Developmental nicotine exposure (DNE) exerts negative consequences on the CNS via the activation of nAChRs that are available early and widely throughout development (refs). In this work, we examined how DNE changed excitatory and inhibitory neurotransmission in brainstem regions involved in central breathing control. Previous work using the brainstem-spinal cord preparation had shown that DNE augmented the respiratory-related response to AMPA, muscimol (a GABAA agonist), and glycine (Luo et al., 2004; Luo et al., 2007; Pilarski and Fregosi, 2009a). These studies used a split-bath preparation in which a drug (AMPA, muscimol, or glycine) was applied to medulla, and the frequency of the respiratory response (in the form of spontaneous, rhythmic bursting activity) was recorded from cervical nerve 4 (C4), which provides output to the diaphragm. Although these studies showed that DNE AMPA, GABA(A), and glycine neurotransmission in the medulla, the regions mediating the effect and the mechanism of DNE's action remained unclear. In this study we tested the hypothesis that the observed changes in respiratory burst frequency were mediated through the preBötzinger complex (preBötC), and the mechanism of enhanced activity involved an upregulation of neurotransmitter receptors. Additionally, we were interested in studying the effect of DNE on breathing-related motor pools, and therefore studied DNE's effect on excitatory and inhibitory neurotransmission in the XIIMN. We approached these questions and aims using a combination of techniques, including extracellular recordings from whole nerve output in rhythmic brainstem slices, immunohistochemistry, and Western blotting. We found enhanced AMPA, GABA(A), and glycine neurotransmission in the XIIMN and preBötC, and varying changes in neurotransmitter receptor expression in both groups. Additionally, we found a decrease in motoneuron soma size in XII motoneurons that stained positively for the glycine receptor. Overall, this study shows that DNE alters inhibitory and excitatory neurotransmission in both the preBötC and XIIMN, and that these changes may be mediated through a combination of change in cell size and receptor expression.

No description available.

Several adaptive filters were investigated to enhance speech auditory brainstem responses (speech ABR). The objective was to shorten the long recording time currently needed by the standard coherent averaging method to obtain acceptable performance, which has limited the clinical adoption of speech ABR. Five algorithms were implemented: Wiener Filter (WF), Steepest Descent (SD), Adaptive Noise Cancellation (ANC) based on Least-Mean-Square error (LMS) and normalized LMS error (nLMS), and a multi-adaptive cascade combination of SD and LMS. The performance of the adaptive filters was assessed on speech ABR data gathered from several subjects and compared with coherent averaging using the overall Signal-to-Noise Ratio (SNR), the local SNR around the fundamental frequency and the first formant, and Mean-Square-Error (MSE) in the time and frequency domains. The adaptive filters could reduce the time needed, by at least one order of magnitude, for obtaining comparable signal quality as that obtained with coherent averaging.

Several adaptive filters were investigated to enhance speech auditory brainstem responses (speech ABR). The objective was to shorten the long recording time currently needed by the standard coherent averaging method to obtain acceptable performance, which has limited the clinical adoption of speech ABR. Five algorithms were implemented: Wiener Filter (WF), Steepest Descent (SD), Adaptive Noise Cancellation (ANC) based on Least-Mean-Square error (LMS) and normalized LMS error (nLMS), and a multi-adaptive cascade combination of SD and LMS. The performance of the adaptive filters was assessed on speech ABR data gathered from several subjects and compared with coherent averaging using the overall Signal-to-Noise Ratio (SNR), the local SNR around the fundamental frequency and the first formant, and Mean-Square-Error (MSE) in the time and frequency domains. The adaptive filters could reduce the time needed, by at least one order of magnitude, for obtaining comparable signal quality as that obtained with coherent averaging.

No description available.

Several adaptive filters were investigated to enhance speech auditory brainstem responses (speech ABR). The objective was to shorten the long recording time currently needed by the standard coherent averaging method to obtain acceptable performance, which has limited the clinical adoption of speech ABR. Five algorithms were implemented: Wiener Filter (WF), Steepest Descent (SD), Adaptive Noise Cancellation (ANC) based on Least-Mean-Square error (LMS) and normalized LMS error (nLMS), and a multi-adaptive cascade combination of SD and LMS. The performance of the adaptive filters was assessed on speech ABR data gathered from several subjects and compared with coherent averaging using the overall Signal-to-Noise Ratio (SNR), the local SNR around the fundamental frequency and the first formant, and Mean-Square-Error (MSE) in the time and frequency domains. The adaptive filters could reduce the time needed, by at least one order of magnitude, for obtaining comparable signal quality as that obtained with coherent averaging.

