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Integrative and Comparative Biology Oct 2017Context is critical to the adaptive value of communication. Sensory systems such as the auditory system represent an important juncture at which information on... (Review)
Review
Context is critical to the adaptive value of communication. Sensory systems such as the auditory system represent an important juncture at which information on physiological state or social valence can be added to communicative information. However, the neural pathways that convey context to the auditory system are not well understood. The serotonergic system offers an excellent model to address these types of questions. Serotonin fluctuates in the mouse inferior colliculus (IC), an auditory midbrain region important for species-specific vocalizations, during specific social and non-social contexts. Furthermore, serotonin is an indicator of the valence of event-based changes within individual social interactions. We propose a model in which the brain's social behavior network serves as an afferent effector of the serotonergic dorsal raphe nucleus in order to gate contextual release of serotonin in the IC. Specifically, discrete vasopressinergic nuclei within the hypothalamus and extended amygdala that project to the dorsal raphe are functionally engaged during contexts in which serotonin fluctuates in the IC. Since serotonin strongly influences the responses of IC neurons to social vocalizations, this pathway could serve as a feedback loop whereby integrative social centers modulate their own sources of input. The end result of this feedback would be to produce a process that is geared, from sensory input to motor output, toward responding appropriately to a dynamic external world.
Topics: Animals; Auditory Perception; Brain; Inferior Colliculi; Mice; Neural Pathways; Rats; Serotonin; Social Behavior
PubMed: 28985384
DOI: 10.1093/icb/icx055 -
Nature Communications 2013Electrical and transcranial magnetic stimulations have proven to be therapeutically beneficial for patients suffering from neurological disorders. Moreover, these...
Electrical and transcranial magnetic stimulations have proven to be therapeutically beneficial for patients suffering from neurological disorders. Moreover, these stimulation technologies have provided invaluable tools for investigating nervous system functions. Despite this success, these technologies have technical and practical limitations impeding the maximization of their full clinical and preclinical potential. Recently, micro-magnetic stimulation, which may offer advantages over electrical and transcranial magnetic stimulation, has proven effective in activating the neuronal circuitry of the retina in vitro. Here we demonstrate that this technology is also capable of activating neuronal circuitry on a systems level using an in vivo preparation. Specifically, the application of micro-magnetic fields to the dorsal cochlear nucleus activates inferior colliculus neurons. Additionally, we demonstrate the efficacy and characteristics of activation using different magnetic stimulation parameters. These findings provide a rationale for further exploration of micro-magnetic stimulation as a prospective tool for clinical and preclinical applications.
Topics: Animals; Central Nervous System; Evoked Potentials; Inferior Colliculi; Magnetic Phenomena; Male; Mesocricetus; Neurons
PubMed: 24030203
DOI: 10.1038/ncomms3463 -
Frontiers in Neural Circuits 2022Located in the midbrain, the inferior colliculus (IC) plays an essential role in many auditory computations, including speech processing and sound localization. The...
Located in the midbrain, the inferior colliculus (IC) plays an essential role in many auditory computations, including speech processing and sound localization. The right and left sides of the IC are interconnected by a dense fiber tract, the commissure of the IC (CoIC), that provides each IC with one of its largest sources of input (i.e., the contralateral IC). Despite its prominence, the CoIC remains poorly understood. Previous studies using anterograde and retrograde tract-tracing showed that IC commissural projections are predominately homotopic and tonotopic, targeting mirror-image locations in the same frequency region in the contralateral IC. However, it is unknown whether specific classes of neurons, particularly inhibitory neurons which constitute ~10%-40% of the commissural projection, follow this pattern. We, therefore, examined the commissural projections of Neuropeptide Y (NPY) neurons, the first molecularly identifiable class of GABAergic neurons in the IC. Using retrograde tracing with Retrobeads (RB) in NPY-hrGFP mice of both sexes, we found that NPY neurons comprise ~11% of the commissural projection. Moreover, focal injections of Retrobeads showed that NPY neurons in the central nucleus of the IC exhibit a more divergent and heterotopic commissural projection pattern than non-NPY neurons. Thus, commissural NPY neurons are positioned to provide lateral inhibition to the contralateral IC. Through this circuit, sounds that drive activity in limited regions on one side of the IC likely suppress activity across a broader region in the contralateral IC.
