Perineuronal nets and the inhibitory cirtuitry of the auditory midbrain: Evidence for subtypes of gabaergic neurons

Perineuronal nets (PNs) are aggregates of extracellular matrix molecules that surround subsets of neurons throughout the central nervous system (Celio and Blumcke, 1994). PNs appear postnatally and often in association with the closing of periods of heightened plasticity, for example in zebra finch song nuclei around the time of song learning (Balmer et al., '09). PNs are present throughout the adult auditory system, however little information is available about subcortical PNs in general, and subcortical auditory PNs in particular (Sonntag et al., '15). Preliminary data indicates a large number of PNs in the inferior colliculus (IC), a major auditory hub. Reports of PNs in the inferior colliculus (IC) vary widely in the description of their distribution (Seeger et al., '94; Atoji et al., '97; Friauf, '00; Hilbig et al., '07), and although PNs are preferentially associated with GABAergic interneurons in other brain areas (Kosaka and Heizmann, '89; Hartig et al., '92), the neurotransmitter phenotype of IC PN-surrounded neurons has not been described. Additionally, nothing is known about the circuitry of PN-surrounded IC neurons. The likely association of PNs with GABAergic cells leads to the question of whether PN-surrounded IC cells fall into the small GABAergic (SG) or large GABAergic (LG) categories described by Ito et al. (2009). Preliminary data suggests an association with the LG group, based on an association between PNs and dense rings of terminals containing vesicular glutamate transporter 2 (VGLUT2- a marker of LG cells). There is currently no information about the projections of PN-surrounded IC neurons. As stated above, PNs are associated with interneurons in other areas, however all IC neurons are believed to have projections outside of the IC (Oliver et al., '91). An association with GABA cells makes it likely that PN-surrounded IC cells will project to either the medial geniculate body (MGB) or the contralateral IC, as these are the two main projections of IC GABA cells (Gonzalez-Hernandez et al., '96; Winer et al., '96). A larger proportion of the IC-MGB pathway is GABAergic, making this the more likely target. The lack of information about the distribution, neurotransmitter phenotype, and circuitry of PN-surrounded neurons in the IC is a major roadblock to understanding the function of PNs in hearing.