Behavioral Neuroscience publications

Accurate temporal processing of sound is essential for detecting word structures in speech. Maternal smoking affects speech processing in newborns and may influence child language development; however, it is unclear how neonatal exposure to nicotine, present in cigarettes, affects the normal development of temporal processing. The present study used the gap-induced prepulse inhibition (gap-PPI) of the acoustic startle response to investigate the effects of neonatal nicotine exposure on the normal development of gap detection, a behavioral testing procedure of auditory temporal resolution. Neonatal rats were injected twice per day with saline (control), 1mg/kg nicotine (N-1 mg) or 5 mg/kg nicotine (N-5 mg) from postnatal day 8-12 (P8-P12). During the first month after birth, rats showed poor gap-PPI in all three groups. At P45 and P60, gap-PPI in control rats improved significantly, whereas rats exposed to nicotine exhibited less improvement. At P60, the gap-detection threshold in the N-5 mg group was significantly higher than in the control group, suggesting that neonatal nicotine exposure affects the normal development of gap-detection acuity. Additionally, 1h after receiving an acute nicotine injection (1 mg/kg), gap-PPI recorded in adult rats from the N-5 mg group showed a temporary significant improvement. These results suggest that neonatal nicotine exposure reduces gap-PPI implying an impairment of the normal development of auditory temporal processing by inducing changes in cholinergic systems.

The survival of the auditory nerve in cases of sensorineural hearing loss is believed to be a major factor in effective cochlear implant function. The current study assesses two measures of cochlear implant thresholds following a post-deafening treatment intended to halt auditory nerve degeneration. We used an adenoviral construct containing a gene insert for brain-derived neurotrophic factor (BDNF), a construct that has previously been shown to promote neuronal survival in a number of biological systems. We implanted ototoxically deafened guinea pigs with a multichannel cochlear implant and delivered a single inoculation of an adenovirus suspension coding for BDNF (Ad.BDNF) into the scala tympani at the time of implantation. Thresholds to electrical stimulation were assessed both psychophysically and electrophysiologically over a period of 80 days. Spiral ganglion cell survival was analyzed at the 80 days time point. Compared to the control group, the Ad.BDNF treated group had lower psychophysical and electrophysiological thresholds as well as higher survival of spiral ganglion cells. Electrophysiological, but not psychophysical, thresholds correlated well with the density of spiral ganglion cells. These results indicate that the changes in the anatomy of the auditory nerve induced by the combination of Ad.BDNF inoculation and the electrical stimulation used for testing improved functional measures of CI performance.

On the basis of its primary circuit it has been postulated that the olfactory bulb (OB) is analogous to the retina in mammals. In retina, repeated exposure to the same visual stimulus results in a neural representation that remains relatively stable over time, even as the meaning of that stimulus to the animal changes. Stability of stimulus representation at early stages of processing allows for unbiased interpretation of incoming stimuli by higher order cortical centers. The alternative is that early stimulus representation is shaped by previously derived meaning, which could allow more efficient sampling of odor space providing a simplified yet biased interpretation of incoming stimuli. This study helps place the olfactory system on this continuum of subjective versus objective early sensory representation. Here we show that odor responses of the output cells of the OB, mitral cells, change transiently during a go-no-go odor discrimination task. The response changes occur in a manner that increases the ability of the circuit to convey information necessary to discriminate among closely related odors. Remarkably, a switch between which of the two odors is rewarded causes mitral cells to switch the polarity of their divergent responses. Taken together these results redefine the function of the OB as a transiently modifiable (active) filter, shaping early odor representations in behaviorally meaningful ways.

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.

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.

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.

Rodent ultrasonic vocalizations (USVs) are ethologically critical social signals. Rats emit 22kHz USVs and 50kHz USVs, respectively, in conjunction with negative and positive affective states. Little is known about what controls emotional reactivity to these social signals. Using male Sprague-Dawley rats, we examined unconditional and conditional freezing behavior in response to the following auditory stimuli: three 22kHz USVs, a discontinuous tone whose frequency and on-off pattern matched one of the USVs, a continuous tone with the same or lower frequencies, a 4kHz discontinuous tone with an on-off pattern matched to one of the USVs, and a 50kHz USV. There were no differences among these stimuli in terms of the unconditional elicitation of freezing behavior. Thus, the stimuli were equally neutral before conditioning. During differential fear conditioning, one of these stimuli (the CS(+)) always co-terminated with a footshock unconditional stimulus (US) and another stimulus (the CS(-)) was explicitly unpaired with the US. There were no significant differences among these cues in CS(+)-elicited freezing behavior. Thus, the stimuli were equally salient or effective as cues in supporting fear conditioning. When the CS(+) was a 22kHz USV or a similar stimulus, rats discriminated based on the principal frequency and/or the temporal pattern of the stimulus. However, when these same stimuli served as the CS(-), discrimination failed due to generalization from the CS(+). Thus, the stimuli differed markedly in the specificity of conditioning. This strikingly asymmetrical stimulus generalization is a novel bias in discrimination.

