Biomedical subjects

J L Fitzakerley

Publications and source records attributed to J L Fitzakerley.

10 recordsLinked to original sources

PubMed1998

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.

Animals↗

PubMed1997

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.

Action Potentials↗

PubMed1995

Activity-dependent responses of developing cochlear nuclear neurons to microionophoretically-applied amino acids.

The experimental purpose of this investigation was to determine whether the efficacy of glutamate, N-methyl-D-aspartate (NMDA) and/or GABA is related to the activity state of neurons in the cochlear nuclear complex (CN). The hypothesis tested was that changes in discharge activity produced by glutamatergic and GABAergic ligands are, or may be, greater when neurons are stimulated at moderate to high acoustic levels compared to near threshold stimulation levels, when activity levels are high or low, respectively. All neurons from which discharge rate vs. sound pressure level curves were tested during simultaneous administration of amino acids exhibited characteristics commensurate with an activity-dependent system; at high sound levels, when discharge rates were elevated relative to rates produced by low level stimuli, both glutamate-induced increments and GABA-induced decrements in discharge rate were enhanced. The relationship between discharge rate and amino acid efficacy was a uniform property of neurons sampled throughout the first two postnatal weeks of development. In adults, preliminary indications are that activity-dependent neurotransmitter efficacy is characteristic of some cells, but not others. The activity-dependent nature of endogenous amino acid neurotransmission was demonstrated through the microionophoretic administration of NMDA and GABAA selective antagonists, D-alpha-aminoadipate (D alpha AA) and 2-amino-5-phosphonovalerate (APV), and bicuculline (BIC), respectively. These results suggest that postsynaptic actions elicited by membrane receptors subserving amino acid neurotransmission within the CN are activity-dependent.

2-Amino-5-phosphonovalerate↗

PubMed1994

Responses of peripheral auditory neurons to two-tone stimuli during development: I. Correlation with frequency selectivity.

The responses of peripheral auditory neurons to two-tone stimuli were used to inferentially examine the nature of cochlear processing during development. Rate suppression was not seen in the youngest animals, and was first observed at 77 gestational days, in units exhibiting adultlike frequency selectivity. Suppression was highly correlated with the degree of tuning, and neurons were segregated into three classes based on these responses. Broadly tuned neurons (type IB) with low characteristic frequencies (CFs) did not exhibit suppression, and were observed early in postnatal life. Sharply tuned, but still immature neurons (type IS) exhibited suppression, but to a lesser degree than mature neurons (type M). One interpretation of these results is that basilar membrane mechanics are linear during the final stages of cochlear development, indicating that the immature signal transduction process is fundamentally different from that of adults.

Acoustic Stimulation↗

PubMed1994

Responses of peripheral auditory neurons to two-tone stimuli during development: II. Factors related to neural responsiveness.

In an accompanying paper (Fitzakerley et al., 1994), it was demonstrated that there is a significant developmental correlation between the appearance of tuning and two-tone suppression. However, it was also found that some sharply tuned neurons meeting minimal adult standards did not exhibit suppression. Therefore, in order to investigate other factors that may be related to the demonstration of suppression in peripheral auditory neurons, the relationship of two-tone suppression with various parameters related to neural responsiveness was studied in perinatal kittens. A positive correlation was made between the observance of suppression and driven discharge rate, characteristic frequency (CF), and threshold, all properties which change significantly during the final stages of cochlear differentiation. In older animals, suppression was also observed in higher percentages of neurons having low spontaneous rates (< 1 spk/s). Suppression was evoked less often by test tones placed below CF than above CF in neurons recorded from younger animals, and was generally produced by a narrower range of test tone intensities than those recorded from adults. As a result, the conventional description of suppression as observed in peripheral auditory neurons in mature animals must be extended to include these factors when responses of immature neurons are considered.

Acoustic Stimulation↗

PubMed1994

Responses of peripheral auditory neurons to two-tone stimuli during development: III. Rate facilitation.

