-
Journal of Chemical Neuroanatomy Oct 2021Acetylcholine (ACh) is a neuromodulator that has been implicated in multiple roles across the brain, including the central auditory system, where it sets neuronal...
Acetylcholine (ACh) is a neuromodulator that has been implicated in multiple roles across the brain, including the central auditory system, where it sets neuronal excitability and gain and affects plasticity. In the cerebral cortex, subtypes of GABAergic interneurons are modulated by ACh in a subtype-specific manner. Subtypes of GABAergic neurons have also begun to be described in the inferior colliculus (IC), a midbrain hub of the auditory system. Here, we used male and female mice (Mus musculus) that express fluorescent protein in cholinergic cells, axons, and boutons to look at the association between ACh and four subtypes of GABAergic IC cells that differ in their associations with extracellular markers, their soma sizes, and their distribution within the IC. We found that most IC cells, including excitatory and inhibitory cells, have cholinergic boutons closely associated with their somas and proximal dendrites. We also found that similar proportions of each of four subtypes of GABAergic cells are closely associated with cholinergic boutons. Whether the different types of GABAergic cells in the IC are differentially regulated remains unclear, as the response of cells to ACh is dependent on which types of ACh receptors are present. Additionally, this study confirms the presence of these four subtypes of GABAergic cells in the mouse IC, as they had previously been identified only in guinea pigs. These results suggest that cholinergic projections to the IC modulate auditory processing via direct effects on a multitude of inhibitory circuits.
Topics: Animals; Cholinergic Neurons; Female; Inferior Colliculi; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Inhibition; Presynaptic Terminals; Vesicular Glutamate Transport Protein 2
PubMed: 34186203
DOI: 10.1016/j.jchemneu.2021.101998 -
The Journal of Neuroscience : the... Aug 2020The lateral cortex of the inferior colliculus (LCIC) forms a nexus between diverse multisensory, motor, and neuromodulatory streams. Like other integration hubs, it...
The lateral cortex of the inferior colliculus (LCIC) forms a nexus between diverse multisensory, motor, and neuromodulatory streams. Like other integration hubs, it contains repeated neurochemical motifs with distinct inputs: GABA-rich modules are innervated by somatosensory structures, while auditory inputs to the LCIC target the surrounding extramodular matrix. To investigate potential mechanisms of convergence between these input streams, we used laser photostimulation circuit mapping to interrogate local LCIC circuits in adult mice of both sexes and found that input patterns are highly dependent on cell type (GABAergic/non-GABAergic) and location (module/matrix). At the circuit level, these inputs yield a directional flow of local information, primarily from the matrix to the modules. Further, the two compartments were found to project to distinct targets in the midbrain and thalamus. These data show that, while connectional modularity in the LCIC gives rise to segregated input-output channels, local circuits provide the architecture for integration between these two streams. Modularity is a widespread motif across the brain involving the segregation of structures into discrete subregions based on dichotomies in neurochemical expression or connectivity. The inferior colliculus is one such modular structure, containing auditory-recipient matrix regions and GABA-rich modules that are innervated by somatosensory inputs. While modularity suggests segregation of processing streams, here we show that local circuits in the inferior colliculus connect the module and matrix regions, providing an avenue for integration of information across compartments.
Topics: Animals; Auditory Pathways; Female; GABAergic Neurons; Inferior Colliculi; Male; Membrane Potentials; Mice, Transgenic; Neural Pathways; Neurons; Somatosensory Cortex
PubMed: 32665405
DOI: 10.1523/JNEUROSCI.0646-20.2020 -
The Journal of Comparative Neurology Mar 2017Descending projections from the thalamus and related structures to the midbrain are evolutionarily highly conserved. However, the basic organization of this auditory...
Descending projections from the thalamus and related structures to the midbrain are evolutionarily highly conserved. However, the basic organization of this auditory thalamotectal pathway has not yet been characterized. The purpose of this study was to obtain a better understanding of the anatomical and neurochemical features of this pathway. Analysis of the distributions of retrogradely labeled cells after focal injections of retrograde tracer into the inferior colliculus (IC) of the mouse revealed that most of the subcortical descending projections originated in the brachium of the IC and the paralaminar portions of the auditory thalamus. In addition, the vast majority of thalamotectal cells were found to be negative for the calcium-binding proteins calbindin, parvalbumin, or calretinin. Using two different strains of GAD-GFP mice, as well as immunostaining for GABA, we found that a subset of neurons in the brachium of the IC is GABAergic, suggesting that part of this descending pathway is inhibitory. Finally, dual retrograde injections into the IC and amygdala plus corpus striatum as well into the IC and auditory cortex did not reveal any double labeling. These data suggest that the thalamocollicular pathway comprises a unique population of thalamic neurons that do not contain typical calcium-binding proteins and do not project to other paralaminar thalamic forebrain targets, and that a previously undescribed descending GABAergic pathway emanates from the brachium of the IC. J. Comp. Neurol. 525:885-900, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Auditory Pathways; Female; Image Processing, Computer-Assisted; Inferior Colliculi; Male; Mice; Microscopy, Confocal; Neurons
PubMed: 27560718
DOI: 10.1002/cne.24106 -
Journal of Visualized Experiments : JoVE Feb 2020When investigating neural circuits, a standard limitation of the in vitro patch clamp approach is that axons from multiple sources are often intermixed, making it...
