Inferior collicular cells that project to the auditory thalamus are increasingly surrounded by perineuronal nets with age

Mafi, Amir M.; Russ, Matthew; Hofer, Lindsay; Pham, Vincent Q.; Young, Jesse W.; Mellott, Jeffrey G.

doi:10.1016/j.neurobiolaging.2021.04.001

Cited by 5 publications

(22 citation statements)

References 114 publications

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“…Given that (1) FGF-2 contributes to dendritic arborization and synaptic plasticity, (2) DCVs often carry contents such growth factors that play a role in synaptogenesis, and (3) the aged IC has a loss of dendrites and synapses, the IC may undergo a number of plastic events during middle age ( Helfert et al, 1999 ; Sorra et al, 2006 ; Li et al, 2020 ). Further supporting the theory of increased plasticity with aging in the IC, perineuronal nets (organized extracellular matrix that have substantial roles in neural plasticity) increase with aging in the IC ( Fader et al, 2016 ; Bosiacki et al, 2019 ; Mafi et al, 2020 , 2021 ; Almassri et al, 2023 ). Taken altogether, the increase of DCVs in the aging IC may contribute to elements of dendritic and synaptic plasticity.…”

Section: Discussionmentioning

confidence: 55%

“…The FBN rat is a recommended aging model by the National Institute on Aging as it has a longer median lifespan than other strains of mice and rats ( Lipman et al, 1996 ; Lipman, 1997 ). Of note, the FBN rat is routinely used as a characterized model for aging, in particular for studies of the central auditory system ( Caspary et al, 2008 ; Cai et al, 2018 ; Caspary and Llano, 2018 ; Robinson et al, 2019 ; Mafi et al, 2020 , 2021 , 2022 ; Kommajosyula et al, 2021 ). We have chosen to use four age groups in this study.…”

Section: Discussionmentioning

confidence: 99%

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Age-related upregulation of dense core vesicles in the central inferior colliculus

Mellott,

Duncan,

Busby

et al. 2024

Front. Cell. Neurosci.

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Presbycusis is one of the most prevalent disabilities in aged populations of industrialized countries. As we age less excitation reaches the central auditory system from the periphery. To compensate, the central auditory system [e.g., the inferior colliculus (IC)], downregulates GABAergic inhibition to maintain homeostatic balance. However, the continued downregulation of GABA in the IC causes a disruption in temporal precision related to presbycusis. Many studies of age-related changes to neurotransmission in the IC have therefore focused on GABAergic systems. However, we have discovered that dense core vesicles (DCVs) are significantly upregulated with age in the IC. DCVs can carry neuropeptides, co-transmitters, neurotrophic factors, and proteins destined for the presynaptic zone to participate in synaptogenesis. We used immuno transmission electron microscopy across four age groups (3-month; 19-month; 24-month; and 28-month) of Fisher Brown Norway rats to examine the ultrastructure of DCVs in the IC. Tissue was stained post-embedding for GABA immunoreactivity. DCVs were characterized by diameter and by the neurochemical profile (GABAergic/non-GABAergic) of their location (bouton, axon, soma, and dendrite). Our data was collected across the dorsolateral to ventromedial axis of the central IC. After quantification, we had three primary findings. First, the age-related increase of DCVs occurred most robustly in non-GABAergic dendrites in the middle and low frequency regions of the central IC during middle age. Second, the likelihood of a bouton having more than one DCV increased with age. Lastly, although there was an age-related loss of terminals throughout the IC, the proportion of terminals that contained at least one DCV did not decline. We interpret this finding to mean that terminals carrying proteins packaged in DCVs are spared with age. Several recent studies have demonstrated a role for neuropeptides in the IC in defining cell types and regulating inhibitory and excitatory neurotransmission. Given the age-related increase of DCVs in the IC, it will be critical that future studies determine whether (1) specific neuropeptides are altered with age in the IC and (2) if these neuropeptides contribute to the loss of inhibition and/or increase of excitability that occurs during presbycusis and tinnitus.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Age-related upregulation of dense core vesicles in the central inferior colliculus

Mellott,

Duncan,

Busby

et al. 2024

Front. Cell. Neurosci.

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“…Animal studies demonstrated in vivo evidence supporting the IC's central gain hypothesis. Mafi et al demonstrated an increased expression of perineural nests, which are known to reduce synaptic plasticity, in aging rats on both GABAergic and non‐GABAergic cells of the IC 50 . These findings could explain decreased connectivity between the IC and auditory cortex and lead to therapeutic potentials in the foreseeable future.…”

Section: Discussionmentioning

confidence: 98%

“…Mafi et al demonstrated an increased expression of perineural nests, which are known to reduce synaptic plasticity, in aging rats on both GABAergic and non-GABAergic cells of the IC. 50 These findings could explain decreased connectivity between the IC and auditory cortex and lead to therapeutic potentials in the foreseeable future. Additionally, the findings from Mafi et al support the occurrence of intrinsic changes in the IC.…”

Section: Heschl's Gyrus (Hg)mentioning

confidence: 98%

Functional Brain Regions Linked to Tinnitus Pathology and Compensation During Task Performance: A Systematic Review

Jimoh

Marouf

Zenke

et al. 2023

Otolaryngol.--head neck surg.

