Janet L. Fitzakerley

Expression of Shal potassium channel subunits in the adult and developing cochlear nucleus of the mouse

The pattern of expression of potassium (K(+)) channel subunits is thought to contribute to the establishment of the unique discharge characteristics exhibited by cochlear nucleus (CN) neurons. This study describes the developmental distribution of mRNA for the three Shal channel subunits Kv4.1, Kv4.2 and Kv4.3 within the mouse CN, as assessed with in situ hybridization and RT-PCR techniques. Kv4.1 was not present in CN at any age. Kv4.2 mRNA was detectable as early as postnatal day 2 (P2) in all CN subdivisions, and continued to be constitutively expressed throughout development. Kv4.2 was abundantly expressed in a variety of CN cell types, including all of the major projection neuron classes (i.e., octopus, bushy, stellate, fusiform, and giant cells). In contrast, Kv4.3 was expressed at lower levels and by fewer cell types. Kv4.3-labeled cells were more prevalent in ventral subdivisions than in the dorsal CN. Kv4.3 expression was significantly delayed developmentally in comparison to Kv4.2, as it was detectable only after P14. Although the techniques employed in this study detect mRNA and not protein, it can be inferred from the differential distribution of Kv4 transcripts that CN neurons selectively regulate the expression of Shal K(+) channels among individual neurons throughout development.

Survival and differentiation of neurons cultured from the mouse cochlear nucleus on extracellular matrix components

This study was designed to determine the effects of several extracellular matrix (ECM) proteins on the survival and differentiation of cochlear nucleus (CN) neurons grown in primary cell culture. CN neurons were successfully grown on laminin, collagen and fibronectin, but neuronal survival was significantly decreased on all three substrates relative to poly-D-lysine controls. In addition, analysis of dendrite organization patterns indicated that CN neurons branched more extensively when grown on poly-D-lysine than on any of the ECM components tested. Although dendrite growth has been shown to depend strongly on the presence of ECM components in other neuronal systems, the data from these experiments do not support the hypothesis that laminin, collagen or fibronectin is necessary for the survival and differentiation of CN neurons.

Properties of cochlear nucleus neurons in primary culture

Dissociated primary cell cultures were derived from the cochlear nuclei (CN) of postnatal rats using standard techniques. Cultured cells differentiated morphologically, but their dendritic profiles were generally less specialized than those of CN cells in vivo. Physiologically, cultured cells could be divided into three classes: tonic, phasic and non-spiking cells, which differed in many of their fundamental biophysical properties. The percentage of cultured cells that spiked repetitively increased over time to a maximum of 85% at 6 days. However, the percentage of cells that produced action potentials decreased with time in culture, from 91% during the first 8 days to less than 40% after 9 days. CN cells were successfully cultured in both serum-supplemented and serum-free (Neurobasal) media. More neurons survived at low plating densities in Neurobasal than in medium containing serum, although neuronal survival was similar at higher densities. Few neurons raised in the serum-free medium were spontaneously active; other response properties were similar to those of cells grown in the presence of serum. Although differentiation of CN cells in culture did not completely mirror the in vivo developmental pattern, these experiments demonstrate that primary culture represents a viable method for the in vitro study of CN neurons.

Neuroscientists' classroom visits positively impact student attitudes

The primary recommendation of the 2010 President’s Council of Advisors on Science and Technology report on K-12 education was to inspire more students so that they are motivated to study science. Scientists’ visits to classrooms are intended to inspire learners and increase their interest in science, but verifications of this impact are largely qualitative. Our primary goal was to evaluate the impact of a longstanding Brain Awareness classroom visit program focused on increasing learners understanding of their own brains. Educational psychologists have established that neuroscience training sessions can improve academic performance and shift attitudes of students from a fixed mindset to a growth mindset. Our secondary goal was to determine whether short interactive Brain Awareness scientist-in-the-classroom sessions could similarly alter learners’ perceptions of their own potential to learn. Teacher and student surveys were administered in 4th-6th grade classrooms throughout Minnesota either before or after one-hour Brain Awareness sessions that engaged students in activities related to brain function. Teachers rated the Brain Awareness program as very valuable and said that the visits stimulated students’ interest in the brain and in science. Student surveys probed general attitudes towards science and their knowledge of neuroscience concepts (particularly the ability of the brain to change). Significant favorable improvements were found on 10 of 18 survey statements. Factor analyses of 4805 responses demonstrated that Brain Awareness presentations increased positive attitudes toward science and improved agreement with statements related to growth mindset. Overall effect sizes were small, consistent with the short length of the presentations. Thus, the impact of Brain Awareness presentations was positive and proportional to the efforts expended, demonstrating that short, scientist-in-the-classroom visits can make a positive contribution to primary school students’ attitudes toward science and learning.

