Throughout the brain in a broad range of animal species, synaptic connections between neurons are arranged in layers, or laminae. Laminae are formed by the axons of input neurons connecting with the dendrites of target neurons, and laminae are distinctly organized such that a single lamina contains synapses that share similar functional properties. While research over the last few decades has elucidated many of the molecular mechanisms that guide the formation of this synaptic layering, the purpose of synaptic lamination remains largely unclear.

In a recent study, researchers Nikolas Nikolaou and Martin P. Meyer of King's College London (UK) asked whether synaptic lamination is crucial to the development and function of neural circuits (Neuron 88, 999–1013; 2015). The authors addressed this question using a mutant zebrafish line that lacks the typically organized synaptic lamination of input axons from retinal ganglion cells (RGC) of the eye into the optic tectum, a brain structure that controls higher level visual functions such as prey capture.

Neurons in the optic tectum are direction-selective, meaning that they respond specifically to visual stimuli moving in one direction. This directional specificity in tectal neurons is driven by precise connections with RGCs that are themselves direction-selective. By comparing direction-selectivity in tectal neurons at early and late stages of synapse formation, Nikolaou and Meyer found that although the absence of synaptic layering slowed circuit development in the mutant zebrafish, ultimately the tectal circuits in mutant and wild-type zebrafish became functionally indistinguishable. Nikolaou and Meyer also found that although the mutant zebrafish never regained synaptic lamination, the tectal circuits exhibited full functional recovery of direction-selectivity. When they examined how such a recovery could occur, the authors discovered that the direction-selective tectal neurons adjusted their dendrites to find and connect with incoming RGC axons that they needed to pair with in order to receive directional information. Nikolaou and Meyer attribute this connection in the absence of laminar organization to structural plasticity, or the ability of neurons to alter their morphology and synapses.

These findings demonstrate that the developing brain can overcome the loss of even fundamental and conserved processes such as synaptic lamination. This work suggests that one important purpose of synaptic lamination might be to speed the development of neuronal circuits, and it shows that if given enough time, a disordered brain can set itself straight.