Approximately 25% of peripheral auditory neurons having low characteristic frequencies (CFs) and broad tuning, and recorded from immature animals, responded to two-tone stimuli with increases in discharge rate greater than predicted by linear summation of the responses to probe tones (facilitation), in contrast to the two-tone suppression observed in adult animals and in more sharply tuned immature neurons. Facilitation was not seen after 81 gestational days and was not observed when test tones produced a substantial increase in rate when presented alone. The fact that some neural responses were facilitated under conditions of two-tone stimulation during the final stages of cochlear differentiation provides additional evidence that signal transduction is fundamentally different in neonatal kittens than in adults. A linear model of basilar membrane mechanics coupled to nonlinear neural processes is proposed which can account for the production of facilitation.

Acoustic Stimulation↗

PubMed1993

Development of glutamate and NMDA sensitivity of neurons within the cochlear nuclear complex of kittens.

1. The effects of glutamate, N-methyl-D-aspartate (NMDA), and NMDA receptor antagonists, D-alpha-aminoadipate (D alpha AA) and 2-amino-5-phosphonovalerate (APV), microionophoretically applied onto neurons in the caudal divisions (posteroventral and dorsal subnuclei) of the cochlear nuclear complex (CN), were investigated during postnatal development in kittens with the use of extracellular techniques. From birth through postnatal day 7, microionophoretically applied glutamate elevated the acoustically evoked discharge rates of nearly 80% of neurons studied. Although fewer neurons were studied with the use of NMDA, approximately 65% of these responded to this glutamatergic agonist, and no developmental changes in the percentage of responsive neurons were observed. The actions of NMDA antagonists were studied in a relatively small number of neurons, and results support the supposition that glutamate, or a glutamate-like substance, acts as a CN neurotransmitter throughout postnatal life. 2. Approximately 64% of CN neurons encountered among neonatal animals were unresponsive to acoustic stimulation, even at the highest output levels available (> 120 dB SPL). That percentage declined monotonically during the next three postnatal days, such that approximately 23% of neurons encountered were unresponsive to acoustic stimulation on the third day. Essentially all encountered neurons were responsive to acoustic stimulation by the middle of the second postnatal week. Under conditions of simultaneous glutamate and acoustic stimulation, neurons in this general class of "acoustically unresponsive" neurons segregated into two groups. Glutamate increased spontaneous discharge rate in 45% of the neurons studied, however, these units remained acoustically unresponsive during combined sound and excitatory amino acid stimulation (group A1). In the second group (A2), 55% of the neurons that were acoustically unresponsive under control (sound alone) conditions responded to the acoustic component of the combined acoustic and glutamate stimulation (the experimental condition) in a frequency-dependent manner. A2 neurons exhibited temporal firing patterns characteristic of acoustically responsive neurons of corresponding age, suggesting that these neurons are functionally connected to the auditory periphery, whereas A1 neurons are not. 3. Dose-response curves were either sigmoidal or linear over the range that measurements were made, and maximum discharge rates evoked by high doses of glutamate in the youngest animals studied tended to be lower than those produced by acoustic stimulation alone in older animals. These results suggest that intrinsic properties contribute to the mechanism(s) that limits neuronal responsiveness. Average dose-response curve slopes were higher for neurons recorded from older animals, also indicating that intrinsic properties regulating dynamic response range are acquired postnatally in the kitten CN.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1990

GABA actions within the caudal cochlear nucleus of developing kittens.