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.

Previous studies have shown large decreases in cochlear implant psychophysical detection thresholds during the weeks following the onset of electrical testing. The current study sought to determine the variables underlying these threshold decreases by examining the effects of four deafening and implantation procedures on detection thresholds and implant impedances. Thirty-two guinea pigs were divided into four matched groups. Group I was deafened and implanted Day 0 and began electrical testing Day 1. Group II was deafened and implanted Day 0 and began electrical testing Day 45. Group III was deafened Day 0, implanted Day 45 and began electrical testing Day 46. Group IV was not predeafened but was implanted Day 0 and began electrical testing Day 1. All groups showed threshold decreases over time but the magnitude of change, time course and final stable threshold levels depended on the type and time course of treatment. Impedances increased over the first two weeks following the onset of electrical testing except in Group II. Results suggest that multiple mechanisms underlie the observed threshold shifts including (1) recovery of the cochlea from a temporary pathology caused by the deafening and/or implantation procedures, (2) effects of electrical stimulation on the auditory pathway, and (3) tissue growth in the implanted cochlea. They also suggest that surviving hair cells influence electrical threshold levels.

The acoustical cues for sound location are generated by spatial- and frequency-dependent filtering of propagating sound waves by the head and external ears. Although rats have been a common model system for anatomy, physiology, and psychophysics of localization, there have been few studies of the acoustical cues available to rats. Here, directional transfer functions (DTFs), the directional components of the head-related transfer functions, were measured in six adult rats. The cues to location were computed from the DTFs. In the frontal hemisphere, spectral notches were present for frequencies from ∼16to30kHz; in general, the frequency corresponding to the notch increased with increases in source elevation and in azimuth toward the ipsilateral ear. The maximum high-frequency envelope-based interaural time differences (ITDs) were 130μs, whereas low-frequency (<3.5kHz) fine-structure ITDs were 160μs; both types of ITDs were larger than predicted from spherical head models. Interaural level differences (ILDs) strongly depended on location and frequency. Maximum ILDs were <10dB for frequencies <8kHz and were as large as 20–40dB for frequencies >20kHz. Removal of the pinna eliminated the spectral notches, reduced the acoustic gain and ILDs, altered the acoustical axis, and reduced the ITDs.

The lateral superior olive (LSO) is one of the earliest sites in the auditory pathway that is involved in processing acoustical cues to sound location. Here, we tested the hypothesis that LSO neurons can signal small changes in interaural level differences (ILDs), a cue to horizontal sound location, of pure tones based on discharge rate consistent with psychophysical performance in the discrimination of ILDs. Neural thresholds for ILD discrimination were determined from the discharge rates and associated response variability of single units in response to 300 ms tones in the LSO of barbiturate-anesthetized cats using detection theory. Neural response variability was well described by a power function of the mean rate, both in individual neurons and collectively; LSO neurons were less variable than expected from a Poisson process. Compared with psychophysical data, the best-threshold ILDs of single LSO neurons were comparable with or better than behavior over the full range of frequencies (0.3–35 kHz) and pedestal ILDs (±25 dB) explored in this study. With a pedestal ILD of 0 dB, ILD increments of 1 dB could be discriminated by some neurons, with a median of 4.35 dB across neurons. For pedestal ILDs away from 0 dB, the best-threshold ILDs were as low as 0.5 dB, with a median of 2.3 dB. These findings support the hypothesis that the LSO plays a role in the extraction of ILD, and that the representation of ILD by LSO neurons may set a lower bound on the behavioral sensitivity to ILDs.

