Auditory Neurophysiology publications

Sensory systems adapt their neural code to changes in the sensory environment, often on multiple time scales. Here, we report a new form of adaptation in a first-order auditory interneuron (AN2) of crickets. We characterize the response of the AN2 neuron to amplitude-modulated sound stimuli and find that adaptation shifts the stimulus-response curves toward higher stimulus intensities, with a time constant of 1.5 s for adaptation and recovery. The spike responses were thus reduced for low-intensity sounds. We then address the question whether adaptation leads to an improvement of the signal's representation and compare the experimental results with the predictions of two competing hypotheses: infomax, which predicts that information conveyed about the entire signal range should be maximized, and selective coding, which predicts that "foreground" signals should be enhanced while "background" signals should be selectively suppressed. We test how adaptation changes the input-response curve when presenting signals with two or three peaks in their amplitude distributions, for which selective coding and infomax predict conflicting changes. By means of Bayesian data analysis, we quantify the shifts of the measured response curves and also find a slight reduction of their slopes. These decreases in slopes are smaller, and the absolute response thresholds are higher than those predicted by infomax. Most remarkably, and in contrast to the infomax principle, adaptation actually reduces the amount of encoded information when considering the whole range of input signals. The response curve changes are also not consistent with the selective coding hypothesis, because the amount of information conveyed about the loudest part of the signal does not increase as predicted but remains nearly constant. Less information is transmitted about signals with lower intensity.

Neurons selective for frequency modulated (FM) sweeps are common in auditory systems across different vertebrate groups and may underlie representation of species-specific vocalizations. Studies on mechanisms of FM sweep selectivity have primarily focused on sideband inhibition. Here, we present the first evidence for facilitatory mechanisms of FM sweep selectivity. Facilitatory interactions were found in 46 of 264 (17%) neurons tuned in the echolocation range (25–60 kHz) in the auditory cortex of the pallid bat. These neurons respond poorly to individual tones but are facilitated by combinations of tones with specific spectral and temporal intervals. Facilitation neurons show remarkable sensitivity to sub-millisecond differences in time delays between the two tones. Interestingly, the range of delays eliciting facilitation is not fixed but varies systematically with frequency difference between the two tones. Properties of facilitation strongly predict selectivity for the direction and rate of FM sweeps. Together with previous studies, there appear to be at least three mechanisms underlying FM rate and direction selectivity: sideband inhibition, duration tuning, and facilitation. Interestingly, similar mechanisms underlie direction and velocity tuning in the visual system, suggesting the evolution of similar computations across sensory systems to process dynamic sensory stimuli.

Auditory neurons are likely adapted to process complex stimuli, such as vocalizations, which contain spectrotemporal modulations. However, basic properties of auditory neurons are often derived from tone pips presented in isolation, which lack spectrotemporal modulations. In this context, it is unclear how to deduce the functional role of auditory neurons from their tone pip-derived tuning properties. In this study, spectrotemporal receptive fields (STRFs) were obtained from responses to multi-tone stimulus ensembles differing in their average spectrotemporal density (i.e., number of tone pips per second). STRFs for different stimulus densities were derived from multiple single-unit activity (MUA) and local field potentials (LFPs), simultaneously recorded in primary auditory cortex of cats. Consistent with earlier studies, we found that the spectral bandwidth was narrower for MUA compared with LFPs. Both neural firing rate and LFP amplitude were reduced when the density of the stimulus ensemble increased. Surprisingly, we found that increasing the spectrotemporal sound density revealed with increasing clarity an over-representation of response peaks at frequencies of ∼3, 5, 10, and 20 kHz, in both MUA- and LFP-derived STRFs. Although the decrease in spectral bandwidth and neural activity with increasing stimulus density can likely be accounted for by forward suppression, the mechanisms underlying the over-representation of the octave-spaced response peaks are unclear. Plausibly, the over-representation may be a functional correlate of the periodic pattern of corticocortical connections observed along the tonotopic axis of cat auditory cortex.