Topics: Animals; Auditory Pathways; Female; GABAergic Neurons; Inferior Colliculi; Male; Mesencephalon; Mice; Neuropeptide Y; Sound Localization
PubMed: 35693026
DOI: 10.3389/fncir.2022.871924 -
PLoS Biology Oct 2018Temporal analysis of sound is fundamental to auditory processing throughout the animal kingdom. Echolocating bats are powerful models for investigating the underlying...
Temporal analysis of sound is fundamental to auditory processing throughout the animal kingdom. Echolocating bats are powerful models for investigating the underlying mechanisms of auditory temporal processing, as they show microsecond precision in discriminating the timing of acoustic events. However, the neural basis for microsecond auditory discrimination in bats has eluded researchers for decades. Combining extracellular recordings in the midbrain inferior colliculus (IC) and mathematical modeling, we show that microsecond precision in registering stimulus events emerges from synchronous neural firing, revealed through low-latency variability of stimulus-evoked extracellular field potentials (EFPs, 200-600 Hz). The temporal precision of the EFP increases with the number of neurons firing in synchrony. Moreover, there is a functional relationship between the temporal precision of the EFP and the spectrotemporal features of the echolocation calls. In addition, EFP can measure the time difference of simulated echolocation call-echo pairs with microsecond precision. We propose that synchronous firing of populations of neurons operates in diverse species to support temporal analysis for auditory localization and complex sound processing.
Topics: Acoustic Stimulation; Animals; Auditory Pathways; Auditory Perception; Biophysical Phenomena; Chiroptera; Computer Simulation; Echolocation; Evoked Potentials, Auditory; Female; Inferior Colliculi; Male; Models, Neurological; Neurons; Sound Localization; Time Perception
PubMed: 30365484
DOI: 10.1371/journal.pbio.2006422 -
Toxicology and Applied Pharmacology Sep 2018Acute exposure to high concentrations of HS causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better...
Acute exposure to high concentrations of HS causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute HS-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute HS-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of HS. HS induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-HS exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm HS-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed HS exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of HS-induced neurotoxicity.
Topics: Animals; Behavior, Animal; Gene Expression; Hydrogen Sulfide; Inferior Colliculi; Inhalation Exposure; Intracranial Hemorrhages; Male; Mice; Mice, Inbred C57BL; Neurotoxicity Syndromes; Oxidative Stress; Proteomics; Seizures; Signal Transduction
PubMed: 29932956
DOI: 10.1016/j.taap.2018.06.001 -
The Journal of Neuroscience : the... Aug 2023The inferior colliculus (IC) is a midbrain hub critical for perceiving complex sounds, such as speech. In addition to processing ascending inputs from most auditory...
The inferior colliculus (IC) is a midbrain hub critical for perceiving complex sounds, such as speech. In addition to processing ascending inputs from most auditory brainstem nuclei, the IC receives descending inputs from auditory cortex that control IC neuron feature selectivity, plasticity, and certain forms of perceptual learning. Although corticofugal synapses primarily release the excitatory transmitter glutamate, many physiology studies show that auditory cortical activity has a net inhibitory effect on IC neuron spiking. Perplexingly, anatomy studies imply that corticofugal axons primarily target glutamatergic IC neurons while only sparsely innervating IC GABA neurons. Corticofugal inhibition of the IC may thus occur largely independently of feedforward activation of local GABA neurons. We shed light on this paradox using electrophysiology in acute IC slices from fluorescent reporter mice of either sex. Using optogenetic stimulation of corticofugal axons, we find that excitation evoked with single light flashes is indeed stronger in presumptive glutamatergic neurons compared with GABAergic neurons. However, many IC GABA neurons fire tonically at rest, such that sparse and weak excitation suffices to significantly increase their spike rates. Furthermore, a subset of glutamatergic IC neurons fire spikes during repetitive corticofugal activity, leading to polysynaptic excitation in IC GABA neurons owing to a dense intracollicular connectivity. Consequently, recurrent excitation amplifies corticofugal activity, drives spikes in IC GABA neurons, and generates substantial local inhibition in the IC. Thus, descending signals engage intracollicular inhibitory circuits despite apparent constraints of monosynaptic connectivity between auditory cortex and IC GABA neurons. Descending "corticofugal" projections are ubiquitous across mammalian sensory systems, and enable the neocortex to control subcortical activity in a predictive or feedback manner. Although corticofugal neurons are glutamatergic, neocortical activity often inhibits subcortical neuron spiking. How does an excitatory pathway generate inhibition? Here we study the corticofugal pathway from auditory cortex to inferior colliculus (IC), a midbrain hub important for complex sound perception. Surprisingly, cortico-collicular transmission was stronger onto IC glutamatergic compared with GABAergic neurons. However, corticofugal activity triggered spikes in IC glutamate neurons with local axons, thereby generating strong polysynaptic excitation and feedforward spiking of GABAergic neurons. Our results thus reveal a novel mechanism that recruits local inhibition despite limited monosynaptic convergence onto inhibitory networks.
