Deafness-induced plasticity in the mature central auditory system

Studies in rats and guinea pigs indicate that local changes in inhibitory transmitters may underlie deafness-induced plastic changes in electrophysiological responsiveness of cells of the mature central auditory system. Following 21 days of bilateral deafness there is an increase in evoked Fos-immunoreactive neurones in the central nucleus of the inferior colliculus (CIC) to contralateral cochlear electrical stimulation, compared with normal or 1-day deafened animals. Deafness is also associated with a dramatic reduction in the population of CIC neurones that respond with suppression of activity to electrical stimulation. Moreover, in vivo microdialysis reveals a marked decrease in gamma-aminobutyric acid (GABA) release from the CIC cells in deafened animals. The results may have general implications for the mediation of central nervous system plasticity induced by deafferentation of sensory input.     

How the owl resolves auditory coding ambiguity

The barn owl (Tyto alba) uses interaural time difference (ITD) cues to localize sounds in the horizontal plane. Low-order binaural auditory neurons with sharp frequency tuning act as narrow-band coincidence detectors; such neurons respond equally well to sounds with a particular ITD and its phase equivalents and are said to be phase ambiguous. Higher-order neurons with broad frequency tuning are unambiguously selective for single ITDs in response to broad-band sounds and show little or no response to phase equivalents. Selectivity for single ITDs is thought to arise from the convergence of parallel, narrow-band frequency channels that originate in the cochlea. ITD tuning to variable bandwidth stimuli was measured in higher-order neurons of the owl's inferior colliculus to examine the rules that govern the relationship between frequency channel convergence and the resolution of phase ambiguity. Ambiguity decreased as stimulus bandwidth increased, reaching a minimum at 2-3 kHz. Two independent mechanisms appear to contribute to the elimination of ambiguity: one suppressive and one facilitative. The integration of information carried by parallel, distributed processing channels is a common theme of sensory processing that spans both modality and species boundaries. The principles underlying the resolution of phase ambiguity and frequency channel convergence in the owl may have implications for other sensory systems, such as electrolocation in electric fish and the computation of binocular disparity in the avian and mammalian visual systems.     

The functionally and physiologically plastic adult auditory system

The potential for functional and underlying physiological change in the adult auditory system is examined through review and evaluation of several sets of literature including auditory deprivation and recovery, auditory learning after hearing aid fitting, auditory abilities of normal listeners exposed to masking noise, and neural plasticity in the sensory and motor systems of animals. This tutorial review is meant for the reader who may be interested in auditory learning and who would like to have a summary and evaluation of the various findings to date. The focus of the review is the effect that various findings of auditory learning may have on hearing aid fitting and selection.     

Development of AMPA-selective glutamate receptors in the auditory brainstem of the barn owl

AMPA receptor specific antibodies were used to study the distribution and development of glutamate receptor subtypes (GluR1-4) in nucleus magnocellularis, angularis, laminaris, and the superior olive of the barn owl. Each nucleus in the adult barn owl expresses characteristic levels of AMPA receptor subtypes, and all are enriched in the subunits associated with rapid desensitization (GluR2 and 4). In the auditory hindbrain of the barn owl, the levels of expression of all AMPA receptors were very low at the time of hatching. In all nuclei, the level of GluR1 immunoreactivity was low to undetectable at all ages studied. In the cochlear nuclei, angularis and magnocellularis, levels of GluR2/3 and GluR4 immunoreactivity increased over the first 2 weeks after hatching, coinciding with the morphological maturation of auditory nerve terminals in NM. In the nucleus laminaris and in the superior olive, GluR2/3 and GluR4 immunoreactivity reached adult-like patterns by 3 weeks after hatching. Thus, adult-like patterns of immunoreactivity appeared at least 1 month before the end of the sensitive period in all nuclei studied.     

