Spinal cord representation of motor cortex plasticity reflects corticospinal tract LTP

2021 ◽  
Vol 118 (52) ◽  
pp. e2113192118
Author(s):  
Alzahraa Amer ◽  
Jianxun Xia ◽  
Michael Smith ◽  
John H. Martin
Keyword(s):  
Spinal Cord ◽  
Motor Cortex ◽  
Corticospinal Tract ◽  
Cervical Spinal Cord ◽  
Long Term Potentiation ◽  
Dependent Manner ◽  
Term Potentiation ◽  
Spinal Cord Segment ◽  
Spinal Interneuron ◽  
Activity Dependent

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced muscle function, the effects on the corticospinal projection to spinal neurons has not yet been thoroughly studied. Here, we investigate a spinal locus for corticospinal tract (CST) plasticity in anesthetized rats using multichannel recording of motor-evoked, intraspinal local field potentials (LFPs) at the sixth cervical spinal cord segment. We produced LTP by intermittent theta burst electrical stimulation (iTBS) of the wrist area of MCX. Approximately 3 min of MCX iTBS potentiated the monosynaptic excitatory LFP recorded within the CST termination field in the dorsal horn and intermediate zone for at least 15 min after stimulation. Ventrolaterally, in the spinal cord gray matter, which is outside the CST termination field in rats, iTBS potentiated an oligosynaptic negative LFP that was localized to the wrist muscle motor pool. Spinal LTP remained robust, despite pharmacological blockade of iTBS-induced LTP within MCX using MK801, showing that activity-dependent spinal plasticity can be induced without concurrent MCX LTP. Pyramidal tract iTBS, which preferentially activates the CST, also produced significant spinal LTP, indicating the capacity for plasticity at the CST–spinal interneuron synapse. Our findings show CST monosynaptic LTP in spinal interneurons and demonstrate that spinal premotor circuits are capable of further modifying descending MCX control signals in an activity-dependent manner.

Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex

1996 ◽  
Vol 75 (5) ◽  
pp. 1765-1778 ◽  
Author(s):  
G. Hess ◽  
C. D. Aizenman ◽  
J. P. Donoghue
Keyword(s):  
Motor Cortex ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Intracellular Recordings ◽  
Recording Site ◽  
Horizontal Connections ◽  
Term Potentiation ◽  
Activity Dependent

1. The present studies investigated conditions for the induction of long-term potentiation (LTP) in the local horizontal pathways of layers II/III in the primary motor cortex (MI) of the adult rat. Field potential and intracellular recordings demonstrated synaptic interactions across the superficial layers within MI that could be enhanced transiently by focal application of the gamma-aminobuturic acid-A receptor antagonist bicuculline methiodide (Bic) at the recording site. 2. Field potentials evoked in the superficial MI horizontal pathways increased in amplitude after tetanizing, theta burst stimulation (TBS), but only when Bic was applied transiently at the recording site immediately before TBS. In the absence of Bic, TBS failed to produce long-lasting increases in horizontally evoked field responses. By contrast, TBS delivery during focal Bic application increased field potential amplitudes by 25-35% when measured 25-30 min after stimulation. The amount of potentiation was greater when two converging horizontal inputs were stimulated together but was not increased with higher intensity stimulation. Persistent effects of Bic application alone were evident. However, these effects were small unless Bic application continued until evoked field potential amplitude increase exceeded 200% of baseline. 3. The synaptic nature of field potential increases were confirmed using intracellular recordings of layer II/III neurons located near field potential electrodes. 4. LTP also could be induced without Bic application by cotetanization of vertical pathways simultaneously with horizontal activation. Vertical conditioning alone at 2 Hz, which affects inhibitory efficacy, was shown to transiently relieve depression of successive responses that ordinarily occurs during a burst of three horizontal stimuli. These results suggest that LTP of horizontal pathways may be regulated by spatiotemporal interactions between horizontal and vertical pathways. 5. Horizontal LTP was blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid, thereby implicating NMDA-receptor activation in LTP induction for these pathways. 6. The results confirm and extend our previous finding that the potential for activity-dependent modification of synaptic connections exists within the intrinsic horizontal connections of the superficial cortical layers. Synaptic modification across horizontally connected neurons appears to be regulated both by the arrangement of intrinsic circuitry and by the availability of mechanisms for modification at individual synapses. The properties of horizontal connections indicate that they form a spatial substrate and provide an activity-dependent mechanism for plasticity of adult cortical representations.

