Elsevier

Brain Research

Volume 1465, 17 July 2012, Pages 34-47
Brain Research

Research Report
Neonatal conductive hearing loss disrupts the development of the Cat-315 epitope on perineuronal nets in the rat superior olivary complex

https://doi.org/10.1016/j.brainres.2012.05.024Get rights and content

Abstract

The critical period is a postnatal window characterized by a high level of experience-dependent neuronal plasticity in the central nervous system and sensory deprivation during this period significantly impacts neurological function. Perineuronal nets (PNNs) are specialized aggregates of the extracellular matrix which ensheath neuronal cell bodies, primary dendrites and axon hillocks and function in neuronal protection and stabilize synapses. PNNs are generally not present at birth, but reach adult-like patterns by the end of the third or fourth postnatal week. Their appearance is believed to mark the close of the critical period and sensory deprivation during this epoch disrupts development of PNNs. Here we investigate the postnatal development of two PNN markers (Wisteria floribunda agglutinin [WFA] and Cat-315) and the effect of neonatal conductive hearing loss (CHL) on their development. Our data indicates that these PNN markers are not present in the superior olivary complex (SOC) at birth, but develop over the first four postnatal weeks in different temporal patterns and also that neonatal CHL results in a significant decrease in the number of SOC neurons associated with Cat-315 reactive PNNs.

Highlights

► The SOC is a collection of brainstem neurons that function in hearing. ► PNNs surround the soma and primary dendrites and function to stabilize the synapse. ► In the SOC, epitopes on PNNs that are not present at birth appear soon after hearing onset. ► CHL alters cell morphology and inhibits development of Cat-315 PNNs in the SOC.

Introduction

Perineuronal nets (PNNs) are specialized constructs of the neural extracellular matrix (nECM) that ensheath the soma, dendrites and initial axon segment of select neuronal populations (Atoji et al., 1989, Brückner et al., 1993, Lander et al., 1998) and function in a multitude of physiological processes (Celio et al., 1998, Dityatev and Schachner, 2003, Morris and Henderson, 2000). In the post-embryonic brain, PNNs appear to limit critical period plasticity and stabilize synapses; experimental digestion of PNNs in the adult brain induces a state of elevated plasticity (Hockfield et al., 1990, Kwok et al., 2008, Pizzorusso et al., 2002, Sur et al., 1988) and leaves memory traces in the amygdala susceptible to erasure (Gogolla et al., 2009). Given the importance of these extracellular structures, the distribution of PNNs in the central nervous system is not uniform—PNNs are plentiful in the auditory brainstem by postnatal day (P) 21 (Cant and Benson, 2006, Friauf, 2000, Köppe et al., 1997, Lurie et al., 1997) but develop slightly later (P35) and are less common in cortical areas (Brückner et al., 2000, Guimarães et al., 1990, Köppe et al., 1997, McRae et al., 2007). The association of neurons with PNNs varies by cell type, age and sensory experience (McRae et al., 2007, Pantazopoulos et al., 2008, Schmidt et al., 2010, Wagoner and Kulesza, 2009, Wintergerst et al., 1996). Further, there is evidence that PNN distribution varies by species (Brückner et al., 2006). Indeed, it is well established that the nECM is incomplete at birth, but PNNs (in rodents) develop rapidly in sensory systems, reaching an adult-like pattern by the end of the 3rd–4th postnatal week (Brückner et al., 2000, Friauf, 2000, Köppe et al., 1997, Lurie et al., 1997, Seeger et al., 1994). Further, maturation of PNNs appear to mark the close of the critical period, a developmental window characterized by a high level of sensory experience-dependent neuronal plasticity (Lurie et al., 1997, McRae et al., 2007, Pizzorusso et al., 2002). In fact it has been hypothesized that the presence of PNNs inhibits formation of new synapses (Celio and Blümcke, 1994). This is significant, since sensory deprivation during the critical period is known to have a lasting impact on neurological function (Clopton and Silverman, 1977, Wiesel and Hubel, 1963) and inhibits the formation of some PNNs in the spinal cord (Kalb and Hockfield, 1988), somatosensory cortex (McRae et al., 2007), lateral geniculate body and visual cortex (Guimarães et al., 1990, Sur et al., 1988). Finally, it should be noted that certain disease states have been associated with deterioration of PNNs (Creutzfeldt–Jakob—Belichenko et al., 1999; schizophrenia—Pantazopoulos et al., 2010). Thus, the normal PNN pattern in a brain region/nucleus seems to indicate the normal progression through activity-dependent developmental processes and normal neurological function.