Our sense of gravitation and linear acceleration is mediated by stimulation of vestibular hair cells through displacement of otoconia in the utricle and saccule (the gravity receptor organ). We recently showed that otoconin-90 (Oc90) deletion led to formation of giant otoconia. In the present study, we determined the extent to which the giant otoconia affected balance and gravity receptor sensory input and compared the findings with other otoconia mutants. We employed a wide spectrum of balance behavioral tests, including reaching and air-righting reflexes, gait, swimming, beam-crossing, rotorod latencies, and a direct measure of gravity receptor input, vestibular evoked potentials (VsEPs). All tests on homozygous adult mutants consistently ranked the order of imbalance as (from worst to best) Nox3(het)<otopetrin 1(tlt)<Oc90 null<Oc90 wild type and C57Bl/6 mice using systematic statistical comparisons of the frequency of occurrence or the severity of abnormal functions. This order coincides with the degree of otoconia deficiencies and is consistent with VsEP measures. Notably, all mice (except Nox3(het)) showed remarkable learned adaptation to peripheral vestibular deficits by staying on the rotating rod significantly longer in each successive trial, and the rate and extent of such learned improvements ranked the same order as their initial balance ability. Despite the vestibular morbidity, Oc90 null mice had normal hearing, as measured by auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). The study demonstrates that the remnant otoconia mass in Oc90 nulls does stimulate the gravity receptor organs, which was likely responsible for the improved balance performance relative to strains with absent otoconia. Furthermore, the combination of direct electrophysiological measures and a series of behavioral tests can be used to interpret the imbalance severity arising from altered inputs from the gravity receptor end organ.

The mammalian auditory system is the temporally most precise sensory modality: To localize low-frequency sounds in space, the binaural system can resolve time differences between the ears with microsecond precision. In contrast, the binaural system appears sluggish in tracking changing interaural time differences as they arise from a low-frequency sound source moving along the horizontal plane. For a combined psychophysical and electrophysiological approach, we created a binaural stimulus, called “Phasewarp,” that can transmit rapid changes in interaural timing. Using this stimulus, the binaural performance in humans is significantly better than reported previously and comparable with the monaural performance revealed with amplitude-modulated stimuli. Parallel, electrophysiological recordings of binaural brainstem neurons in the gerbil show fast temporal processing of monaural and different types of binaural modulations. In a refined electrophysiological approach that was matched to the psychophysics, the seemingly faster binaural processing of the Phasewarp was confirmed. The current data provide both psychophysical and physiological evidence against a general, hard-wired binaural sluggishness and reconcile previous contradictions of electrophysiological and psychophysical estimates of temporal binaural performance.

Neurons in the superior paraolivary nucleus (SPON) of the rat respond to the offset of pure tones with a brief burst of spikes. Medial nucleus of the trapezoid body (MNTB) neurons, which inhibit the SPON, produce a sustained pure tone response followed by an offset response characterized by a period of suppressed spontaneous activity. This MNTB offset response is duration dependent and critical to the formation of SPON offset spikes [Kadner A, Kulesza RJ Jr, Berrebi AS (2006) Neurons in the medial nucleus of the trapezoid body and superior paraolivary nucleus of the rat may play a role in sound duration coding. J Neurophysiol. 95:1499-1508; Kulesza RJ Jr, Kadner A, Berrebi AS (2007) Distinct roles for glycine and GABA in shaping the response properties of neurons in the superior paraolivary nucleus of the rat. J Neurophysiol 97:1610-1620]. Here we examine the temporal resolution of the rat's MNTB/SPON circuit by assessing its capability to i) detect gaps in tones, and ii) synchronize to sinusoidally amplitude modulated (SAM) tones. Gap detection was tested by presenting two identical pure tone markers interrupted by gaps ranging from 0 to 25 ms duration. SPON neurons responded to the offset of the leading marker even when the two markers were separated only by their ramps (i.e. a 0 ms gap); longer gap durations elicited progressively larger responses. MNTB neurons produced an offset response at gap durations of 2 ms or longer, with a subset of neurons responding to 0 ms gaps. SAM tone stimuli used the unit's characteristic frequency as a carrier, and modulation rates ranged from 40 to 1160 Hz. MNTB neurons synchronized to modulation rates up to approximately 1 kHz, whereas spiking of SPON neurons decreased sharply at modulation rates >or=400 Hz. Modulation transfer functions based on spike count were all-pass for MNTB neurons and low-pass for SPON neurons; the modulation transfer functions based on vector strength were low-pass for both nuclei, with a steeper cutoff for SPON neurons. Thus, the MNTB/SPON circuit encodes episodes of low stimulus energy, such as gaps in pure tones and troughs in amplitude modulated tones. The output of this circuit consists of brief SPON spiking episodes; their potential effects on the auditory midbrain and forebrain are discussed.

