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Biomedical subjects

Andrew J King

Publications and source records attributed to Andrew J King.

At least 19 recordsLinked to original sources
PubMed2006

Physiological and anatomical evidence for multisensory interactions in auditory cortex.

Recent studies, conducted almost exclusively in primates, have shown that several cortical areas usually associated with modality-specific sensory processing are subject to influences from other senses. Here we demonstrate using single-unit recordings and estimates of mutual information that visual stimuli can influence the activity of units in the auditory cortex of anesthetized ferrets. In many cases, these units were also acoustically responsive and frequently transmitted more information in their spike discharge patterns in response to paired visual-auditory stimulation than when either modality was presented by itself. For each stimulus, this information was conveyed by a combination of spike count and spike timing. Even in primary auditory areas (primary auditory cortex [A1] and anterior auditory field [AAF]), approximately 15% of recorded units were found to have nonauditory input. This proportion increased in the higher level fields that lie ventral to A1/AAF and was highest in the anterior ventral field, where nearly 50% of the units were found to be responsive to visual stimuli only and a further quarter to both visual and auditory stimuli. Within each field, the pure-tone response properties of neurons sensitive to visual stimuli did not differ in any systematic way from those of visually unresponsive neurons. Neural tracer injections revealed direct inputs from visual cortex into auditory cortex, indicating a potential source of origin for the visual responses. Primary visual cortex projects sparsely to A1, whereas higher visual areas innervate auditory areas in a field-specific manner. These data indicate that multisensory convergence and integration are features common to all auditory cortical areas but are especially prevalent in higher areas.

Acoustic Stimulation↗
PubMed2006

Chronic low-dose angiotensin II infusion increases venomotor tone by neurogenic mechanisms.

The purpose of this study was to identify changes in venomotor tone in the chronic low-dose angiotensin II (Ang II) model of hypertension and to establish the contribution of sympathetic nerve activation to these venomotor tone changes. Male Sprague-Dawley rats were acclimatized to a 0.4% or 2.0% NaCl diet for 7 days and then catheterized to allow chronic and repeated measures of arterial pressure, central venous pressure, and mean circulatory filling pressure (MCFP), an index of venous smooth muscle tone, in conscious undisturbed rats. After 4 days of recovery and a 3-day control period, an Ang II or physiological saline-filled osmotic minipump was implanted subcutaneously to deliver Ang II (150 ng/kg per minute) or vehicle control for 14 days. MCFP was measured in duplicate before and after acute ganglionic blockade with hexamethonium (30 mg/kg i.v.) on control day 2 and Ang II infusion on days 1, 3, 7, and 14. Blood volume was also measured on these days and was unchanged for the duration of the study in all of the groups. Arterial pressure was increased for the duration of Ang II infusion in rats on both 0.4% and 2% NaCl diets, but the increase was significantly greater in the 2% NaCl group and completely abolished by hexamethonium. MCFP was significantly increased for the entire Ang II infusion period only in rats fed 2% NaCl, and this increase was completely abolished by hexamethonium. We conclude that the combination of chronic low-dose Ang II infusion and high dietary salt intake engages the sympathetic nervous system to increase venomotor tone.

Angiotensin II↗
PubMed2006

Auditory neuroscience: activating the cortex without sound.

Sensory brain areas are usually characterized by their responses to external stimuli; however, neuroimaging studies have now shown that activation of auditory cortex occurs spontaneously and can be induced during silence by stimulus expectancy or mental imagery.

Acoustic Stimulation↗
PubMed2006

The ferret auditory cortex: descending projections to the inferior colliculus.

Descending corticofugal projections are thought to play a critical role in shaping the responses of subcortical neurons. Here, we examine the origins and targets of ferret auditory corticocollicular projections. We show that the ectosylvian gyrus (EG), where the auditory cortex is located, can be subdivided into middle, anterior, and posterior regions according to the pattern of cytochrome oxidase staining and immunoreactivity for the neurofilament antibody SMI32. Injection of retrograde tracers in the inferior colliculus (IC) labeled large layer V pyramidal cells throughout the EG and adjacent sulci. Each region of the EG has a different pattern of descending projections. Neurons in the primary auditory fields in the middle EG project to the lateral nucleus (LN) of the ipsilateral IC and bilaterally to the dorsal cortex and dorsal part of the central nucleus (CN). The projection to these dorsomedial regions of the IC is predominantly ipsilateral and topographically organized. The secondary cortical fields in the posterior EG target the same midbrain areas but exclude the CN of the IC. A smaller projection to the ipsilateral LN also arises from the anterior EG, which is the only region of auditory cortex to target tegmental areas surrounding the IC, including the superior colliculus, periaqueductal gray, intercollicular tegmentum, and cuneiform nucleus. This pattern of corticocollicular connectivity is consistent with regional differences in physiological properties and provides another basis for subdividing ferret auditory cortex into functionally distinct areas.

