Staying connected: interneuron development in the mouse visual pathway

Posted by Biome on 30th December 2013 - 0 Comments

The dorsal lateral geniculate nucleus (dLGN) is a processing station located in a central part of the brain called the thalamus, and serves to relay visual information between the retina and the cerebral cortex. Lying at the heart of a key sensory pathway, the dLGN is a powerful model for investigating how developing sensory systems are refined. It contains two main neuronal cell types: thalamocortical relay neurons that receive information from retinal ganglion cells (RGCs) and excite visual cortical neurons, and intrinsic interneurons that also receive information from RGCs but inhibit thalamocortical relay neurons. Relay neurons dominate the dLGN and have therefore been a focus of much research. In a recent study published in Neural Development, William Guido from the University of Louisville, USA, and colleagues use transgenic mice to take a closer look at the less examined intrinsic interneurons.

In mice at birth, RGCs project from both eyes and terminate diffusely on thalamocortical relay cells in the dLGN, with each relay cell receiving inputs from multiple RGCs. The RGCs then undergo an activity-dependent refinement that prunes back this diffuse pattern such that each relay cell maintains inputs from just one to three RGCs by three weeks of age. This process segregates the projections from the two eyes into non-overlapping, eye-specific domains and results in a five- to six-fold reduction in inputs to relay neurons. Generating similar information about interneurons has proven more difficult as they are fewer in number, sparsely dispersed, and not readily identifiable using DIC microscopy.

To circumvent these technical obstacles, Guido and colleagues generated a transgenic mouse expressing GFP specifically in dLGN interneurons. Visualising these cells in acute slices of the thalamus, revealed that the interneurons were evenly distributed throughout the dLGN. Next, these GFP-expressing interneurons were targeted for whole cell electrophysiological recordings. The authors estimated the number of retinal inputs each interneuron received by electrically stimulating the optic tract and measuring the subsequent excitatory postsynaptic potentials generated by the interneurons. Similar to thalamocortical relay cells, the interneurons received many retinal inputs at birth. However, unlike relay cells, there was no detectable decline in the number of inputs over the first five weeks of life, with interneurons maintaining between eight and ten inputs each.

These findings indicate that different cell types in the dLGN undergo different processes of maturation. The authors suggest that the lack of pruning observed in the number of retinal inputs converging onto a single interneuron may be important for their inhibitory function, as this appears to require coordinated inputs from multiple RGCs. In addition to the lack of pruning, the authors were unable to detect plateau-like depolarisations in interneurons. In relay cells retinal activity has been shown to evoke these depolarisations via a specific calcium channel, which is associated with the refinement of retinal projections into eye-specific domains. The absence of these plateau-like depolarisations in interneurons may provide a clue to the wider mechanism underlying cell type specific pruning.