CS03-01 - Learning and memory in pain pathways

2011 ◽  
Vol 26 (S2) ◽  
pp. 1774-1774
Author(s):  
J. Sandkühler
Keyword(s):  
Long Term Potentiation ◽  
Projection Neurons ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Pain Pathways ◽  
Term Potentiation ◽  
Promising Target ◽  
C Fibre ◽  
High Doses ◽  
Activity Dependent

Hyperalgesia frequently results from injuries or inflammation of peripheral tissues, including nervous tissue and paradoxically also from the treatment with μ-opioid receptor agonists. Compelling evidence indicates that signal amplification in central pain pathways plays an important role for the maintenance of hyperalgesia1. In superficial spinal dorsal horn synaptic transmission between nociceptive C-fibres and lamina I projection neurons can be potentiated for prolonged periods of time in an activity dependent manner. These forms of synaptic long-term potentiation (LTP) can be securely prevented when opioids are applied during afferent stimulation. The blockage of LTP induction by opioids is a likely mechanism or pre-emptive analgesia. Upon withdrawal from high doses of opioids, however, LTP may develop at C-fibre synapses. During the latter form of LTP induction presynaptic activity at C-fibres is depressed rather than enhanced. Despite these fundamental differences in the induction, activity dependent- and opioidergic LTP share signalling pathways. This includes the activation of NMDA receptors, the rise in postsynaptic Ca2+ concentration and the activation of protein kinase C. Induction of opioidergic LTP further requires postsynaptic G-protein coupling which is in contrast to the presynaptic inhibition by opioids. LTP induction is abolished by blocking the Ca2+ rise upon withdrawal from the opioids. It is likely that the potentiation in synaptic strength translates into enhanced pain behaviour1. Plasticity at the first synapse in pain pathways is a promising target for the prevention and treatment of hyperalgesia of various origins.

scholarly journals Neuronal Activity-Dependent Accumulation of Arc in Astrocytes

2020 ◽  
Author(s):  
Yuheng Jiang ◽  
Antonius M.J. VanDongen
Keyword(s):  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Early Gene ◽  
Dependent Manner ◽  
Pharmacological Agents ◽  
Network Activation ◽  
Term Potentiation ◽  
Activity Dependent

AbstractThe immediate-early gene Arc is a master regulator of synaptic plasticity and plays a critical role in memory consolidation. However, there has not been a comprehensive analysis of the itinerary of Arc protein, linking its function at different subcellular locations with corresponding time points after neuronal network activation. When cultured hippocampal neurons are treated with a combination of pharmacological agents to induce long term potentiation, they express high levels of Arc, allowing to study its spatiotemporal distribution. Our experiments show that neuronal activity-induced Arc expression was not restricted to neurons, but that its spatiotemporal dynamics involved a shift to astrocytes at a later timepoint. Specifically, astrocytic Arc is not due to endogenous transcription, but is dependent on the production of neuronal Arc and accumulates potentially via the recently reported intercellular transfer mechanism through Arc capsids. In conclusion, we found that Arc accumulates within astrocytes in a neuronal activity-dependent manner, which is independent of endogenous astrocytic Arc transcription, therefore highlighting the need to study the purpose of this pool of Arc, especially in learning and memory.