Animals↗
PubMed2006

Training-induced plasticity of auditory localization in adult mammals.

Accurate auditory localization relies on neural computations based on spatial cues present in the sound waves at each ear. The values of these cues depend on the size, shape, and separation of the two ears and can therefore vary from one individual to another. As with other perceptual skills, the neural circuits involved in spatial hearing are shaped by experience during development and retain some capacity for plasticity in later life. However, the factors that enable and promote plasticity of auditory localization in the adult brain are unknown. Here we show that mature ferrets can rapidly relearn to localize sounds after having their spatial cues altered by reversibly occluding one ear, but only if they are trained to use these cues in a behaviorally relevant task, with greater and more rapid improvement occurring with more frequent training. We also found that auditory adaptation is possible in the absence of vision or error feedback. Finally, we show that this process involves a shift in sensitivity away from the abnormal auditory spatial cues to other cues that are less affected by the earplug. The mature auditory system is therefore capable of adapting to abnormal spatial information by reweighting different localization cues. These results suggest that training should facilitate acclimatization to hearing aids in the hearing impaired.

Adaptation, Physiological↗
PubMed2006

Binaural-level functions in ferret auditory cortex: evidence for a continuous distribution of response properties.

Many previous studies have subdivided auditory neurons into a number of physiological classes according to various criteria applied to their binaural response properties. However, it is often unclear whether such classifications represent discrete classes of neurons or whether they merely reflect a potentially convenient but ultimately arbitrary partitioning of a continuous underlying distribution of response properties. In this study we recorded the binaural response properties of 310 units in the auditory cortex of anesthetized ferrets, using an extensive range of interaural level differences (ILDs) and average binaural levels (ABLs). Most recordings were from primary auditory fields on the middle ectosylvian gyrus and from neurons with characteristic frequencies >5 kHz. We used simple multivariate statistics to quantify a fundamental coding feature: the shapes of the binaural response functions. The shapes of all 310 binaural response surfaces were represented as points in a five-dimensional principal component space. This space captured the underlying shape of all the binaural response surfaces. The distribution of binaural level functions was not homogeneous because some shapes were more common than others. Despite this, clustering validation techniques revealed no evidence for the existence of discrete, or partially overlapping, clusters that could serve as a basis for an objective classification of binaural-level functions. We also examined the gradients of the response functions for the population of units; these gradients were greatest near the midline, which is consistent with free-field data showing that cortical neurons are most sensitive to changes in stimulus location in this region of space.

Acoustic Stimulation↗
PubMed2006

Development of contralateral and ipsilateral frequency representations in ferret primary auditory cortex.

Little is known about the maturation of functional maps in the primary auditory cortex (A1) after the onset of sensory experience. We used intrinsic signal imaging to examine the development of the tonotopic organization of ferret A1 with respect to contralateral and ipsilateral tone stimulation. Sound-evoked responses were recorded as early as postnatal day (P) 33, a few days after hearing onset. From P36 onwards, pure tone stimuli evoked restricted, tonotopically organized patches of activity. There was an age-dependent increase in the cortical area representing each octave, with a disproportionate expansion of cortical territory representing frequencies > 4 kHz after P60. Similar tonotopic maps were observed following stimulation of the contralateral and ipsilateral ears. During the first few weeks following hearing onset, no differences were found in the area of cortical activation or in the magnitude of the optical responses evoked by stimulation of each ear. In older animals, however, contralateral stimuli evoked stronger responses and activated a larger A1 area than ipsilateral stimuli. Our findings indicate that neither the tonotopic organization nor the representation of inputs from each ear reach maturity until approximately 1 month after hearing onset. These results have important implications for cortical signal processing in juvenile animals.

Acoustic Stimulation↗
PubMed2005

Size selective and volume exclusion effects on ion transfer at the silicalite modified liquid-liquid interface.

