scholarly journals Voluntary Behavior and Training Conditions Modulate in vivo Extracellular Glucose and Lactate in the Mouse Primary Motor Cortex

2022 ◽  
Vol 15 ◽  
Author(s):  
Alexandria Béland-Millar ◽  
Claude Messier

Learning or performing new behaviors requires significant neuronal signaling and is metabolically demanding. The metabolic cost of performing a behavior is mitigated by exposure and practice which result in diminished signaling and metabolic requirements. We examined the impact of novel and habituated wheel running, as well as effortful behaviors on the modulation of extracellular glucose and lactate using biosensors inserted in the primary motor cortex of mice. We found that motor behaviors produce increases in extracellular lactate and decreases in extracellular glucose in the primary motor cortex. These effects were modulated by experience, novelty and intensity of the behavior. The increase in extracellular lactate appears to be strongly associated with novelty of a behavior as well as the difficulty of performing a behavior. Our observations are consistent with the view that a main function of aerobic glycolysis is not to fuel the current neuronal activity but to sustain new bio-infrastructure as learning changes neural networks, chiefly through the shuttling of glucose derived carbons into the pentose phosphate pathway for the biosynthesis of nucleotides.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Radoslav I Raychev ◽  
Jeffrey Saver ◽  
Scott Brown ◽  
Gary Duckwiler ◽  
Reza Jahan ◽  
...  

Background: Targeted eloquence-based tissue reperfusion within the primary motor cortex may have differential effect on disability as compared to the traditional volume-based (TICI) reperfusion after endovascular thrombectomy (EVT) in setting of acute ischemic stroke (AIS). Methods: We explored the impact of eloquent reperfusion (ER) within primary motor cortex (PMC) on clinical outcome (mRS) in AIS patients undergoing EVT. ER was defined as presence of flow on final digital subtraction angiography (DSA) within four main cortical branches, supplying the PMC (MCA - precentral, central, anterior parietal; ACA- pericallosal) and graded as absent (0), partial (1), and complete (2). Prospectively collected data from two centers were analyzed. Multivariable analysis was conducted to assess the impact of ER on 90-day disability (mRS) among patients with anterior circulation occlusion who achieved partial reperfusion (TICI 2 a and b). Results: Among the 125 patients who met study criteria, median age was 73, median NIHSS was 16, median ASPECTS was 7, 48% (60/125) were female, and 36.8% achieved functional independence (mRS 0-2) at 90 days. ER distribution was: Absent (0) in 19/125 (15.2%); Partial (1) in 52/125 (41.6%), and Complete (2) in 54/125 (43.2%). TICI 2b was achieved in 102/125 (81.6%) and ER was substantially higher in those patients (p<0.001). In multivariate analysis, in addition to age and sICH, ER had a profound independent impact on 90-day disability (OR 6.10, p=0.001 for ER 1 vs 0; and OR 9.87, p<0.001 for ER 2 vs 0). In contrast, extent of total partial reperfusion (TICI 2b vs 2a) was not related to 90-day disability. Conclusions: Our findings support that eloquent PMC-tissue reperfusion is a major determinant of functional outcome, more impactful than volume-based degree of partial reperfusion. More aggressive, PMC-targeted revascularization among patients with non-eloquent partial reperfusion may further improve post-stroke disability after EVT.


2018 ◽  
Author(s):  
Johanna Neuner ◽  
Elena Katharina Schulz-Trieglaff ◽  
Sara Gutiérrez-Ángel ◽  
Fabian Hosp ◽  
Matthias Mann ◽  
...  

AbstractHuntington’s disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies in human patients and mouse HD models suggest that disturbances of neuronal function in the neocortex play an important role in the disease onset and progression. However, the precise nature and time course of cortical alterations in HD have remained elusive. Here, we use chronicin vivotwo-photon calcium imaging to monitor the activity of single neurons in layer 2/3 of the primary motor cortex in awake, behaving R6/2 transgenic HD mice and wildtype littermates. R6/2 mice show age-dependent changes in neuronal activity with a clear increase in activity at the age of 8.5 weeks, preceding the onset of motor and neurological symptoms. Furthermore, quantitative proteomics demonstrate a pronounced downregulation of synaptic proteins in the cortex, and histological analyses in R6/2 mice and HD patient samples reveal reduced inputs from parvalbumin-positive interneurons onto layer 2/3 pyramidal cells. Thus, our study provides a time-resolved description as well as mechanistic details of cortical circuit dysfunction in HD.Significance statementFuntional alterations in the cortex are believed to play an important role in the pathogenesis of Huntington’s disease (HD). However, studies monitoring cortical activity in HD modelsin vivoat a single-cell resultion are still lacking. We have used chronic two-photon imaging to investigate changes in the activity of single neurons in the primary motor cortex of awake presymptomatic HD mice. We show that neuronal activity increases before the mice develop disease symptoms. Our histological analyses in mice and in human HD autopsy cases furthermore demonstrate a loss inhibitory synaptic terminals from parvalbimun-positive interneurons, revealing a potential mechanism of cortical circuit impairment in HD.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Desmond Agboada ◽  
Mohsen Mosayebi Samani ◽  
Asif Jamil ◽  
Min-Fang Kuo ◽  
Michael A. Nitsche

