Publications using TDT

Mammalian neuromuscular synapses undergo an activity-dependent competitive transition from multiple to single innervation during postnatal life. The presence of temporally correlated motor neuron activity, which, in part, is controlled by gap junctional coupling within the spinal cord, appears to modulate synapse elimination. Postnatal injection of dizocilpine maleate (MK801), a specific NMDA antagonist, has been shown to maintain gap junctional coupling among motor neurons. Thus, we tested the hypothesis that MK801 would maintain correlated motor neuron activity and delay postnatal synapse elimination. Temporally correlated motor neuron activity, which is normally lost during the second postnatal week, was maintained and synaptic competition was delayed by several days in 2-week-old mice injected daily with MK801. MK801 appears to modulate motor neuron activity patterns through enhancing mRNA expression of multiple connexins within the spinal cord and delaying motor neuron growth. Our results suggest that MK801 injection preserves correlated neural activity via both synaptic mechanisms and maintenance of gap junctional coupling among neurons within the spinal cord, ultimately delaying synapse elimination.

In complex scenes, the identity of an auditory object can build up across seconds. Given that attention operates on perceptual objects, this perceptual buildup may alter the efficacy of selective auditory attention over time. Here, we measured identification of a sequence of spoken target digits presented with distracter digits from other directions to investigate the dynamics of selective attention. Performance was better when the target location was fixed rather than changing between digits, even when listeners were cued as much as 1 s in advance about the position of each subsequent digit. Spatial continuity not only avoided well known costs associated with switching the focus of spatial attention, but also produced refinements in the spatial selectivity of attention across time. Continuity of target voice further enhanced this buildup of selective attention. Results suggest that when attention is sustained on one auditory object within a complex scene, attentional selectivity improves over time. Similar effects may come into play when attention is sustained on an object in a complex visual scene, especially in cases where visual object formation requires sustained attention.

Objectives/Hypothesis: The cochlear amplifier is required for the exquisite sensitivity of mammalian hearing. Outer hair cells underlie the cochlear amplifier and they are unique in that they maintain an intracellular turgor pressure. Changing the turgor pressure of an isolated outer hair cells through osmotic challenge modulates its ability to produce electromotile force. We sought to determine the effect of osmotic challenge on cochlear function. Study Design: In vivo animal study. Methods: Hypotonic and hypertonic artificial perilymph was perfused through the scala tympani of anesthetized guinea pigs. Cochlear function was assessed by measuring the compound action potential, distortion product otoacoustic emissions, the cochlear microphonic, and the endocochlear potential. Results: Hypotonic perilymph decreased and hypertonic perilymph increased compound action potential and distortion product otoacoustic emission thresholds in a dose‐dependent and reversible manner. The cochlear microphonic quadratic distortion product magnitude increased after hypotonic perfusion and decreased with hypertonic perfusion. There were no changes in the stimulus intensity growth curve of the low‐frequency cochlear microphonic. The endocochlear potential was not affected by perilymph osmolality. Conclusions: These data demonstrate that perilymph osmolality can modulate cochlear function and are consistent with what would be expected if outer hair cells turgor pressure changes the gain of the cochlear amplifier in vivo.

Implantable microfabricated microelectrode arrays represent a versatile and powerful tool to record electrophysiological activity across multiple spatial locations in the brain. Spikes and field potentials, however, correspond to only a fraction of the physiological information available at the neural interface. In urethane-anesthetized rats, microfabricated microelectrode arrays were implanted acutely for simultaneous recording of striatal local field potentials, spikes, and electrically evoked dopamine overflow on the same spatiotemporal scale. During these multi-modal recordings we observed (1) that the amperometric method used to detect dopamine did not significantly influence electrophysiological activity, (2) that electrical stimulation in the medial forebrain bundle (MFB) region resulted in electrochemically transduced dopamine transients in the striatum that were spatially heterogeneous within at least 200 microm, and (3) following MFB stimulation, dopamine levels and electrophysiological activity within the striatum exhibited similar temporal profiles. These neural probes are capable of incorporating customized microelectrode geometries and configurations, which may be useful for examining specific spatiotemporal relationships between electrical and chemical signaling in the brain.

