Electrophysiology publications

Tinnitus chronically affects between 10–15% of the population but, despite its prevalence, the underlying mechanisms are still not properly understood. One experimental model involves administration of high doses of sodium salicylate, as this is known to reliably induce tinnitus in both humans and animals. Guinea pigs were implanted with chronic electrocorticography ( EC oG) electrode arrays, with silver‐ball electrodes placed on the dura over left and right auditory cortex. Two more electrodes were positioned over the cerebellum to monitor auditory brainstem responses ( ABR s). We recorded resting‐state and auditory evoked neural activity from awake animals before and 2 h following salicylate administration (350 mg/kg; i.p.). Large increases in click‐evoked responses (> 100%) were evident across the whole auditory cortex, despite significant reductions in wave I ABR amplitudes (in response to 20 kHz tones), which are indicative of auditory nerve activity. In the same animals, significant decreases in 6–10 Hz spontaneous oscillations (alpha waves) were evident over dorsocaudal auditory cortex. We were also able to demonstrate for the first time that cortical evoked potentials can be inhibited by a preceding gap in background noise [gap‐induced pre‐pulse inhibition ( PPI )], in a similar fashion to the gap‐induced inhibition of the acoustic startle reflex that is used as a behavioural test for tinnitus. Furthermore, 2 h following salicylate administration, we observed significant deficits in PPI of cortical responses that were closely aligned with significant deficits in behavioural responses to the same stimuli. Together, these data are suggestive of neural correlates of tinnitus and oversensitivity to sound (hyperacusis).

Extracting temporal periodicities and envelope shapes of sounds is important for listening within complex auditory scenes but declines behaviorally with age. Here, we recorded local field potentials ( LFP s) and spikes to investigate how ageing affects the neural representations of different modulation rates and envelope shapes in the inferior colliculus of rats. We specifically aimed to explore the input–output ( LFP ‐spike) response transformations of inferior colliculus neurons. Our results show that envelope shapes up to 256‐Hz modulation rates are represented in the neural synchronisation phase lags in younger and older animals. Critically, ageing was associated with (i) an enhanced gain in onset response magnitude from LFP s to spikes; (ii) an enhanced gain in neural synchronisation strength from LFP s to spikes for a low modulation rate (45 Hz); (iii) a decrease in LFP synchronisation strength for higher modulation rates (128 and 256 Hz) and (iv) changes in neural synchronisation strength to different envelope shapes. The current age‐related changes are discussed in the context of an altered excitation‐inhibition balance accompanying ageing.

Inhibition plays a crucial role in neural signal processing, shaping and limiting responses. In the auditory system, inhibition already modulates second order neurons in the cochlear nucleus, e.g. spherical bushy cells (SBCs). While the physiological basis of inhibition and excitation is well described, their functional interaction in signal processing remains elusive. Using a combination of in vivo loose-patch recordings, iontophoretic drug application, and detailed signal analysis in the Mongolian Gerbil, we demonstrate that inhibition is widely co-tuned with excitation, and leads only to minor sharpening of the spectral response properties. Combinations of complex stimuli and neuronal input-output analysis based on spectrotemporal receptive fields revealed inhibition to render the neuronal output temporally sparser and more reproducible than the input. Overall, inhibition plays a central role in improving the temporal response fidelity of SBCs across a wide range of input intensities and thereby provides the basis for high-fidelity signal processing.

How natural communication sounds are spatially represented across the inferior colliculus, the main center of convergence for auditory information in the midbrain, is not known. The neural representation of the acoustic stimuli results from the interplay of locally differing input and the organization of spectral and temporal neural preferences that change gradually across the nucleus. This raises the question of how similar the neural representation of the communication sounds is across these gradients of neural preferences, and whether it also changes gradually. Analyzed neural recordings were multi-unit cluster spike trains from guinea pigs presented with a spectrotemporally rich set of eleven species-specific communication sounds. Using cross-correlation, we analyzed the response similarity of spiking activity across a broad frequency range for neurons of similar and different frequency tuning. Furthermore, we separated the contribution of the stimulus to the correlations to investigate whether similarity is only attributable to the stimulus, or, whether interactions exist between the multi-unit clusters that lead to neural correlations and whether these follow the same representation as the response correlations. We found that similarity of responses is dependent on the neurons' spatial distance for similarly and differently frequency-tuned neurons, and that similarity decreases gradually with spatial distance. Significant neural correlations exist, and contribute to the total response similarity. Our findings suggest that for multi-unit clusters in the mammalian inferior colliculus, the gradual response similarity with spatial distance to natural complex sounds is shaped by neural interactions and the gradual organization of neural preferences.

