Expression of group II mGluRs in the inferior colliculus, medial geniculate body, and auditory cortex increases with age.

Metabotropic glutamate receptors (mGluRs) are widely expressed throughout the central nervous system. They are linked to G-protein coupled receptors and are known to modulate synaptic transmission. The data regarding their expression in auditory structures are not systematic and mainly originate from physiological studies where expression was used to support physiological findings.

Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.

Growing evidence suggests that neuropeptide signaling shapes auditory computations. We previously showed that neuropeptide Y (NPY) is expressed in the inferior colliculus (IC) by a population of GABAergic stellate neurons and that NPY regulates the strength of local excitatory circuits in the IC. NPY neurons were initially characterized using the NPY-hrGFP mouse, in which humanized renilla green fluorescent protein (hrGFP) expression indicates NPY expression at the time of assay, i.

Differential cholinergic innervation of lemniscal versus non-lemniscal regions of the inferior colliculus.

The inferior colliculus (IC), a midbrain hub for integration of auditory information, receives dense cholinergic input that could modulate nearly all aspects of hearing. A key step in understanding cholinergic modulation is to identify the source(s) and termination patterns of cholinergic input. These issues have not been addressed for the IC in mice, an increasingly important model for study of hearing.

Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.

Growing evidence suggests that neuropeptide signaling shapes auditory computations. We previously showed that neuropeptide Y (NPY) is expressed in the inferior colliculus (IC) by a population of GABAergic stellate neurons and that NPY regulates the strength of local excitatory circuits in the IC. NPY neurons were initially characterized using the NPY-hrGFP reporter mouse, in which hrGFP expression indicates NPY expression at the time of assay, i.

Characterization of three cholinergic inputs to the cochlear nucleus.

Acetylcholine modulates responses throughout the auditory system, including at the earliest brain level, the cochlear nucleus (CN). Previous studies have shown multiple sources of cholinergic input to the CN but information about their relative contributions and the distribution of inputs from each source is lacking. Here, we used staining for cholinergic axons and boutons, retrograde tract tracing, and acetylcholine-selective anterograde tracing to characterize three sources of acetylcholine input to the CN in mice.

Neurotransmitter phenotype and axonal projection patterns of VIP-expressing neurons in the inferior colliculus.

Neurons in the inferior colliculus (IC), the midbrain hub of the central auditory pathway, send ascending and descending projections to other auditory brain regions, as well as projections to other sensory and non-sensory brain regions. However, the axonal projection patterns of individual classes of IC neurons remain largely unknown. Vasoactive intestinal polypeptide (VIP) is a neuropeptide expressed by subsets of neurons in many brain regions.

Dense cholinergic projections to auditory and multisensory nuclei of the intercollicular midbrain.

Cholinergic axons from the pedunculopontine tegmental nucleus (PPT) innervate the inferior colliculus where they are positioned to modulate both excitatory and inhibitory circuits across the central nucleus and adjacent cortical regions. More rostral regions of the auditory midbrain include the nucleus of the brachium of the inferior colliculus (NBIC), the intercollicular tegmentum (ICt) and the rostral pole of the inferior colliculus (ICrp). These regions appear especially important for multisensory integration and contribute to orienting behavior and many aspects of auditory perception.

Multiple Sources of Cholinergic Input to the Superior Olivary Complex.

The superior olivary complex (SOC) is a major computation center in the brainstem auditory system. Despite previous reports of high expression levels of cholinergic receptors in the SOC, few studies have addressed the functional role of acetylcholine in the region. The source of the cholinergic innervation is unknown for all but one of the nuclei of the SOC, limiting our understanding of cholinergic modulation.

Cholinergic boutons are closely associated with excitatory cells and four subtypes of inhibitory cells in the inferior colliculus.

Acetylcholine (ACh) is a neuromodulator that has been implicated in multiple roles across the brain, including the central auditory system, where it sets neuronal excitability and gain and affects plasticity. In the cerebral cortex, subtypes of GABAergic interneurons are modulated by ACh in a subtype-specific manner. Subtypes of GABAergic neurons have also begun to be described in the inferior colliculus (IC), a midbrain hub of the auditory system.

Group II Metabotropic Glutamate Receptors Modulate Sound Evoked and Spontaneous Activity in the Mouse Inferior Colliculus.

Little is known about the functions of Group II metabotropic glutamate receptors (mGluRs2/3) in the inferior colliculus (IC), a midbrain structure that is a major integration region of the central auditory system. We investigated how these receptors modulate sound-evoked and spontaneous firing in the mouse IC We first performed immunostaining and tested hearing thresholds to validate vesicular GABA transporter (VGAT)-ChR2 transgenic mice on a mixed CBA/CaJ x C57BL/6J genetic background. Transgenic animals allowed for optogenetic cell-type identification.

Endogenous Cholinergic Signaling Modulates Sound-Evoked Responses of the Medial Nucleus of the Trapezoid Body.

The medial nucleus of trapezoid body (MNTB) is a major source of inhibition in auditory brainstem circuitry. The MNTB projects well-timed inhibitory output to principal sound-localization nuclei in the superior olive (SOC) as well as other computationally important centers. Acoustic information is conveyed to MNTB neurons through a single calyx of Held excitatory synapse arising from the cochlear nucleus.

