Injury-Induced Plasticity
In response to stress or injury, neurons can upregulate synaptic activity, a process known as injury-induced plasticity. For RGCs exposed to elevated IOP, this could include changes in gene expression to maintain or strengthen synapses, which is known as homeostatic synaptic plasticity. It could also include dendritic remodeling and/or other modifications.
Homeostatic Synaptic Plasticity
Homeostatic synaptic plasticity (above) occurs when a neuron detects changes in its firing rate due to stress, injury or some other factor. To maintain its firing rate, the neuron will increase receptor trafficking to the synapse and/or alter receptor function via expression of alternate receptor isoforms. Using immunohisto-chemistry and electrophysiology we can examine homeostatic synaptic plasticity in RGCs following IOP elevation.
Synaptic plasticity is in large part regulated by post-synaptic calcium levels. This is true for long term plasticity (learning and memory) and for shorter term changes, such as homeostatic synaptic plasticity. The calcium channel transient receptor potential vanilloid 1 (TRPV1) has been shown to contribute to long term plasticity (above left; see Ho 2012 on Publication page) and may play a role in homeostatic synaptic plasticity. TRPV1 is expressed by RGCs (above right) as shown by its localization to the nerve fiber layer (NFL), ganglion cell layer (GCL) and inner plexiform layer (IPL).
Microbead injection to elevate IOP resulted in the upregulation of TRPV1 (red) in the nerve fiber layer (NFL), ganglion cell layer (GCL) and inner plexiform layer (IPL; above left). Elevated IOP also increased the colocalization of TRPV1 (red) with the post-synaptic density protein PSD-95 (green; above right) in the IPL. These data suggest TRPV1 may be involved in RGC homeostatic synaptic plasticity following injury due to elevated IOP, but without electrophysiological data we cannot be sure TRPV1 localization at the synapse affects RGC function.
Combining electrophysiology with pharmacological tools, such as receptor agonists and antagonists, we can examine the influence of various ion channels on homeostatic synaptic plasticity. For example, treatment with a TRPV1 agonist increased firing rate in RGCs from mice exposed to moderate IOP elevation only (above). This suggests TRPV1 is sensitized by moderate IOP elevation, but not by high IOP elevation. The sensitization was specific to TRPV1 as an antagonist to the channel counteracted the effect.
