Single Unit publications

Although information theoretic approaches have been used extensively in the analysis of the neural code, they have yet to be used to describe how information is accumulated in time while sensory systems are categorizing dynamic sensory stimuli such as speech sounds or visual objects. Here, we present a novel method to estimate the cumulative information for stimuli or categories. We further define a time-varying categorical information index that, by comparing the information obtained for stimuli versus categories of these same stimuli, quantifies invariant neural representations. We use these methods to investigate the dynamic properties of avian cortical auditory neurons recorded in zebra finches that were listening to a large set of call stimuli sampled from the complete vocal repertoire of this species. We found that the time-varying rates carry 5 times more information than the mean firing rates even in the first 100 ms. We also found that cumulative information has slow time constants (100-600 ms) relative to the typical integration time of single neurons, reflecting the fact that the behaviorally informative features of auditory objects are time-varying sound patterns. When we correlated firing rates and information values, we found that average information correlates with average firing rate but that higher-rates found at the onset response yielded similar information values as the lower-rates found in the sustained response: the onset and sustained response of avian cortical auditory neurons provide similar levels of independent information about call identity and call-type. Finally, our information measures allowed us to rigorously define categorical neurons; these categorical neurons show a high degree of invariance for vocalizations within a call-type. Peak invariance is found around 150 ms after stimulus onset. Surprisingly, call-type invariant neurons were found in both primary and secondary avian auditory areas.

Auditory cortex is required for sound localisation, but how neural firing in auditory cortex underlies our perception of sound sources in space remains unclear. Specifically, whether neurons in auditory cortex represent spatial cues or an integrated representation of auditory space across cues is not known. Here, we measured the spatial receptive fields of neurons in primary auditory cortex (A1) while ferrets performed a relative localisation task. Manipulating the availability of binaural and spectral localisation cues had little impact on ferrets’ performance, or on neural spatial tuning. A subpopulation of neurons encoded spatial position consistently across localisation cue type. Furthermore, neural firing pattern decoders outperformed two-channel model decoders using population activity. Together, these observations suggest that A1 encodes the location of sound sources, as opposed to spatial cue values.

Interactions between the prefrontal cortex (PFC) and mediodorsal thalamus are critical for cognitive flexibility, yet the underlying computations are unknown. To investigate frontothalamic substrates of cognitive flexibility, we developed a behavioral task in which mice switched between different sets of learned cues that guided attention toward either visual or auditory targets. We found that PFC responses reflected both the individual cues and their meaning as task rules, indicating a hierarchical cue-to-rule transformation. Conversely, mediodorsal thalamus responses reflected the statistical regularity of cue presentation and were required for switching between such experimentally specified cueing contexts. A subset of these thalamic responses sustained context-relevant PFC representations, while another suppressed the context-irrelevant ones. Through modeling and experimental validation, we find that thalamic-mediated suppression may not only reduce PFC representational interference but could also preserve unused cortical traces for future use. Overall, our study provides a computational foundation for thalamic engagement in cognitive flexibility.

Frequency tuning and phase-locking are two fundamental properties generated in the cochlea, enabling but also limiting the coding of sounds by the auditory nerve (AN). In humans, these limits are unknown, but high resolution has been postulated for both properties. Electrophysiological recordings from the AN of normal-hearing volunteers indicate that human frequency tuning, but not phase-locking, exceeds the resolution observed in animal models.

Vocal communication is a sensory-motor process requiring auditory self-monitoring to correct errors and to ensure accurate vocal production. When presented with altered speech feedback, humans rapidly change their speech to compensate. Although previous evidence has demonstrated suppression of auditory cortex during both speech and animal vocalization, the specific role of auditory cortex in such feedback-dependent control is unknown. Here we show the relationship between neural activity in the auditory cortex and feedback-dependent vocal control in marmoset monkeys. We demonstrate that marmosets, like humans, exhibit feedback control of vocal acoustics. We further show that feedback-sensitive activity of auditory cortex neurons predict such compensatory vocal changes. Finally, we demonstrate that electrical microstimulation of auditory cortex rapidly evokes similar changes in vocal production. These results are evidence for a causal role of auditory cortex in vocal self-monitoring and feedback-dependent control, and have implications for understanding human speech motor control.

A function of the auditory system is to accurately determine the location of a sound source. The main cues for sound location are interaural time (ITD) and level (ILD) differences. Humans use both ITD and ILD to determine the azimuth. Thus far, the conception of sound localization in barn owls was that their facial ruff and asymmetrical ears generate a two-dimensional grid of ITD for azimuth and ILD for elevation. We show that barn owls also use ILD for azimuthal sound localization when ITDs are ambiguous. For high-frequency narrowband sounds, midbrain neurons can signal multiple locations, leading to the perception of an auditory illusion called a phantom source. Owls respond to such an illusory percept by orienting toward it instead of the true source. Acoustical measurements close to the eardrum reveal a small ILD component that changes with azimuth, suggesting that ITD and ILD information could be combined to eliminate the illusion. Our behavioral data confirm that perception was robust against ambiguities if ITD and ILD information was combined. Electrophysiological recordings of ILD sensitivity in the owl’s midbrain support the behavioral findings indicating that rival brain hemispheres drive the decision to orient to either true or phantom sources. Thus, the basis for disambiguation, and reliable detection of sound source azimuth, relies on similar cues across species as similar response to combinations of ILD and narrowband ITD has been observed in humans.