The authors examined whether progressively training humans and rats to perform a difficult auditory identification task led to larger improvements than extensive training with highly similar sounds (the easy-to-hard effect). Practice improved humans' ability to distinguish sounds regardless of the training regimen. However, progressively trained subjects were more accurate and showed more generalization, despite significantly less training with the stimuli that were the most difficult to distinguish. Rats showed less capacity to improve with practice but still benefited from progressive training. These findings indicate that transitioning from an easier to a more difficult task during training can facilitate, and in some cases may be essential for, auditory perceptual learning. The results are not predicted by an explanation that assumes interaction of generalized excitation and inhibition but are consistent with a hierarchical account of perceptual learning in which the representational precision required to distinguish stimuli determines the mechanisms engaged during learning.

Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.

Perception of complex sounds depends on the encoding of the dynamic and static structures within the ongoing stimulus by the auditory system. Aging has been associated with deficits in both areas, thus, the difficulty that the elderly have in speech comprehension could due to hearing loss, or to a loss of temporal sensitivity, or some combination of both. We investigated the effects of sensorineural hearing loss (SNHL) on neural correlates of temporal resolution by recording the responses of inferior colliculus neurons to a gap detection paradigm. We used C57BL/6 (C57) strain of laboratory mouse, which carries the Ahl deafness gene that initiates a progressive high frequency SNHL beginning at about 2 months of age and rapidly progresses to total deafness by 18 months. We compared gap encoding from inferior collicular neurons from young, normal-hearing C57 mice and middle-aged, hearing-impaired, C57 mice, quantifying minimal gap threshold, and recovery functions. The proportion of unit types, spontaneous rates and degree of monotonicity were comparable between young and middle-aged C57 mice. As expected, single unit thresholds were elevated by 30-40 dB in middle-aged C57 mice. However, no significant differences in mean minimal gap thresholds or in the slopes of the gap recovery functions were found between the two age groups. Thus, the results suggest that moderate high frequency SNHL does not affect temporal processing as measured by the gap detection paradigm.

The clawed frog Xenopus laevis produces vocalizations consisting of distinct patterns of clicks. This study provides the first description of spontaneous, pure-tone and communication-signal evoked discharge properties of auditory nerve (n.VIII) fibers and dorsal medullary nucleus (DMN) cells in an obligatorily aquatic anuran. Responses of 297 n.VIII and 253 DMN units are analyzed for spontaneous rates (SR), frequency tuning, rate-intensity functions, and firing rate adaptation, with a view to how these basic characteristics shape responses to recorded call stimuli. Response properties generally resemble those in partially terrestrial anurans. Broad tuning exists across characteristic frequencies (CFs). Threshold minima are -101 dB re 1 mm/s at 675 Hz; -87 dB at 1,600 Hz; and -61 dB at 3,000 Hz (-90, -77, and -44 dB re 1 Pa, respectively), paralleling the peak frequency of vocalizations at 1.2-1.6 kHz with approximately 500 Hz in 3 dB bandwidth. SRs range from 0 to 80 (n.VIII) and 0 to 73 spikes/s (DMN). Nerve and DMN units of all CFs follow click rates in natural calls, < or =67 clicks/s and faster. Units encode clicks with a single spike, double spikes, or bursts. Spike times correlate closely with click envelopes. No temporal filtering for communicative click rates occurs in either n.VIII or the DMN.

Pretraining lesions of rat perirhinal cortex (PR) severely impair pavlovian fear conditioning to a 22 kHz ultrasonic vocalization (USV) cue. However, PR lesions are without significant effect when the cue is a continuous tone at the same or a lower frequency. Here we examined fear-conditioning-produced changes in single-unit firing elicited in rat PR by a 22 kHz tone cue or a 22 kHz USV cue. Chronic recording electrodes were introduced from the lateral surface of the skull. Altogether, 200 well isolated units were studied in 28 rats. Overall, 73% of the recorded single units (145 of 200 units) evidenced statistically significant firing changes in response to the tone or USV conditional stimulus (CS) after it had been paired several times with an aversive unconditional stimulus (US). Interestingly, 33% of units (66 of 200 units) that were initially CS-unresponsive became CS-responsive after conditioning. After conditioning, there were two notable differences between single-unit responses elicited by the USV cue and those elicited by the tone cue. First, 11% of the units (14 of 123 units) recorded from the USV-conditioned group displayed a precisely timed increase in firing rate during the 260 ms interval in which the US had previously occurred. This US-timed response was unique to the USV-conditioned group. Second, the mean latency of cue-elicited firing was ∼30 ms longer in the USV-conditioned group than in the tone-conditioned group. These cue-specific differences in acquired firing latencies and acquired firing patterns suggest that spectrotemporal properties of a CS can control the essential circuitry or neurophysiological mechanisms underlying fear conditioning.