scholarly journals Rapid appetitive transitions are sculpted by amygdala to accumbens pathways

2021 ◽  
Author(s):  
E. Zayra Millan ◽  
Jun Hua Lim ◽  
John Power ◽  
Gavan McNally

Foraging, pursuit, and predation rapidly transition into behavioral quiescence during reward capture and consumption. While appetitive-consummatory dissociations are embedded at both psychological and neural levels, the mechanisms controlling switches or transitions between appetitive seeking and consummatory behaviors remain poorly understood. Here we identify the BLA→AcbSh pathway as critical to these transitions by showing that this pathway inhibits the appetitive seeking response in the presence of consummatory demands. Using an appetitive cue-discrimination task in male rats, we show that reward delivery is a significant driver of seeking inhibition and that a BLA→AcbSh pathway mediates this inhibition. This role in suppressing seeking responses during periods of consumption was not due to a general suppression of behavior because responding to other cues during the same test was unaffected. Moreover, it was specific to the BLA→AcbSh pathway, because the contribution of the BLA→AcbC pathway to appetitive switching was distinct and modest. State-dependent silencing of BLA→AcbSh revealed that the modulation of seeking before and after reward delivery are co-dependent. Finally, we found that BLA terminals in AcbSh have functional connectivity to LH-projecting AcbSh neurons, thereby identifying a BLA→AcbSh→LH pathway as a putative route for the rapid regulation of appetitive behaviors. Taken together, these findings suggest that the BLA→AcbSh pathway is a core component of an appetitive switching system, recruited under conditions requiring rapid or dynamic shifts in appetitive behavior, and that this pathway enables these shifts by actively inhibiting seeking.

2019 ◽  
Vol 31 (10) ◽  
pp. 1484-1490 ◽  
Author(s):  
Mohsen Naji ◽  
Giri P. Krishnan ◽  
Elizabeth A. McDevitt ◽  
Maxim Bazhenov ◽  
Sara C. Mednick

Central and autonomic nervous system activities are coupled during sleep. Cortical slow oscillations (SOs; <1 Hz) coincide with brief bursts in heart rate (HR), but the functional consequence of this coupling in cognition remains elusive. We measured SO–HR temporal coupling (i.e., the peak-to-peak interval between downstate of SO event and HR burst) during a daytime nap and asked whether this SO–HR timing measure was associated with temporal processing speed and learning on a texture discrimination task by testing participants before and after a nap. The coherence of SO–HR events during sleep strongly correlated with an individual's temporal processing speed in the morning and evening test sessions, but not with their change in performance after the nap (i.e., consolidation). We confirmed this result in two additional experimental visits and also discovered that this association was visit-specific, indicating a state (not trait) marker. Thus, we introduce a novel physiological index that may be a useful marker of state-dependent processing speed of an individual.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert A. McCutcheon ◽  
Toby Pillinger ◽  
Maria Rogdaki ◽  
Juan Bustillo ◽  
Oliver D. Howes

AbstractAlterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p < 0.05) and did not differ significantly between patients and controls (p > 0.85). Study B involved 19 individuals with schizophrenia and 17 controls and found that increases in glutamate concentrations induced by riluzole were linked to increases in connectivity localised to the salience network (p < 0.05), and the relationship did not differ between patients and controls (p > 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.


2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.


2020 ◽  
Author(s):  
Jian Kong ◽  
Yiting Huang ◽  
Jiao Liu ◽  
Siyi Yu ◽  
Ming Cheng ◽  
...  

Abstract Background: This study aims to investigate the resting state functional connectivity (rsFC) changes of the hypothalamus in Fibromyalgia patients and the modulation effect of effective treatments. Methods: Fibromyalgia patients and matched healthy controls (HC’s) were recruited. Resting state fMRI data were collected from fibromyalgia patients before and after a 12-week Tai Chi intervention and once from HC’s. Results: Data analysis showed that fibromyalgia patients displayed significantly decreased medial hypothalamus (MH) rsFC with the thalamus and amygdala when compared to HC’s at baseline. After the intervention, fibromyalgia patients showed increased (normalized) MH rsFC in the thalamus and amygdala. Effective connectivity analysis showed disrupted MH and thalamus interaction in fibromyalgia, which nonetheless could be partially restored by Tai Chi. Conclusions: Elucidating the role of the diencephalon and limbic system in the pathophysiology and development of fibromyalgia may facilitate the development of new treatment methods for this prevalent disorder. Trial registration: Trial registration ClinicalTrials.gov Identifier: NCT02407665. Registered 3 April 2015 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02407665