Species differences in perception have been linked to divergence in gross neuroanatomical features of sensory pathways. The anatomical and physiological basis of evolutionary change in sensory processing at cellular and circuit levels, however, is poorly understood. Here, we show how specific changes to a sensory microcircuit are associated with the evolution of a novel perceptual ability. In mormyrid fishes, the ability to detect variation in electric communication signals is correlated with an enlargement of the midbrain exterolateral nucleus (EL), and a differentiation into separate anterior (ELa) and posterior (ELp) regions. We show that the same cell types and connectivity are found in both EL and ELa/ELp. The evolution of ELa/ELp, and the concomitant ability to detect signal variation, is associated with a lengthening of incoming hindbrain axons to form delay lines, allowing for fine temporal analysis of signals. The enlargement of this brain region is also likely due to an overall increase in cell numbers, which would allow for processing of a wider range of timing information.

A key function of the brain is to provide a stable representation of an object's location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system, and auditory cortex is necessary for sound localization. However, the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects; here we recorded spatial receptive fields in the auditory cortex of freely moving ferrets. We found that most spatially tuned neurons represented sound source location relative to the head across changes in head position and direction. In addition, we also recorded a small number of neurons in which sound location was represented in a world-centered coordinate frame. We used measurements of spatial tuning across changes in head position and direction to explore the influence of sound source distance and speed of head movement on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas, for both populations, modulation was stronger at faster movement speeds. Our findings suggest that early auditory cortex primarily represents sound source location relative to ourselves but that a minority of cells can represent sound location in the world independent of our own position.

Perceptual constancy requires neural representations that are selective for object identity, but also tolerant for identity-preserving transformations. How such representations arise in the brain and contribute to perception remains unclear. Here we studied tolerant representations of sound identity in the auditory system by recording multi-unit activity in tonotopic auditory cortex of ferrets discriminating the identity of vowels which co-varied across orthogonal stimulus dimensions (fundamental frequency, sound level, location and voicing). We found that neural decoding of vowel identity was most successful across the same orthogonal dimensions over which animals generalized their behavior. We also decoded orthogonal sound features and behavioral variables including choice and accuracy to show a behaviorally-relevant, multivariate and multiplexed representation of sound, with each variable represented over a distinct time-course. Finally, information content and timing of sound feature encoding was modulated by task-engagement and training, suggesting that tolerant representations during perceptual constancy are attentionally and experience-dependent.

The objective of this study was to demonstrate the efficacy of acute inactivation of brain areas by cooling in the behaving ferret and to demonstrate that cooling auditory cortex produced a localisation deficit that was specific to auditory stimuli. The effect of cooling on neural activity was measured in anesthetized ferret cortex. The behavioural effect of cooling was determined in a benchmark sound localisation task in which inactivation of primary auditory cortex (A1) is known to impair performance. Cooling strongly suppressed the spontaneous and stimulus-evoked firing rates of cortical neurons when the cooling loop was held at temperatures below 10°C, and this suppression was reversed when the cortical temperature recovered. Cooling of ferret auditory cortex during behavioural testing impaired sound localisation performance, with unilateral cooling producing selective deficits in the hemifield contralateral to cooling, and bilateral cooling producing deficits on both sides of space. The deficit in sound localisation induced by inactivation of A1 was not caused by motivational or locomotor changes since inactivation of A1 did not affect localisation of visual stimuli in the same context.

Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug. Using chemogenetic approaches, we increase VTA activity to mechanistically link oestrous cycle-dependent enhancement of VTA firing to enhanced cocaine affinity at DAT and subsequent reward processing. These data have implications for sexual dimorphism in addiction vulnerability and define a mechanism by which cellular activity results in protein alterations that contribute to dysfunctional learning and reward processing.

Maximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo . We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets.

Recently, we reported evidence for a novel mechanism of peripheral sensory coding based on oscillatory synchrony. Spontaneously oscillating electroreceptors in weakly electric fish (Mormyridae) respond to electrosensory stimuli with a phase reset that results in transient synchrony across the receptor population (Baker et al., 2015). Here, we asked whether the central electrosensory system actually detects the occurrence of synchronous oscillations among receptors. We found that electrosensory stimulation elicited evoked potentials in the midbrain exterolateral nucleus at a short latency following receptor synchronization. Frequency tuning in the midbrain resembled peripheral frequency tuning, which matches the intrinsic oscillation frequencies of the receptors. These frequencies are lower than those in individual conspecific signals, and instead match those found in collective signals produced by groups of conspecifics. Our results provide further support for a novel mechanism for sensory coding based on the detection of oscillatory synchrony among peripheral receptors.

Successful speech perception in real-world environments requires that the auditory system segregate competing voices that overlap in frequency and time into separate streams. Vowels are major constituents of speech and are comprised of frequencies (harmonics) that are integer multiples of a common fundamental frequency (F0). The pitch and identity of a vowel are determined by its F0 and spectral envelope (formant structure), respectively. When two spectrally overlapping vowels differing in F0 are presented concurrently, they can be readily perceived as two separate “auditory objects” with pitches at their respective F0s. A difference in pitch between two simultaneous vowels provides a powerful cue for their segregation, which in turn, facilitates their individual identification. The neural mechanisms underlying the segregation of concurrent vowels based on pitch differences are poorly understood. Here, we examine neural population responses in macaque primary auditory cortex (A1) to single and double concurrent vowels (/a/ and /i/) that differ in F0 such that they are heard as two separate auditory objects with distinct pitches. We find that neural population responses in A1 can resolve, via a rate-place code, lower harmonics of both single and double concurrent vowels. Furthermore, we show that the formant structures, and hence the identities, of single vowels can be reliably recovered from the neural representation of double concurrent vowels. We conclude that A1 contains sufficient spectral information to enable concurrent vowel segregation and identification by downstream cortical areas.

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.