1. The effects of gamma-aminobutyric acid (GABA), microionophoretically applied onto neurons within the dorsal and posteroventral divisions (i.e., caudal regions) of the cochlear nucleus (CN), were studied during postnatal development in kittens with the use of extracellular recording techniques. Approximately 80% of all neurons encountered within the caudal CN responded to exogenously applied GABA regardless of neuronal response type or postnatal age. 2. GABA reduced acoustically evoked as well as spontaneous discharge rates in a dose-dependent manner at all ages studied, and generally abolished discharge activity at sufficiently high doses (i.e., ejection currents). Dose-response curves generated during acoustic stimulation by varying GABA ejection current were sigmoidal at all ages studied, and the range of slopes relating discharge rate to applied currents increased during the first 10 postnatal days. 3. Neural thresholds to acoustic stimuli were elevated, and slopes of discharge-rate-versus-sound-pressure-level curves were depressed regardless of age when GABA was microionophoresed onto CN neurons. 4. GABA's capacity to reduce spontaneous or acoustically evoked discharge rates was a voltage-dependent phenomenon directly related to control discharge rates (i.e., efficacy was high when discharge rates were high) for neurons recorded from both immature and mature animals. 5. A small set of neurons recorded from animals younger than 2 wk exhibited prolonged GABA "activation" and "deactivation" times (i.e., times required to achieve 90% of the maximal effect evoked by GABA and to recover from that effect, respectively) and may represent a group of actively differentiating units. 6. Bicuculline microionophoresis effectively blocked the actions of exogenously applied GABA and endogenous GABA, which, presumably, was synaptically released as a result of acoustic stimulation. The actions of bicuculline were dose dependent in animals ranging in age from 2 postnatal days to adulthood. These results suggest that recognition sites for GABA and bicuculline and the ionophore associated with the GABA receptor are present and functionally coupled in the caudal CN before the developmental period during which the full complement of inhibitory projections form synaptic contacts with these cells.

Acoustic Stimulation↗

PubMed1988

Connections of a vagal communicating branch in the ferret. II. Central projections.

There is increasing interest in the central mechanisms involved in the regulation of gastrointestinal function. The ferret is becoming widely used for research in this area. However, knowledge of the brain stem organization of this species is inadequate. As part of an on-going study designed to provide information regarding the site of termination of abdominal afferents, the central connections of a supradiaphragmatic vagal communicating branch were determined in the ferret through the use of the horseradish peroxidase (HRP) tracing technique. The branch was exposed using a thoracotomy and HRP crystals were applied to the cut ventral end of the branch. Following a 72 hour survival period, the animals were reanesthetized and perfused. The brain stem was removed and processed using the tetramethylbenzidine method. Afferent terminals were found bilaterally in the nucleus of the solitary tract (nTS), area postrema (AP), the dorsal motor nucleus of the vagus (DMV), the external cuneate nucleus (ECN) and the principal subnucleus of the inferior olive (IOP). This is the first study of a brain stem projection of a specific vagal branch in this species, and demonstrates the similarities and differences which exist between the ferret and other species.

Animals↗

PubMed1988

Connections of a vagal communicating branch in the ferret. I. Pathways and cell body location.

In contrast to most other species, ferrets possess a single communicating branch connecting the dorsal and ventral vagal trunks immediately rostral to the diaphragm. This branch is being used in physiological studies of gastrointestinal function and emesis. However, the fibre routes which pass through this branch are not known. In this study, the afferent and efferent pathways within this supradiaphragmatic vagal communicating branch of the ferret were studied through the use of the horseradish peroxidase (HRP) tracing technique. The region of the branch was exposed using a thoracotomy and HRP crystals were applied to one of the following: (A) the ventral end of the communicating branch, (B) the dorsal end of the communicating branch, (C) the distal end of the dorsal vagal trunk rostral to the communicating branch or (D) the distal end of the ventral vagal trunk rostral to the communicating branch. Following a 72 hour survival period, the animals were reanaesthetized and perfused. The superior cervical and nodose ganglia and the brain stem were processed using the tetramethylbenzidine method. Following application of HRP to the cut ventral end of the communicating branch, labelled cell bodies were found in the left and right nodose ganglia and in the left dorsal motor nucleus of the vagus. After HRP application to the cut dorsal end of the communicating branch, labelled cells were found in the left and right nodose ganglia. No HRP containing cell bodies were found following HRP application to the cut distal end of either the dorsal or the ventral vagal trunk. These results indicate that several afferent pathways exist within the branch, although only one consistently labelled efferent pathway was found.

Afferent Pathways↗