The primary auditory cortex is now known to be involved in learning and memory, as well as auditory perception. For example, spectral tuning often shifts toward or to the frequency of the conditioned stimulus during associative learning. As previous research has focused on tonal frequency, less is known about how learning might alter temporal parameters of response in the auditory cortex. This study addressed the effects of learning on the fidelity of temporal processing. Adult male rats were trained to avoid shock that was signaled by an 8.0 kHz tone. A novel control group received non-contingent tone and shock with shock probability decreasing over days to match the reduced number of shocks received by the avoidance group as they mastered the task. An untrained (nai ve) group served as a baseline. Following training, neuronal responses to white noise and a broad spectrum of tones were determined across the primary auditory cortex in a terminal experiment with subjects under general anesthesia. Avoidance conditioning significantly improved the precision of spike-timing: the coefficient of variation of 1st spike latency was significantly reduced in avoidance animals compared to controls and nai ves, both for tones and for noise. Additionally, avoidance learning was accompanied by a reduction of the latency of peak response, by 2.0-2.5 ms relative to nai ves and approximately 1.0 ms relative to controls. The shock-matched controls also exhibited significantly shorter peak latency of response than nai ves, demonstrating the importance of this non-avoidance control. Plasticity of temporal processing showed no evidence of frequency specificity and developed independently of the non-temporal parameters magnitude of response, frequency tuning and neural threshold, none of which were facilitated. The facilitation of temporal processing suggests that avoidance learning may increase synaptic strength either within the auditory cortex, in the subcortical auditory system, or both.

Experience-dependent plastic changes in the central sensory systems are due to activation of both the sensory and neuromodulatory systems. Nonspecific changes of cortical auditory neurons elicited by pseudoconditioning are quite different from tone-specific changes of the neurons elicited by auditory fear conditioning. Therefore the neural circuit evoking the nonspecific changes must also be different from that evoking the tone-specific changes. We first examined changes in the response properties of cortical auditory neurons of the big brown bat elicited by pseudoconditioning with unpaired tonal (CS u ) and electric leg (US u ) stimuli and found that it elicited nonspecific changes to CS u (a heart-rate decrease, an auditory response increase, a broadening of frequency tuning, and a decrease in threshold) and, in addition, a small tone-specific change to CS u (a small short-lasting best-frequency shift) only when CS u frequency was 5 kHz lower than the best frequency of a recorded neuron. We then examined the effects of drugs on the cortical changes elicited by the pseudoconditioning. The development of the nonspecific changes was scarcely affected by atropine (a muscarinic cholinergic receptor antagonist) and mecamylamine (a nicotinic cholinergic receptor antagonist) applied to the auditory cortex and by muscimol (a GABA A -receptor agonist) applied to the somatosensory cortex. However, these drugs abolished the small short-lasting tone-specific change as they abolished the large long-lasting tone-specific change elicited by auditory fear conditioning. Our current results indicate that, different from the tone-specific change, the nonspecific changes depend on neither the cholinergic neuromodulator nor the somatosensory cortex.

As part of an ongoing study of age-related changes in auditory processing, sensitivity to small changes in frequency were assessed using the cortical auditory evoked potential, P1-N1-P2, in younger and older adults with normal hearing. Behavioral measures have shown age-related differences in intensity and frequency discrimination that are larger at lower than higher frequencies. However, substantial individual differences and equivocal results among studies have been reported. This variability may reflect differences in tasks and procedures, as well as subject variables, such as hearing sensitivity and level of attention. To minimize these subject variables, the P1-N1-P2 response was investigated using a passive listening paradigm. Subjects were 10 younger and 10 older adults. The P1-N1-P2 was elicited by a 150-ms change in frequency in otherwise continuous 500-Hz and 3000-Hz pure tones presented at 70 dB SPL. P1-N1-P2 threshold was defined as the smallest change in frequency needed to evoke a P1-N1-P2 response. Furthermore, a frequency-dependent aging effect was observed for P1-N1-P2 thresholds, such that older subjects were significantly less sensitive to the frequency change than younger subjects, with significantly larger age-related differences at 500 Hz than at 3000 Hz. Age-related changes in response latencies and amplitude of the P1-N1-P2 response were also evident at 500 and 3000 Hz. These results are consistent with age-related changes in the central auditory system and suggest that changes in frequency discrimination abilities of older adults may be, in part, related to changes in preattentive levels of auditory processing.