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.

Although the cholinergic system has long been implicated in the formation of memory, there had been no direct demonstration that activation of this system can actually induce specific behavioral memory. We have evaluated the "cholinergic-memory" hypothesis by pairing a tone with stimulation of the nucleus basalis (NB), which provides acetylcholine to the cerebral cortex. We found that such pairing induces behaviorally-validated auditory memory. NB-induced memory has the key features of natural memory: it is associative, highly-specific and rapidly induced. Moreover, the level of NB stimulation controls the amount of detail in memory about the tonal conditioned stimulus. While consistent with the hypothesis that properly-timed release of acetylcholine (ACh) during natural learning is sufficient to induce memory, pharmacological evidence has been lacking. This study asked whether scopolamine, a muscarinic antagonist, impairs or prevents the formation of NB-induced memory. Adult male rats were first tested for responses (disruption of ongoing respiration) to tones (1-15 kHz), constituting a pre-training behavioral frequency generalization gradient (BFGG). Then, they received a single session of 200 trials of a tone (8.00 kHz, 70 dB, 2 s) paired with electrical stimulation of the NB (100 Hz, 0.2 s). Immediately after training, they received either scopolamine (1.0 mg/kg, i.p.) or saline. Twenty-four hours later, they were tested for specific memory by obtaining post-training BFGGs. The saline group developed CS-specific memory, manifested by maximum increase in response specific to the CS frequency band. In contrast, the scopolamine group exhibited no such memory. These findings indicate that NB-induced specific associative behavioral memory requires the action of intrinsic acetylcholine at muscarinic receptors, and supports the hypothesis that natural memory formation engages the nucleus basalis and muscarinic receptors.

The relationship between outer hair cell (OHC) loss and cochlear sensitivity is still unclear, because in many animal models there exist surviving but dysfunctional OHCs and also injured/dead inner hair cells (IHC). Styrene is an ototoxic agent, which targets and destroys OHCs starting from the third row to the second and first rows depending on the exposure level. The remaining cells may be less affected. In this experiment, rats were exposed to styrene by gavage at different doses (200-800 mg/kg/day) for varying periods (5 days/week for 3-12 weeks). An interesting finding was that the cochlear sensitivity was not affected in a few rats with all OHCs in the third row being destroyed by styrene. A further loss of OHCs was usually accompanied with a linear input/output (I/O) function of cochlear compound action potentials (CAP), indicating the loss of cochlear amplification. However, normal CAP amplitudes at the highest stimulation level of 90 dB SPL were often observed when all OHCs were destroyed, indicating normal function of the remaining IHCs. The OHC-loss/hearing-loss relation appeared to be a sigmoid-type function. Initially, styrene-induced OHC losses (<33%) did not result in a significant threshold shift. Then CAP threshold shift increased dramatically with OHC loss from 33% to 66%. Then, CAP threshold changed less with OHC loss. The data suggest a tri-modal relationship between OHC loss and cochlear amplification. That is, under the condition that all surviving OHCs are ideally functioning, the cochlear amplifier is not affected until 33% of OHCs are absent, then the gain of the amplifier decreases proportionally with the OHC loss, and at last the amplifier may fail completely when more than 67% of OHCs are lost.

Distortion-product otoacoustic emissions (DPOAEs) were measured in a New World primate, the common marmoset (Callithrix jacchus). We determined the optimal primary-tone frequency ratio (f(2)/f(1)) to generate DPOAEs of maximal amplitude between 3 and 24 kHz. The optimal f(2)/f(1), determined by varying f(2)/f(1) from 1.02 to 1.40 using equilevel primary tones, decreased with increasing f(2) frequency between 3 and 17 kHz, and increased at 24 kHz. The optimal f(2)/f(1) ratio increased with increasing primary-tone levels from 50 to 74 dB SPL. When all stimulus parameters were considered, the mean optimal f(2)/f(1) was 1.224-1.226. Additionally, we determined the effect of reducing L(2) below L(1). Decreasing L(2) below L(1) by 0, 5, and 10 dB (f(2)/f(1)=1.21) minimally affected DPOAE strength. DPOAE levels were stronger in females than males and stronger in the right ear than the left, just as in humans. This study is the first to measure OAEs in the marmoset, and the results indicate that the effect of varying the frequency ratio and primary-tone level difference on marmoset DPOAEs is similar to the reported effects in humans and Old World primates.