scholarly journals Dynamic Regulation of NMDA Receptor Transmission

2011 ◽  
Vol 105 (1) ◽  
pp. 162-171 ◽  
Author(s):  
Abigail C. Gambrill ◽  
Granville P. Storey ◽  
Andres Barria
Keyword(s):  
Synaptic Plasticity ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Dependent Manner ◽  
Dynamic Regulation ◽  
Low Frequency Stimulation ◽  
Term Potentiation ◽  
Frequency Stimulation ◽  
Activity Dependent

N-methyl-d-aspartate receptors (NMDARs) are critical for establishing, maintaining, and modifying glutamatergic synapses in an activity-dependent manner. The subunit composition, synaptic expression, and some of the properties of NMDARs are regulated by synaptic activity, affecting processes like synaptic plasticity. NMDAR transmission is dynamic, and we were interested in studying the effect of acute low or null synaptic activity on NMDA receptors and its implications for synaptic plasticity. Periods of no stimulation or low-frequency stimulation increased NMDAR transmission. Changes became stable after periods of 20 min of low or no stimulation. These changes in transmission have a postsynaptic origin and are explained by incorporation of GluN2B-containing receptors to synapses. Importantly, periods of low or no stimulation facilitate long-term potentiation induction. Moreover, recovery after a weak preconditioning stimulus that normally blocks subsequent potentiation is facilitated by a nonstimulation period. Thus synaptic activity dynamically regulates the level of NMDAR transmission adapting constantly the threshold for plasticity.

scholarly journals DREAM Controls the On/Off Switch of Specific Activity-Dependent Transcription Pathways

2013 ◽  
Vol 34 (5) ◽  
pp. 877-887 ◽  
Author(s):  
Britt Mellström ◽  
Ignasi Sahún ◽  
Ana Ruiz-Nuño ◽  
Patricia Murtra ◽  
Rosa Gomez-Villafuertes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Learning And Memory ◽  
Specific Activity ◽  
Long Term Potentiation ◽  
Specific Gene ◽  
Dependent Manner ◽  
Modify Activity ◽  
Term Potentiation ◽  
Activity Dependent ◽  
The Brain

Changes in nuclear Ca2+homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstreamregulatoryelementantagonistmodulator), also known as calsenilin/KChIP-3 (K+channelinteractingprotein 3), is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory.

scholarly journals Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons

2012 ◽  
Vol 107 (4) ◽  
pp. 1058-1066 ◽  
Author(s):  
Peng Zhang ◽  
John E. Lisman
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Ca1 Neurons ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Term Potentiation ◽  
Activity Dependent

CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.

A critical reappraisal of corticospinal tract somatotopy and its role in traumatic cervical spinal cord syndromes

2021 ◽  
pp. 1-7
Author(s):  
Allan D. Levi ◽  
Jan M. Schwab
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Upper Extremity ◽  
Corticospinal Tract ◽  
Cervical Spinal Cord ◽  
Hand Function ◽  
Cervical Spinal Cord Injury ◽  
Pathophysiological Mechanism ◽  
Cord Injury ◽  
Central Cord Syndrome

The corticospinal tract (CST) is the preeminent voluntary motor pathway that controls human movements. Consequently, long-standing interest has focused on CST location and function in order to understand both loss and recovery of neurological function after incomplete cervical spinal cord injury, such as traumatic central cord syndrome. The hallmark clinical finding is paresis of the hands and upper-extremity function with retention of lower-extremity movements, which has been attributed to injury and the sparing of specific CST fibers. In contrast to historical concepts that proposed somatotopic (laminar) CST organization, the current narrative summarizes the accumulated evidence that 1) there is no somatotopic organization of the corticospinal tract within the spinal cord in humans and 2) the CST is critically important for hand function. The evidence includes data from 1) tract-tracing studies of the central nervous system and in vivo MRI studies of both humans and nonhuman primates, 2) selective ablative studies of the CST in primates, 3) evolutionary assessments of the CST in mammals, and 4) neuropathological examinations of patients after incomplete cervical spinal cord injury involving the CST and prominent arm and hand dysfunction. Acute traumatic central cord syndrome is characterized by prominent upper-extremity dysfunction, which has been falsely predicated on pinpoint injury to an assumed CST layer that specifically innervates the hand muscles. Given the evidence surveyed herein, the pathophysiological mechanism is most likely related to diffuse injury to the CST that plays a critically important role in hand function.