The superior olivary complex (SOC) is a conglomerate of brainstem nuclei which comprise the first major site of convergence of information from both ears and functions in the localization of sound sources, encoding temporal features of sound and descending modulation of the organ of Corti (see reviews by Heffner and Masterton, 1990, Oliver, 2000, Schofield, 2010, Schwartz, 1992, Spangler and Warr, 1991, Thompson and Schofield, 2000). The SOC includes the medial and lateral superior olives (MSO and LSO, respectively, both of which receive input from both ears), the superior paraolivary nucleus (SPON) and the medial, ventral and lateral nuclei of the trapezoid body (MNTB, VNTB and LNTB respectively). In the rat, the external auditory meatus is closed until about P12, but high intensity sounds can elicit responses as early as P7 by bone conduction; mature conductive hearing is achieved by P15 and adult-like auditory thresholds are achieved by P22 (Geal-Dor et al., 1993). Even though SOC neurons achieve mature membrane properties soon after hearing onset (Chirila et al., 2007, Harris et al., 2005, Magnusson et al., 2005), many features (e.g. synaptic kinetics, discharge rates, response latency) depend on sensory experience and continue to mature through the 4th postnatal week (Sanes and Rubel, 1988, Sanes et al., 1992, Scott et al., 2005, Sonntag et al., 2009, Walcher et al., 2011, Webster, 1983b). Normal maturation of auditory brainstem circuits requires an intact cochlea and auditory nerve: permanent lesions (e.g. cochlear ablation) result in atrophy of auditory brainstem neurons (Kitzes et al., 1995, Kotak and Sanes, 1997, Nordeen et al., 1983, Russell and Moore, 1999, Russell and Moore, 2002). Further, it is clear that transient conductive hearing loss (CHL) during the early postnatal critical period disturbs normal auditory function in the midbrain (Mogdans and Knudsen, 1993, Popescu and Polley, 2010, Silverman and Clopton, 1977) and auditory cortex (Popescu and Polley, 2010, Xu et al., 2007), and results in elevated auditory thresholds (Walger et al., 1989), an enhanced acoustic startle reflex and increased risk for sound induced seizures (Sun et al., 2011). Additionally, in the cochlear nuclei and SOC, neonatal CHL has been shown to cause significant reductions in neuronal cell body size (Coleman and O'Connor, 1979, Webster, 1983a, Webster, 1983b, Webster, 1988, Webster and Webster, 1979) and altered dendritic arbors (Feng and Rogowski, 1980, Torrero et al., 1999).

It is clear that achieving an adult pattern of PNNs marks the closure of the sensory critical period (in visual and somatosensory cortex) and that normal and meaningful neuronal activity is required during this critical period for proper development and function. Further, if evoked activity is disrupted, normal sensory processing cannot be achieved. Based on these observations in other sensory systems, we propose that long-standing auditory dysfunction, resulting from early auditory deprivation, is related (at least in part) to disruptions in the nECM and specifically PNNs. We hypothesize that neonatal CHL (as a model of temporary hearing loss in children) will significantly alter the morphology of SOC neurons and reduce the number of PNNs in the SOC.

