Christine V. Portfors

Efficient Encoding of Vocalizations in the Auditory Midbrain

An important question in sensory neuroscience is what coding strategies and mechanisms are used by the brain to detect and discriminate among behaviorally relevant stimuli. There is evidence that sensory systems migrate from a distributed and redundant encoding strategy at the periphery to a more heterogeneous encoding in cortical structures. It has been hypothesized that heterogeneity is an efficient encoding strategy that minimizes the redundancy of the neural code and maximizes information throughput. Evidence of this mechanism has been documented in cortical structures. In this study, we examined whether heterogeneous encoding of complex sounds contributes to efficient encoding in the auditory midbrain by characterizing neural responses to behaviorally relevant vocalizations in the mouse inferior colliculus (IC). We independently manipulated the frequency, amplitude, duration, and harmonic structure of the vocalizations to create a suite of modified vocalizations. Based on measures of both spike rate and timing, we characterized the heterogeneity of neural responses to the natural vocalizations and their perturbed variants. Using information theoretic measures, we found that heterogeneous response properties of IC neurons contribute to efficient encoding of behaviorally relevant vocalizations.

Engineered Deafness Reveals That Mouse Courtship Vocalizations Do Not Require Auditory Experience

Auditory experience during development is necessary for normal language acquisition in humans. Although songbirds, some cetaceans, and maybe bats may also be vocal learners, vocal learning has yet to be well established for a laboratory mammal. Mice are potentially an excellent model organism for studying mechanisms underlying vocal communication. Mice vocalize in different social contexts, yet whether they learn their vocalizations remains unresolved. To address this question, we compared ultrasonic courtship vocalizations emitted by chronically deaf and normal hearing adult male mice. We deafened CBA/CaJ male mice, engineered to express diphtheria toxin (DT) receptors in hair cells, by systemic injection of DT at postnatal day 2 (P2). By P9, almost all inner hair cells were absent and by P16 all inner and outer hair cells were absent in DTR mice. These mice did not show any auditory brainstem responses as adults. Wild-type littermates, also treated with DT at P2, had normal hair cells and normal auditory brainstem responses. We compared the temporal structure of vocalization bouts, the types of vocalizations, the patterns of syllables, and the acoustic features of each syllable type emitted by hearing and deaf males in the presence of a female. We found that almost all of the vocalization features we examined were similar in hearing and deaf animals. These findings indicate that mice do not need auditory experience during development to produce normal ultrasonic vocalizations in adulthood. We conclude that mouse courtship vocalizations are not acquired through auditory feedback-dependent learning.

Spectral integration in the inferior colliculus of the CBA/CaJ mouse

The inferior colliculus receives a massive convergence of inputs and in the mustached bat, this convergence leads to the creation of neurons in the inferior colliculus that integrate information across multiple frequency bands. These neurons are tuned to multiple frequency bands or are combination-sensitive; responding best to the combination of two signals of different frequency composition. The importance of combination-sensitive neurons in processing echolocation signals is well described, and it has been thought that combination sensitivity is a neural specialization for echolocation behaviors. Combination sensitivity and other response properties indicative of spectral integration have not been thoroughly examined in the inferior colliculus of non-echolocating mammals. In this study we tested the hypothesis that integration across frequencies occurs in the inferior colliculus of mice. We tested excitatory frequency response areas in the inferior colliculus of unanesthetized mice by varying the frequency of a single tone between 6 and 100 kHz. We then tested combination-sensitive responses by holding one tone at the units best frequency, and varying the frequency and intensity of a second tone. Thirty-two percent of the neurons were tuned to multiple frequency bands, 16% showed combination-sensitive facilitation and another 12% showed combination-sensitive inhibition. These findings suggests that the neural mechanisms underlying processing of complex sounds in the inferior colliculus share some common features among mammals as different as the bat and the mouse.

Responses to Combinations of Tones in the Nuclei of the Lateral Lemniscus

Combination-sensitive neurons integrate specific spectral and temporal elements in biologically important sounds, and they may underlie the analysis of biosonar and social vocalizations. Combination-sensitive neurons are found in the forebrain of a variety of vertebrates. In the mustached bat, they also occur in the central nucleus of the inferior colliculus (ICC). However, it is not known where combination-sensitive response properties emerge. To address this question, we used a two-tone paradigm to examine responses of single units to combination stimuli in a brainstem structure, the nuclei of the lateral lemniscus (NLL). We recorded and histologically localized 101 single units in the NLL. The majority (82%) of units had a single excitatory frequency tuning curve. Seven units had two separate excitatory frequency tuning curves but displayed no combinatorial interaction. Twelve units were combination-sensitive. Of these, three units were facilitated by the combination of two separate frequency bands and nine units were inhibited by combinatorial stimuli. The three facilitatory neurons had excitatory responses tuned to the second harmonic constant frequency (CF2, 57-60 kHz) component of the biosonar signal and were facilitated by a second signal within the first harmonic (Hl, 24-30 kHz) of the biosonar call. Most of the inhibitory interactions occurred between signals in the frequency bands associated with the frequency-modulated (FM) components of the biosonar call. The strongest combinatorial effects (facilitatory and inhibitory) were elicited by simultaneous onset of the two signals (i.e., 0 ms delay). All combination-sensitive units were in the intermediate nucleus of the NLL (INLL), which in bats is a hypertrophied structure that projects strongly to combination-sensitive neurons in the ICC. Thus, the combination-sensitive neurons in the INLL may impart their response properties onto ICC neurons. However, the small number of facilitatory combination-sensitive neurons in the NLL suggests that the majority of these combinatorial responses originate in the ICC.

