scholarly journals Basal ganglia and cortical control of thalamic rebound spikes

2018 ◽  
Author(s):  
Mohammadreza Mohagheghi Nejad ◽  
Stefan Rotter ◽  
Robert Schmidt
Keyword(s):  
Basal Ganglia ◽  
Neural Activity ◽  
Output Neurons ◽  
Cortical Excitation ◽  
Sensory Responses ◽  
Rebound Spiking ◽  
Motor Thalamus ◽  
The Impact ◽  
Motor Signals

AbstractBasal ganglia output neurons transmit motor signals by decreasing their firing rate during movement. This decrease can lead to post-inhibitory rebound spikes in thalamocortical neurons in motor thalamus. While in healthy animals neural activity in the basal ganglia is markedly uncorrelated, in Parkinson’s disease neural activity becomes pathologically correlated. Here we investigated the impact of correlations in the basal ganglia output on the transmission of motor signals to motor thalamus using a Hodgkin-Huxley model of a thalamocortical neuron. We found that correlations in the basal ganglia output disrupt the transmission of motor signals via rebound spikes by decreasing the signal-to-noise ratio and increasing the trial-to-trial variability. We further examined the role of brief sensory responses in basal ganglia output neurons and the effect of cortical excitation of motor thalamus in modulating rebound spiking. Interestingly, both the sensory responses and cortical inputs could either promote or suppress the generation of rebound spikes depending on their timing relative to the motor signal. Finally, in the model rebound spiking occurred despite the presence of moderate levels of excitation, indicating that rebound spiking might be feasible in a parameter regime relevant also in vivo. Overall, our model provides novel insights into the transmission of motor signals from the basal ganglia to motor thalamus by suggesting new functional roles for active decorrelation and sensory responses in the basal ganglia, as well as cortical excitation of motor thalamus.

scholarly journals Optogenetic activation of the inhibitory nigro-collicular circuit evokes orienting movements in mice

2020 ◽  
Author(s):  
C.A. Villalobos ◽  
M.A. Basso
Keyword(s):  
Basal Ganglia ◽  
Substantia Nigra ◽  
High Frequency ◽  
Current Model ◽  
Optogenetic Stimulation ◽  
Output Neurons ◽  
Rebound Spiking ◽  
Stimulation Of

ABSTRACTIn contrast to predictions from the current model of basal ganglia (BG) function, we report here that increasing inhibition from the BG to the superior colliculus (SC) through the substantia nigra (nigra) using in vivo optogenetic activation of GABAergic terminals in mice, produces contralateral orienting movements. Orienting movements resulting from activation of inhibitory nigral terminals are unexpected because decreases and not increases, in nigral activity are generally associated with orienting movements. To determine how orienting movements may result from activation of inhibitory terminals, we performed a series of slice experiments and found that the same optogenetic stimulation of nigral terminals used in vivo, evoked post-inhibitory rebound depolarization and spiking in SC output neurons in vitro. Only high frequency (100Hz) stimulation evoked contralateral movements in vivo and triggered rebound spiking in vitro. The latency of orienting movements relative to the stimulation in vivo was similar to the latency of rebound spiking in vitro. Taken together, our results point toward a novel hypothesis that inhibition from the BG may play an active rather than passive role in the generation of orienting movements in mice.

scholarly journals The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lulu Yao ◽  
Zongliang Wang ◽  
Di Deng ◽  
Rongzhen Yan ◽  
Jun Ju ◽  
...  
Keyword(s):  
Neural Activity ◽  
Brain Activity ◽  
Brain Slices ◽  
Unit Recording ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
Neural Spiking ◽  
In Vivo Calcium Imaging ◽  
The Impact