When investigating neural circuits, a standard limitation of the in vitro patch clamp approach is that axons from multiple sources are often intermixed, making it difficult to isolate inputs from individual sources with electrical stimulation. However, by using channelrhodopsin assisted circuit mapping (CRACM), this limitation can now be overcome. Here, we report a method to use CRACM to map ascending inputs from lower auditory brainstem nuclei and commissural inputs to an identified class of neurons in the inferior colliculus (IC), the midbrain nucleus of the auditory system. In the IC, local, commissural, ascending, and descending axons are heavily intertwined and therefore indistinguishable with electrical stimulation. By injecting a viral construct to drive expression of a channelrhodopsin in a presynaptic nucleus, followed by patch clamp recording to characterize the presence and physiology of channelrhodopsin-expressing synaptic inputs, projections from a specific source to a specific population of IC neurons can be mapped with cell type-specific accuracy. We show that this approach works with both Chronos, a blue light-activated channelrhodopsin, and ChrimsonR, a red-shifted channelrhodopsin. In contrast to previous reports from the forebrain, we find that ChrimsonR is robustly trafficked down the axons of dorsal cochlear nucleus principal neurons, indicating that ChrimsonR may be a useful tool for CRACM experiments in the brainstem. The protocol presented here includes detailed descriptions of the intracranial virus injection surgery, including stereotaxic coordinates for targeting injections to the dorsal cochlear nucleus and IC of mice, and how to combine whole cell patch clamp recording with channelrhodopsin activation to investigate long-range projections to IC neurons. Although this protocol is tailored to characterizing auditory inputs to the IC, it can be easily adapted to investigate other long-range projections in the auditory brainstem and beyond.
Topics: Animals; Axons; Brain Mapping; Channelrhodopsins; Color; Electric Stimulation; Electrophysiology; Gene Expression Regulation; Inferior Colliculi; Mice; Neurons; Patch-Clamp Techniques
PubMed: 32090997
DOI: 10.3791/60760 -
The Journal of Comparative Neurology Nov 2018In the multimodal lateral cortex of the inferior colliculus (LCIC), there are two neurochemically and connectionally distinct compartments, termed modular and...
In the multimodal lateral cortex of the inferior colliculus (LCIC), there are two neurochemically and connectionally distinct compartments, termed modular and extramodular zones. Modular fields span LCIC layer 2 and are recipients of somatosensory afferents, while encompassing extramodular domains receive auditory inputs. Recently, in developing mice, we identified several markers (among them glutamic acid decarboxylase, GAD) that consistently label the same modular set, and a reliable extramodular marker, calretinin, (CR). Previous reports from our lab show similar modular-extramodular patterns for certain Eph-ephrin guidance members, although their precise alignment with the developing LCIC neurochemical framework has yet to be addressed. Here we confirm in the nascent LCIC complementary GAD/CR-positive compartments, and characterize the registry of EphA4 and ephrin-B2 expression patterns with respect to its emerging modular-extramodular organization. Immunocytochemical approaches in GAD67-GFP knock-in mice reveal patchy EphA4 and ephrin-B2 domains that precisely align with GAD-positive LCIC modules, and are complementary to CR-defined extramodular zones. Such patterning was detectable neonatally, yielding discrete compartments prior to hearing onset. A dense plexus of EphA4-positive fibers filled modules, surrounding labeled ephrin-B2 and GAD cell populations. The majority of observed GABAergic neurons within modular boundaries were also positive for ephrin-B2. These results suggest an early compartmentalization of the LCIC that is likely instructed in part through Eph-ephrin guidance mechanisms. The overlap of developing LCIC neurochemical and guidance patterns is discussed in the context of its seemingly segregated multimodal input-output streams.
Topics: Animals; Auditory Pathways; Ephrin-B2; Female; Inferior Colliculi; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Neurons; Receptor, EphA4
PubMed: 30156295
DOI: 10.1002/cne.24525 -
Cerebral Cortex (New York, N.Y. : 1991) Mar 2013Psychophysical, clinical, and imaging evidence suggests that consonant and vowel sounds have distinct neural representations. This study tests the hypothesis that...
