Decreases in rat locomotor activity as a result of changes in synaptic transmission to neurons within the mesencephalic locomotor region

1993 ◽  
Vol 71 (5-6) ◽  
pp. 394-406 ◽  
Author(s):  
Stefan M. Brudzynski ◽  
Michael Wu ◽  
Gordon J. Mogenson
Keyword(s):  
Nucleus Accumbens ◽  
Synaptic Transmission ◽  
Synaptic Input ◽  
Cobalt Chloride ◽  
Critical Role ◽  
Ventral Pallidum ◽  
Functional Region ◽  
Mesencephalic Locomotor Region ◽  
Freely Behaving

The mesencephalic locomotor region is defined as a functional region sending signals to the spinal cord generators of rhythmical limb movements for locomotion. It has been shown that the mesencephalic locomotor region plays a critical role in locomotion initiated from the nucleus accumbens or from the subpallidal region. However, there are conflicting data on whether synaptic input from the nucleus accumbens – subpallidal region to the mesencephalic locomotor region mediates locomotion. The purpose of the study was to determine the role of synaptic input to different subregions of the mesencephalic locomotor region in locomotion induced by injecting dopamine into the nucleus accumbens or by injecting picrotoxin into the subpallidal region in freely behaving rats. Synaptic transmission in the mesencephalic locomotor region was eliminated by excitotoxic lesions or was reversibly interrupted by injecting cobalt chloride, which can block synaptic transmission. Excitotoxic lesions or injections of cobalt into subregions of the mesencephalic locomotor region significantly decreased, although did not completely block, locomotion. The most effective sites for cobalt- and lesion-induced reduction in locomotion were consistent with localization of the mesencephalic locomotor region. Effective sites for cobalt and lesions markedly overlapped but were not identical. The results indicate that synaptic transmission within the mesencephalic locomotor region contributes to dopamine- or picrotoxin-induced locomotion.Key words: locomotion, mesencephalic locomotor region, nucleus accumbens, ventral pallidum, dopamine, picrotoxin, excitotoxins, cobalt chloride.

Mitochondrial Ca2+ Buffering Regulates Synaptic Transmission Between Retinal Amacrine Cells

2002 ◽  
Vol 87 (3) ◽  
pp. 1426-1439 ◽  
Author(s):  
Kathryn Medler ◽  
Evanna L. Gleason
Keyword(s):  
Synaptic Transmission ◽  
Mitochondrial Membrane ◽  
Amacrine Cell ◽  
Critical Role ◽  
Amacrine Cells ◽  
Normal Function ◽  
Inner Mitochondrial Membrane ◽  
Physiological Properties ◽  
Low Levels

The diverse functions of retinal amacrine cells are reliant on the physiological properties of their synapses. Here we examine the role of mitochondria as Ca2+ buffering organelles in synaptic transmission between GABAergic amacrine cells. We used the protonophore p-trifluoromethoxy-phenylhydrazone (FCCP) to dissipate the membrane potential across the inner mitochondrial membrane that normally sustains the activity of the mitochondrial Ca2+ uniporter. Measurements of cytosolic Ca2+ levels reveal that prolonged depolarization-induced Ca2+ elevations measured at the cell body are altered by inhibition of mitochondrial Ca2+ uptake. Furthermore, an analysis of the ratio of Ca2+ efflux on the plasma membrane Na-Ca exchanger to influx through Ca2+ channels during voltage steps indicates that mitochondria can also buffer Ca2+ loads induced by relatively brief stimuli. Importantly, we also demonstrate that mitochondrial Ca2+ uptake operates at rest to help maintain low cytosolic Ca2+ levels. This aspect of mitochondrial Ca2+ buffering suggests that in amacrine cells, the normal function of Ca2+-dependent mechanisms would be contingent upon ongoing mitochondrial Ca2+ uptake. To test the role of mitochondrial Ca2+ buffering at amacrine cell synapses, we record from amacrine cells receiving GABAergic synaptic input. The Ca2+ elevations produced by inhibition of mitochondrial Ca2+uptake are localized and sufficient in magnitude to stimulate exocytosis, indicating that mitochondria help to maintain low levels of exocytosis at rest. However, we found that inhibition of mitochondrial Ca2+ uptake during evoked synaptic transmission results in a reduction in the charge transferred at the synapse. Recordings from isolated amacrine cells reveal that this is most likely due to the increase in the inactivation of presynaptic Ca2+ channels observed in the absence of mitochondrial Ca2+ buffering. These results demonstrate that mitochondrial Ca2+ buffering plays a critical role in the function of amacrine cell synapses.

scholarly journals Distinct role of nucleus accumbens D2-MSN projections to ventral pallidum in different phases of motivated behavior

2020 ◽  
Author(s):  
Carina Soares-Cunha ◽  
Raquel Correia ◽  
Ana Verónica Domingues ◽  
Bárbara Coimbra ◽  
Nivaldo AP de Vasconcelos ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Behavioral Effect ◽  
Ventral Pallidum ◽  
Medium Spiny Neurons ◽  
Motivated Behavior ◽  
Spiny Neurons ◽  
Reward Delivery ◽  
Instrumental Task ◽  
Motivated Behaviors

AbstractThe nucleus accumbens (NAc) is a key region in motivated behaviors. NAc medium spiny neurons (MSNs) are divided into those expressing dopamine receptor D1 or D2. Classically, D1- and D2-MSNs have been described as having opposing roles in reinforcement but recent evidence suggests a more complex role for D2-MSNs.Here we show that optogenetic modulation of D2-MSN to ventral pallidum (VP) projections during different stages of motivated behavior has contrasting effects in motivation. Activation of D2-MSN-VP projections during a reward-predicting cue results in increased motivational drive, whereas activation at reward delivery results in decreased motivation; optical inhibition has the opposite behavioral effect. In addition, in a free choice instrumental task, animals prefer the lever that originates one pellet in opposition to pellet plus D2-MSN-VP optogenetic activation, and vice versa for optogenetic inhibition.In summary, D2-MSN-VP projections play different (and even opposing) roles in distinct phases of motivated behavior.

