© Springer Science+Business Media LLC 2017. Lateralization of brain function has primarily been studied at the macroscopic level. Studies have detected gross anatomical differences in neuron types, numbers, distribution, and connectivity and related these to functional divisions between the two hemispheres. Comparatively little is known about lateralization of synaptic function. A notable exception to this is the recently uncovered lateralization of receptor composition, structure, and function of hippocampal Cornu Ammonis (CA)3–CA1 synapses in rodents. Electrophysiological and electron microscopic studies have revealed that synapses made by the left CA3 onto CA1 neurons on either side of the hippocampus exhibit distinct receptor composition and morphology from those made by the right CA3. Here, we discuss how optogenetic activation and silencing methods have been employed to investigate the consequences of this lateralization for synaptic physiology and circuit organization during learning. The results suggest two general conclusions. First, the spatiotemporal precision of optogenetic tools enables the dissection of lateralization of circuit function in unprecedented detail. Second, seemingly subtle molecular and subcellular lateralizations can translate into prominent differences in circuit function across the hemispheres.
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