Project description:The sense of hearing originates in the cochlea, which detects sounds across dynamic sensory environments. Like other peripheral organs, the cochlea is subjected to environmental insults, including loud, damage-inducing sounds. In response to internal and external stimuli, the central nervous system directly modulates cochlear function through olivocochlear neurons (OCNs), which are located in the brainstem and innervate the cochlear sensory epithelium. One population of OCNs, the lateral olivocochlear (LOC) neurons, target spiral ganglion neurons (SGNs), the primary sensory neurons of the ear. LOCs alter their transmitter expression for days to weeks in response to noise exposure (NE), suggesting that they are well-positioned to tune SGN excitability over long time periods in response to auditory experience. To examine how LOCs affect auditory function after NE, we characterized the transcriptional profiles of OCNs and found that LOCs exhibit transient changes in gene expression after NE, including upregulation of multiple neuropeptide-encoding genes.
Project description:In order to characterize the various subpopulations of neurons present in the inner ear, we dissected out the cochleas from wild-type mice, removing non-neuronal populations as possible, then dissociated the tissue to obtain a single cell suspension and profiled these by single cell RNA-Seq.
Project description:Deprivation of peripheral nerve input by cochlear removal in young mice results in dramatic neuron death in the cochlear nucleus (CN). The same manipulation in older mice does not result in significant loss. The molecular basis of this critical period of vulnerability remains largely unknown. Here we identified genes regulated at early time points after cochlear removal at ages when neurons are vulnerable (postnatal day (P)7) or invulnerable (P21) to this challenge. Afferent deprivation regulated very different sets of genes at P7 and P21. These genes showed a variety of functions at both ages, but surprisingly there was no net increase in pro-apoptotic genes at P7. A large set of upregulated immune-related genes was identified at P21. Experiment Overall Design: Mice received unilateral cochlear removals. At 6, 12, 24, and 48 hours after surgery, the CN ipsilateral and contralateral were removed, and RNA isolated from separate pools of tissue for each replicate. Deafferented CN were compared to age-matched and time-matched contralateral, control CN to identify genes regulated by cochlear removal at age P7 and P21.
Project description:Significant changes in the expression of synaptic and inflammatory genes were observed early after damage, during regeneration of the fibers and synapses, and after completion of in vitro regeneration between afferent neurons and cochlear hair cells.
Project description:The cochlear nucleus is the first central pathway involved in the processing of peripheral auditory activity. It is heterogeneous in neuronal populations and physiologic responses and is organized in three major subdivisions: the anterior ventral cochlear nucleus (AVCN), the posterior ventral cochlear nucleus (PVCN) and the dorsal cochlear nucleus (DCN). Although each region demonstrates multiple cell types and functions, there are predominant populations of neurons in each region that underlie the principal role each subdivision plays in auditory processing. Little is known of the underlying genetic contribution to these properties. This study sought to identify genes expressed in the subdivisions of the cochlear nucleus that may account for the anatomical and physiological characteristics of each subdivision. These data provide a genetic basis for understanding normal auditory processing in the cochlear nucleus and a template for investigating changes that may occur with hearing loss, the generation and percept of tinnitus, and central processing disorders. Keywords: normal, comparative Brown Norway rats (n=40, female, 45days) were anesthetized and decapitated. Brains were rapidly removed and the subdivisions of the cochlear nucleus (AVCN, PVCN and DCN) dissected on dry ice. Total RNA was extracted and tested for concentration and purity by spectrophotometry and integrity by gel electrophoresis. SAGE was performed using the NlaIII enzyme and Invitrogen SAGE kit. Concatemers were commercially sequenced and imported into eSAGE (Margulies and Innis, 2000) for tag extraction and frequency.
Project description:The cochlear nucleus is the first central pathway involved in the processing of peripheral auditory activity. It is heterogeneous in neuronal populations and physiologic responses and is organized in three major subdivisions: the anterior ventral cochlear nucleus (AVCN), the posterior ventral cochlear nucleus (PVCN) and the dorsal cochlear nucleus (DCN). Although each region demonstrates multiple cell types and functions, there are predominant populations of neurons in each region that underlie the principal role each subdivision plays in auditory processing. Little is known of the underlying genetic contribution to these properties. This study sought to identify genes expressed in the subdivisions of the cochlear nucleus that may account for the anatomical and physiological characteristics of each subdivision. These data provide a genetic basis for understanding normal auditory processing in the cochlear nucleus and a template for investigating changes that may occur with hearing loss, the generation and percept of tinnitus, and central processing disorders. Keywords: normal, comparative
Project description:We analyzed whether cochlear removal-induced transcriptional changes in the cochlear nucleus (CN) were due to loss of electrical activity in the 8th nerve. Pharmacological activity blockade of the auditory nerve for 24 h resulted in similar expression changes for only a subset of genes. Thus, an additional factor not dependent on action potential-mediated signaling must also regulate transcriptional responses to deafferentation in the CN.