Pharmacological specialization of learned auditory responses in the inferior colliculus of the barn owl

Neural tuning for interaural time difference (ITD) in the optic tectum of the owl is calibrated by experience-dependent plasticity occurring in the external nucleus of the inferior colliculus (ICX). When juvenile owls are subjected to a sustained lateral displacement of the visual field by wearing prismatic spectacles, the ITD tuning of ICX neurons becomes systematically altered; ICX neurons acquire novel auditory responses, termed "learned responses," to ITD values outside their normal, pre-existing tuning range. In this study, we compared the glutamatergic pharmacology of learned responses with that of normal responses expressed by the same ICX neurons. Measurements were made in the ICX using iontophoretic application of glutamate receptor antagonists. We found that in early stages of ITD tuning adjustment, soon after learned responses had been induced by experience-dependent processes, the NMDA receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP-5) preferentially blocked the expression of learned responses of many ICX neurons compared with that of normal responses of the same neurons. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked learned and normal responses equally. After long periods of prism experience, preferential blockade of learned responses by AP-5 was no longer observed. These results indicate that NMDA receptors play a preferential role in the expression of learned responses soon after these responses have been induced by experience-dependent processes, whereas later in development or with additional prism experience (we cannot distinguish which), the differential NMDA receptor-mediated component of these responses disappears. This pharmacological progression resembles the changes that occur during maturation of glutamatergic synaptic currents during early development.     

Learning-induced physiological memory in adult primary auditory cortex: receptive fields plasticity, model, and mechanisms

It is well established that the functional organization of adult sensory cortices, including the auditory cortex, can be modified by deafferentation, sensory deprivation, or selective sensory stimulation. This paper reviews evidence establishing that the adult primary auditory cortex develops physiological plasticity during learning. Determination of frequency receptive fields before and at various times following aversive classical conditioning and instrumental avoidance learning in the guinea pig reveals increased neuronal responses to the pure tone frequency used as a conditioned stimulus (CS). In contrast, responses to the pretraining best frequency and other non-CS frequencies are decreased. These opposite changes are often sufficient to shift cellular tuning toward or even to the frequency of the CS. Learning-induced receptive field (RF) plasticity (i) is associative (requires pairing tone and shock), (ii) highly specific to the CS frequency (e.g., limited to this frequency +/- a small fraction of an octave), (iii) discriminative (specific increased response to a reinforced CS+ frequency but decreased response to a nonreinforced CS- frequency), (iv) develops extremely rapidly (within 5 trials, the fewest trials tested), and (v) is retained indefinitely (tested to 8 weeks). Moreover, RF plasticity is robust and not due to arousal, but can be expressed in the deeply anesthetized subject. Because learning- induced RF plasticity has the major characteristics of associative memory, it is therefore referred to as "physiological memory". We developed a model of RF plasticity based on convergence in the auditory cortex of nucleus basalis cholinergic effects acting at muscarinic receptors, with lemniscal and nonlemniscal frequency information from the ventral and magnocellular divisions of the medial geniculate nucleus, respectively. In the model, the specificity of RF plasticity is dependent on Hebbian rules of covariance. This aspect was confirmed in vivo using microstimulation techniques. Further, the model predicts that pairing a tone with activation of the nucleus basalis is sufficient to induce RF plasticity similar to that obtained in behavioral learning. This prediction has been confirmed. Additional tests of the model are described. RF plasticity is thought to translate the acquired significance of sound into an increased frequency representation of behaviorally important stimuli.     

Rapidly induced auditory plasticity: the ventriloquism aftereffect

Cortical representational plasticity has been well documented after peripheral and central injuries or improvements in perceptual and motor abilities. This has led to inferences that the changes in cortical representations parallel and account for the improvement in performance during the period of skill acquisition. There have also been several examples of rapidly induced changes in cortical neuronal response properties, for example, by intracortical microstimulation or by classical conditioning paradigms. This report describes similar rapidly induced changes in a cortically mediated perception in human subjects, the ventriloquism aftereffect, which presumably reflects a corresponding change in the cortical representation of acoustic space. The ventriloquism aftereffect describes an enduring shift in the perception of the spatial location of acoustic stimuli after a period of exposure of spatially disparate and simultaneously presented acoustic and visual stimuli. Exposure of a mismatch of 8 degrees for 20-30 min is sufficient to shift the perception of acoustic space by approximately the same amount across subjects and acoustic frequencies. Given that the cerebral cortex is necessary for the perception of acoustic space, it is likely that the ventriloquism aftereffect reflects a change in the cortical representation of acoustic space. Comparisons between the responses of single cortical neurons in the behaving macaque monkey and the stimulus parameters that give rise to the ventriloquism aftereffect suggest that the changes in the cortical representation of acoustic space may begin as early as the primary auditory cortex.     

Prepulse inhibition of the startle response in mice: Relationship to hearing loss and auditory system plasticity.