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.

Background: Fundamental for understanding the evolution of communication systems is both the variation in a signal and how this affects the behavior of receivers, as well as variation in preference functions of receivers, and how this affects the variability of the signal. However, individual differences in female preference functions and their proximate causation have rarely been studied. Methodology/principal findings: Calling songs of male field crickets represent secondary sexual characters and are subject to sexual selection by female choice. Following predictions from the "matched filter hypothesis" we studied the tuning of an identified interneuron in a field cricket, known for its function in phonotaxis, and correlated this with the preference of the same females in two-choice trials. Females vary in their neuronal frequency tuning, which strongly predicts the preference in a choice situation between two songs differing in carrier frequency. A second "matched filter" exists in directional hearing, where reliable cues for sound localization occur only in a narrow frequency range. There is a strong correlation between the directional tuning and the behavioural preference in no-choice tests. This second "matched filter" also varies widely in females, and surprisingly, differs on average by 400 Hz from the neuronal frequency tuning. Conclusions/significance: Our findings on the mismatch of the two "matched filters" would suggest that the difference in these two filters appears to be caused by their evolutionary history, and the different trade-offs which exist between sound emission, transmission and detection, as well as directional hearing under specific ecological settings. The mismatched filter situation may ultimately explain the maintenance of considerable variation in the carrier frequency of the male signal despite stabilizing selection.

Interaural time difference (ITD) plays a central role in many auditory functions, most importantly in sound localization. The classic model for how ITD is computed was put forth by Jeffress (1948). One of the predictions of the Jeffress model is that the neurons that compute ITD should behave as cross-correlators. Whereas cross-correlation-like properties of the ITD-computing neurons have been reported, attempts to show that the shape of the ITD response function is determined by the spectral tuning of the neuron, a core prediction of cross-correlation, have been unsuccessful. Using reverse correlation analysis, we demonstrate in the barn owl that the relationship between the spectral tuning and the ITD response of the ITD-computing neurons is that predicted by cross-correlation. Moreover, we show that a model of coincidence detector responses derived from responses to binaurally uncorrelated noise is consistent with binaural interaction based on cross-correlation. These results are thus consistent with one of the key tenets of the Jeffress model. Our work sets forth both the methodology to answer whether cross-correlation describes coincidence detector responses and a demonstration that in the barn owl, the result is that expected by theory.

Vertebrates can modulate the sound levels entering their inner ears in the face of intense external sound or during their own vocalizations. Middle ear muscle contractions restrain the motion of the middle ear ossicles, attenuating the transmission of low-frequency sound and thereby protecting the hair cells in the inner ear. Here we show that the Chinese concave-eared torrent frog, Odorrana tormota , can tune its ears dynamically by closing its normally open Eustachian tubes. Contrary to the belief that the middle ear in frogs permanently communicates with the mouth, O. tormota can close this connection by contraction of the submaxillary and petrohyoid muscles, drastically reducing the air volume behind the eardrums. Mathematical modeling and laser Doppler vibrometry revealed that the reduction of this air volume increases the middle ear impedance, resulting in an up to 20 dB gain in eardrum vibration at high frequencies (10–32 kHz) and 26 dB attenuation at low frequencies (3–10 kHz). Eustachian tube closure was observed in the field during calling and swallowing. Besides a potential role in protecting the inner ear from intense low-frequency sound and high buccal air pressure during calling, this previously unrecognized vertebrate mechanism may unmask the high-frequency calls of this species from the low-frequency stream noise which dominates the environment. This mechanism also protects the thin tympanic membranes from injury during swallowing of live arthropod prey.

