Altered GABA and somatostatin modulation of proprioceptive feedback after spinal cord injury in lamprey

Svensson, Erik; Kim, Oliver; Parker, Dianne

doi:10.1016/j.neuroscience.2013.01.017

Cited by 18 publications

(22 citation statements)

References 42 publications

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“…Changes in modulation could occur directly through changes in the properties of transmitter receptors or second messenger pathways, indirectly through altered interactions between modulatory systems as a result of the loss or reduction of one or more transmitter systems, or through state-dependent effects caused by the lesion-induced changes in cellular and synaptic properties. The different effects of 5-HT in unlesioned and lesioned animals shown here add to the evidence of changes in modulatory effects after spinal cord lesions (Svensson et al, 2013 ). In unlesioned animals, 5-HT had effects that should generally reduced excitation, shown by the consistent, albeit non-significant, hyperpolarization of the membrane potential and the reduction of evoked EPSP amplitudes and spontaneous EPSPs, but in lesioned animals both of these effects were absent.…”

Section: Discussionsupporting

confidence: 72%

“…Our previous analyses have shown that cellular and synaptic properties of larval motor neurons and spinal interneurons are altered below the lesion site (Cooke and Parker, 2009 ). Proprioceptive feedback is also potentiated after lesioning, and the modulation of proprioceptive inputs by GABA and somatostatin is altered (Hoffman and Parker, 2011 ; Svensson et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Changes in functional properties and 5-HT modulation above and below a spinal transection in lamprey

Becker

Parker

2015

Front. Neural Circuits

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In addition to the disruption of neural function below spinal cord injuries (SCI), there also can be changes in neuronal properties above and below the lesion site. The relevance of these changes is generally unclear, but they must be understood if we are to provide rational interventions. Pharmacological approaches to improving locomotor function have been studied extensively, but it is still unclear what constitutes an optimal approach. Here, we have used the lamprey to compare the modulatory effects of 5-HT and lesion-induced changes in cellular and synaptic properties in unlesioned and lesioned animals. While analyses typically focus on the sub-lesion spinal cord, we have also examined effects above the lesion to see if there are changes here that could potentially contribute to the functional recovery. Cellular and synaptic properties differed in unlesioned and lesioned spinal cords and above and below the lesion site. The cellular and synaptic modulatory effects of 5-HT also differed in lesioned and unlesioned animals, again in region-specific ways above and below the lesion site. A role for 5-HT in promoting recovery was suggested by the potential for improvement in locomotor activity when 5-HT was applied to poorly recovered animals, and by the consistent failure of animals to recover when they were incubated in PCPA to deplete 5-HT. However, PCPA did not affect swimming in animals that had already recovered, suggesting a difference in 5-HT effects after lesioning. These results show changes in 5-HT modulation and cellular and synaptic properties after recovery from a spinal cord transection. Importantly, effects are not confined to the sub-lesion spinal cord but also occur above the lesion site. This suggests that the changes may not simply reflect compensatory responses to the loss of descending inputs, but reflect the need for co-ordinated changes above and below the lesion site. The changes in modulatory effects should be considered in pharmacological approaches to functional recovery, as assumptions based on effects in the unlesioned spinal cord may not be justified.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Changes in functional properties and 5-HT modulation above and below a spinal transection in lamprey

Becker

Parker

2015

Front. Neural Circuits

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“…Statistical analyses revealed a significant correlation between GABA accumulation and a higher survival ability of the corresponding identifiable descending neurons (Fernández-López et al, 2014). An electrophysiological study in the spinal cord of lampreys has also found a correlation between higher GABAergic inhibition and a better recovery of function in spinal lesioned animals (Svensson et al, 2013). These data prompted us to hypothesize that, in lampreys, increased GABA signalling after SCI could be favouring the recovery process by promoting survival and axonal regeneration of descending neurons.…”

Section: Introductionmentioning

confidence: 95%

GABA promotes survival and axonal regeneration in identifiable descending neurons after spinal cord injury in larval lampreys