With their essential role in inner ear function, stereocilia of sensory hair cells demonstrate the importance of cellular actin protrusions. Actin packing in stereocilia is mediated by cross-linkers of the plastin, fascin, and espin families. Although mice lacking espin (ESPN) have no vestibular or auditory function, we found that mice that either lacked plastin 1 (PLS1) or had nonfunctional fascin 2 (FSCN2) had reduced inner ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant cross-linker in vestibular stereocilia and the second most abundant protein overall; ESPN only accounted for ∼15% of the total cross-linkers in bundles. Mouse utricle stereocilia lacking PLS1 were shorter and thinner than wild-type stereocilia. Surprisingly, although wild-type stereocilia had random liquid packing of their actin filaments, stereocilia lacking PLS1 had orderly hexagonal packing. Although all three cross-linkers are required for stereocilia structure and function, PLS1 biases actin toward liquid packing, which allows stereocilia to grow to a greater diameter.

Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study.

Background: Incorporating feedback controls based on real-time measures of pathological brain activity may improve deep brain stimulation (DBS) approaches for the treatment of Parkinson's disease (PD). Excessive beta oscillations in subthalamic nucleus (STN) local field potentials (LFP) have been proposed as a potential biomarker for closed-loop DBS (CL-DBS). Objective: In a non-human primate PD model we compared CL-DBS, which delivered stimulation only when STN LFP beta activity was elevated, to traditional continuous DBS (tDBS). Methods: Therapeutic effects of CL-DBS and tDBS relative to the Off-DBS condition were evaluated via a clinical rating scale and objective measures of movement speed during a cued reaching task. Results: CL-DBS was comparable to tDBS at reducing rigidity, while reducing the amount of time DBS was on by ≈50%; however, only tDBS improved bradykinesia during the reaching behavior. This was likely due to reach-related reductions in beta amplitude that influence the timing and duration of stimulation in the CL-DBS condition. Conclusion: These results illustrate the potential utility of closed-loop DBS devices for PD based on STN beta LFP levels. They also point to possible consequences in behavioral tasks when restricting real-time sensing to a single LFP frequency that itself is modulated during performance of such tasks. The present study provides data that suggest alternate algorithms or more than one physiological biomarker may be required to optimize the performance of behavioral tasks and demonstrates the value of using multiple objective measures when evaluating the efficacy of closed-loop DBS systems.

Tonotopic map plasticity in the adult auditory cortex (AC) is a well established and oft-cited measure of auditory associative learning in classical conditioning paradigms. However, its necessity as an enduring memory trace has been debated, especially given a recent finding that the areal expansion of core AC tuned to a newly relevant frequency range may arise only transiently to support auditory learning. This has been reinforced by an ethological paradigm showing that map expansion is not observed for ultrasonic vocalizations (USVs) or for ultrasound frequencies in postweaning dams for whom USVs emitted by pups acquire behavioral relevance. However, whether transient expansion occurs during maternal experience is not known, and could help to reveal the generality of cortical map expansion as a correlate for auditory learning. We thus mapped the auditory cortices of maternal mice at postnatal time points surrounding the peak in pup USV emission, but found no evidence of frequency map expansion for the behaviorally relevant high ultrasound range in AC. Instead, regions tuned to low frequencies outside of the ultrasound range show progressively greater suppression of activity in response to the playback of ultrasounds or pup USVs for maternally experienced animals assessed at their pups’ postnatal day 9 (P9) to P10, or postweaning. This provides new evidence for a lateral-band suppression mechanism elicited by behaviorally meaningful USVs, likely enhancing their population-level signal-to-noise ratio. These results demonstrate that tonotopic map enlargement has limits as a construct for conceptualizing how experience leaves neural memory traces within sensory cortex in the context of ethological auditory learning.

Zebrafish are increasingly used in auditory studies, in part due to the development of several transgenic lines that express hair cell-specific fluorescent proteins. However, it is largely unknown how transgene expression influences auditory phenotype. We previously observed reduced auditory sensitivity in adult Brn3c:mGFP transgenic zebrafish, which express membrane-bound green fluorescent protein (GFP) in sensory hair cells. Here, we examine the auditory sensitivity of zebrafish from multiple transgenic and background strains. We recorded auditory evoked potentials in adult animals and observed significantly higher auditory thresholds in three lines that express hair cell-specific GFP. There was no obvious correlation between hair cell density and auditory thresholds, suggesting that reduced sensitivity was not due to a reduction in hair cell density. FM1-43 uptake was reduced in Brn3c:mGFP fish but not in other lines, suggesting that a mechanotransduction defect may be responsible for the auditory phenotype in Brn3c animals, but that alternate mechanisms underlie the increased AEP thresholds in other lines. We found reduced prepulse inhibition (a measure of auditory-evoked behavior) in larval Brn3c animals, suggesting that auditory defects develop early in this line. We also found significant differences in auditory sensitivity between adults of different background strains, akin to strain differences observed in mouse models of auditory function. Our results suggest that researchers should exercise caution when selecting an appropriate zebrafish transgenic or background strain for auditory studies.

