One critical piece of information that needs to be determined is how much neurons change their behavior, or 'character', after they are mechanically injured. For our purposes, we define 'character' to describe the complete set of properties that the neuron is expressing at the time of stimulation - this includes the specific type, number, and location of membrane receptors, channels, and exchangers, the snapshot of genes expressed within the cell, the transcriptional state, and the location/movement of molecules within the cell.
If there is even a slight change in the neuronal character, there may be a dramatic change in the function of the neuron, its response to drug treatment, and its long term connectivity in a neural network. Therefore, understanding how and why the neuronal state may change after injury - as well as the inherent plasticity in this response - will provide an important starting point for developing treatments that may change over time, or may guide the neuron through its own recovery process.
We have a project ongoing in lab that illustrates this concept. The project focuses on GABA receptors on the surface of neurons, and how they are a very important receptor in controlling the response after mechanical injury. Neuronal GABA receptors in the brain are very common, and their function is to control the level of chloride within the neuron. For some time, it has been known that a major inhibitory neurotransmitter in the brain (GABA) actually has two phases - it first functions as an excitatory neurotransmitter in young, immature neurons and then changes into an inhibitory transmitter when the neuron matures. The changing mode of neurotransmission is not because the GABA receptor changes its structure as the neuron matures, or ages, in culture. Evidence in the literature points to the relative lack of certain membrane extruders/exchangers for chloride as the reason GABA has such a different action over time in culture. This phenomenon is not limited to culture, either. There is evidence that the same changes occur for neurons in the brain as the brain grows and matures.
The varying composition of receptors, extruders/exchangers, and channels suggests that the neuron can (and will) be a highly dynamic system, capable of changing over time. It's not surprising, since neurons have shown an inherent ability for plasticity over time. In addition, it also suggests that the neuronal response to a stimulus such as the GABA neurotransmitter will be very dependent on its 'state space' at the moment of stimulation.