Topographical distribution of delay-tuned responses in the mustached bat inferior colliculus.

In the mustached bat, delay-tuned neurons respond best to specific delays between the first harmonic frequency modulated (FM) component (FM1; 24-29 kHz) of the emitted biosonar pulse and a higher harmonic FM component in returning echoes (e.g. FM3, 72-89 kHz). These delay-tuned, combinatorial responses predominate in the inferior colliculus (IC) of the mustached bat. This study examined the topographical distribution of delay-tuned neurons in the 72-89 kHz frequency representation of the IC. We recorded and histologically localized 163 single units. Ninety units were facilitated and 41 were inhibited by the combination of two frequencies in the 24-29 kHz and 72-89 kHz ranges. The facilitatory responses were selective for delays up to 20 ms between the two signals. To determine if delay-tuned neurons were topographically organized, we plotted the dorsomedio-ventrolateral and caudo-rostral positions of each unit versus its best delay. Best delay was not correlated with either location. Response latency to best frequency tones was topographically organized, but was not correlated with best delay. This indicates that the latency axis in the IC is unrelated to the delay tuning of these combinatorial neurons. Because delay-tuned neurons are not topographically organized in the IC but are in the auditory cortex, our findings suggest that the creation and organization of delay-tuned neurons occur at different stages in the ascending auditory system.

Excitatory and facilitatory frequency response areas in the inferior colliculus of the mustached bat

In the mustached bats central nucleus of the inferior colliculus (ICC), many neurons display facilitatory or inhibitory responses when presented with two tones of distinctly different frequencies. Our previous studies have focused on spectral interactions between specific frequency bands contained in the bats sonar vocalization. In this study, we describe excitatory and facilitatory frequency response areas across all frequencies in the mustached bats audible range. We show that many neurons in the ICC have more extensive frequency interactions than previously documented. We recorded responses of 96 single units to single tones and combinations of two tones. Best frequencies of the units ranged from 59-15 kHz. Forty-one units had a single, excitatory frequency response area. The rest of the units had more complex frequency tuning that included multiple excitatory frequency response areas and facilitatory frequency response areas. Some of the facilitatory frequency interactions were between one sound with energy in a sonar frequency band and a second sound with energy in a non-sonar frequency band. We also found that neurons could be facilitated by more than one additional frequency band. Our findings of extensive frequency interactions in the ICC of the mustached bat suggest that some neurons may be well suited for the analysis of complex sounds, possibly including social communication sounds.

The role of ultrasonic vocalizations in mouse communication

Human speech and language underlie many aspects of social behavior and thus understanding their ultimate evolutionary function and proximate genetic and neural mechanisms is a fundamental goal in neuroscience. Mouse ultrasonic vocalizations have recently received enormous attention as possible models for human speech. This attention has raised the question of whether these vocalizations are learned and what roles they play in communication. In this review, we first discuss recent evidence that ultrasonic vocalizations are not learned. We then review current evidence addressing how adult vocalizations may communicate courtship, territorial and/or other information. While there is growing evidence that these signals play key roles in communication, many important questions remain unanswered.

Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory systems ability to process complex sounds such as speech.

Just-noticeable difference in the speed of cyclopean motion in depth and the speed of cyclopean motion within a frontoparallel plane.

Weber fractions for discriminating the speed and displacement of a cyclopean target moving in depth ranged, respectively, from .07-.17 and .06-.13 over 6 observers. Corresponding data for a noncyclopean target were .07-.20 and .06-.12. For motion parallel to the frontal plane, corresponding data were .09-.20 .06-.16, and .05-.13. All Weber fractions were independent of the direction of motion and of near versus far disparity. All observers based their judgments entirely on the task-relevant variable and ignored task-irrelevant variables in all cases. We conclude that speed and displacement are encoded independently and in parallel for motion in depth and for motion within a frontoparallel plane.

Design principles of sensory processing in cerebellum-like structures: Early stage processing of electrosensory and auditory objects

Cerebellum-like structures are compared for two sensory systems: electrosensory and auditory. The electrosensory lateral line lobe of mormyrid electric fish is reviewed and the neural representation of electrosensory objects in this structure is modeled and discussed. The dorsal cochlear nucleus in the auditory brainstem of mammals is reviewed and new data are presented that characterize the responses of neurons in this structure in the mouse. Similarities between the electrosensory and auditory cerebellum-like structures are shown, in particular adaptive processes that may reduce responses to predictable stimuli. We suggest that the differences in the types of sensory objects may drive the differences in the anatomical and physiological characteristics of these two cerebellum-like structures.