Physical features of sensory stimuli are fixed, but sensory perception is context dependent. The precise mechanisms that govern contextual modulation remain unknown. Here, we trained mice to switch between two contexts: passively listening to pure tones and performing a recognition task for the same stimuli. Two-photon imaging showed that many excitatory neurons in auditory cortex were suppressed during behavior, while some cells became more active. Whole-cell recordings showed that excitatory inputs were affected only modestly by context, but inhibition was more sensitive, with PV+, SOM+, and VIP+ interneurons balancing inhibition and disinhibition within the network. Cholinergic modulation was involved in context switching, with cholinergic axons increasing activity during behavior and directly depolarizing inhibitory cells. Network modeling captured these findings, but only when modulation coincidently drove all three interneuron subtypes, ruling out either inhibition or disinhibition alone as sole mechanism for active engagement. Parallel processing of cholinergic modulation by cortical interneurons therefore enables context-dependent behavior.

The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. SIGNIFICANCE STATEMENT The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we found that variability of the neural response becomes smaller during task performance, thereby improving neural detection thresholds.

Investigations into mechanisms in various cortical areas can be greatly improved and supported by stable recording of single neuronal activity. In this study, fine silicon wire electrodes (diameter 3 μm, length 160 μm) are fabricated by vapor–liquid–solid (VLS) growth with the aim of stabilizing recording and reducing the invasiveness on the measurement procedure. The electrode is fabricated on a modular 1 × 1 mm 2 conductive silicon block that can be assembled into a number of different device packages, for example on rigid or flexible printed circuit boards (PCB). After plating with a 5 μm diameter platinum black, the needle exhibits an electrical impedance of ~100 kΩ at 1 kHz in saline. The in vivo recording capability of the device is demonstrated using mice, and spike signals with peak-to-peak amplitudes of 200−300 μV in the range 0.5−3 kHz are stably detected, including single-unit activities in cortical layer 2/3. In addition, the device packaged with a flexible PCB shows stable unit recordings for 98.5 min (n = 4). Consequently, our modular, low-invasive needle electrode block devices present an effective route for single-unit recordings in vivo , as well as demonstrating adaptability in device design for a diverse range of experiments.

Objective . Behavioral neuroscience studies in freely moving rodents require small, light-weight implants to facilitate neural recording and stimulation. Our goal was to develop an integrated package of 3D printed parts and assembly aids for labs to rapidly fabricate, with minimal training, an implant that combines individually positionable microelectrodes, an optical fiber, zero insertion force (ZIF-clip) headstage connection, and secondary recording electrodes, e.g. for electromyography (EMG). Approach . Starting from previous implant designs that position recording electrodes using a control screw, we developed an implant where the main drive body, protective shell, and non-metal components of the microdrives are 3D printed in parallel. We compared alternative shapes and orientations of circuit boards for electrode connection to the headstage, in terms of their size, weight, and ease of wire insertion. We iteratively refined assembly methods, and integrated additional assembly aids into the 3D printed casing. Main results . We demonstrate the effectiveness of the OptoZIF Drive by performing real time optogenetic feedback in behaving mice. A novel feature of the OptoZIF Drive is its vertical circuit board, which facilities direct ZIF-clip connection. This feature requires angled insertion of an optical fiber that still can exit the drive from the center of a ring of recording electrodes. We designed an innovative 2-part protective shell that can be installed during the implant surgery to facilitate making additional connections to the circuit board. We use this feature to show that facial EMG in mice can be used as a control signal to lock stimulation to the animal’s motion, with stable EMG signal over several months. To decrease assembly time, reduce assembly errors, and improve repeatability, we fabricate assembly aids including a drive holder, a drill guide, an implant fixture for microelectode ‘pinning’, and a gold plating fixture. Significance . The expanding capability of optogenetic tools motivates continuing development of small optoelectric devices for stimulation and recording in freely moving mice. The OptoZIF Drive is the first to natively support ZIF-clip connection to recording hardware, which further supports a decrease in implant cross-section. The integrated 3D printed package of drive components and assembly tools facilities implant construction. The easy interfacing and installation of auxiliary electrodes makes the OptoZIF Drive especially attractive for real time feedback stimulation experiments.