AbstractSize and duration of the neuroplastic effects of tDCS depend on stimulation parameters, including stimulation duration and intensity of current. The impact of stimulation parameters on physiological effects is partially non-linear. To improve the utility of this intervention, it is critical to gather information about the impact of stimulation duration and intensity on neuroplasticity, while expanding the parameter space to improve efficacy. Anodal tDCS of 1–3 mA current intensity was applied for 15–30 minutes to study motor cortex plasticity. Sixteen healthy right-handed non-smoking volunteers participated in 10 sessions (intensity-duration pairs) of stimulation in a randomized cross-over design. Transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEP) were recorded as outcome measures of tDCS effects until next evening after tDCS. All active stimulation conditions enhanced motor cortex excitability within the first 2 hours after stimulation. We observed no significant differences between the three stimulation intensities and durations on cortical excitability. A trend for larger cortical excitability enhancements was however observed for higher current intensities (1 vs 3 mA). These results add information about intensified tDCS protocols and suggest that the impact of anodal tDCS on neuroplasticity is relatively robust with respect to gradual alterations of stimulation intensity, and duration.


2018 ◽  
Author(s):  
Gerard Derosiere ◽  
David Thura ◽  
Paul Cisek ◽  
Julie Duque

AbstractDecisions about actions typically involve a period of deliberation that ends with the commitment to a choice and the motor processes overtly expressing that choice. Previous studies have shown that neural activity in sensorimotor areas, including the primary motor cortex (M1), correlates with deliberation features during action selection. Yet, the causal contribution of these areas to the decision process remains unclear. Here, we investigated whether M1 determines choice commitment, or whether it simply reflects decision signals coming from upstream structures and instead mainly contributes to the motor processes that follow commitment. To do so, we tested the impact of a disruption of M1 activity, induced by continuous theta burst stimulation (cTBS), on the behavior of human subjects in (1) a simple reaction time (SRT) task allowing us to estimate the duration of the motor processes and (2) a modified version of the tokens task (Cisek et al., 2009), which allowed us to estimate subjects’ time of commitment as well as accuracy criterion. The efficiency of cTBS was attested by a reduction in motor evoked potential amplitudes following M1 disruption, as compared to those following a sham stimulation. Furthermore, M1 cTBS lengthened SRTs, indicating that motor processes were perturbed by the intervention. Importantly, all of the behavioral results in the tokens task were similar following M1 disruption and sham stimulation, suggesting that the contribution of M1 to the deliberation process is potentially negligible. Taken together, these findings favor the view that M1 contribution is downstream of the decision process.New and noteworthyDecisions between actions are ubiquitous in the animal realm. Deliberation during action choices entails changes in the activity of the sensorimotor areas controlling those actions, but the causal role of these areas is still often debated. Using continuous theta burst stimulation, we show that disrupting the primary motor cortex (M1) delays the motor processes that follow instructed commitment but does not alter volitional deliberation, suggesting that M1 contribution may be downstream of the decision process.


2001 ◽  
Vol 85 (2) ◽  
pp. 869-885 ◽  
Author(s):  
S. N. Baker ◽  
R. Spinks ◽  
A. Jackson ◽  
R. N. Lemon

Neural synchronization in the cortex, and its potential role in information coding, has attracted much recent attention. In this study, we have recorded long spike trains (mean, 33,000 spikes) simultaneously from multiple single neurons in the primary motor cortex (M1) of two conscious macaque monkeys performing a precision grip task. The task required the monkey to use its index finger and thumb to move two spring-loaded levers into a target, hold them there for 1 s, and release for a food reward. Synchrony was analyzed using a time-resolved cross-correlation method, normalized using an estimate of the instantaneous firing rate of the cell. This was shown to be more reliable than methods using trial-averaged firing rate. A total of 375 neurons was recorded from the M1 hand area; 235 were identified as pyramidal tract neurons. Synchrony was weak [mean k′ = 1.05 ± 0.04 (SD)] but widespread among pairs of M1 neurons (218/1359 pairs with above-chance synchrony), including output neurons. Synchrony usually took the form of a broad central peak [average width, 18.7 ± 8.7 (SD) ms]. There were marked changes during different phases of the task. As a population, synchrony was greatest during the steady hold period in striking contrast to the averaged cell firing rate, which was maximal when the animal was moving the levers into target. However, the modulation of synchrony during task performance showed considerable variation across individual cell pairs. Two types of synchrony were identified: oscillatory (with periodic side lobes in the cross-correlation) and nonoscillatory. Their relative contributions were quantified by filtering the cross-correlations to exclude either frequencies from 18 to 37 Hz or all higher and lower frequencies. At the peak of population synchrony during the hold period, about half (51.7% in one monkey, 56.2% in the other) of the synchronization was within this oscillatory bandwidth. This study provides strong support for assemblies of neurons being synchronized during specific phases of a complex task with potentially important consequences for both information processing within M1 and for the impact of M1 commands on target motoneurons.


