Research ReportNeonatal conductive hearing loss disrupts the development of the Cat-315 epitope on perineuronal nets in the rat superior olivary complex
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)
- et al.
Immunohistochemical localization of neurocan in the lower auditory nuclei of the dog
Hear. Res.
(1997) - et al.
Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex
Exp. Neurol.
(2010) - et al.
Early destruction of the extracellular matrix around parvalbumin-immunoreactive interneurons in Creutzfeldt–Jakob disease
Neurobiol. Dis.
(1999) - et al.
Immunohistochemical localization of chondroitin sulfate in normal and pathological human muscle
J. Neurol. Sci.
(1986) - et al.
Organization of brain extracellular matrix in the Chilean fat-tailed mouse opossum Thylamys elegans (Waterhouse, 1839)
J. Chem. Neuroanat.
(2006) - et al.
Wisteria floribunda lectin is associated with specific cell types in the ventral cochlear nucleus of the gerbil, Meriones unguiculatus
Hear. Res.
(2006) - et al.
Perineuronal nets—a specialized form of extracellular matrix in the adult nervous system
Brain Res. Brain Res. Rev.
(1994) - et al.
Perineuronal nets: past and present
Trends Neurosci.
(1998) - et al.
Effects of monaural and binaural sound deprivation on cell development in the anteroventral cochlear nucleus of rats
Exp. Neurol.
(1979) - et al.
Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation
Neuroscience
(2006)