In the present study, we have developed a multi-modal instrument that combines laser speckle imaging, arterial blood pressure, and electroencephalography (EEG) to quantitatively assess cerebral blood flow (CBF), mean arterial pressure (MAP), and brain electrophysiology before, during, and after asphyxial cardiac arrest (CA) and resuscitation. Using the acquired data, we quantified the time and magnitude of the CBF hyperemic peak and stabilized hypoperfusion after resuscitation. Furthermore, we assessed the correlation between CBF and MAP before and after stabilized hypoperfusion. Finally, we examined when brain electrical activity resumes after resuscitation from CA with relation to CBF and MAP, and developed an empirical predictive model to predict when brain electrical activity resumes after resuscitation from CA. Our results show that: 1) more severe CA results in longer time to stabilized cerebral hypoperfusion; 2) CBF and MAP are coupled before stabilized hypoperfusion and uncoupled after stabilized hypoperfusion; 3) EEG activity (bursting) resumes after the CBF hyperemic phase and before stabilized hypoperfusion; 4) CBF predicts when EEG activity resumes for 5-min asphyxial CA, but is a poor predictor for 7-min asphyxial CA. Together, these novel findings highlight the importance of using multi-modal approaches to investigate CA recovery to better understand physiological processes and ultimately improve neurological outcome.

Listeners with normal hearing thresholds (NHTs) differ in their ability to steer attention to whatever sound source is important. This ability depends on top-down executive control, which modulates the sensory representation of sound in the cortex. Yet, this sensory representation also depends on the coding fidelity of the peripheral auditory system. Both of these factors may thus contribute to the individual differences in performance. We designed a selective auditory attention paradigm in which we could simultaneously measure envelope following responses (EFRs, reflecting peripheral coding), onset event-related potentials (ERPs) from the scalp (reflecting cortical responses to sound) and behavioral scores. We performed two experiments that varied stimulus conditions to alter the degree to which performance might be limited due to fine stimulus details vs. due to control of attentional focus. Consistent with past work, in both experiments we find that attention strongly modulates cortical ERPs. Importantly, in Experiment I, where coding fidelity limits the task, individual behavioral performance correlates with subcortical coding strength (derived by computing how the EFR is degraded for fully masked tones compared to partially masked tones); however, in this experiment, the effects of attention on cortical ERPs were unrelated to individual subject performance. In contrast, in Experiment II, where sensory cues for segregation are robust (and thus less of a limiting factor on task performance), inter-subject behavioral differences correlate with subcortical coding strength. In addition, after factoring out the influence of subcortical coding strength, behavioral differences are also correlated with the strength of attentional modulation of ERPs. These results support the hypothesis that behavioral abilities amongst listeners with NHTs can arise due to both subcortical coding differences and differences in attentional control, depending on stimulus characteristics and task demands.

Objective: To develop a large animal model of spinal cord injury (SCI), for use in translational studies of spinal cord stimulation (SCS) in the treatment of spasticity. We seek to establish thresholds for the SCS parameters associated with reduction of post-SCI spasticity in the pelvic limbs, with implications for patients. Study design: The weight-drop method was used to create a moderate SCI in adult sheep, leading to mild spasticity in the pelvic limbs. Electrodes for electromyography (EMG) and an epidural spinal cord stimulator were then implanted. Behavioral and electrophysiological data were taken during treadmill ambulation in six animals, and in one animal with and without SCS at 0.1, 0.3, 0.5, and 0.9 V. Setting: All surgical procedures were carried out at the University of Iowa. The gait measurements were made at Iowa State University. Material and methods: Nine adult female sheep were used in these institutionally approved protocols. Six of them were trained in treadmill ambulation prior to SCI surgeries, and underwent gait analysis pre- and post-SCI. Stretch reflex and H-reflex measurements were also made in conscious animals. Results: Gait analysis revealed repeatable quantitative differences in 20% of the key kinematic parameters of the sheep, pre- and post-SCI. Hock joint angular velocity increased toward the normal pre-injury baseline in the animal with SCS at 0.9 V. Conclusion: The ovine model is workable as a large animal surrogate suitable for translational studies of novel SCS therapies aimed at relieving spasticity in patients with SCI.

Prolonged wakefulness is thought to gradually increase ‘sleep need’ and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours.