In vertebrate auditory systems, specialized combination-sensitive neurons analyze complex vocal signals by integrating information across multiple frequency bands. We studied combination-sensitive interactions in neurons of the inferior colliculus (IC) of awake mustached bats, using intracellular somatic recording with sharp electrodes. Facilitated combinatorial neurons are coincidence detectors, showing maximum facilitation when excitation from low- and high-frequency stimuli coincide. Previous work showed that facilitatory interactions originate in the IC, require both low and high frequency–tuned glycinergic inputs, and are independent of glutamatergic inputs. These results suggest that glycinergic inputs evoke facilitation through either postinhibitory rebound or direct depolarizing mechanisms. However, in 35 of 36 facilitated neurons, we observed no evidence of low frequency–evoked transient hyperpolarization or depolarization that was closely related to response facilitation. Furthermore, we observed no evidence of shunting inhibition that might conceal inhibitory inputs. Since these facilitatory interactions originate in IC neurons, the results suggest that inputs underlying facilitation are electrically segregated from the soma. We also recorded inhibitory combinatorial interactions, in which low frequency sounds suppress responses to higher frequency signals. In 43% of 118 neurons, we observed low frequency–evoked hyperpolarizations associated with combinatorial inhibition. For these neurons, we conclude that low frequency–tuned inhibitory inputs terminate on neurons primarily excited by high-frequency signals; these inhibitory inputs may create or enhance inhibitory combinatorial interactions. In the remainder of inhibited combinatorial neurons (57%), we observed no evidence of low frequency–evoked hyperpolarizations, consistent with observations that inhibitory combinatorial responses may originate in lateral lemniscal nuclei.

The purpose of this study was to determine how closely the auditory brainstem response (ABR) can estimate sensorineural threshold shifts in rats exposed to loud sound. Behavioral and ABR thresholds were obtained for tones or noise before and after exposure to loud sound. The results showed that the ABR threshold shift obtained with tone pips estimated the initial pure-tone threshold shifts to within ±5dB 11% of the time and the permanent pure-tone threshold shifts 55% of the time, both with large errors. Determining behavioral thresholds for the same tone pips used for the ABR did not improve the agreement between the measures. In contrast, the ABR obtained with octave noise estimated the initial threshold shifts for that noise to within ±5dB 25% of the time and the permanent threshold shifts 89% of the time, with much smaller errors. Thus, it appears that the noise-evoked ABR is more accurate in estimating threshold shift than the tone-evoked ABR.

The central auditory system creates various types of neurons tuned to different acoustic parameters other than a specific frequency. The response latency of auditory neurons typically shortens with an increase in stimulus intensity. However, ∼10% of collicular neurons of the little brown bat show a “paradoxical latency-shift (PLS)”: long latencies to intense sounds but short latencies to weak sounds. These neurons presumably are involved in the processing of target distance information carried by a pair of an intense biosonar pulse and its weak echo. Our current studies show that collicular PLS neurons of the big brown bat are modulated by the corticofugal (descending) system. Electric stimulation of cortical auditory neurons evoked two types of changes in the PLS neurons, depending on the relationship in the best frequency (BF) between the stimulated cortical and recorded collicular neurons. When the BF was matched between them, the cortical stimulation did not shift the BFs of the collicular neurons and shortened their response latencies at intense sounds so that the PLS became smaller. When the BF was unmatched, however, the cortical stimulation shifted the BFs of the collicular neurons and lengthened their response latencies at intense sounds, so that the PLS became larger. Cortical electric stimulation also modulated the response latencies of non-PLS neurons. It produced an inhibitory frequency tuning curve or curves. Our findings indicate that corticofugal feedback is involved in shaping the spectrotemporal patterns of responses of subcortical auditory neurons presumably through inhibition.

Neurons in the inferior colliculus (IC), one of the major integrative centers of the auditory system, process acoustic information converging from almost all nuclei of the auditory brain stem. During this integration, excitatory and inhibitory inputs arrive to auditory neurons at different time delays. Result of this integration determines timing of IC neuron firing. In the mammalian IC, the range of the first spike latencies is very large (5-50 ms). At present, a contribution of excitatory and inhibitory inputs in controlling neurons' firing in the IC is still under debate. In the present study we assess the role of excitation and inhibition in determining first spike response latency in the IC. Postsynaptic responses were recorded to pure tones presented at neuron's characteristic frequency or to downward frequency modulated sweeps in awake bats. There are three main results emerging from the present study: (1) the most common response pattern in the IC is hyperpolarization followed by depolarization followed by hyperpolarization, (2) latencies of depolarizing or hyperpolarizing responses to tonal stimuli are short (3-7 ms) whereas the first spike latencies may vary to a great extent (4-26 ms) from one neuron to another, and (3) high threshold hyperpolarization preceded long latency spikes in IC neurons exhibiting paradoxical latency shift. Our data also show that the onset hyperpolarizing potentials in the IC have very small jitter (<100 micros) across repeated stimulus presentations. The results of this study suggest that inhibition, arriving earlier than excitation, may play a role as a mechanism for delaying the first spike latency in IC neurons.