Cholinergic Projections From the Pedunculopontine Tegmental Nucleus Contact Excitatory and Inhibitory Neurons in the Inferior Colliculus.

The inferior colliculus processes nearly all ascending auditory information. Most collicular cells respond to sound, and for a majority of these cells, the responses can be modulated by acetylcholine (ACh). The cholinergic effects are varied and, for the most part, the underlying mechanisms are unknown.

Perineuronal nets and subtypes of GABAergic cells differentiate auditory and multisensory nuclei in the intercollicular area of the midbrain.

The intercollicular region, which lies between the inferior and superior colliculi in the midbrain, contains neurons that respond to auditory, visual, and somatosensory stimuli. Golgi studies have been used to parse this region into three distinct nuclei: the intercollicular tegmentum (ICt), the rostral pole of the inferior colliculus (ICrp), and the nucleus of the brachium of the IC (NBIC). Few reports have focused on these nuclei, especially the ICt and the ICrp, possibly due to lack of a marker that distinguishes these areas and is compatible with modern methods.

Generation of a ChAT mouse line without the early onset hearing loss typical of the C57BL/6J strain.

The development of knockin mice with Cre recombinase expressed under the control of the promoter for choline acetyltransferase (ChAT) has allowed experimental manipulation of cholinergic circuits. However, currently available ChAT mouse lines are on the C57BL/6J strain background, which shows early onset age-related hearing loss attributed to the Cdh23 mutation (a.k.

A novel class of inferior colliculus principal neurons labeled in vasoactive intestinal peptide-Cre mice.

Located in the midbrain, the inferior colliculus (IC) is the hub of the central auditory system. Although the IC plays important roles in speech processing, sound localization, and other auditory computations, the organization of the IC microcircuitry remains largely unknown. Using a multifaceted approach in mice, we have identified vasoactive intestinal peptide (VIP) neurons as a novel class of IC principal neurons.

Bilateral projections to the thalamus from individual neurons in the inferior colliculus.

The medial geniculate body (MG) receives a large input from the ipsilateral inferior colliculus (IC) and a smaller but substantial input from the contralateral IC. Both crossed and uncrossed inputs comprise a large percentage of glutamatergic cells and a smaller percentage of GABAergic cells. We used double labeling with fluorescent retrograde tracers to identify individual IC cells that project bilaterally to the MGs in adult guinea pigs.

Subtypes of GABAergic cells in the inferior colliculus.

The inferior colliculus occupies a central position in ascending and descending auditory pathways. A substantial proportion of its neurons are GABAergic, and these neurons contribute to intracollicular circuits as well as to extrinsic projections to numerous targets. A variety of types of evidence - morphology, physiology, molecular markers - indicate that the GABAergic cells can be divided into at least four subtypes that serve different functions.

GABAergic and non-GABAergic projections to the superior colliculus from the auditory brainstem.

The superior colliculus (SC) contains an auditory space map that is shaped by projections from several subcortical auditory nuclei. Both GABAergic (inhibitory) and excitatory cells contribute to these inputs, but there are contradictory reports regarding the sources of these inputs. We used retrograde tracing techniques in guinea pigs to identify cells in the auditory brainstem that project to the SC.

Perineuronal nets in subcortical auditory nuclei of four rodent species with differing hearing ranges.

Perineuronal nets (PNs) are aggregates of extracellular matrix molecules that surround some neurons in the brain. While PNs occur widely across many cortical areas, subcortical PNs are especially associated with motor and auditory systems. The auditory system has recently been suggested as an ideal model system for studying PNs and their functions.

Anterograde Tract Tracing for Assaying Axonopathy and Transport Deficits in Glaucoma.

Whether to stage degeneration or investigate early pathology in glaucoma, examination of axonal structure and function is essential. There are a wide variety of methods available to investigators using animal models of glaucoma, with varying utilities depending on the questions asked. Here, we describe the use of anterograde neuronal tract tracing using cholera toxin B (CTB) for the determination of axon transport integrity of the retinofugal projection.

Persistence of intact retinal ganglion cell terminals after axonal transport loss in the DBA/2J mouse model of glaucoma.

Axonal transport defects are an early pathology occurring within the retinofugal projection of the DBA/2J mouse model of glaucoma. Retinal ganglion cell (RGC) axons and terminals are detectable after transport is affected, yet little is known about the condition of these structures. We examined the ultrastructure of the glaucomatous superior colliculus (SC) with three-dimensional serial block-face scanning electron microscopy to determine the distribution and morphology of retinal terminals in aged mice exhibiting varying levels of axonal transport integrity.

Extracellular Molecular Markers and Soma Size of Inhibitory Neurons: Evidence for Four Subtypes of GABAergic Cells in the Inferior Colliculus.

Unlabelled: 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.

Excitatory and inhibitory projections in parallel pathways from the inferior colliculus to the auditory thalamus.

Individual subdivisions of the medial geniculate body (MG) receive a majority of their ascending inputs from 1 or 2 subdivisions of the inferior colliculus (IC). This establishes parallel pathways that provide a model for understanding auditory projections from the IC through the MG and on to auditory cortex. A striking discovery about the tectothalamic circuit was identification of a substantial GABAergic component.