Section snippets

Development of WFA-PNNs in the SOC

Figs. 1A and B illustrate the pattern of WFA-labeling and a characteristic WFA-PNN in the SOC of the adult rat (P100–120). At P0 there are very few WFA-PNNs in the brainstem or cerebellum, although occasional PNNs are observed in the reticular formation and spinal trigeminal nucleus. At P0, labeling is often seen around blood vessels and within many cells along the 4th ventricle. At P12, a few SOC neurons have a distinct cell body coating of WFA-labeling and extra-somatic labeling is observed

General remarks

To date, this is the first quantitative report on the development of WFA and Cat-315 reactive PNNs in the rat SOC. Our investigation demonstrates that these PNN markers are not present in the SOC at birth, develop rapidly over the first four postnatal weeks and by P28 the vast majority of SOC neurons (> 90% of MNTB and MSO neurons) are associated with PNNs. This is in stark contrast to forebrain regions where generally no more that 15% of neurons are associated with PNNs (Guimarães et al., 1990,

Experimental procedures

All animal handling procedures were approved by the LECOM Institutional Animal Use and Care Committee.

Acknowledgments

The experiments described in this report were supported by the LECOM Department of Research and the LECOM Research Collective. The authors would like to thank Drs. Thomas Corso and Jack Caldwell for their helpful comments and suggestions throughout these studies.

References (103)

  • A.S. Feng et al.

    Effects of monaural and binaural occlusion on the morphology of neurons in the medial superior olivary nucleus of the rat

    Brain Res.

    (1980)
  • M. Geal-Dor et al.

    Development of hearing in neonatal rats: air and bone conducted ABR thresholds

    Hear. Res.

    (1993)
  • K.A. Giamanco et al.

    Perineuronal net formation and structure in aggrecan knockout mice

    Neuroscience

    (2010)
  • S.B. Inbody et al.

    Binaural response characteristics of single neurons in the medial superior olivary nucleus of the albino rat

    Brain Res.

    (1981)
  • J. Mogdans et al.

    Early monaural occlusion alters the neural map of interaural level differences in the inferior colliculus of the barn owl

    Brain Res.

    (1993)
  • H. Pantazopoulos et al.

    Total number, distribution, and phenotype of cells expressing chondroitin sulfate proteoglycans in the normal human amygdala

    Brain Res.

    (2008)
  • M.V. Popescu et al.

    Monaural deprivation disrupts development of binaural selectivity in auditory midbrain and cortex

    Neuron

    (2010)
  • F.A. Russell et al.

    Ultrastructural transynaptic effects of unilateral cochlear ablation in the gerbil medial superior olive

    Hear. Res.

    (2002)
  • D.H. Sanes et al.

    Refinement of dendritic arbors along the tonotopic axis of the gerbil lateral superior olive

    Brain Res. Dev. Brain Res.

    (1992)
  • E. Schmidt et al.

    Distribution of perineuronal nets in the human superior olivary complex

    Hear. Res.

    (2010)
  • G. Seeger et al.

    Mapping of perineuronal nets in the rat brain stained by colloidal iron hydroxide histochemistry and lectin cytochemistry

    Neuroscience

    (1994)
  • G. Srinivasan et al.

    Functional glutamatergic and glycinergic inputs to several superior olivary nuclei of the rat revealed by optical imaging

    Neuroscience

    (2004)
  • W. Sun et al.

    Early age conductive hearing loss causes audiogenic seizure and hyperacusis behavior

    Hear. Res.

    (2011)
  • J. Wagoner et al.

    Topographical and cellular distribution of perineuronal nets in the human cochlear nucleus

    Hear. Res.

    (2009)
  • D.B. Webster

    Auditory neuronal sizes after a unilateral conductive hearing loss

    Exp. Neurol.

    (1983)
  • E.S. Wintergerst et al.

    The proteoglycan DSD-1-PG occurs in perineuronal nets around parvalbumin-immunoreactive interneurons of the rat cerebral cortex

    Int. J. Dev. Neurosci.