The interaural time difference (ITD) is the primary auditory cue used by the barn owl for localization in the horizontal direction. ITD is initially computed by circuits consisting of axonal delay lines from one of the cochlear nuclei and coincidence detector neurons in the nucleus laminaris (NL). NL projects directly to the anterior part of the dorsal lateral lemniscal nucleus (LLDa), and this area projects to the core of the central nucleus of the inferior colliculus (ICcc) in the midbrain. To show the selectivity of an NL neuron for ITD requires averaging of responses over several stimulus presentations for each ITD. In contrast, ICcc neurons detect their preferred ITD in a single burst of stimulus. We recorded extracellularly the responses of LLDa neurons to ITD in anesthetized barn owls and show that this ability is already present in LLDa, raising the possibility that ICcc inherits its noise reduction property from LLDa.

Synucleins are widely expressed synaptic proteins within the central nervous system that have been implicated in such neurodegenerative disorders as Parkinson's disease. In this study, an initial characterization of all three synucleins, alpha-, beta-, and gamma-synuclein, within the cochlea was undertaken. Reverse transcriptase-polymerase chain reaction (PCR) demonstrated all three synuclein mRNA species within microdissected cochlear tissue. Quantitative PCR suggests that beta-synuclein is the most abundantly expressed form, followed by gamma- and then alpha-synuclein. Western blot analysis similarly demonstrates all three synuclein proteins within microdissected cochlear tissue. Immunofluorescence localizes the three synucleins predominantly to the efferent neuronal system at the efferent outer hair cell synapse, with some additional localization within the efferent tunnel-crossing fibers (alpha- and gamma-synuclein), spiral ganglion (beta-synuclein), inner spiral bundle (gamma-synuclein), and stria vascularis (alpha- > beta-synuclein). Developmentally, gamma-synuclein can be seen in the region of the outer hair cells by E19, while alpha- and beta-synuclein do not clearly appear there until approximately P10. Additional studies in a null-mutant gamma-synuclein mouse show no histological changes in the organ of Corti with normal hair cell and spiral ganglion cell counts, and normal ABR and DPOAE thresholds in wild-type vs mutant littermates. Together, these results localize synucleins to the efferent cholinergic neuronal auditory system, pointing to a role in normal auditory function, and raising the potential implications for their role in auditory neurodegenerative disorders. However, gamma-synuclein alone is not required for the development and maintenance of normal hearing through P21. Whether overlapping roles of the other synucleins help compensate for the loss of gamma-synuclein remains to be determined.

Background: The mammalian auditory cortex can be subdivided into various fields characterized by neurophysiological and neuroarchitectural properties and by connections with different nuclei of the thalamus. Besides the primary auditory cortex, echolocating bats have cortical fields for the processing of temporal and spectral features of the echolocation pulses. This paper reports on location, neuroarchitecture and basic functional organization of the auditory cortex of the microchiropteran bat Phyllostomus discolor (family: Phyllostomidae). Results: The auditory cortical area of P. discolor is located at parieto-temporal portions of the neocortex. It covers a rostro-caudal range of about 4800 mum and a medio-lateral distance of about 7000 mum on the flattened cortical surface. The auditory cortices of ten adult P. discolor were electrophysiologically mapped in detail. Responses of 849 units (single neurons and neuronal clusters up to three neurons) to pure tone stimulation were recorded extracellularly. Cortical units were characterized and classified depending on their response properties such as best frequency, auditory threshold, first spike latency, response duration, width and shape of the frequency response area and binaural interactions. Based on neurophysiological and neuroanatomical criteria, the auditory cortex of P. discolor could be subdivided into anterior and posterior ventral fields and anterior and posterior dorsal fields. The representation of response properties within the different auditory cortical fields was analyzed in detail. The two ventral fields were distinguished by their tonotopic organization with opposing frequency gradients. The dorsal cortical fields were not tonotopically organized but contained neurons that were responsive to high frequencies only. Conclusion: The auditory cortex of P. discolor resembles the auditory cortex of other phyllostomid bats in size and basic functional organization. The tonotopically organized posterior ventral field might represent the primary auditory cortex and the tonotopically organized anterior ventral field seems to be similar to the anterior auditory field of other mammals. As most energy of the echolocation pulse of P. discolor is contained in the high-frequency range, the non-tonotopically organized high-frequency dorsal region seems to be particularly important for echolocation.

