Peripheral Nerve Injury Induces Immediate Increases in Layer V Neuronal Activity

Abstract

Background Peripheral nerve injury leads to changes in neuronal activity in the contralateral and ipsilateral primary somatosensory cortices (S1), which may lead to enduring sensory dysfunction and pain. Plasticity in the barrel and visual cortices has been shown to occur in a layer-specific manner. However, little is known about the layer specific changes associated with limb injury. Objective To determine the layer-specific changes in neuronal activity associated with short-term plasticity induced by peripheral nerve injury in the rat. Methods In vivo electrophysiology recordings (multiunit activity and local field potential) and high-resolution functional magnetic resonance imaging techniques were applied to characterize neuronal and hemodynamic responses across the depth of S1 contralateral and ipsilateral to the injury. Results Within 60 minutes following injury, atypical increases in neuronal and hemodynamic responses in the deprived S1, ipsilateral to the noninjured limb, were observed in response to stimulation of the noninjured limb. The most prominent increases in neuronal activity in the deprived S1 occurred in layer V. Conclusion Layer V neurons provide the major output of S1 and they send and receive transcallosal input. Thus, the immediate changes in neuronal firing patterns in layer V induced by the injury, can adversely affect the activity of subcortical regions and also interfere with normal cortical processing and interhemispheric communication. Therefore, a rehabilitation strategy that targets layer V neurons activity and starts immediately after the injury may benefit the functional outcome.

Evidence for Impaired Plasticity after Traumatic Brain Injury in the Developing Brain

“…Indeed, transcallosal-mediated plasticity has been shown to play a significant role in recovery and rehabilitation after stroke and peripheral nerve injuries. [47][48][49][50][51] In an animal model of peripheral nerve injury, altered transcallosal communication was observed to occur within minutes after injury 52 and persist for weeks. [28][29][30] In these cases, the postinjury changes in transcallosal connections resulted in increased cortical inhibition.…”

Molecular Neuroimaging of Post-Injury Plasticity

“…Nerve injury often results in significant and long-term changes in neuronal activity, which is manifested by altered electrophysiological and functional magnetic resonance imaging (fMRI) responses in cortical areas contralateral and ipsilateral to the injury (Pelled et al, 2007; Pelled et al, 2009; Pawela et al, 2010; Li et al, 2011; Han et al, 2013). While evidence suggests that these neurophysiological changes correlate with the degree of sensory dysfunction and pain in patients (Flor et al, 1995; Lundborg, 2003; Ephraim et al, 2005; Navarro et al, 2007), the cellular mechanisms leading to these neuronal alterations remain unclear.…”

“…Despite refined surgical techniques, the clinical outcome in adults is generally poor, with persisting sensory and pain problems (Lundborg, 2003). Previously, we demonstrated that neurons located in layer V of the affected primary somatosensory cortex (S1) (contralateral to the injured limb) are specifically vulnerable to injury (Pelled et al, 2009; Han et al, 2013). Moreover, it appears that the neuronal population in layer V that shows the greatest changes in firing rate post-injury are the inhibitory interneurons (Pelled et al, 2009; Li et al, 2011).…”

Non-invasive neuromodulation using rTMS and the Electromagnetic-Perceptive Gene (EPG) facilitates plasticity after nerve injury

“…The results suggest that an immediate, acute, rTMS intervention may be more effective compared to rTMS treatments that begins in the sub-acute phase. This builds on a growing bulk of evidence demonstrating that peripheral nerve injury leads to immediate changes in neural function that may dictate the degree of future rehabilitation 12,14,37,[49][50][51] . Immediate changes in both spontaneous and evoked neural activity have been also demonstrated in models of spinal cord injury 52 .…”

“…For example, human studies suggest a strong correlation between abnormal post-injury cortical responses that are often observed with fMRI to the degree of sensory dysfunctions and phantom limb pain [2][3][4] . The neural mechanisms implicated in the post-injury cortical changes have been extensively studied in animal models; Studies indicate that peripheral injury evokes cellular mechanisms effecting immediate 5 and long-term [6][7][8][9] function of the primary somatosensory cortex (S1) contralateral and ipsilateral to the injured limb. These mechanisms include alteration in the excitation-inhibition balance 10 , changes in GABAergic function 11 , and increases in the activity of inhibitory interneurons in cortical layer 5 (L5) in the affected (deprived) cortex [12][13][14] .…”