Sea turtles spend much of their life in aquatic environments, but critical portions of their life cycle, such as nesting and hatching, occur in terrestrial environments, suggesting that it may be important for them to detect sounds in both air and water. In this study we compared underwater and aerial hearing sensitivities in five juvenile green sea turtles (Chelonia mydas) by measuring auditory evoked potential responses to tone pip stimuli. Green sea turtles detected acoustic stimuli in both media, responding to underwater stimuli between 50 and 1600 Hz and aerial stimuli between 50 and 800 Hz, with maximum sensitivity between 200 and 400 Hz underwater and 300 and 400 Hz in air. When underwater and aerial hearing sensitivities were compared in terms of pressure, green sea turtle aerial sound pressure thresholds were lower than underwater thresholds, however they detected a wider range of frequencies underwater. When thresholds were compared in terms of sound intensity, green sea turtle sound intensity level thresholds were 2-39 dB lower underwater particularly at frequencies below 400 Hz. Acoustic stimuli may provide important environmental cues for sea turtles. Further research is needed to determine how sea turtles behaviorally and physiologically respond to sounds in their environment.

Normalization of altered glutamate neurotransmission through activation of the mGluR2 has emerged as a new approach to treat schizophrenia. These studies describe a potent brain penetrant mGluR2 positive allosteric modulator (PAM), SAR218645. The compound behaves as a selective PAM of mGluR2 in recombinant and native receptor expression systems, increasing the affinity of glutamate at mGluR2 as inferred by competition and GTPγ 35 S binding assays. SAR218645 augmented the mGluR2-mediated response to glutamate in a rat recombinant mGluR2 forced-coupled Ca 2+ mobilization assay. SAR218645 potentiated mGluR2 agonist-induced contralateral turning. When SAR218645 was tested in models of the positive symptoms of schizophrenia, it reduced head twitch behavior induced by DOI, but it failed to inhibit conditioned avoidance and hyperactivity using pharmacological and transgenic models. Results from experiments in models of the cognitive symptoms associated with schizophrenia showed that SAR218645 improved MK-801-induced episodic memory deficits in rats and attenuated working memory impairment in NMDA Nr1 neo−/− mice. The drug reversed disrupted latent inhibition and auditory-evoked potential in mice and rats, respectively, two endophenotypes of schizophrenia. This profile positions SAR218645 as a promising candidate for the treatment of cognitive symptoms of patients with schizophrenia, in particular those with abnormal attention and sensory gating abilities.

Human aging studies suggest that an increased use of top-down knowledge-based resources would compensate for degraded upstream acoustic information to accurately identify important temporally rich signals. Sinusoidal amplitude-modulated (SAM) stimuli have been used to mimic the fast-changing temporal features in speech and species-specific vocalizations. Single units were recorded from auditory thalamus [medial geniculate body (MGB)] of young awake, aged awake, young anesthetized, and aged anesthetized rats. SAM stimuli were modulated between 2 and 1024 Hz with the modulation frequency ( f m) changed randomly (RAN) across trials or sequentially (SEQ) after several repeated trials. Units were found to be RAN-preferring, SEQ-preferring, or nonselective based on total firing rate. Significant anesthesia and age effects were found. The majority (86%) of young anesthetized units preferred RAN SAM stimuli; significantly fewer young awake units (51%, p < 0.0001) preferred RAN SAM signals with 16% preferring SEQ SAM. Compared with young awake units, there was a significant increase of aged awake units preferring SEQ SAM (30%, p < 0.05). We examined RAN versus SEQ differences across f ms by measuring selective f m areas under the rate modulation transfer function curve. The largest age-related differences from awake animals were found for mid-to-high f ms in MGB units, with young units preferring RAN SAM while aged units showed a greater preference for SEQ-presented SAM. Together, these findings suggest that aged MGB units/animals employ increased top-down mediated stimulus context to enhance processing of “expected” temporally rich stimuli, especially at more challenging higher f ms. SIGNIFICANCE STATEMENT Older individuals compensate for impaired ascending acoustic information by increasing use of cortical cognitive and attentional resources. The interplay between ascending and descending influences in the thalamus may serve to enhance the salience of speech signals that are degraded as they ascend to the cortex. The present findings demonstrate that medial geniculate body units from awake rats show an age-related preference for predictable modulated signals relative to randomly presented signals, especially at higher, more challenging modulation frequencies. Conversely, units from anesthetized animals, with little top-down influences, strongly preferred randomly presented modulated sequences. These results suggest a neuronal substrate for an age-related increase in experience/attentional-based influences in processing temporally complex auditory information in the auditory thalamus.