Topics: Mice; Animals; Inferior Colliculi; Auditory Cortex; Axons; GABAergic Neurons; Glutamates; Auditory Pathways; Acoustic Stimulation; Mammals
PubMed: 37308295
DOI: 10.1523/JNEUROSCI.0626-23.2023 -
The European Journal of Neuroscience Aug 2022Schroeder-phase harmonic tone complexes have been used in physiological and psychophysical studies in several species to gain insight into cochlear function. Each pitch...
Schroeder-phase harmonic tone complexes have been used in physiological and psychophysical studies in several species to gain insight into cochlear function. Each pitch period of the Schroeder stimulus contains a linear frequency sweep; the duty cycle, sweep velocity, and direction are controlled by parameters of the phase spectrum. Here, responses to a range of Schroeder-phase harmonic tone complexes were studied both behaviorally and in neural recordings from the auditory nerve and inferior colliculus of Mongolian gerbils. Gerbils were able to discriminate Schroeder-phase harmonic tone complexes based on sweep direction, duty cycle, and/or velocity for fundamental frequencies up to 200 Hz. Temporal representation in neural responses based on the van Rossum spike-distance metric, with time constants of either 1 ms or related to the stimulus' period, was compared with average discharge rates. Neural responses and behavioral performance were both expressed in terms of sensitivity, d', to allow direct comparisons. Our results suggest that in the auditory nerve, stimulus fine structure is represented by spike timing, whereas envelope is represented by rate. In the inferior colliculus, both temporal fine structure and envelope appear to be represented best by rate. However, correlations between neural d' values and behavioral sensitivity for sweep direction were strongest for both temporal metrics, for both auditory nerve and inferior colliculus. Furthermore, the high sensitivity observed in the inferior colliculus neural rate-based discrimination suggests that these neurons integrate across multiple inputs arising from the auditory periphery.
Topics: Acoustic Stimulation; Animals; Auditory Perception; Cochlear Nerve; Gerbillinae; Inferior Colliculi; Neurophysiology; Perception
PubMed: 35724973
DOI: 10.1111/ejn.15744 -
Hearing Research May 2016Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the...
Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA-ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph-ephrin guidance in establishing juxtaposed continuous and discrete neural maps in the developing IC prior to experience.
Topics: Afferent Pathways; Animals; Auditory Pathways; Brain Mapping; Brain Stem; Cochlear Nucleus; Ephrin-A4; Ephrin-B2; Ephrin-B3; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genotype; Inferior Colliculi; Mice; Neurogenesis; Olivary Nucleus
PubMed: 26906676
DOI: 10.1016/j.heares.2016.02.013 -
Hearing Research Jun 2018Auditory brainstem implants (ABIs) can restore useful hearing to persons with deafness who cannot benefit from cochlear implants. However, the quality of hearing...
Responses of neurons in the feline inferior colliculus to modulated electrical stimuli applied on and within the ventral cochlear nucleus; Implications for an advanced auditory brainstem implant.