2021 ◽  
Author(s):  
Andrew Lynn ◽  
Eric D. Wilkey ◽  
Gavin Price

The human brain comprises multiple canonical networks, several of which are distributed across frontal, parietal, and temporooccipital regions. Studies report both positive and negative correlations between children’s math skills and the strength of functional connectivity among these regions during math-related tasks and at rest. Yet, it is unclear how the relation between children’s math skills and functional connectivity map onto patterns of distributed whole-brain connectivity, canonical network connectivity, and whether these relations are consistent across different task-states. We used connectome-based predictive modeling to test whether functional connectivity during number comparison and at rest predicts children’s math skills (N=31, Mage=9.21years) using distributed whole-brain connections versus connections among canonical networks. We found that weaker connectivity distributed across the whole brain and weaker connectivity between key math-related brain regions in specific canonical networks predicts better math skills in childhood. The specific connections predicting math skills, and whether they were distributed or mapped onto canonical networks, varied between tasks, suggesting that state-dependent rather than trait-level functional network architectures support children’s math skills. Furthermore, the current predictive modeling approach moves beyond brain-behavior correlations and toward building models of brain connectivity that may eventually aid in predicting future math skills.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yi Liang ◽  
Chunli Chen ◽  
Fali Li ◽  
Dezhong Yao ◽  
Peng Xu ◽  
...  

Epileptic seizures are considered to be a brain network dysfunction, and chronic recurrent seizures can cause severe brain damage. However, the functional brain network underlying recurrent epileptic seizures is still left unveiled. This study is aimed at exploring the differences in a related brain activity before and after chronic repetitive seizures by investigating the power spectral density (PSD), fuzzy entropy, and functional connectivity in epileptic patients. The PSD analysis revealed differences between the two states at local area, showing postseizure energy accumulation. Besides, the fuzzy entropies of preseizure in the frontal, central, and temporal regions are higher than that of postseizure. Additionally, attenuated long-range connectivity and enhanced local connectivity were also found. Moreover, significant correlations were found between network metrics (i.e., characteristic path length and clustering coefficient) and individual seizure number. The PSD, fuzzy entropy, and network analysis may indicate that the brain is gradually impaired along with the occurrence of epilepsy, and the accumulated effect of brain impairment is observed in individuals with consecutive epileptic bursts. The findings of this study may provide helpful insights into understanding the network mechanism underlying chronic recurrent epilepsy.


1984 ◽  
Vol 246 (1) ◽  
pp. G8-G15 ◽  
Author(s):  
R. B. Sewell ◽  
S. S. Barham ◽  
A. R. Zinsmeister ◽  
N. F. LaRusso

We tested the hypothesis that hepatocyte microtubules modulate the biliary excretion of endogenous and exogenous constituents of hepatocyte lysosomes. We collected bile via bile fistulas from male rats before and after acute administration of colchicine and vinblastine, agents known to bind to hepatocyte microtubules; rats were then killed and livers were homogenized for biochemical analyses or processed for electron microscopy. Colchicine caused biphasic, parallel alterations in the biliary excretion of three lysosomal enzymes compared with control rats given saline or lumicolchicine; a peak rise in enzyme outputs of approximately 175% at 45-60 min after colchicine administration was followed by a sustained fall to approximately 25% of control values, which persisted for 2-4 h. When hepatocyte lysosomes were prelabeled in vivo by administration of [3H]Triton WR-1339, a nonionic detergent that is sequestered in hepatic lysosomes, the biliary excretion of radiolabel in response to colchicine paralleled the biliary excretion of the three lysosomal enzymes. Vinblastine also induced a biphasic response in biliary lysosomal enzyme output that was similar to that produced by colchicine administration. Morphometric analysis of electron micrographs of rat livers demonstrated changes in the number of lysosomelike vesicles in the vicinity of bile canaliculi after colchicine and vinblastine administration; the initial increase in lysosomal enzyme secretion was associated with a significant decrease in the number of pericanalicular lysosomes after both agents, while the subsequent decrease in enzyme secretion coincided with an increase in the number of pericanalicular lysosomes after vinblastine.(ABSTRACT TRUNCATED AT 250 WORDS)


1997 ◽  
Vol 272 (3) ◽  
pp. E422-E428 ◽  
Author(s):  
A. J. Sips ◽  
R. Barto ◽  
J. C. Netelenbos ◽  
W. J. van der Vijgh

