Single Unit publications

Perception is characterized by a reciprocal exchange of predictions and prediction error signals between neural regions. However, the relationship between such sensory mismatch responses and hierarchical predictive processing has not yet been demonstrated at the neuronal level in the auditory pathway. We recorded single-neuron activity from different auditory centers in anaesthetized rats and awake mice while animals were played a sequence of sounds, designed to separate the responses due to prediction error from those due to adaptation effects. Here we report that prediction error is organized hierarchically along the central auditory pathway. These prediction error signals are detectable in subcortical regions and increase as the signals move towards auditory cortex, which in turn demonstrates a large-scale mismatch potential. Finally, the predictive activity of single auditory neurons underlies automatic deviance detection at subcortical levels of processing. These results demonstrate that prediction error is a fundamental component of singly auditory neuron responses.

Hidden hearing refers to the functional deficits in hearing without deterioration in hearing sensitivity. This concept is proposed based upon recent finding of massive noise-induced damage on ribbon synapse between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea without significant permanent threshold shifts (PTS). Presumably, such damage may cause coding deficits in auditory nerve fibers (ANFs). However, such deficits had not been detailed except that a selective loss of ANFs with low spontaneous rate (SR) was reported. In the present study, we investigated the dynamic changes of ribbon synapses and the coding function of ANF single units in one month after a brief noise exposure that caused a massive damage of ribbon synapses but no PTS. The synapse count and functional response measures indicates a large portion of the disrupted synapses were re-connected. This is consistent with the fact that the change of SR distribution due to the initial loss of low SR units is recovered quickly. However, ANF coding deficits were developed later with the re-establishment of the synapses. The deficits were found in both intensity and temporal processing, revealing the nature of synaptopathy in hidden hearing loss.

Stimulus-specific adaptation (SSA) in single neurons of the auditory cortex was suggested to be a potential neural correlate of the mismatch negativity (MMN), a widely studied component of the auditory event-related potentials (ERP) that is elicited by changes in the auditory environment. However, several aspects on this SSA/MMN relation remain unresolved. SSA occurs in the primary auditory cortex (A1), but detailed studies on SSA beyond A1 are lacking. To study the topographic organization of SSA, we mapped the whole rat auditory cortex with multiunit activity recordings, using an oddball paradigm. We demonstrate that SSA occurs outside A1 and differs between primary and nonprimary cortical fields. In particular, SSA is much stronger and develops faster in the nonprimary than in the primary fields, paralleling the organization of subcortical SSA. Importantly, strong SSA is present in the nonprimary auditory cortex within the latency range of the MMN in the rat and correlates with an MMN-like difference wave in the simultaneously recorded local field potentials (LFP). We present new and strong evidence linking SSA at the cellular level to the MMN, a central tool in cognitive and clinical neuroscience.

Auditory information relayed by auditory nerve fibers and somatosensory information relayed by granule cell parallel fibers converge on the fusiform cells (FCs) of the dorsal cochlear nucleus, the first brain station of the auditory pathway. In vitro, parallel fiber synapses on FCs exhibit spike-timing-dependent plasticity with Hebbian learning rules, partially mediated by the NMDA receptor (NMDAr). Well-timed bimodal auditory-somatosensory stimulation, in vivo equivalent of spike-timing-dependent plasticity, can induce stimulus-timing-dependent plasticity (StTDP) of the FCs spontaneous and tone-evoked firing rates. In healthy guinea pigs, the resulting distribution of StTDP learning rules across a FC neural population is dominated by a Hebbian profile while anti-Hebbian, suppressive and enhancing LRs are less frequent. In this study, we investigate in vivo, the NMDAr contribution to FC baseline activity and long term plasticity. We find that blocking the NMDAr decreases the synchronization of FC- spontaneous activity and mediates differential modulation of FC rate-level functions such that low, and high threshold units are more likely to increase, and decrease, respectively, their maximum amplitudes. Three significant alterations in mean learning-rule profiles were identified: transitions from an initial Hebbian profile towards (1) an anti-Hebbian; (2) a suppressive profile; and (3) transitions from an anti-Hebbian to a Hebbian profile. FC units preserving their learning rules showed instead, NMDAr-dependent plasticity to unimodal acoustic stimulation, with persistent depression of tone-evoked responses changing to persistent enhancement following the NMDAr antagonist. These results reveal a crucial role of the NMDAr in mediating FC baseline activity and long-term plasticity which have important implications for signal processing and auditory pathologies related to maladaptive plasticity of dorsal cochlear nucleus circuitry.