In mammals, the basic computations required for azimuthal sound localization are performed by a group of auditory brainstem nuclei known as the superior olivary complex (SOC). The lateral superior olive (LSO), in the SOC, aids in sound localization by computing intensity differences between sounds arriving at the two ears. It does this by comparing excitatory input from the ipsilateral anteroventral cochlear nucleus (AVCN) with inhibitory input from the ipsilateral medial nucleus of the trapezoid body (MNTB), which is driven by the contralateral AVCN. In order for sounds to be accurately localized, the AVCN-LSO and MNTB-LSO projections must be aligned with each other in a frequency-dependent manner. Rough alignment occurs over the course of development, but a significant amount of circuit refinement is required to achieve adult-like precision. Two types of refinement occur in these pathways: 1) physiological, or functional refinement; and 2) anatomical refinement. Little is known about the latter type of refinement in the AVCN-LSO pathway. In order to study this, I conducted a variety of experiments all aimed at anterogradely labeling a small number of cells projecting from the AVCN to the LSO in juvenile rats. I experimented with several approaches in order to develop the technique of ex vivo, sparse axon labeling in this area of the brain. I show the optimal technique developed after testing various tracers, application methods, and incubation times, among others. This optimized technique can now be used in a future experiment that will uncover and describe anatomical refinement in the AVCN-LSO pathway of the auditory brainstem. / Thesis / Master of Science (MSc)

When administered systemically, benzodiazepine receptor agonists have been shown to increase food intake in a number of species. Conversely, benzodiazepine receptor inverse agonists bring about reliable decreases in feeding. The aim of the experiments reported in this thesis was to investigate the brain and behavioural mechanisms involved in the effects of benzodiazepines on ingestion. The effect on food intake of microinjection of the benzodiazepine receptor agonist midazolam into the brainstem of the rat was investigated. A reliable hyperphagic response was elicited following injection of midazolam into both the IVth ventricle and the parabrachial nucleus (PEN). This increase in intake was reversed by pretreatment with the selective benzodiazepine receptor antagonist flumazenil. These results suggest that benzodiazepine receptors located in the brainstem, specifically in the PEN, may be responsible for the effects of benzodiazepines on ingestion. In further experiments, a microstructural approach was adopted which involved analyzing the effects of benzodiazepine ligands on the detailed pattern of licking for both a carbohydrate and a fat in the rat. The effects of midazolam were similar to the effects of increasing concentration. The effects of the benzodiazepine receptor inverse agonist Ro 15-4513 were similar to the effects of decreasing concentration. These results suggest that benzodiazepines influence ingestive behaviour by modulating palatability. The proposal that benzodiazepines may interact with opioids to influence feeding behaviour was examined in Chapters 7 and 8. Although the effects of the opioid agonist morphine and the opioid antagonist naloxone on licking behaviour were not the same as the effects of benzodiazepine ligands, naloxone blocked the effects of midazolam. These results suggest that the effects of benzodiazepine on palatability may depend on release of endogenous opioid peptides. This work has implications for understanding the neural control of ingestive behaviour and may help in developing new therapies for clinical disorders such as anorexia and bulimia.

Cochlear implants provide hearing to people who are deaf, by electrically stimulating the auditory nerve. Children with a single cochlear implant suffer deficiencies inherent to unilateral hearing, including inability to locate sounds. A second cochlear implant may improve sound localization, which normally requires interpretation of differences in sound intensity and time of arrival between two ears. Currently, it is unknown whether these cues are available to children who were provided with a second cochlear implant after a period of using one implant alone. We asked whether such children could interpret inter-implant level and timing cues. Results indicated that children using two cochlear implants detected level cues but had difficulty interpreting timing cues. Further, children rarely reported that sounds were perceived to come from the middle. Children receiving bilateral cochlear implants sequentially do not process bilateral auditory cues normally but can use inter-implant level cues to make judgments about where sound is coming from.

Cochlear implants provide hearing to people who are deaf, by electrically stimulating the auditory nerve. Children with a single cochlear implant suffer deficiencies inherent to unilateral hearing, including inability to locate sounds. A second cochlear implant may improve sound localization, which normally requires interpretation of differences in sound intensity and time of arrival between two ears. Currently, it is unknown whether these cues are available to children who were provided with a second cochlear implant after a period of using one implant alone. We asked whether such children could interpret inter-implant level and timing cues. Results indicated that children using two cochlear implants detected level cues but had difficulty interpreting timing cues. Further, children rarely reported that sounds were perceived to come from the middle. Children receiving bilateral cochlear implants sequentially do not process bilateral auditory cues normally but can use inter-implant level cues to make judgments about where sound is coming from.