Paradoxical relationship between frequency selectivity and threshold sensitivity during auditory-nerve fiber development

The acquisition of adult-like frequency selectivity is generally assumed to be the tightly coupled to improvements in threshold sensitivity during cochlear development. In this study, frequency versus threshold (tuning) curves obtained from 1108 auditory-nerve fibers were used to investigate the relationship between tuning and threshold at characteristic frequency (CF) during postnatal development in kittens. At the earliest ages included in this study, sharpness was within the adult range, but thresholds were significantly higher than adult values. Tuning and thresholds improved along different exponential time courses that varied with CF. For units with CFs below 1 kHz, tuning curve slopes below CF matured earliest, followed by CF threshold, and then by slopes above CF. In contrast, for CFs above 1 kHz, the high-frequency slopes matured first, followed by threshold and then by slope below CF. One interpretation of these results is that tuning and thresholds are not tightly coupled in immature animals. Paradoxically, however, high-frequency slopes were correlated with threshold for individual units at all ages, suggesting that the relationship between tuning and threshold is maintained during development. This contradiction can be resolved by a developmental model that features a functional separation between cochlear nonlinearities and mechanical/electrical conversion.

Genetics of guanylyl cyclase pathways in the cochlea and their influence on hearing

Although hearing loss is the most common sensory deficit in Western societies, there are no successful pharmacological treatments for this disorder. Recent experiments have demonstrated that manipulation of intracellular cyclic guanosine monophosphate (cGMP) concentrations can have both beneficial and harmful effects on hearing. In this review, we will examine the role of cGMP as a key second messenger involved in many aspects of cochlear function and discuss the known functions of downstream effectors of cGMP in sound processing. The nitric oxide-stimulated soluble guanylyl cyclase system (sGC) and the two natriuretic peptide-stimulated particulate GCs (pGCs) will be more extensively covered because they have been studied most thoroughly. The cochlear GC systems are attractive targets for medical interventions that improve hearing while simultaneously representing an under investigated source of sensorineural hearing loss.

Heart murmur detection/classification using Cochlea-Like Pre-Processing and Artificial Intelligence

In this research paper, we used a novel approach to pre-process the heart sound signals by altering the electrical signal in a similar way as is done by human cochlea before they go to Artificial Intelligence (AI) for murmur detection/classification. Cochlea-like pre-processing changes the spectral contents of the heart sounds to enhance the murmur information which can then be detected/classified more accurately by AI circuitry. We designed a heart murmur detection/classification system based upon this approach and tested this system using simulated sounds of various murmur types. Our test results show that this approach significantly improves heart murmur detection/classification accuracy.

Development of an Animal Model to Test an Active Noise Cancellation System for Infant Incubators

Medical, therapeutic and technological advancements, including the use of neonatal incubators and the development of neonatal intensive care units (NICUs), have significantly increased the survival of premature and ill infants. However, high levels of noise in the NICU result in numerous adverse health effects, including hearing loss, sleep disturbances and other forms of stress. Even normal levels of ambient noise may be of considerable risk for the most premature infants. It is well documented that the mammalian auditory system is most vulnerable to environmental influences immediately after the time that it first begins to function. In humans, the critical period spans approximately weeks 24–30 of gestation, which corresponds to the age when the most extremely premature infants are now able to survive ex utero. Premature infants are, therefore, at high risk for environmentally-induced hearing loss. Development of techniques that increase the amount of protection against noise-induced hearing loss (NIHL) could significantly improve quality of life, both while neonates are in the NICU, and long term. The long-term goal of our research is to develop a version of an existing active noise cancellation (ANC) system that can be used to reduce sound levels in NICU incubators, in a manner that does not require considerable space. The core component of the ANC system is a carbon nanotube-based transparent actuator, which is controlled by an adaptive controller so that an exact out-of-phase anti-noise can be produced from the actuator (Yu et al, 2005, 2007). The basic principle of the ANC system is to cancel the unwanted primary noise through the introduction of a destructive anti-noise sound. Experimental results showed that a reduction of greater than 15 dB in the primary noise can be achieved by the ANC system (Yu et al. 2007). Ultimately, this transparent actuator could be built into the side of an infant incubator, providing noise protection without adding equipment to the already crowded NICU environment. Before human trials can begin, animal studies must be completed to demonstrate that the ANC system can prevent the hearing loss that results from exposure to incubator noise during the critical period. One complication in animal testing is that individual species respond to different frequency ranges. For example, the human cochlea is most sensitive to sound frequencies between 2 and 5 kHz, while mice respond best between 8 and 16 kHz. It was hypothesized that a frequency translation based on the cochlear frequency/place relationship could be used to convert incubator noise into an appropriate stimulus for testing of the ANC in mice. Neonatal mice were exposed to untranslated incubator noise (IN) or frequency-shifted incubator noise (FSIN) during the critical period, and hearing sensitivity was measured following the noise exposure. IN had no effect on acoustic thresholds, but FSIN caused a moderately severe (60–70 dB) high frequency hearing loss in all mice tested. Based on these data, the FSIN stimulus represents the first accurate model of neonatal noise-induced hearing loss. Future experiments will use this model to test the ability of the ANC system to protect against NIHL.

Heart Murmur Detection∕Classification System Using Cochlea-Like Pre-Processing

University of Minnesota M.S. thesis. January 2010. Major: Electrical and Computer Engineering. Advisor: Prof. M. Imran Hayee. i computer file (PDF); vi, 48 pages. Ill. (some col.)