Abstract Background N-methyl-D-aspartate receptor (NMDAR) hypofunction has been proposed to underlie the pathogenesis of schizophrenia. Specifically, reduced function of NMDARs leads to altered balance between excitation and inhibition which further drives neural network malfunctions. Clinical studies suggested that NMDAR modulators (glycine, D-serine, D-cycloserine and glycine transporter inhibitors) may be beneficial in treating schizophrenia patients. Preclinical evidence also suggested that these NMDAR modulators may enhance synaptic NMDAR function and synaptic plasticity in brain slices. However, an important issue that has not been addressed is whether these NMDAR modulators modulate neural activity/spiking in vivo. Methods By using in vivo calcium imaging and single unit recording, we tested the effect of D-cycloserine, sarcosine (glycine transporter 1 inhibitor) and glycine, on schizophrenia-like model mice. Results In vivo neural activity is significantly higher in the schizophrenia-like model mice, compared to control mice. D-cycloserine and sarcosine showed no significant effect on neural activity in the schizophrenia-like model mice. Glycine induced a large reduction in movement in home cage and reduced in vivo brain activity in control mice which prevented further analysis of its effect in schizophrenia-like model mice. Conclusions We conclude that there is no significant impact of the tested NMDAR modulators on neural spiking in the schizophrenia-like model mice.

scholarly journals Using temperature to analyse the neural basis of a latent temporal decision

2020 ◽  
Author(s):  
Tiago Monteiro ◽  
Filipe S. Rodrigues ◽  
Margarida Pexirra ◽  
Bruno F. Cruz ◽  
Ana I. Gonçalves ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Neural Activity ◽  
Time Course ◽  
Neuronal Population ◽  
Judgment Task ◽  
Neural Basis ◽  
Behavioral Measures ◽  
Population Activity ◽  
Loop Control ◽  
The Impact

AbstractTime, like space, is a fundamental dimension of the environment, critical for much of brain function. Yet, its neural bases are poorly understood. One prominent hypothesis posits that time is implicit in the state of neuronal population activity as it evolves along reproducible trajectories in the space of possible firing patterns. We tested this hypothesis in the striatum, an input area of the basal ganglia known to contain neural activity whose time-course correlates with behavioral measures of timing. Using a custom thermoelectric implant capable of closed-loop control of temperature in striatal tissue, we measured the impact of temperature increases and decreases on both optogenetically induced striatal population activity and the behavior of rats performing a temporal judgment task. Cooler temperatures caused dilation, and warmer temperatures contraction, of both neural activity and the pattern of judgments in time. In contrast, temperature did not affect low level timing of movements. These data demonstrate that the time-course of evolving striatal population activity dictates the speed of a latent timing process that is used to guide decision-making but that is not used to specify the details of movement execution, with broad implications for understanding both the neural basis of timing and, more generally, the role of basal ganglia circuits in behavior.

scholarly journals An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sho Aoki ◽  
Jared B Smith ◽  
Hao Li ◽  
Xunyi Yan ◽  
Masakazu Igarashi ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Ventral Striatum ◽  
Motor Output ◽  
Functional Domain ◽  
Closed Loops ◽  
Dorsolateral Striatum ◽  
Parallel Circuits ◽  
Motor Loop ◽  
Motor Thalamus

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

scholarly journals Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys

2016 ◽  
Vol 115 (1) ◽  
pp. 470-485 ◽  
Author(s):  
Annaelle Devergnas ◽  
Erdong Chen ◽  
Yuxian Ma ◽  
Ikuma Hamada ◽  
Damien Pittard ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Oscillatory Activity ◽  
Electron Microscopic Level ◽  
Dopamine Depletion ◽  
Frequency Range ◽  
Electron Microscopic ◽  
Motor Thalamus

Conventional anti-Parkinsonian dopamine replacement therapy is often complicated by side effects that limit the use of these medications. There is a continuing need to develop nondopaminergic approaches to treat Parkinsonism. One such approach is to use medications that normalize dopamine depletion-related firing abnormalities in the basal ganglia-thalamocortical circuitry. In this study, we assessed the potential of a specific T-type calcium channel blocker (ML218) to eliminate pathologic burst patterns of firing in the basal ganglia-receiving territory of the motor thalamus in Parkinsonian monkeys. We also carried out an anatomical study, demonstrating that the immunoreactivity for T-type calcium channels is strongly expressed in the motor thalamus in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. At the electron microscopic level, dendrites accounted for >90% of all tissue elements that were immunoreactive for voltage-gated calcium channel, type 3.2-containing T-type calcium channels in normal and Parkinsonian monkeys. Subsequent in vivo electrophysiologic studies in awake MPTP-treated Parkinsonian monkeys demonstrated that intrathalamic microinjections of ML218 (0.5 μl of a 2.5-mM solution, injected at 0.1–0.2 μl/min) partially normalized the thalamic activity by reducing the proportion of rebound bursts and increasing the proportion of spikes in non-rebound bursts. The drug also attenuated oscillatory activity in the 3–13-Hz frequency range and increased gamma frequency oscillations. However, ML218 did not normalize Parkinsonism-related changes in firing rates and oscillatory activity in the beta frequency range. Whereas the described changes are promising, a more complete assessment of the cellular and behavioral effects of ML218 (or similar drugs) is needed for a full appraisal of their anti-Parkinsonian potential.