Prepulse inhibition was used with C57BL/6J (C57) mice to assess behavioral-perceptual correlates of previously demonstrated physiological changes in the central auditory system associated with age-related hearing loss. Normal-hearing CBA/CaJ (CBA) mice and DBA/2J (DBA) mice, which exhibit extremely rapid hearing loss, were also tested. Tone prepulse stimuli (S1s) were presented 100 ms prior to a startle-evoking noise stimulus (S2), and a decrease in startle amplitude served as the measure of startle modification. As high-frequency hearing declined in C57 mice between 1 and 12 mo of age, the efficacy of lower-frequency S1s was significantly enhanced. CBA mice exhibited no age-related changes in startle modification. DBA mice exhibited changes similar to those observed in C57s but at an accelerated rate. The enhanced behavioral saliency of low and middle frequencies in C57 and DBA mice appears to be a consequence of neural plasticity in the central auditory system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early experience and plasticity of song in adult male zebra finches (Taeniopygia guttata).

Zebra finches (Taeniopygia guttata) learn song primarily at 35–65 days of age, but birds deprived of experience at that stage may modify their songs later. Experiments on 5 groups examined the effect of varying early social experience on the plasticity of adult song. Major changes of song in adulthood were rare, and new syllables were memorized only in the more socially impoverished groups. Most songs underwent minor changes, in syllable structure or stereotypy, as well as in the addition or deletion of syllables. Two factors appeared to be important in determining the amount of change: the extent of social deprivation that the bird had experienced and, in the case of group-reared birds, the degree of song matching between social companions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experience-dependent plasticity in adult rat barrel cortex

This study tested the hypothesis that the receptive fields (RFs) of neurons in the adult sensory cortex are shaped by the recent history of sensory experience. Sensory experience was altered by a brief period of "whisker pairing": whiskers D2 and either D1 or D3 were left intact, while all other whiskers on the right side of the face were trimmed close to the fur. The animals were anesthetized 64-66 h later and the responses of single neurons in contralateral cortical barrel D2 to stimulation of whisker D2 (the center RF) and the four neighboring whiskers (D1, D3, C2, and E2; the excitatory surround RF) were measured. Data from 79 cells in four rats with whiskers paired were compared to data from 52 cells in four rats with untrimmed whiskers (control cases). During the period of whisker pairing, the RFs of cells in barrel D2 changed in three ways: (i) the response to the center RF, whisker D2, increased by 39%, (ii) the response to the paired surround RF whisker increased by 85-100%, and (iii) the response to all clipped (unpaired) surround RF whiskers decreased by 9-42%. In the control condition, the response of barrel D2 cells to the two neighboring whiskers, D1 and D3, was equal. After whisker pairing, the response to the paired neighbor of D2 was more than twice as large as the response to the cut neighbor of D2. These findings indicate that a brief change in the pattern of sensory activity can alter the configuration of cortical RFs, even in adult animals.     

A theoretical framework for the study of adult cognitive plasticity.

Does plasticity contribute to adult cognitive development, and if so, in what ways? The vague and overused concept of plasticity makes these controversial questions difficult to answer. In this article, we refine the notion of adult cognitive plasticity and sharpen its conceptual distinctiveness. According to our framework, adult cognitive plasticity is driven by a prolonged mismatch between functional organismic supplies and environmental demands and denotes the brain's capacity for anatomically implementing reactive changes in behavioral flexibility (i.e., the possible range of performance and function). We distinguish between 2 interconnected but distinct cognitive outcomes of adult cognitive plasticity: alterations in processing efficiency and alterations in representations. We demonstrate the usefulness of our framework in evaluating and interpreting (a) increments in frontal brain activations in the course of normal aging and (b) the effects of cognitive training in adulthood and old age. Finally, we outline new research questions and predictions generated by the present framework and recommend design features for future cognitive-training studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid development of learning-induced receptive field plasticity in the auditory cortex.