Auditory brainstem implants (ABIs) can restore useful hearing to persons with deafness who cannot benefit from cochlear implants. However, the quality of hearing restored by ABIs rarely is comparable to that provided by cochlear implants in persons for whom those are appropriate. In an animal model, we evaluated elements of a prototype of an ABI in which the functions of macroelectrodes on the surface of the dorsal cochlear nucleus would be integrated with the function of multiple penetrating microelectrodes implanted into the ventral cochlear nucleus. The surface electrodes would convey most of the range of loudness percepts while the intranuclear microelectrodes would sharpen and focus pitch percepts. In the present study, stimulating electrodes were implanted chronically on the surface of the animal's dorsal cochlear nucleus (DCN) and also within their ventral cochlear nucleus (VCN). Recording microelectrodes were implanted into the central nucleus of the inferior colliculus (ICC). The electrical stimuli were sinusoidally modulated stimulus pulse trains applied on the DCN and within the VCN. Temporal encoding of neuronal responses was quantified as vector strength (VS) and as full-cycle rate of neuronal activity in the ICC. VS and full-cycle AP rate were measured for 4 stimulation modes; continuous and transient amplitude modulation of the stimulus pulse trains, each delivered via the macroelectrode on the surface of the DCN and then by the intranuclear penetrating microelectrodes. In the proposed clinical device the functions of the surface and intranuclear microelectrodes could best be integrated if there is minimal variation in the neuronal responses across the range of modulation depth, modulation frequencies, and across the four stimulation modes. In this study VS did vary as much as 34% across modulation frequency and modulation depth within a stimulation mode, and up to 40% between modulation modes. However, these intra- and inter-mode variances differed for different stimulation rates, and at 500 Hz the inter-mode differences in VS and across the range of modulation frequencies and modulation depths was
= 24% and the intra-modal differences were= 15%. The findings were generally similar for rate encoding of modulation depth, although the depth of transient amplitude modulation delivered by the surface electrode was weakly encoded as full-cycle rate. Overall, our findings support the concept of a clinical ABI that employs surface stimulation and intranuclear microstimulation in an integrated manner.Topics: Animals; Auditory Brain Stem Implants; Auditory Pathways; Auditory Perception; Cats; Cochlear Nucleus; Electric Stimulation; Evoked Potentials; Hearing; Inferior Colliculi; Loudness Perception; Materials Testing; Models, Animal; Neurons; Pitch Perception; Prosthesis Design
PubMed: 29573880
DOI: 10.1016/j.heares.2018.03.009 -
Journal of Neurophysiology Sep 2014Recognition and localization of a sound are the major functions of the auditory system. In real situations, the listener and different degrees of reverberation transform...
Recognition and localization of a sound are the major functions of the auditory system. In real situations, the listener and different degrees of reverberation transform the signal between the source and the ears. The present study was designed to provide these transformations and examine their influence on neural responses. Using the virtual auditory space (VAS) method to create anechoic and moderately and highly reverberant environments, we found the following: 1) In reverberation, azimuth tuning was somewhat degraded with distance whereas the direction of azimuth tuning remained unchanged. These features remained unchanged in the anechoic condition. 2) In reverberation, azimuth tuning and envelope synchrony were degraded most for neurons with low best frequencies and least for neurons with high best frequencies. 3) More neurons showed envelope synchrony to binaural than to monaural stimulation in both anechoic and reverberant environments. 4) The percentage of envelope-coding neurons and their synchrony decreased in reverberation with distance, whereas it remained constant in the anechoic condition. 5) At far distances, for both binaural and monaural stimulation, the neural gain in reverberation could be as high as 30 dB and as much as 10 dB higher than those in the anechoic condition. 6) The majority of neurons were able to code both envelope and azimuth in all of the environments. This study provides a foundation for understanding the neural coding of azimuth and envelope synchrony at different distances in reverberant and anechoic environments. This is necessary to understand how the auditory system processes "where" and "what" information in real environments.
Topics: Animals; Evoked Potentials, Auditory; Inferior Colliculi; Neurons; Rabbits; Sound Localization; Wakefulness
PubMed: 24944219
DOI: 10.1152/jn.00826.2013