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

Nicotinic acetylcholine receptors (nAChRs) contribute to sensory-cognitive function, as demonstrated by evidence that nAChR activation enhances, and nAChR blockade impairs, neural processing of sensory stimuli and sensory-cognitive behavior. To better understand the relationship between nAChR function and behavior, here we compare the strength of nAChR-mediated physiology in individual animals to their prior auditory behavioral performance. Adult rats were trained on an auditory-cued, active avoidance task over 4 days and classified as "good," "intermediate" or "poor" performers based on their initial rate of learning and eventual level of performance. Animals were then anesthetized, and tone-evoked local field potentials (LFPs) recorded in layer 4 of auditory cortex (ACx) before and after a test dose of nicotine (0.7mg/kg, s.c.) or saline. In "good" performers, nicotine enhanced LFP amplitude and decreased response threshold to characteristic frequency (CF) stimuli, yet had opposite effects (decreased amplitude, increased threshold) on responses to spectrally distant stimuli; i.e., cortical receptive fields became more selective for CF stimuli. In contrast, nicotine had little effect on LFP amplitude in "intermediate" or "poor" performing animals. Nicotine did, however, reduce LFP onset latency in all three groups, indicating that all received an effective dose of the drug. Our findings suggest that nicotinic regulation of cortical receptive fields may be a distinguishing feature of the best-performing animals, and may facilitate sensory-related learning by enhancing receptive field selectivity.

Cochlear implant speech processors transmit temporal features of sound as amplitude modulation of constant-rate electrical pulse trains. This study evaluated the central representation of amplitude modulation in the form of phase-locked firing of neurons in the auditory cortex. Anesthetized pigmented guinea pigs were implanted with cochlear electrode arrays. Stimuli were 254 pulse/s (pps) trains of biphasic electrical pulses, sinusoidally modulated with frequencies of 10–64 Hz and modulation depths of −40 to −5 dB re 100% (i.e., 1–56.2% modulation). Single- and multiunit activity was recorded from multi-site silicon-substrate probes. The maximum frequency for significant phase locking (limiting modulation frequency) was ≥60 Hz for 42% of recording sites, whereas phase locking to pulses of unmodulated pulse trains rarely exceeded 30 pps. The strength of phase locking to frequencies ≥40 Hz often varied nonmonotonically with modulation depth, commonly peaking at modulation depths around −15 to −10 dB. Cortical phase locking coded modulation frequency reliably, whereas a putative rate code for frequency was confounded by rate changes with modulation depth. Group delay computed from the slope of mean phase versus modulation frequency tended to increase with decreasing limiting modulation frequency. Neurons in cortical extragranular layers had lower limiting modulation frequencies than did neurons in thalamic afferent layers. Those observations suggest that the low-pass characteristic of cortical phase locking results from intracortical filtering mechanisms. The results show that cortical neurons can phase lock to modulated electrical pulse trains across the range of modulation frequencies and depths presented by cochlear implant speech processors.

Auditory neurons must represent accurately a wide range of sound levels using firing rates that vary over a far narrower range of levels. Recently, we demonstrated that this "dynamic range problem" is lessened by neural adaptation, whereby neurons adjust their input-output functions for sound level according to the prevailing distribution of levels. These adjustments in input-output functions increase the accuracy with which levels around those occurring most commonly are coded by the neural population. Here, we examine how quickly this adaptation occurs. We recorded from single neurons in the auditory midbrain during a stimulus that switched repeatedly between two distributions of sound levels differing in mean level. The high-resolution analysis afforded by this stimulus showed that a prominent component of the adaptation occurs rapidly, with an average time constant across neurons of 160 ms after an increase in mean level, much faster than our previous experiments were able to assess. This time course appears to be independent of both the timescale over which sound levels varied and that over which sound level distributions varied, but is related to neural characteristic frequency. We find that adaptation to an increase in mean level occurs more rapidly than to a decrease. Finally, we observe an additional, slow adaptation in some neurons, which occurs over a timescale of tens of seconds. Our findings provide constraints in the search for mechanisms underlying adaptation to sound level. They also have functional implications for the role of adaptation in the representation of natural sounds.

