in MC4R expression in the hippocampus and hypothalamus. Methods: Ethanol-preferring Sprague Dawley rats were selected offering access to 20% ethanol on alternate days for 4 weeks (intermittent access protocol). After this time, animals were i.p. administered an MC4R agonist peptide in the last 2 days of the protocol. Then, the expression of the proinflammatory cytokines interleukin 6 (IL-6), interleukin 1-beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured in the hippocampus, hypothalamus and prefrontal cortex. It was also evaluated if ethanol intake produces alterations in the expression of MC4R in the hippocampus and the hypothalamus. Results: Alcohol consumption increased the expression of MC4R in the hippocampus and the hypothalamus. The administration of the MC4R agonist reduced IL-6, IL-1β and TNF-α levels in hippocampus, hypothalamus and prefrontal cortex, to those observed in control rats that did not drink alcohol. Conclusion: High ethanol consumption produces an increase in the expression of MC4R in the hippocampus and hypothalamus. The administration of a synthetic MC4R-agonist peptide prevents neuroinflammation induced by alcohol consumption in the hippocampus, hypothalamus, and prefrontal cortex. These results could explain the effect of α-MSH and other synthetic MC4R agonists in decreasing alcohol intake through the reduction of the ethanol-induced inflammatory response in the brain.


Author(s):  
Walter Ott

Descartes’s treatment of perception in the Optics, though published before the Meditations, contains a distinct account of sensory experience. The end of the chapter suggests some reasons for this oddity, but that the two accounts are distinct is difficult to deny. Descartes in the present work topples the brain image from its throne. In its place, we have two mechanisms, one purely causal, the other inferential. Where the proper sensibles are concerned, the ordination of nature suffices to explain why a given sensation is triggered on the occasion of a given brain motion. The same is true with regard to the common sensibles. But on top of this purely causal story, Descartes re-introduces his doctrine of natural geometry.


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