Classical conditioning induces frequency-specific receptive field (RF) plasticity in the auditory cortex after relatively brief training (30 trials), characterized by increased response to the frequency of the CS and decreased responses to other frequencies, including the pretraining best frequency (BF). This experiment determined the development of this CS-specific RF plasticity. Guinea pigs underwent classical conditioning to a tonal frequency, and receptive fields of neurons in the auditory cortex were determined before and after 5, 15, and 30 CS–UCS (unconditioned stimulus) pairings, as well as 1 hr posttraining. Highly selective RF changes were observed as early as the first 5 training trials. They culminated after 15 trials, then stabilized after 30 trials and 1 hr posttraining. The rapid development of RF plasticity satisfies a criterion for its involvement in the neural bases of a specific associative memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excitation produced by Schroeder-phase complexes: evidence for fast-acting compression in the auditory system

A series of experiments compared the excitation produced in an auditory filter centered on 1100 Hz by two complexes, both of which consisted of harmonics 2-20 of a 100-Hz fundamental. When the components had a level of 69 dB SPL each, summing them in positive Schroeder phase produced substantially less forward masking of an 1100-Hz signal than when the components were summed in negative Schroeder phase. This difference decreased with decreases in overall masker level. Listeners also reported that the components of the positive-phase masker close to 1100 Hz were quieter than the corresponding components in the negative-phase masker. The data are explained using Kohlrausch and Sander's [J. Acoust. Soc. Am. 97, 1817-1829 (1995)] finding that the response of an 1100-Hz auditory filter to the positive-phase complex shows marked peaks and dips, whereas that to the negative-phase complex does not. It is argued that the peaks in the response to the positive-phase masker are attenuated by fast-acting compression in the auditory system, thereby reducing the excitation produced by that sound. It is also argued that, compared to the power functions commonly used to model "excess masking" and the growth of loudness, the present data reflect greater compression at high levels but less compression at low levels.     

Regeneration of the auditory pathway in adult rats by transplants of fetal brain tissue

The ventral cochlear tract in the brain stem to pons was transected on one side in two groups of adult rats. In one group simple transection was performed, while in the other group tissue from embryos (E14-E16) was used to cover the lesion site. While rats receiving simple transection without transplantation showed no evidence of regeneration, in 30% of the rats receiving transplants of embryonic tissue the axons regrew beyond the transected site and regenerated into the denervated side and terminated at the normal targets. The present findings contradict the widely held view that the adult mammalian central auditory system cannot be restored following damage.     

Neuronal responses across cortical field A1 in plasticity induced by peripheral auditory organ damage

The adult auditory cortex is capable of a plastic reorganization of its tonotopic map after damage to restricted parts of the cochlear sensory epithelium. We examine the precise conditions of cochlear damage required to demonstrate such plasticity in the primary auditory cortex (A1) of the cat and the changes observed in neuronal responses in the A1 which has reorganized in plasticity of the tonotopic map. From these data we attempt to predict the conditions required for similar plasticity to occur in humans after cochlear damage.     

Frequency tuning and spontaneous activity in the auditory nerve and cochlear nucleus magnocellularis of the barn owl Tyto alba

Single-unit recordings were obtained from the brain stem of the barn owl at the level of entrance of the auditory nerve. Auditory nerve and nucleus magnocellularis units were distinguished by physiological criteria, with the use of the response latency to clicks, the spontaneous discharge rate, and the pattern of characteristic frequencies encountered along an electrode track. The response latency to click stimulation decreased in a logarithmic fashion with increasing characteristic frequency for both auditory nerve and nucleus magnocellularis units. The average difference between these populations was 0.4-0.55 ms. The average most sensitive thresholds were approximately 0 dB SPL and varied little between 0.5 and 9 kHz. Frequency-threshold curves showed the simple V shape that is typical for birds, with no indication of a low-frequency tail. Frequency selectivity increased in a gradual, power-law fashion with increasing characteristic frequency. There was no reflection of the unusual and greatly expanded mapping of higher frequencies on the basilar papilla of the owl. This observation is contrary to the equal-distance hypothesis that relates frequency selectivity to the spatial representation in the cochlea. On the basis of spontaneous rates and/or sensitivity there was no evidence for distinct subpopulations of auditory nerve fibers, such as the well-known type I afferent response classes in mammals. On the whole, barn owl auditory nerve physiology conformed entirely to the typical patterns seen in other bird species. The only exception was a remarkably small spread of thresholds at any one frequency, this being only 10-15 dB in individual owls. Average spontaneous rate was 72.2 spikes/s in the auditory nerve and 219.4 spikes/s for nucleus magnocellularis. This large difference, together with the known properties of endbulb-of-Held synapses, suggests a convergence of approximately 2-4 auditory nerve fibers onto one nucleus magnocellularis neuron. Some auditory nerve fibers as well as nucleus magnocellularis units showed a quasiperiodic spontaneous discharge with preferred intervals in the time-interval histogram. This phenomenon was observed at frequencies as high as 4.7 kHz.     