The applicability of stable strontium as a marker for measuring intestinal calcium absorption is mainly dependent on the validity of the assumption that calcium and strontium are absorbed with a constant ratio. Up to now, it is not clear whether this ratio is affected by intervention therapy. Therefore, preclinical screening of this ratio before and after treatment is indispensable for a clinical calcium absorption test based on the use of stable strontium as a marker. We studied the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D(3)], a potent enhancer of active intestinal calcium absorption, on the pharmacokinetics of both calcium-45 and strontium in adult male rats, in a short-term dose-finding study [0-50 ng 1,25(OH)2D(3)/100 g body weight] and also in a placebo-controlled study in which 12.5 ng 1,25(OH)2D(3)/100 g body weight were applied to assess the long-term pharmacokinetics. The mean bioavailability (true absorption) was 33% for calcium and 19% for strontium (ratio 1.7:1), whereas, after 1,25(OH)2D(3) pretreatment, it was 73 and 43% (ratio 1.7:1), respectively. These findings demonstrate that intestinal strontium absorption has, like intestinal calcium absorption, an active component. Moreover, they underscore the applicability of stable strontium as a tool for investigating calcium absorption under various conditions.


2005 ◽  
Vol 94 (6) ◽  
pp. 3788-3794 ◽  
Author(s):  
Gexin Wang ◽  
Bin Tang ◽  
Richard J. Traub

Previous studies suggest the lumbosacral (LS) spinal cord processes acute colorectal stimuli whereas the thoracolumbar (TL) and LS spinal segments process inflammatory stimuli. In this study, the effects of colorectal distention (CRD) on TL and LS dorsal horn neuronal activity were recorded in Nembutal-anesthetized male rats both with and without colonic inflammation. Both single cells (before and after inflammation) and populations (multiple cells from noninflamed or inflamed rats) were studied. CRD-responsive neurons had excitatory Abrupt (on–off with stimulus) or Sustained (prolonged after discharge) responses or were Inhibited by CRD. In noninflamed rats, a significantly greater percentage of LS neurons (63% Abrupt, 27% Sustained) were excited by CRD than TL neurons (61% Abrupt, 3% Sustained). The remaining cells were Inhibited (10% LS, 36% TL). LS Abrupt neurons had lower thresholds and greater response magnitudes to CRD compared with TL Abrupt neurons. After colonic inflammation, TL neurons became more excitable: the percentage of Inhibited neurons decreased, the response magnitude of Abrupt neurons increased, and the threshold decreased. In contrast, in single-cell recordings, the response of LS Sustained neurons increased, whereas LS Abrupt neurons decreased. These data suggest that in noninflamed rats, the net response to CRD of TL visceroceptive spinal sensory neurons is less than that of LS neurons. Colonic inflammation increases the net response of TL neurons and differentially modulates the response of LS neurons. These differences may contribute to the functional dichotomy between the TL and LS spinal segments in processing acute and inflammatory colorectal pain.


2000 ◽  
Vol 84 (3) ◽  
pp. 1186-1193 ◽  
Author(s):  
Peter T. Morgan ◽  
Ray Perrins ◽  
Philip E. Lloyd ◽  
Klaudiusz R. Weiss

Intrinsic and extrinsic neuromodulation are both thought to be responsible for the flexibility of the neural circuits (central pattern generators) that control rhythmic behaviors. Because the two forms of modulation have been studied in different circuits, it has been difficult to compare them directly. We find that the central pattern generator for biting in Aplysia is modulated both extrinsically and intrinsically. Both forms of modulation increase the frequency of motor programs and shorten the duration of the protraction phase. Extrinsic modulation is mediated by the serotonergic metacerebral cell (MCC) neurons and is mimicked by application of serotonin. Intrinsic modulation is mediated by the cerebral peptide-2 (CP-2) containing CBI-2 interneurons and is mimicked by application of CP-2. Since the effects of CBI-2 and CP-2 occlude each other, the modulatory actions of CBI-2 may be mediated by CP-2 release. Although the effects of intrinsic and extrinsic modulation are similar, the neurons that mediate them are active predominantly at different times, suggesting a specialized role for each system. Metacerebral cell (MCC) activity predominates in the preparatory (appetitive) phase and thus precedes the activation of CBI-2 and biting motor programs. Once the CBI-2s are activated and the biting motor program is initiated, MCC activity declines precipitously. Hence extrinsic modulation prefacilitates biting, whereas intrinsic modulation occurs during biting. Since biting inhibits appetitive behavior, intrinsic modulation cannot be used to prefacilitate biting in the appetitive phase. Thus the sequential use of extrinsic and intrinsic modulation may provide a means for premodulation of biting without the concomitant disruption of appetitive behaviors.


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