Intricate mesoscale organization of the anterior commissure in the rhesus monkey, with implications for neuroimaging

The anterior commissure (AC) is generally identified as one of the major interhemispheric pathways. Anatomical results, however, indicate that it has significant ipsilateral components. Further, as reported here, the ipsilaterally projecting axons are organized as a system of narrow, quasi-parallel stripes, especially prominent at the transverse decussation. These appear as a medio-lateral array in coronal tissue sections, but at higher magnification can be seen to consist of axonal segments aggregated in an obliquely anterior-posterior (AP) trajectory. This is counter-oriented to the interstripe surround. For the rhesus macaque, we present evidence that individual stripes align in a 3D volume as thin AP oriented sheets or lamellae. The stripelike pattern in coronal sections is easily identified at early prenatal developmental stages (E70, by acetylcholinesterase), well before the onset of myelination in the AC, possibly pointing to a significant molecular influence underlying the stripelike formation. The functional significance of this non-homogeneous organization remains to be established but may in part relate to a segregation of glutamatergic interhemispheric pathways and transmitter-mixed, non-glutamatergic ipsilateral components. Given this, the AC is better viewed as an interhemispheric pathway only at the midline, but otherwise as a mixed ipsi- and contralateral pathway. The segregation of the stripe/interstripe systems and the absence of the ipsilateral component at the midline is relevant for evaluating volumetric and other changes in the AC over lifespan, in pathological conditions, and for interpreting and designing connectivity studies. The complex mesoarchitecture and pronounced lateral vs. midline subdivision need to be taken into consideration in neuroimaging studies.