The Vertical Lobe of Cephalopods

2017 ◽  
pp. 558-574 ◽  
Author(s):  
Ana Turchetti-Maia ◽  
Tal Shomrat ◽  
Binyamin Hochner
Keyword(s):  
Complex Networks ◽  
Long Term Potentiation ◽  
Learning Networks ◽  
Neuronal Circuitry ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Matrix Organization ◽  
Activity Dependent ◽  
Similar Organization

We show that the cephalopod vertical lobe (VL) is a promising system for assessing the function and organization of the neuronal circuitry mediating complex learning and memory behavior. Studies in octopus and cuttlefish VL networks suggest an independent evolutionary convergence into a matrix organization of a divergence-convergence (“fan-out fan-in”) network with activity-dependent long-term plasticity mechanisms. These studies also show, however, that the properties of the neurons, neurotransmitters, neuromodulators, and mechanisms of induction and maintenance of long-term potentiation are different from those evolved in vertebrates and other invertebrates, and even highly variable among these two cephalopod species. This suggests that complex networks may have evolved independently multiple times and that, even though memory and learning networks share similar organization and cellular processes, there are many molecular ways of constructing them.

scholarly journals Segmental analysis in cervical spinal cord injury reveals the recovery potential of hand muscles with preserved corticospinal tract: Insights beyond impairment scales

2021 ◽  
Author(s):  
Gustavo Balbinot ◽  
Guijin Li ◽  
Sukhvinder Kalsi-Ryan ◽  
Rainer Abel ◽  
Doris Maier ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Muscle Strength ◽  
Evoked Potentials ◽  
Corticospinal Tract ◽  
Cervical Spinal Cord ◽  
Hand Muscles ◽  
Recovery Potential ◽  
Strength Recovery ◽  
Cord Injury

Cervical spinal cord injury (SCI) severely impacts widespread bodily functions with extensive impairments for individuals, who prioritize regaining hand function. Although prior work has focused on the recovery at the person-level, the factors determining the recovery potential of individual muscles are poorly understood. There is a need for changing this paradigm in the field by moving beyond person-level classification of residual strength and sacral sparing to a muscle-specific analysis with a focus on the role of corticospinal tract (CST) sparing. The most striking part of human evolution involved the development of dextrous hand use with a respective expansion of the sensorimotor cortex controlling hand movements, which, because of the extensive CST projections, may constitute a drawback after SCI. Here, we investigated the muscle-specific natural recovery after cervical SCI in 748 patients from the European Multicenter Study about SCI (EMSCI), one of the largest datasets analysed to date. All participants were assessed within the first 4 weeks after SCI and re-assessed at 12, 24, and 48 weeks. Subsets of individuals underwent electrophysiological multimodal evaluations to discern CST and lower motor neuron (LMN) integrity [motor evoked potentials (MEP): N = 203; somatosensory evoked potentials (SSEP): N = 313; nerve conduction studies (NCS): N = 280]. We show the first evidence of the importance of CST sparing for proportional recovery in SCI, which is known in stroke survivors to represent the biological limits of structural and functional plasticity. In AIS D, baseline strength is a good predictor of segmental muscle strength recovery, while the proportionality in relation to baseline strength is lower for AIS B/C and breaks for AIS A. More severely impaired individuals showed non-linear and more variable recovery profiles, especially for hand muscles, while measures of CST sparing (by means of MEP) improved the prediction of hand muscle strength recovery. Therefore, assessment strategies for muscle-specific motor recovery in acute SCI improve by accounting for CST sparing and complement gross person-level predictions. The latter is of paramount importance for clinical trial outcomes and to target neurorehabilitation of upper limb function, where any single muscle function impacts the outcome of independence in cervical SCI.

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