Microglial peri-somatic abutments classify two novel types of GABAergic neuron in the inferior colliculus
Samuel David Webb1, Llwyd David Orton1,2
1Department of Life Sciences, Manchester Metropolitan University, Manchester, UK.
Abstract:
Emerging evidence suggests functional roles for microglia in the healthy, mature nervous system. However, we know little of the cellular density and ramified morphology of microglia in sensory systems, and even less of their inter-relationship with inhibitory neurons. We therefore conducted fluorescent multi-channel immunohistochemistry and confocal microscopy in guinea pigs of both sexes for Iba1, GAD67, GFAP, calbindin, and calretinin. We explored these markers in the inferior colliculi (IC), which contain sub-regions specialized for different aspects of auditory processing. First, we found that while the density of Iba1+ somata is similar throughout the IC parenchyma, Iba1+ microglia in dorsal cortex are significantly more ramified than those in the central nucleus or lateral cortex. Conversely, Iba1+ ramifications in ventral central nucleus, a region with the highest density of GAD67+ (putative GABAergic) neurons in IC, are longer with fewer ramifications. Second, we observed extensive abutments of ramified Iba1+ processes onto GAD67+ somata throughout the whole IC and developed novel measures to quantify these. Cluster analyses revealed two novel sub-types of GAD67+ neuron that differ in the quantity of Iba1+ somatic abutments they receive. Unlike previous classification schemes for GAD67+ neurons in IC, these clusters are not related to GAD67+ soma size. Taken together, these data demonstrate that microglial ramifications vary between IC sub-regions in the healthy, adult IC, possibly related to the ongoing demands of their niche. Furthermore, Iba1+ abutments onto neuronal somata are a novel means by which GAD67+ neurons can be classified.
Insights
Microglia ramification varies across auditory processing regions in the brain. These immune cells interact with inhibitory neurons, revealing new ways to classify neurons based on microglial contact.
Area of Science:
- Neuroscience
- Immunology
- Auditory Neuroscience
Background:
- Microglia play roles in the mature nervous system, but their density and morphology in sensory systems, especially their relationship with inhibitory neurons, are poorly understood.
- The inferior colliculi (IC) are key auditory processing centers with specialized sub-regions.
Purpose of the Study:
- To investigate the cellular density and ramified morphology of microglia in different sub-regions of the inferior colliculi (IC).
- To explore the inter-relationship between microglia and inhibitory (GAD67+) neurons within the IC.
- To identify novel classifications of inhibitory neurons based on microglial interactions.
Main Methods:
- Fluorescent multi-channel immunohistochemistry and confocal microscopy were used in guinea pigs.
- Markers analyzed included Iba1 (microglia), GAD67 (inhibitory neurons), GFAP, calbindin, and calretinin.
- Novel quantitative measures were developed to assess microglial-neuronal interactions.
Main Results:
- Microglial (Iba1+) somatic density was uniform across IC regions, but ramification differed significantly between dorsal cortex, central nucleus, and lateral cortex.
- Microglial ramifications were longer with fewer branches in the ventral central nucleus, correlating with high GAD67+ neuron density.
- Extensive abutments of microglial processes onto GAD67+ neuronal somata were observed, leading to the identification of two novel GAD67+ neuron subtypes based on microglial contact, independent of soma size.
Conclusions:
- Microglial ramification patterns vary across IC sub-regions in the healthy adult brain, potentially adapting to local functional demands.
- Microglial-neuronal interactions, specifically Iba1+ process abutments onto GAD67+ somata, provide a new basis for classifying inhibitory neurons within the auditory system.
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