Basal forebrain stimulation induces discriminative receptive field plasticity in the auditory cortex.

Learning alters receptive field (RF) tuning in the primary auditory cortex (ACx) to emphasize the frequency of a tonal conditioned stimulus. RF plasticity is a candidate substrate of memory, as it is associative, specific, discriminative, rapidly induced, and enduring. The authors hypothesized that it is produced by the release of acetylcholine in the ACx from the basal forebrain (BasF), caused by presentation of reinforced but not nonreinforced conditioned stimuli. Waking adult male Hartley guinea pigs (n?=?16) received 1 of 2 tones followed by BasF stimulation, in a single session of 30 pseudo-random order trials each. RFs from neuronal discharges before and after differential pairing revealed the induction of predicted plasticity, as well as increased responses to the paired tone and decreased responses to the unpaired tone. Thus, highly specific, learning-induced RF plasticity in the ACx may be produced by activation of the BasF by a reinforced conditioned stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation

Neuronal plasticity can be defined as adaptive changes in structure and function of the nervous system, an obvious example of which is the capacity to remember and learn. Long-term potentiation and long-term depression are the experimental models of memory in the central nervous system (CNS), and have been frequently utilized for the analysis of the molecular mechanisms of memory formation. Extensive studies have demonstrated that various kinases and phosphatases regulate neuronal plasticity by phosphorylating and dephosphorylating proteins essential to the basic processes of adaptive changes in the CNS. These proteins include receptors, ion channels, synaptic vesicle proteins, and nuclear proteins. Multifunctional kinases (cAMP-dependent protein kinase, Ca2+/phospholipid-dependent protein kinase, and Ca2+/calmodulin-dependent protein kinases) and phosphatases (calcineurin, protein phosphatases 1, and 2A) that specifically modulate the phosphorylation status of neuronal-signaling proteins have been shown to be required for neuronal plasticity. In general, kinases are involved in upregulation of the activity of target substrates, and phosphatases downregulate them. Although this rule is applicable in most of the cases studied, there are also a number of exceptions. A variety of regulation mechanisms via phosphorylation and dephosphorylation mediated by multiple kinases and phosphatases are discussed.     

Clinical experience with expanded polytetrafluoroethylene (Gore-Tex) grafts for femoropopliteal arterial bypass

Thirty-seven grafts of expanded polytetrafluoroethylene were implanted in 28 patients in whom autogeneous saphenous vein was not available, either for symptoms of severe claudication or limb salvage. The length of follow-up ranges from 8 to 28 months . The patency rate is 86.9 percent for the patients with severe claudication and 71.4 percent in the limb salvage group; the overall patency rate is 81 percent. We believe that expanded polytetrafluoroethylene is a good prosthetic substitute when autogenous vein is unavailable.     

High-frequency auditory feedback is not required for adult song maintenance in Bengalese finches

Male Bengalese finches do not normally change their vocal patterns in adulthood; song is stereotyped and stable over time. Adult song maintenance requires auditory feedback. If adults are deafened, song will degrade within 1 week. We tested whether feedback of all sound frequencies is required for song maintenance. The avian basilar papilla is tonotopically organized; hair cells in the basal region encode high frequencies, and low frequencies are encoded in progressively apical regions. We restricted the spectral range of feedback available to a bird by killing either auditory hair cells encoding higher frequencies or those encoding both high and low frequencies and documented resultant changes in song. Birds were treated with either Amikacin alone to kill high-frequency hair cells or Amikacin and sound exposure to target hair cells across the entire papilla. During treatment, song was recorded from all birds weekly. After treatment and song recording, evoked-potential audiograms were evaluated on each bird, and papillas were evaluated by scanning electron microscopy. Results showed that hair cell damage over 46-63% of the basal papilla and the corresponding high-frequency hearing loss had no effect on song structure. In birds with hair cell damage extending further into the apical region of the papilla and corresponding low-frequency and high-frequency hearing loss, song degradation occurred within 1 week of beginning treatment and was comparable with degradation after surgical deafening. We conclude that either low-frequency spectral cues or temporal cues via feedback of the song amplitude envelope are sufficient for song maintenance in adult Bengalese finches.