Mice are of paramount importance in biomedical research and their vocalizations are a subject of interest for researchers across a wide range of health-related disciplines due to their increasingly important value as a phenotyping tool in models of neural, speech and language disorders. However, the mechanisms underlying the auditory processing of vocalizations in mice are not well understood. The mouse audiogram shows a peak in sensitivity at frequencies between 15-25 kHz, but weaker sensitivity for the higher ultrasonic frequencies at which they typically vocalize. To investigate the auditory processing of vocalizations in mice, we measured evoked potential, single-unit, and multi-unit responses to tones and vocalizations at three different stages along the auditory pathway: the auditory nerve and the cochlear nucleus in the periphery, and the inferior colliculus in the midbrain. Auditory brainstem response measurements suggested stronger responses in the midbrain relative to the periphery for frequencies higher than 32 kHz. This result was confirmed by single- and multi-unit recordings showing that high ultrasonic frequency tones and vocalizations elicited responses from only a small fraction of cells in the periphery, while a much larger fraction of cells responded in the inferior colliculus. These results suggest that the processing of communication calls in mice is supported by a specialization of the auditory system for high frequencies that emerges at central stations of the auditory pathway.

The neural mechanisms of pitch coding have been debated for more than a century. The two main mechanisms are coding based on the profiles of neural firing rates across auditory nerve fibers with different characteristic frequencies (place-rate coding), and coding based on the phase-locked temporal pattern of neural firing (temporal coding). Phase locking precision can be partly assessed by recording the frequency-following response (FFR), a scalp-recorded electrophysiological response that reflects synchronous activity in subcortical neurons. Although features of the FFR have been widely used as indices of pitch coding acuity, only a handful of studies have directly investigated the relation between the FFR and behavioral pitch judgments. Furthermore, the contribution of degraded neural synchrony (as indexed by the FFR) to the pitch perception impairments of older listeners and those with hearing loss is not well known. Here, the relation between the FFR and pure-tone frequency discrimination was investigated in listeners with a wide range of ages and absolute thresholds, to assess the respective contributions of subcortical neural synchrony and other age-related and hearing loss-related mechanisms to frequency discrimination performance. FFR measures of neural synchrony and absolute thresholds independently contributed to frequency discrimination performance. Age alone, i.e., once the effect of subcortical neural synchrony measures or absolute thresholds had been partialed out, did not contribute to frequency discrimination. Overall, the results suggest that frequency discrimination of pure tones may depend both on phase locking precision and on separate mechanisms affected in hearing loss.

The role of the cortico-tectal pathways in the processing of auditory signals was investigated by recording the click-evoked responses and extracellular multiple unit activity in the inferior colliculus (IC) after functional ablation of the auditory cortex (AC) by local intracortical application of a sodium channel blocker, tetrodotoxin (TTX). Click-evoked IC responses (IC-ER) and multiple unit activity in response to tone bursts were recorded with implanted electrodes in the IC of rats lightly anaesthetized with xylazine. Neural activity was recorded before and after the application of TTX into the ipsilateral auditory cortex (AC) through three implanted cannulas in a total dose of 30 ng. The functional status of the AC was monitored by recording click-evoked middle latency responses from a ball electrode implanted on the AC. During inactivation of the AC, IC-ER amplitudes were either increased (48 % of the cases), decreased (32 % of the cases) or not evidently changed (20 % of the cases). Corresponding effects were observed in the firing rate of IC neurons. Functional ablation of the AC also resulted in a significant prolongation of the latencies of individual waves of the IC-ER. However, the discharge pattern of the multiple unit responses, response thresholds and tuning were not altered during AC inactivation. IC neural activity recovered within several hours, and maximally during 2 days. The results reveal principles of the interaction of cortico-tectal pathways with IC neuronal activity.