Loss of temporal processing is characteristic of age-related loss of speech understanding observed in the elderly. Inhibitory glycinergic circuits provide input onto dorsal cochlear nucleus (DCN) projection neurons which likely serve to modulate excitatory responses to time-varying complex acoustic signals. The present study sought to test the hypothesis that age-related loss of inhibition would compromise the ability of output neurons to encode sinusoidally amplitude modulated (SAM) tones. Extracellular recordings were obtained from young and aged FBN rat DCN putative fusiform cells. Stimuli were SAM tones at three modulation depths (100, 50, and 20%) at 30 dB hearing level with the carrier frequency set to the unit's characteristic frequency. Discharge rate and synchrony were calculated to describe SAM responses. There were significant age-related changes in the shape and peak vector strength [best modulation frequency (BMF)] of temporal modulation transfer functions (tMTFs), with no significant age-related changes in rate modulation transfer functions (rMTFs) at BMF. Young neurons exhibited band-pass tMTFs for most SAM conditions while aged fusiform cells exhibited significantly more low-pass or double-peaked tMTFs. There were significant differences in tMTFs between buildup, pauser-buildup, and wide-chopper temporal response types. Young and aged wide-choppers displayed significantly lower vector strength values than the other two temporal DCN response types. Age-related decreases in the number of pauser-buildup response types and increases in wide-chopper types reported previously, could account, in part, for the observed loss of temporal coding of the aged fusiform cell. Age-related changes in SAM coding were similar to changes observed with receptor blockade of glycinergic inhibition onto fusiform cells and consistent with previously observed age-related loss of endogenous glycine levels and changes in normal adult glycine receptor function. DCN changes in SAM coding could, in part, underpin temporal processing deficits observed in the elderly.

We assessed the spatial-tuning properties of units in the cat's anterior auditory field (AAF) and compared them with those observed previously in the primary (A1) and posterior auditory fields (PAF). Multi-channel, silicon-substrate probes were used to record single- and multi-unit activity from the right hemispheres of alpha-chloralose-anesthetized cats. Spatial tuning was assessed using broadband noise bursts that varied in azimuth or elevation. Response latencies were slightly, though significantly, shorter in AAF than A1, and considerably shorter in both of those fields than in PAF. Compared to PAF, spike counts and latencies were more poorly modulated by changes in stimulus location in AAF and A1, particularly at higher sound pressure levels. Moreover, units in AAF and A1 demonstrated poorer level tolerance than units in PAF with spike rates modulated as much by changes in stimulus intensity as changes in stimulus location. Finally, spike-pattern-recognition analyses indicated that units in AAF transmitted less spatial information, on average, than did units in PAF-an observation consistent with recent evidence that PAF is necessary for sound-localization behavior, whereas AAF is not.

Sensory experiences contribute to the development and specialization of signal processing capacities in the mammalian auditory system during a "critical period" of postnatal development. Earlier studies have shown that passive exposure to tonal stimuli during this postnatal epoch induces a large-scale expansion of the representations of those stimuli within the primary auditory cortex (A1) [Zhang LI, Bao S, Merzenich MM (2001) Persistent and specific influences of early acoustic environments on primary auditory cortex. Nat Neurosci 4:1123-1130]. Here, we show that exposing rat pups through the normal critical period epoch and beyond to continuous, un-modulated, moderate-level tones induces no such representational distortion, and in fact disrupts the normal development of frequency response selectivity and tonotopicity all across area A1. The area of cortex responding selectively to continuously exposed sound frequencies was actually reduced, when compared with rats reared in normal environments. Strong exposure-driven plasticity characteristic of the critical period could be induced well beyond the normal end of the critical period, by simply modulating the tonal stimulus. Thus, continuous tone exposure, like continuous noise exposure [Chang EF, Merzenich MM (2003) Environmental noise retards auditory cortical development. Science 300:498-502], ineffectively induces critical period plasticity, and indefinitely blocks the closure of a normally-brief critical period window. These findings again demonstrate the crucial role of temporally structured inputs for inducing the progressive cortical maturational changes that result in the closure of the critical period window.