Changes in GABAA receptor subunit gamma 2 in extensor and flexor motoneurons and astrocytes after spinal cord transection and motor training

GABA signaling plays an important role in the spinal cord response to injury and subsequent motor training. Since benzodiazepines are commonly used to treat muscle spasticity in spinal cord injured subjects and the gamma 2 subunit of the GABA(A) receptor is necessary for benzodiazepine binding, this subunit may be an important factor modulating sensorimotor function after an injury. Changes in gamma 2 levels in muscle-specific motoneurons and surrounding astrocytes were determined similar to 3 months after a complete mid-thoracic spinal cord transection at P5 in non-trained and in step-trained spinal rats. Soleus (ankle extensor) and tibialis anterior (TA, ankle flexor) motor pools were identified using retrograde labeling via intramuscular injections of Fast Blue or Fluoro Gold, respectively. Lumbar spinal cord sections showed gamma 2 immunostaining in both soleus and TA motoneurons and astrocytes. gamma 2 immunoreactivity on the soma of soleus and TA motoneurons in spinal rats was differentially modulated. Compared to intact rats, spinal rats had higher levels of gamma 2 in TA, and lower levels in soleus motoneurons. Step training restored GABA(A) gamma 2 levels towards control values in motoneuronal pools of both muscles. In contrast, the gamma 2 levels were elevated in surrounding astrocytes of both motor pools in spinal rats, and step training had no further effect. Thus, motor training had a specific effect on those neurons that were directly involved with the motor task. Since the gamma 2 subunit is involved with GABA(A) receptor trafficking and synaptic clustering, it appears that this subunit could be an important component of the activity-dependent response of the spinal cord after a spinal injury. (C) 2009 Elsevier B.V. All rights reserved.