Psychophysical, clinical, and imaging evidence suggests that consonant and vowel sounds have distinct neural representations. This study tests the hypothesis that consonant and vowel sounds are represented on different timescales within the same population of neurons by comparing behavioral discrimination with neural discrimination based on activity recorded in rat inferior colliculus and primary auditory cortex. Performance on 9 vowel discrimination tasks was highly correlated with neural discrimination based on spike count and was not correlated when spike timing was preserved. In contrast, performance on 11 consonant discrimination tasks was highly correlated with neural discrimination when spike timing was preserved and not when spike timing was eliminated. These results suggest that in the early stages of auditory processing, spike count encodes vowel sounds and spike timing encodes consonant sounds. These distinct coding strategies likely contribute to the robust nature of speech sound representations and may help explain some aspects of developmental and acquired speech processing disorders.
Topics: Animals; Auditory Cortex; Auditory Perception; Brain Mapping; Discrimination, Psychological; Female; Inferior Colliculi; Neurons; Rats; Rats, Sprague-Dawley
PubMed: 22426334
DOI: 10.1093/cercor/bhs045 -
Medicine Feb 2015The inferior colliculus is a mesencephalic structure endowed with serotonergic fibers that plays an important role in the processing of acoustic information. The...
The inferior colliculus is a mesencephalic structure endowed with serotonergic fibers that plays an important role in the processing of acoustic information. The implication of the neuromodulator serotonin also in the aetiology of sudden unexplained fetal and infant death syndromes and the demonstration in these pathologies of developmental alterations of the superior olivary complex (SOC), a group of pontine nuclei likewise involved in hearing, prompted us to investigate whether the inferior colliculus may somehow contribute to the pathogenetic mechanism of unexplained perinatal death. Therefore, we performed in a wide set of fetuses and infants, aged from 33 gestational weeks to 7 postnatal months and died of both known and unknown cause, an in-depth anatomopathological analysis of the brainstem, particularly of the midbrain. Peculiar neuroanatomical and functional abnormalities of the inferior colliculus, such as hypoplasia/structural disarrangement and immunonegativity or poor positivity of serotonin, were exclusively found in sudden death victims, and not in controls. In addition, these alterations were frequently related to dysgenesis of connected structures, precisely the raphé nuclei and the superior olivary complex, and to nicotine absorption in pregnancy. We propose, on the basis of these results, the involvement of the inferior colliculus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities, and then in pathological conditions underlying a sudden death in vulnerable periods of the autonomic nervous system development, particularly associated to harmful risk factors as cigarette smoking.
Topics: Brain Stem; Female; Fetus; Humans; Immunohistochemistry; Infant, Newborn; Inferior Colliculi; Male; Pregnancy; Raphe Nuclei; Risk Factors; Serotonin; Smoking; Sudden Infant Death; Superior Olivary Complex
PubMed: 25674737
DOI: 10.1097/MD.0000000000000487 -
The Journal of Neuroscience : the... Sep 2017GABAergic neurons in the inferior colliculus (IC) play a critical role in auditory information processing, yet their responses to sound are unknown. Here, we used...
GABAergic neurons in the inferior colliculus (IC) play a critical role in auditory information processing, yet their responses to sound are unknown. Here, we used optogenetic methods to characterize the response properties of GABAergic and presumed glutamatergic neurons to sound in the IC. We found that responses to pure tones of both inhibitory and excitatory classes of neurons were similar in their thresholds, response latencies, rate-level functions, and frequency tuning, but GABAergic neurons may have higher spontaneous firing rates. In contrast to their responses to pure tones, the inhibitory and excitatory neurons differed in their ability to follow amplitude modulations. The responses of both cell classes were affected by their location regardless of the cell type, especially in terms of their frequency tuning. These results show that the synaptic domain, a unique organization of local neural circuits in the IC, may interact with all types of neurons to produce their ultimate response to sound. Although the inferior colliculus (IC) in the auditory midbrain is composed of different types of neurons, little is known about how these specific types of neurons respond to sound. Here, for the first time, we characterized the response properties of GABAergic and glutamatergic neurons in the IC. Both classes of neurons had diverse response properties to tones but were overall similar, except for the spontaneous activity and their ability to follow amplitude-modulated sound. Both classes of neurons may compose a basic local circuit that is replicated throughout the IC. Within each local circuit, the inputs to the local circuit may have a greater influence in determining the response properties to sound than the specific neuron types.
Topics: Animals; Evoked Potentials, Auditory; Female; GABAergic Neurons; Glutamic Acid; Inferior Colliculi; Male; Mice; Mice, Transgenic; Neurotransmitter Agents; Optogenetics; Pitch Perception; Synaptic Transmission
PubMed: 28842411
DOI: 10.1523/JNEUROSCI.0745-17.2017 -
The Journal of Physiology Sep 19941. The central auditory pathway linking the inferior colliculus (IC) and the medial geniculate body (MGB) of the thalamus consists of a segregated ventral lemniscal and...