2018 ◽  
Vol 7 (6) ◽  
pp. 541-553 ◽  
Author(s):  
Magdalena Matysiak-Kucharek ◽  
Magdalena Czajka ◽  
Krzysztof Sawicki ◽  
Marcin Kruszewski ◽  
Lucyna Kapka-Skrzypczak

AbstractMatrix metallopeptidases, commonly known as matrix metalloproteinases (MMPs), are a group of proteolytic enzymes whose main function is the remodeling of the extracellular matrix. Changes in the activity of these enzymes are observed in many pathological states, including cancer metastases. An increasing body of evidence indicates that nanoparticles (NPs) can lead to the deregulation of MMP expression and/or activity both in vitro and in vivo. In this work, we summarized the current state of knowledge on the impact of NPs on MMPs. The literature analysis showed that the impact of NPs on MMP expression and/or activity is inconclusive. NPs exhibit both stimulating and inhibitory effects, which might be dependent on multiple factors, such as NP size and coating or a cellular model used in the research.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Marie-Julie Nokin ◽  
Florence Durieux ◽  
Paul Peixoto ◽  
Barbara Chiavarina ◽  
Olivier Peulen ◽  
...  

Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion. Elevated MG levels resulted in sustained YAP nuclear localization/activity that could be reverted using Carnosine, a scavenger for MG. MG treatment affected Hsp90 chaperone activity and decreased its binding to LATS1, a key kinase of the Hippo pathway. Cancer cells with high MG stress showed enhanced growth and metastatic potential in vivo. These findings reinforce the cumulative evidence pointing to hyperglycemia as a risk factor for cancer incidence and bring renewed interest in MG scavengers for cancer treatment.


NeuroImage ◽  
2003 ◽  
Vol 19 (4) ◽  
pp. 1349-1360 ◽  
Author(s):  
Maxime Guye ◽  
Geoffrey J.M Parker ◽  
Mark Symms ◽  
Philip Boulby ◽  
Claudia A.M Wheeler-Kingshott ◽  
...  

2019 ◽  
Vol 122 (4) ◽  
pp. 1566-1577 ◽  
Author(s):  
Gerard Derosiere ◽  
David Thura ◽  
Paul Cisek ◽  
Julie Duque

Decisions about actions typically involve a period of deliberation that ends with the commitment to a choice and the motor processes overtly expressing that choice. Previous studies have shown that neural activity in sensorimotor areas, including the primary motor cortex (M1), correlates with deliberation features during action selection. However, the causal contribution of these areas to the decision process remains unclear. Here, we investigated whether M1 determines choice commitment or whether it simply reflects decision signals coming from upstream structures and instead mainly contributes to the motor processes that follow commitment. To do so, we tested the impact of a disruption of M1 activity, induced by continuous theta burst stimulation (cTBS), on the behavior of human subjects in 1) a simple reaction time (SRT) task allowing us to estimate the duration of the motor processes and 2) a modified version of the tokens task (Cisek P, Puskas GA, El-Murr S. J Neurosci 29: 11560–11571, 2009), which allowed us to estimate subjects’ time of commitment as well as accuracy criterion. The efficiency of cTBS was attested by a reduction in motor evoked potential amplitudes following M1 disruption compared with those following a sham stimulation. Furthermore, M1 cTBS lengthened SRTs, indicating that motor processes were perturbed by the intervention. Importantly, all of the behavioral results in the tokens task were similar following M1 disruption and sham stimulation, suggesting that the contribution of M1 to the deliberation process is potentially negligible. Taken together, these findings favor the view that M1 contribution is downstream of the decision process. NEW & NOTEWORTHY Decisions between actions are ubiquitous in the animal realm. Deliberation during action choices entails changes in the activity of the sensorimotor areas controlling those actions, but the causal role of these areas is still often debated. With the use of continuous theta burst stimulation, we show that disrupting the primary motor cortex (M1) delays the motor processes that follow instructed commitment but does not alter volitional deliberation, suggesting that M1 contribution may be downstream of the decision process.


2005 ◽  
Vol 93 (3) ◽  
pp. 1486-1497 ◽  
Author(s):  
Jeremy D. Cohen ◽  
Manuel A. Castro-Alamancos

Learning of motor skills may occur as a consequence of changes in the efficacy of synaptic connections in the primary motor cortex. We investigated if learning in a reaching task affects the excitability, short-term plasticity, and long-term plasticity of horizontal connections in layers II–III of the motor cortex. Because training in this task requires animals to be food-deprived, we compared the trained animals with similarly food-deprived untrained animals and normal controls. The results show that the excitability, short-term plasticity, and long-term plasticity of the studied horizontal connections were unaffected by motor learning. However, stress-related effects produced by food deprivation and handling significantly enhanced the expression of long-term depression in these pathways. These results are compatible with the hypothesis that the acquisition of a complex motor skill produces bi-directional changes in synaptic strength that are distributed throughout the complex neural networks of motor cortex, which remains synaptically balanced during learning. The results are incompatible with the idea that learning causes large unidirectional changes in the population response of these neural networks, which may occur instead during certain behavioral states, such as stress.


Sign in / Sign up

Export Citation Format

Share Document