Romaus-Sanjurjo

Ledo-Garcia

Fernández-López

et al. 2018

Preprint

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Phones : +34 881816949 and +34 881816946 Emails: anton.barreiro@usc.es and mcelina.rodicio@usc.es Running title: GABA promotes regeneration after spinal cord injury peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/280891 doi: bioRxiv preprint first posted online Mar. 12, 2018; 2 AbstractIn mammals, spinal cord injury (SCI) causes permanent disability. The poor regenerative capacity of descending neurons is one of the main causes of the lack of recovery after SCI. In addition, the prevention of retrograde degeneration leading to the atrophy or death of descending neurons is an obvious prerequisite for the activation of axonal regeneration. Lampreys show an amazing regenerative capacity after SCI.Recent histological work in lampreys suggested that GABA, which is massively released after a SCI, could promote the survival of descending neurons. Here, we aimed to study if GABA, acting through GABAB receptors, promotes the survival and axonal regeneration of descending neurons of larval sea lampreys after a complete SCI. First, we used in situ hybridization to confirm that identifiable descending neurons of late stage larvae express the gabab1 subunit of the sea lamprey GABAB receptor. We also observed an acute increase in the expression of this subunit in descending neurons after a complete SCI, which further supported the possible role of GABA and GABAB receptors in promoting the survival and regeneration of these neurons. So, we performed gain and loss of function experiments to confirm this hypothesis. Treatments with GABA and baclofen (GABAB agonist) significantly reduced caspase activation in descending neurons 2 weeks after a complete SCI. Long-term treatments with GABOB (a GABA analogue) and baclofen significantly promoted axonal regeneration of descending neurons after SCI. These data indicate that GABAergic signalling through GABAB receptors promotes the survival and regeneration of descending neurons after SCI. Finally, we used morpholinos against the gabab1 subunit to specifically knockdown the expression of the GABAB receptor in descending neurons. Long-term morpholino treatments caused a significant inhibition of axonal regeneration, which shows that endogenous GABA promotes axonal regeneration after a complete SCI in peer-reviewed)

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“…During the recovery process lampreys are able to regenerate axotomized descending axons [ 2 – 4 ] and produce new spinal neurons [ 5 ]. Recent studies have also shown that different neurotransmitters systems adapt and show plastic changes after a spinal cord injury in lampreys, which could also contribute to the recovery of function (serotonergic system: [ 6 , 7 ]; aminoacidergic systems: [ 8 – 10 ]). So, both regeneration and plasticity events appear to contribute to the spontaneous recovery of function in lampreys.…”

Section: Introductionmentioning

confidence: 99%

Full Anatomical Recovery of the Dopaminergic System after a Complete Spinal Cord Injury in Lampreys

et al. 2015

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Following a spinal injury, lampreys at first are paralyzed below the level of transection. However, they recover locomotion after several weeks, and this is accompanied by the regeneration of descending axons from the brain and the production of new neurons in the spinal cord. Here, we aimed to analyse the changes in the dopaminergic system of the sea lamprey after a complete spinal transection by studying the changes in dopaminergic cell numbers and dopaminergic innervation in the spinal cord. Changes in the expression of the D2 receptor were also studied. We report the full anatomical regeneration of the dopaminergic system after an initial decrease in the number of dopaminergic cells and fibres. Numbers of dopaminergic cells were recovered rostrally and caudally to the site of injury. Quantification of dopaminergic profiles revealed the full recovery of the dopaminergic innervation of the spinal cord rostral and caudal to the site of injury. Interestingly, no changes in the expression of the D2 receptor were observed at time points in which a reduced dopaminergic innervation of the spinal cord was observed. Our observations reveal that in lampreys a spinal cord injury is followed by the full anatomical recovery of the dopaminergic system.

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Altered GABA and somatostatin modulation of proprioceptive feedback after spinal cord injury in lamprey

Cited by 18 publications

References 42 publications

Changes in functional properties and 5-HT modulation above and below a spinal transection in lamprey

Changes in functional properties and 5-HT modulation above and below a spinal transection in lamprey

GABA promotes survival and axonal regeneration in identifiable descending neurons after spinal cord injury in larval lampreys

Full Anatomical Recovery of the Dopaminergic System after a Complete Spinal Cord Injury in Lampreys

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