1. The central auditory pathway linking the inferior colliculus (IC) and the medial geniculate body (MGB) of the thalamus consists of a segregated ventral lemniscal and dorsal non-lemniscal projection whose synaptic transmission mechanisms remain unknown. Extracellular and intracellular recordings combined with axonal tract tracing and cell staining were made from lemniscal and non-lemniscal divisions of adult rat MGB maintained acutely in in vitro explants containing parallel tectothalamic projections. 2. Biocytin deposition within the brachium of the IC revealed dense axonal fibres projecting to the MGB. Thin axonal terminals were found throughout the ventral (MGv) and dorsal (MGd) divisions of the MGB. Bushy cells with tufted or bitufted dendritic branches were primarily found in the MGv. In the MGd, cells were mainly seen as stellate neurones having a radiate dendritic arbor. 3. Electrical stimulation of the brachium of IC invariably elicits fast, excitatory synaptic potentials in both MGv and MGd cells. The evoked responses occurred monosynaptically and were exclusively mediated by glutamate acting on both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Non-lemniscal MGd neurones recorded extracellularly exhibited a strong tendency to discharge in bursts in response to brachium stimulation. In contrast, a large proportion of ventral lemniscal cells tended to discharge in single or dual spikes. Intracellularly, MGd cells, but not MGv cells, showed a predominant, slow synaptic potential mediated by NMDA receptors. 4. It is concluded that the central auditory circuitry linking the tectum and the thalamus is connected monosynaptically via glutamatergic synapses. Lemniscal and non-lemniscal thalamic neurones possess distinct response properties which cannot be accounted for by a differential transmitter system or polysynaptic delays as postulated previously.
Topics: Animals; Auditory Pathways; Electric Stimulation; Excitatory Amino Acid Antagonists; Geniculate Bodies; Glutamic Acid; In Vitro Techniques; Inferior Colliculi; Lysine; Male; Microscopy, Electron; Microscopy, Fluorescence; Rats; Receptors, N-Methyl-D-Aspartate; Synapses; Synaptic Transmission
PubMed: 7799222
DOI: 10.1113/jphysiol.1994.sp020290 -
The Journal of Neuroscience : the... May 2016Although bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs, bilateral CI users' sensitivity...
UNLABELLED
Although bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs, bilateral CI users' sensitivity to interaural time differences (ITDs) is still poorer than normal. In particular, ITD sensitivity of most CI users degrades with increasing stimulation rate and is lacking at the high carrier pulse rates used in CI processors to deliver speech information. To gain a better understanding of the neural basis for this degradation, we characterized ITD tuning of single neurons in the inferior colliculus (IC) for pulse train stimuli in an unanesthetized rabbit model of bilateral CIs. Approximately 73% of IC neurons showed significant ITD sensitivity in their overall firing rates. On average, ITD sensitivity was best for pulse rates near 80-160 pulses per second (pps) and degraded for both lower and higher pulse rates. The degradation in ITD sensitivity at low pulse rates was caused by strong, unsynchronized background activity that masked stimulus-driven responses in many neurons. Selecting synchronized responses by temporal windowing revealed ITD sensitivity in these neurons. With temporal windowing, both the fraction of ITD-sensitive neurons and the degree of ITD sensitivity decreased monotonically with increasing pulse rate. To compare neural ITD sensitivity to human performance in ITD discrimination, neural just-noticeable differences (JNDs) in ITD were computed using signal detection theory. Using temporal windowing at lower pulse rates, and overall firing rate at higher pulse rates, neural ITD JNDs were within the range of perceptual JNDs in human CI users over a wide range of pulse rates.
SIGNIFICANCE STATEMENT
Many profoundly deaf people wearing cochlear implants (CIs) still face challenges in everyday situations, such as understanding conversations in noise. Even with CIs in both ears, they have difficulty making full use of subtle differences in the sounds reaching the two ears [interaural time difference (ITD)] to identify where the sound is coming from. This problem is especially acute at the high stimulation rates used in clinical CI processors. This study provides a better understanding of ITD processing with bilateral CIs and shows a parallel between human performance in ITD discrimination and neural responses in the auditory midbrain. The present study is the first report on binaural properties of auditory neurons with CIs in unanesthetized animals.
Topics: Animals; Auditory Perception; Cochlear Implants; Consciousness; Evoked Potentials, Auditory; Female; Hearing; Inferior Colliculi; Neurons; Rabbits
PubMed: 27194332
DOI: 10.1523/JNEUROSCI.3795-15.2016