    (1996)
  • Y. Atoji et al.

    Extracellular matrix of the superior olivary nuclei in the dog

    J. Neurocytol.

    (1989)
  • M.I. Banks et al.

    Intracellular recordings from neurobiotin-labeled cells in brain slices of the rat medial nucleus of the trapezoid body

    J. Neurosci.

    (1992)
  • A. Bartoletti et al.

    Environmental enrichment prevents effects of dark-rearing in the rat visual cortex

    Nat. Neurosci.

    (2004)
  • L.L. Bruce et al.

    Postnatal development of efferent synapses in the rat cochlea

    J. Comp. Neurol.

    (2000)
  • G. Brückner et al.

    Perineuronal nets provide a polyanionic, glia-associated form of microenvironment around certain neurons in many parts of the rat brain

    Glia

    (1993)
  • G. Brückner et al.

    Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R

    J. Comp. Neurol.

    (2000)
  • N.B. Cant et al.

    Projections from the anteroventral cochlear nucleus to the lateral and medial superior olivary nuclei

    J. Comp. Neurol.

    (1986)
  • F.V. Chirila et al.

    Development of gerbil medial superior olive: integration of temporally delayed excitation and inhibition at physiological temperature

    J. Physiol.

    (2007)
  • B.M. Clopton et al.

    Plasticity of binaural interaction. II. Critical period and changes in midline response

    J. Neurophysiol.

    (1977)
  • B.M. Clopton et al.

    Changes in latency and duration of neural responding following developmental auditory deprivation

    Exp. Brain Res.

    (1978)
  • A. Dityatev et al.

    Extracellular matrix molecules and synaptic plasticity

    Nat. Rev. Neurosci.

    (2003)
  • M. Feliciano et al.

    Direct projections from the rat primary auditory neocortex to nucleus sagulum, paralemniscal regions, superior olivary complex and cochlear nuclei

    Aud. Neurosci.

    (1995)
  • E. Friauf

    Development of chondroitin sulfate proteoglycans in the central auditory system of rats correlates with acquisition of mature properties

    Audiol. Neurootol.

    (2000)
  • E. Friauf et al.

    Divergent projections of physiologically characterized rat ventral cochlear nucleus neurons as shown by intra-axonal injection of horseradish peroxidase

    Exp. Brain Res.

    (1988)
  • N. Gogolla et al.

    Perineuronal nets protect fear memories from erasure

    Science

    (2009)
  • J.A. Gordon et al.

    Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse

    J. Neurosci.

    (1996)
  • B. Grothe et al.

    Synaptic inhibition influences the temporal coding properties of medial superior olivary neurons: an in vitro study

    J. Neurosci.

    (1994)
  • A. Guimarães et al.

    Molecular and morphological changes in the cat lateral geniculate nucleus and visual cortex induced by visual deprivation are revealed by monoclonal antibodies Cat-304 and Cat-301

    J. Neurosci.

    (1990)
  • J.A. Harris et al.

    Gene expression differences over a critical period of afferent-dependent neuron survival in the mouse auditory brainstem

    J. Comp. Neurol.

    (2005)
  • J.M. Harrison et al.

    A study of the cochlear nuclei and ascending auditory pathways of the medulla

    J. Comp. Neurol.

    (1962)
  • W. Hartig et al.

    Wisteria floribunda agglutinin-labeled nets surround parvalbumin containing neurons

    Neuroreport

    (1992)
  • R.S. Heffner et al.

    Sound localization: brainstem mechanisms

  • H. Hilbig et al.

    Characterization of neuronal subsets surrounded by perineuronal nets in the rhesus auditory brainstem

    J. Anat.

    (2007)
  • S. Hockfield et al.

    Expression of neural proteoglycans correlates with the acquisition of mature neuronal properties in the mammalian brain

    Cold Spring Harb. Symp. Quant. Biol.

    (1990)
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