The modification of the liquid/liquid interface with membranes of silicalite, a neutral framework zeolite, is used to extend the potential window. This feature allows the observation of the transfer of extremely hydrophilic ions, due to the size-exclusion of organic ions from the interior of the zeolitic framework. Similarly, volume exclusion effects are shown to affect facilitated ion transfer processes involving alkali metal cations. In contrast, proton transfer is largely unaffected by the presence of the zeolite, which is suggestive of more rapid diffusion processes within the interior of the framework. The technique of liquid/liquid electrochemistry should allow the measurement of solution phase transport parameters for ions within microporous hosts.

Journal Article↗
PubMed2005

Interaural timing cues do not contribute to the map of space in the ferret superior colliculus: a virtual acoustic space study.

In this study, we used individualized virtual acoustic space (VAS) stimuli to investigate the representation of auditory space in the superior colliculus (SC) of anesthetized ferrets. The VAS stimuli were generated by convolving broadband noise bursts with each animal's own head-related transfer function and presented over earphones. Comparison of the amplitude spectra of the free-field and VAS signals and of the spatial receptive fields of neurons recorded in the inferior colliculus with each form of stimulation confirmed that the VAS provided an accurate simulation of sounds presented in the free field. Units recorded in the deeper layers of the SC responded predominantly to virtual sound directions within the contralateral hemifield. In most cases, increasing the sound level resulted in stronger spike discharges and broader spatial receptive fields. However, the preferred sound directions, as defined by the direction of the centroid vector, remained largely unchanged across different levels and, as observed in previous free-field studies, varied topographically in azimuth along the rostrocaudal axis of the SC. We also examined the contribution of interaural time differences (ITDs) to map topography by digitally manipulating the VAS stimuli so that ITDs were held constant while allowing other spatial cues to vary naturally. The response properties of the majority of units, including centroid direction, remained unchanged with fixed ITDs, indicating that sensitivity to this cue is not responsible for tuning to different sound directions. These results are consistent with previous data suggesting that sensitivity to interaural level differences and spectral cues provides the basis for the map of auditory space in the mammalian SC.

Acoustic Stimulation↗
PubMed2005

Auditory plasticity: vocal output shapes auditory cortex.

Studies in humans and songbirds have revealed a close link between vocal output and hearing. Now experiments in marmosets have shown that self-generated vocalizations can modulate the activity of neurons in the auditory cortex and even remodel their response properties.

Animals↗
PubMed2005

Multisensory integration: strategies for synchronization.

Recent studies have shown that our ability to match the timing of inputs from objects that can be both seen and heard is highly adaptable and takes into account target depth and the relatively slow speed of sound.

Acoustic Stimulation↗
PubMed2005

Development of the projection from the nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret.

Neurons in the deeper layers of the superior colliculus (SC) have spatially tuned receptive fields that are arranged to form a map of auditory space. The spatial tuning of these neurons emerges gradually in an experience-dependent manner after the onset of hearing, but the relative contributions of peripheral and central factors in this process of maturation are unknown. We have studied the postnatal development of the projection to the ferret SC from the nucleus of the brachium of the inferior colliculus (nBIC), its main source of auditory input, to determine whether the emergence of auditory map topography can be attributed to anatomical rewiring of this projection. The pattern of retrograde labeling produced by injections of fluorescent microspheres in the SC on postnatal day (P) 0 and just after the age of hearing onset (P29), showed that the nBIC-SC projection is topographically organized in the rostrocaudal axis, along which sound azimuth is represented, from birth. Injections of biotinylated dextran amine-fluorescein into the nBIC at different ages (P30, 60, and 90) labeled axons with numerous terminals and en passant boutons throughout the deeper layers of the SC. This labeling covered the entire mediolateral extent of the SC, but, in keeping with the pattern of retrograde labeling following microsphere injections in the SC, was more restricted rostrocaudally. No systematic changes were observed with age. The stability of the nBIC-SC projection over this period suggests that developmental changes in auditory spatial tuning involve other processes, rather than a gross refinement of the projection from the nBIC.

Animals↗
PubMed2005

Functional organization of ferret auditory cortex.