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ObjectiveTo systematically search the literature and organize relevant advancements in the connection between tinnitus and the activity of different functional brain regions using functional magnetic resonance imaging (fMRI).Data SourcesMEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Web of Science, ProQuest Dissertations & Theses Global, Cochrane Database of Systematic Reviews, and PROSPERO from inception to April 2022.Review MethodsStudies with adult human subjects who suffer from tinnitus and underwent fMRI to relate specific regions of interest to tinnitus pathology or compensation were included. In addition, fMRI had to be performed with a paradigm of stimuli that would stimulate auditory brain activity. Exclusion criteria included non‐English studies, animal studies, and studies that utilized a resting state magnetic resonance imaging or other imaging modalities.ResultsThe auditory cortex may work to dampen the effects of central gain. Results from different studies show variable changes in the Heschl's gyrus (HG), with some showing increased activity and others showing inhibition and volume loss. After controlling for hyperacusis and other confounders, tinnitus does not seem to influence the inferior colliculus (IC) activation. However, there is decreased connectivity between the auditory cortex and IC. The cochlear nucleus (CN) generally shows increased activation in tinnitus patients. fMRI evidence indicates significant inhibition of thalamic gating. Activating the thalamus may be of important therapeutic potential.ConclusionPatients with tinnitus have significantly altered neuronal firing patterns, especially within the auditory network, when compared to individuals without tinnitus. Tinnitus and hyperacusis commonly coexist, making differentiation of the effects of these 2 phenomena frequently difficult.

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“…In the IC, as well as nearly every auditory subcortical nucleus, exists populations of perineuronal nets (PNs) that surround non-GABAergic and GABAergic cells ( Bertolotto et al, 1996 ; Hilbig et al, 2007 ; Foster et al, 2014 ; Sonntag et al, 2015 , 2018 ; Balmer, 2016 ; Fader et al, 2016 Beebe et al, 2018 ; Beebe and Schofield, 2018 ; Heusinger et al, 2019 ; Mansour et al, 2019 ; Sucha et al, 2019 ; Mafi et al, 2020 , 2021 ). PNs are specialized structures of extracellular matrix molecules that surround the somas and dendrites of various populations of neurons in the central nervous system ( Cragg, 1979 ; Karetko and Skangiel-Kramska, 2009 ; Sonntag et al, 2015 ; Bosiacki et al, 2019 ; Testa et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Age-related upregulation of perineuronal nets on inferior collicular cells that project to the cochlear nucleus

Almassri,

Ohl,

Iafrate

et al. 2023

Front. Aging Neurosci.

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IntroductionDisruptions to the balance of excitation and inhibition in the inferior colliculus (IC) occur during aging and underlie various aspects of hearing loss. Specifically, the age-related alteration to GABAergic neurotransmission in the IC likely contributes to the poorer temporal precision characteristic of presbycusis. Perineuronal nets (PNs), a specialized form of the extracellular matrix, maintain excitatory/inhibitory synaptic environments and reduce structural plasticity. We sought to determine whether PNs increasingly surround cell populations in the aged IC that comprise excitatory descending projections to the cochlear nucleus.MethodWe combined Wisteria floribunda agglutinin (WFA) staining for PNs with retrograde tract-tracing in three age groups of Fischer Brown Norway (FBN) rats.ResultsThe data demonstrate that the percentage of IC-CN cells with a PN doubles from ~10% at young age to ~20% at old age. This was true in both lemniscal and non-lemniscal IC.DiscussionFurthermore, the increase of PNs occurred on IC cells that make both ipsilateral and contralateral descending projections to the CN. These results indicate that reduced structural plasticity in the elderly IC-CN pathway, affecting excitatory/inhibitory balance and, potentially, may lead to reduced temporal precision associated with presbycusis.

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Inferior collicular cells that project to the auditory thalamus are increasingly surrounded by perineuronal nets with age

Cited by 5 publications

References 114 publications

Age-related upregulation of dense core vesicles in the central inferior colliculus

Age-related upregulation of dense core vesicles in the central inferior colliculus

Functional Brain Regions Linked to Tinnitus Pathology and Compensation During Task Performance: A Systematic Review

Age-related upregulation of perineuronal nets on inferior collicular cells that project to the cochlear nucleus

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