scholarly journals Acetylcholine acts on songbird premotor circuitry to invigorate vocal output

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Paul I Jaffe ◽  
Michael S Brainard
Keyword(s):  
Basal Ganglia ◽  
Neural Activity ◽  
Acetylcholine Receptors ◽  
Sensory Systems ◽  
Muscarinic Acetylcholine Receptors ◽  
Perceptual Sensitivity ◽  
Cholinergic Agonist ◽  
Muscarinic Acetylcholine ◽  
Sensory Responses ◽  
Cortical Regions

Acetylcholine is well-understood to enhance cortical sensory responses and perceptual sensitivity in aroused or attentive states. Yet little is known about cholinergic influences on motor cortical regions. Here we use the quantifiable nature of birdsong to investigate how acetylcholine modulates the cortical (pallial) premotor nucleus HVC and shapes vocal output. We found that dialyzing the cholinergic agonist carbachol into HVC increased the pitch, amplitude, tempo and stereotypy of song, similar to the natural invigoration of song that occurs when males direct their songs to females. These carbachol-induced effects were associated with increased neural activity in HVC and occurred independently of basal ganglia circuitry. Moreover, we discovered that the normal invigoration of female-directed song was also accompanied by increased HVC activity and was attenuated by blocking muscarinic acetylcholine receptors. These results indicate that, analogous to its influence on sensory systems, acetylcholine can act directly on cortical premotor circuitry to adaptively shape behavior.

Self-Organization in the Basal Ganglia with Modulation of Reinforcement Signals

2002 ◽  
Vol 14 (4) ◽  
pp. 819-844 ◽  
Author(s):  
Hiroyuki Nakahara ◽  
Shun-ichi Amari ◽  
Okihide Hikosaka
Keyword(s):  
Basal Ganglia ◽  
Neural Activity ◽  
Neural Circuits ◽  
Self Organization ◽  
Projection Neurons ◽  
Short Term ◽  
Striatal Projection Neurons ◽  
Rapid Changes ◽  
Sensory Cortices ◽  
Sensory Responses

Self-organization is one of fundamental brain computations for forming efficient representations of information. Experimental support for this idea has been largely limited to the developmental and reorganizational formation of neural circuits in the sensory cortices. We now propose that self-organization may also play an important role in short-term synaptic changesinreward-drivenvoluntarybehaviors.Ithasrecentlybeenshown that many neurons in the basal ganglia change their sensory responses flexibly in relation to rewards. Our computational model proposes that the rapid changes in striatal projection neurons depend on the subtle balance between the Hebb-type mechanisms of excitation and inhibition, which are modulated by reinforcement signals. Simulations based on the model are shown to produce various types of neural activity similar to those found in experiments.

Experimental Study of the Impact of Alisma plantago-aquatica Secretions on Pathogenic Bacteria

2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay
Keyword(s):  
Pathogenic Bacteria ◽  
Initial Density ◽  
Biologically Active ◽  
Erysipelothrix Rhusiopathiae ◽  
Natural Focus ◽  
Test Species ◽  
Popula Tions ◽  
And Control ◽  
The Impact

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.

Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

2020 ◽  
Vol 23 ◽  
Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Silver Nanoparticles ◽  
Nuclear Dna ◽  
Liquid Paraffin ◽  
Tail Length ◽  
Hepatic Tissue ◽  
Tissue Destruction ◽  
Group 2 ◽  
The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

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