Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.

Sensory deafferentation produces extensive reorganization of the corresponding deafferented cortex. Little is known, however, about the role of the adjacent intact cortex in this reorganization. Here we show that a complete thoracic transection of the spinal cord immediately increases the responses of the intact forepaw cortex to forepaw stimuli (above the level of the lesion) in anesthetized rats. These increased forepaw responses were independent of the global changes in cortical state induced by the spinal cord transection described in our previous work (Aguilar et al., J Neurosci 2010), as the responses increased both when the cortex was in a silent state (down-state) or in an active state (up-state). The increased responses in the intact forepaw cortex correlated with increased responses in the deafferented hindpaw cortex, suggesting that they could represent different points of view of the same immediate state-independent functional reorganization of the primary somatosensory cortex after spinal cord injury. Collectively, the results of the present study and of our previous study suggest that both state-dependent and state-independent mechanisms can jointly contribute to cortical reorganization immediately after spinal cord injury.

Spinal cord injury (SCI) involves large-scale deafferentation of supraspinal structures in the somatosensory system, producing well-known long-term effects at the thalamo-cortical level. We recently showed that SCI provokes immediate changes in cortical spontaneous and evoked responses and here, we have performed a similar study to define the immediate changes produced in the thalamic ventro-postero-lateral nucleus (VPL) that are associated with the forepaw and hindpaw circuits. Extracellular electrophysiological recordings from the VPL reflected the spontaneous activity and the responses to peripheral electrical stimulation applied to the paws. Accordingly, the activity of the neuronal populations recorded at specific thalamic locations that correspond to the forepaw and hindpaw circuits was recorded under control conditions and immediately after thoracic SCI. The results demonstrate that peripheral inputs from both extremities overlap on neuronal populations in the somatosensory thalamus. In addition, they show that the responses of thalamic neurons to forepaw and hindpaw stimuli are increased immediately after SCI, in association with a specific decrease in spontaneous activity in the hindpaw locations. Finally, the increased thalamic responses after SCI have a state-dependent component in relation with cortical activity. Together, our results indicate that the thalamic changes occurring immediately after SCI could contribute to the cortical changes also detected immediately after such spinal lesions.

Key points Thalamic activity is regulated by corticothalamic feedback from layers 5B and 6. To selectively study the importance of the layer 6 corticothalamic (L6 CT) projection, a transgenic mouse line was used in which layer 6 cells projecting to posterior medial thalamus (POm) were targeted for expression of channelrhodopsin‐2. Repetitive optogenetic stimulation of this sub‐type of L6 cells caused a rapid adaptation in POm spiking output, but had little effect on the spiking activity in the other cortical layers. L6 photoactivation increased POm spiking to the first, but not to subsequent whisker deflections in a 4 Hz train. A sub‐population of L6 CT cells that can cause an initial increase in POm activity, that is not sustained with repetitive stimulation, could indicate that this L6 projection does not modulate ongoing sensory processing, but rather serves to briefly increase POm activity in specific behavioural contexts. Abstract Thalamic activity is regulated by corticothalamic feedback from layers 5B and 6. The nature of these feedback systems differs, one difference being that whereas layer 5 provides ‘driver’ input, the layer 6 input is thought to be ‘modulatory’. To selectively study the importance of the layer 6 corticothalamic (L6 CT) projection, a transgenic mouse line was used in which layer 6 cells projecting to posterior medial thalamus (POm) were targeted for expression of channelrhodopsin‐2 and in vivo electrophysiology recordings were done in urethane‐anaesthetized mice. Pre‐ and postsynaptic targets were identified using tracing techniques and light‐sheet microscopy in cleared intact brains. We find that optogenetic activation of this subtype of L6 CT cells (L6‐Drd1) has little effect on cortical activity, but activates POm. Repetitive photoactivation of L6‐Drd1 cells evoked a reliable response following every photoactivation, whereas in the connected POm area spiking was only initially increased. The response to repetitive whisker stimulation showed a similar pattern with only an initial increase in whisker‐evoked spiking. Furthermore, the increase in whisker‐evoked spiking with optogenetic activation of L6‐Drd1 cells is additive, rather than multiplicative, causing even cells that in the absence of L6 activation produce relatively few spikes to increase their spiking substantially. We show that layer 6 corticothalamic cells can provide a strong, albeit rapidly depressing, input to POm. This type of cortical L6 activity could be important for rapid gain control in POm, rather than providing a modulation in phase with the whisking cycle.

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