How specific aspects of a stimulus are encoded at different stages of neural processing is a critical question in sensory neuroscience. In the present study, we investigated the neural code underlying the perception of stimulus intensity in the somatosensory system. We first characterized the responses of SA1 (slowly adapting type 1), RA (rapidly adapting), and PC (Pacinian) afferents of macaque monkeys to sinusoidal, diharmonic, and bandpass noise stimuli. We then had human subjects rate the perceived intensity of a subset of these stimuli. On the basis of these neurophysiological and psychophysical measurements, we evaluated a series of hypotheses about which aspect(s) of the neural activity evoked at the somatosensory periphery account for perception. We evaluated three types of neural codes. The first consisted of population codes based on the firing rate of neurons located directly under the probe. The second included population codes based on the firing rate of the entire population of active neurons. The third included codes based on the number of active afferents. We found that the response evoked in the localized population is logarithmic with stimulus amplitude (given a constant frequency composition), whereas the population response across all neurons is linear with stimulus amplitude. We conclude that stimulus intensity is best accounted for by the firing rate evoked in afferents located under or near the locus of stimulation, weighted by afferent type.

Noise exposure is one of the most common causes of hearing loss and peripheral damage to the auditory system. A growing literature suggests that the auditory system can compensate for peripheral loss through increased central neural activity. The current study sought to investigate the link between noise exposure, increases in central gain, synaptic reorganization, and auditory function. All axons of the auditory nerve project to the cochlear nucleus, making it a requisite nucleus for sound detection. As the first synapse in the central auditory system, the cochlear nucleus is well positioned to respond plastically to loss of peripheral input. To investigate noise-induced compensation in the central auditory system, we measured auditory brainstem responses (ABRs) and auditory perception and collected tissue from mice exposed to broadband noise. Noise-exposed mice showed elevated ABR thresholds, reduced ABR wave 1 amplitudes, and spiral ganglion neuron loss. Despite peripheral damage, noise-exposed mice were hyperreactive to loud sounds and showed nearly normal behavioral sound detection thresholds. Ratios of late ABR peaks (2–4) relative to the first ABR peak indicated that brainstem pathways were hyperactive in noise-exposed mice, while anatomical analysis indicated there was an imbalance between expression of excitatory and inhibitory proteins in the ventral cochlear nucleus. The results of the current study suggest that a reorganization of excitation and inhibition in the ventral cochlear nucleus may drive hyperactivity in the central auditory system. This increase in central gain can compensate for peripheral loss to restore some aspects of auditory function.

The assembly of uniquely organized sound localization circuits in the brainstem requires precise developmental mechanisms. Glial cells have been shown to shape synaptic connections in the retinogeniculate system during development, but their contributions to specialized auditory synapses have not been identified. Here we investigated the role of microglia in auditory brainstem circuit assembly, focusing on the formation and pruning of the calyx of Held in the medial nucleus of the trapezoid body (MNTB). Microglia were pharmacologically depleted in mice early in development using subcutaneous injections of an inhibitor of colony stimulating factor 1 receptor, which is essential for microglia survival. Brainstems were examined prior to and just after hearing onset, at postnatal days (P) 8 and P13, respectively. We found that at P13 there were significantly more polyinnervated MNTB neurons when microglia were depleted, consistent with a defect in pruning. Expression of glial fibrillary acidic protein (GFAP), a mature astrocyte marker that normally appears in the MNTB late in development, was significantly decreased in microglia-depleted mice at P13, suggesting a delay in astrocyte maturation. Our results demonstrate that monoinnervation of MNTB neurons by the calyx of Held is significantly disrupted or delayed in the absence of microglia. This finding may reflect a direct role for microglia in synaptic pruning. A secondary role for microglia may be in the maturation of astrocytes in MNTB. These findings highlight the significant function of glia in pruning during calyx of Held development.