scholarly journals Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

2015 ◽  
Vol 112 (42) ◽  
pp. E5744-E5752 ◽  
Author(s):  
Kristin L. Arendt ◽  
Zhenjie Zhang ◽  
Subhashree Ganesan ◽  
Maik Hintze ◽  
Maggie M. Shin ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Critical Role ◽  
Signal Transduction Pathway ◽  
Acid Synthesis ◽  
Synaptic Activity ◽  
Homeostatic Synaptic Plasticity ◽  
Dependent Protein

Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity.

Transient loss of interhemispheric functional connectivity following unilateral cortical spreading depression in awake rats

Cephalalgia ◽  
2020 ◽  
pp. 033310242097017
Author(s):  
Lyudmila V Vinogradova ◽  
Elena M Suleymanova ◽  
Tatiana M Medvedeva
Keyword(s):  
Functional Connectivity ◽  
Local Field ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Critical Role ◽  
Local Field Potentials ◽  
Abnormal Behavior ◽  
Field Potentials ◽  
Freely Behaving

Objective Growing evidence shows a critical role of network disturbances in the pathogenesis of migraine. Unilateral pattern of neurological symptoms of aura suggests disruption of interhemispheric interactions during the early phase of a migraine attack. Using local field potentials data from the visual and motor cortices, this study explored effects of unilateral cortical spreading depression, the likely pathophysiological mechanism of migraine aura, on interhemispheric functional connectivity in freely behaving rats. Methods Temporal evolution of the functional connectivity was evaluated using mutual information and phase synchronization measures applied to local field potentials recordings obtained in homotopic points of the motor and visual cortices of the two hemispheres in freely behaving rats after induction of a single unilateral cortical spreading depression in the somatosensory S1 cortex and sham cortical stimulation. Results Cortical spreading depression was followed by a dramatic broadband loss of interhemispheric functional connectivity in the visual and motor regions of the cortex. The hemispheric disconnection started after the end of the depolarization phase of cortical spreading depression, progressed gradually, and terminated by 5 min after initiation of cortical spreading depression. The network impairment had region- and frequency-specific characteristics and was more pronounced in the visual cortex than in the motor cortex. The period of impaired neural synchrony coincided with post-cortical spreading depression electrographic aberrant activation of the ipsilateral cortex and abnormal behavior. Conclusion The study provides the first evidence that unilateral cortical spreading depression induces a reversible loss of functional hemispheric connectivity in the cortex of awake animals. Given a critical role of long-distance cortical synchronization in sensory processing and sensorimotor integration, the post-cortical spreading depression breakdown of functional connectivity may contribute to neuropathological mechanisms of aura generation.

scholarly journals Dopaminergic Projections From the Ventral Tegmental Area to the Nucleus Accumbens Modulate Sevoflurane Anesthesia in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Huan Gui ◽  
Chengxi Liu ◽  
Haifeng He ◽  
Jie Zhang ◽  
Hong Chen ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Critical Role ◽  
Sevoflurane Anesthesia ◽  
Loss Of Righting Reflex ◽  
Delta Band ◽  
Dopaminergic Pathway ◽  
Righting Reflex ◽  
Ventral Tegmental

The role of the dopaminergic pathway in general anesthesia and its potential mechanisms are still unknown. In this study, we usedc-Fos staining combined with calcium fiber photometry recording to explore the activity of ventral tegmental area (VTA) dopaminergic neurons(VTA-DA) and nucleus accumbens (NAc) neurons during sevoflurane anesthesia. A genetically encoded dopamine (DA) sensor was used to investigate thefunction of the NAc in sevoflurane anesthesia. Chemogenetics and optogenetics were used to explore the role of the VTA-DA in sevofluraneanesthesia. Electroencephalogram (EEG) spectra, time of loss of righting reflex (LORR) and recovery of righting reflex (RORR) were recorded asassessment indicators. We found that VTA-DA and NAc neurons were inhibited during the induction period and were activated during the recoveryperiod of sevoflurane anesthesia. The fluorescence signals of dopamine decreased in the induction of and increased in the emergence from sevoflurane anesthesia.Activation of VTA-DA and the VTADA-NAc pathway delayed the induction and facilitated the emergence accompanying with thereduction of delta band and the augmentation of the gamma band. These data demonstrate that VTA-DA neurons play a critical role in modulating sevofluraneanesthesia via the VTADA-NAc pathway.

scholarly journals Loss of O-GlcNAcylation on MeCP2 Thr 203 Leads to Neurodevelopmental Disorders

2020 ◽  
Author(s):  
Juanxian Cheng ◽  
Zhe Zhao ◽  
Liping Chen ◽  
Ruijing Du ◽  
Yan Wu ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neural Development ◽  
Hippocampal Neurons ◽  
Critical Role ◽  
Dendrite Development ◽  
Genome Wide ◽  
Mouse Cerebral Cortex ◽  
Functional Regulation ◽  
Spine Morphogenesis

AbstractMutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials reveal several putative RTT-associated mutations on MECP2, their causative relevance regarding the functional regulation of MeCP2 on the etiologic sites at the protein level require more evidence. In this study, we demonstrate that MeCP2 is dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impairs dendrite development and spine maturation in cultured hippocampal neurons, and disrupts neuronal migration, dendritic spine morphogenesis and dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreases neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via BDNF.

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