Multiple topographic representations of sensory space are common in the nervous system and presumably allow organisms to separately process particular features of incoming sensory stimuli that vary widely in their attributes. We compared the response properties of sensory neurons within three maps of the body surface that are arranged strictly in parallel to two classes of stimuli that mimic prey and conspecifics, respectively. We used information-theoretic approaches and measures of phase locking to quantify neuronal responses. Our results show that frequency tuning in one of the three maps does not depend on stimulus class. This map acts as a low-pass filter under both conditions. A previously described stimulus-class-dependent switch in frequency tuning is shown to occur in the other two maps. Only a fraction of the information encoded by all neurons could be recovered through a linear decoder. Particularly striking were low-pass neurons the information of which in the high-frequency range could not be decoded linearly. We then explored whether intrinsic cellular mechanisms could partially account for the differences in frequency tuning across maps. Injection of a Ca 2+ chelator had no effect in the map with low-pass characteristics. However, injection of the same Ca 2+ chelator in the other two maps switched the tuning of neurons from band-pass/high-pass to low-pass. These results show that Ca 2+ -dependent processes play an important part in determining the functional roles of different sensory maps and thus shed light on the evolution of this important feature of the vertebrate brain.

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.

Spatial release from masking was studied in a three-talker soundfield listening experiment. The target talker was presented at 0° azimuth and the maskers were either colocated or symmetrically positioned around the target, with a different masker talker on each side. The symmetric placement greatly reduced any “better ear” listening advantage. When the maskers were separated from the target by ±15°, the average spatial release from masking was 8dB. Wider separations increased the release to more than 12dB. This large effect was eliminated when binaural cues and perceived spatial separation were degraded by covering one ear with an earplug and earmuff. Increasing reverberation in the room increased the target-to-masker ratio (T∕M) for the separated, but not colocated, conditions reducing the release from masking, although a significant advantage of spatial separation remained. Time reversing the masker speech improved performance in both the colocated and spatially separated cases but lowered T∕M the most for the colocated condition, also resulting in a reduction in the spatial release from masking. Overall, the spatial tuning observed appears to depend on the presence of interaural differences that improve the perceptual segregation of sources and facilitate the focus of attention at a point in space.

The amount of acoustic information that native and non-native listeners need for syllable identification was investigated by comparing the performance of monolingual English speakers and native Spanish speakers with either an earlier or a later age of immersion in an English-speaking environment. Duration-preserved silent-center syllables retaining 10, 20, 30, or 40ms of the consonant-vowel and vowel-consonant transitions were created for the target vowels /i, ɪ, eɪ, ε, æ/ and /ɑ/, spoken by two males in /bVb/ context. Duration-neutral syllables were created by editing the silent portion to equate the duration of all vowels. Listeners identified the syllables in a six-alternative forced-choice task. The earlier learners identified the whole-word and 40ms duration-preserved syllables as accurately as the monolingual listeners, but identified the silent-center syllables significantly less accurately overall. Only the monolingual listener group identified syllables significantly more accurately in the duration-preserved than in the duration-neutral condition, suggesting that the non-native listeners were unable to recover from the syllable disruption sufficiently to access the duration cues in the silent-center syllables. This effect was most pronounced for the later learners, who also showed the most vowel confusions and the greatest decrease in performance from the whole word to the 40ms transition condition.

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.

To observe neural activity in animals engaged in natural behavior, it is often desirable to minimize or eliminate restraint of the animal. We have developed a simple system for recording from single units in unrestrained cats. An implant with multiple guide tubes and a tiny microdrive is placed inside the recording chamber. An indwelling Pt-Ir microelectrode is advanced incrementally during recording sessions that occur over a period of weeks or months. Electrodes can be easily replaced. We obtain excellent recording stability, and also have been able to sample extensively from a region of cortex or brain stem in a single animal. The essential electronics have been miniaturized and sewn into a light-weight walking jacket, so that we can collect data from a cat who is not connected to any fixed equipment.