We characterized the functional organization of different fields within the auditory cortex of anaesthetized ferrets. As previously reported, the primary auditory cortex, A1, and the anterior auditory field, AAF, are located on the middle ectosylvian gyrus. These areas exhibited a similar tonotopic organization, with high frequencies represented at the dorsal tip of the gyrus and low frequencies more ventrally, but differed in that AAF neurons had shorter response latencies than those in A1. On the basis of differences in frequency selectivity, temporal response properties and thresholds, we identified four more, previously undescribed fields. Two of these are located on the posterior ectosylvian gyrus and were tonotopically organized. Neurons in these areas responded robustly to tones, but had longer latencies, more sustained responses and a higher incidence of non-monotonic rate-level functions than those in the primary fields. Two further auditory fields, which were not tonotopically organized, were found on the anterior ectosylvian gyrus. Neurons in the more dorsal anterior area gave short-latency, transient responses to tones and were generally broadly tuned with a preference for high (>8 kHz) frequencies. Neurons in the other anterior area were frequently unresponsive to tones, but often responded vigorously to broadband noise. The presence of both tonotopic and non-tonotopic auditory cortical fields indicates that the organization of ferret auditory cortex is comparable to that seen in other mammals.

Acoustic Stimulation↗
PubMed2005

Encoding of virtual acoustic space stimuli by neurons in ferret primary auditory cortex.

Recent studies from our laboratory have indicated that the spatial response fields (SRFs) of neurons in the ferret primary auditory cortex (A1) with best frequencies > or =4 kHz may arise from a largely linear processing of binaural level and spectral localization cues. Here we extend this analysis to investigate how well the linear model can predict the SRFs of neurons with different binaural response properties and the manner in which SRFs change with increases in sound level. We also consider whether temporal features of the response (e.g., response latency) vary with sound direction and whether such variations can be explained by linear processing. In keeping with previous studies, we show that A1 SRFs, which we measured with individualized virtual acoustic space stimuli, expand and shift in direction with increasing sound level. We found that these changes are, in most cases, in good agreement with predictions from a linear threshold model. However, changes in spatial tuning with increasing sound level were generally less well predicted for neurons whose binaural frequency-time receptive field (FTRF) exhibited strong excitatory inputs from both ears than for those in which the binaural FTRF revealed either a predominantly inhibitory effect or no clear contribution from the ipsilateral ear. Finally, we found (in agreement with other authors) that many A1 neurons exhibit systematic response latency shifts as a function of sound-source direction, although these temporal details could usually not be predicted from the neuron's binaural FTRF.

Acoustic Stimulation↗
PubMed2005

Encoding stimulus information by spike numbers and mean response time in primary auditory cortex.

Neurons can transmit information about sensory stimuli via their firing rate, spike latency, or by the occurrence of complex spike patterns. Identifying which aspects of the neural responses actually encode sensory information remains a fundamental question in neuroscience. Here we compared various approaches for estimating the information transmitted by neurons in auditory cortex in two very different experimental paradigms, one measuring spatial tuning and the other responses to complex natural stimuli. We demonstrate that, in both cases, spike counts and mean response times jointly carry essentially all the available information about the stimuli. Thus, in auditory cortex, whereas spike counts carry only partial information about stimulus identity or location, the additional availability of relatively coarse temporal information is sufficient in order to extract essentially all the sensory information available in the spike discharge pattern, at least for the relatively short stimuli (<approximately 100 ms) commonly used in auditory research.

Acoustic Stimulation↗
PubMed2004

Auditory neuroscience: a time for coincidence?

Mammals and birds appear to encode timing differences between the ears, a major cue for auditory localization, in fundamentally different ways. It now appears that results from different species can be accommodated within a single general framework.

Animals↗
PubMed2004

Functional topography of converging visual and auditory inputs to neurons in the rat superior colliculus.

We have used a slice preparation of the infant rat midbrain to examine converging inputs onto neurons in the deeper multisensory layers of the superior colliculus (dSC). Electrical stimulation of the superficial visual layers (sSC) and of the auditory nucleus of the brachium of the inferior colliculus (nBIC) evoked robust monosynaptic responses in dSC cells. Furthermore, the inputs from the sSC were found to be topographically organized as early as the second postnatal week and thus before opening of the eyes and ear canals. This precocious topography was found to be sculpted by GABAA-mediated inhibition of a more widespread set of connections. Tracer injections in the nBIC, both in coronal slices as well as in hemisected brains, confirmed a robust projection originating in the nBIC with distinct terminals in the proximity of the cell bodies of dSC neurons. Combined stimulation of the sSC and nBIC sites revealed that the presumptive visual and auditory inputs are summed linearly. Finally, whereas either input on its own could manifest a significant degree of paired-pulse facilitation, temporally offset stimulation of the two sites revealed no synaptic interactions, indicating again that the two inputs function independently. Taken together, these data provide the first detailed intracellular analysis of convergent sensory inputs onto dSC neurons and form the basis for further exploration of multisensory integration and developmental plasticity.

Acoustic Stimulation↗