title: Extracellular Molecular Markers and Soma Size of Inhibitory Neurons: Evidence for Four Subtypes of GABAergic Cells in the Inferior Colliculus.
abstract: Inhibition plays an important role in shaping responses to stimuli throughout the CNS, including in the inferior colliculus (IC), a major hub in both ascending and descending auditory pathways. Subdividing GABAergic cells has furthered the understanding of inhibition in many brain areas, most notably in the cerebral cortex. Here, we seek the same understanding of subcortical inhibitory cell types by combining staining for two types of extracellular markers--perineuronal nets (PNs) and perisomatic rings of terminals expressing vesicular glutamate transporter 2 (VGLUT2)--to subdivide IC GABAergic cells in adult guinea pigs. We found four distinct groups of GABAergic cells in the IC: (1) those with both a PN and a VGLUT2 ring; (2) those with only a PN; (3) those with only a VGLUT2 ring; and (4) those with neither marker. In addition, these four GABAergic subtypes differ in their soma size and distribution among IC subdivisions. Functionally, the presence or absence of VGLUT2 rings indicates differences in inputs, whereas the presence or absence of PNs indicates different potential for plasticity and temporal processing. We conclude that these markers distinguish four GABAergic subtypes that almost certainly serve different roles in the processing of auditory stimuli within the IC.
  
  
  CONCLUSIONS
  GABAergic inhibition plays a critical role throughout the brain. Identification of subclasses of GABAergic cells (up to 15 in the cerebral cortex) has furthered the understanding of GABAergic roles in circuit modulation. Inhibition is also prominent in the inferior colliculus, a subcortical hub in auditory pathways. Here, we use two extracellular markers to identify four distinct groups of GABAergic cells. Perineuronal nets and perisomatic rings of glutamatergic boutons are present in many subcortical areas and often are associated with inhibitory cells, but they have rarely been used to identify inhibitory subtypes. Our results further the understanding of inhibition in the inferior colliculus and suggest that these extracellular molecular markers may provide a key to distinguishing inhibitory subtypes in many subcortical areas.
authors.affiliation: Northeast Ohio Medical University, Rootstown, Ohio 44272, and Kent State University, Kent, Ohio 44240.
authors.forename: Nichole L
authors.identifier: http://orcid.org/0000-0003-3692-7986
authors.initials: NL
authors.lastname: Beebe
authors.affiliation: Northeast Ohio Medical University, Rootstown, Ohio 44272, and Kent State University, Kent, Ohio 44240.
authors.forename: Jesse W
authors.identifier: http://orcid.org/0000-0001-5358-9339
authors.initials: JW
authors.lastname: Young
authors.affiliation: Northeast Ohio Medical University, Rootstown, Ohio 44272, and.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Mellott
authors.affiliation: Northeast Ohio Medical University, Rootstown, Ohio 44272, and Kent State University, Kent, Ohio 44240 bschofie@neomed.edu.
authors.forename: Brett R
authors.initials: BR
authors.lastname: Schofield
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000166:cytology / Q000502:physiology*; D015415:Biomarkers; D048429:Cell Size; D005110:Extracellular Space / Q000502:physiology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006168:Guinea Pigs; D007245:Inferior Colliculi / Q000166:cytology / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D015415:Biomarkers; D050599:Vesicular Glutamate Transport Protein 2; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase
keywords: GABA; VGLUT2; auditory; inhibition; perineuronal net; plasticity