Multiple Sources of Cholinergic Input to the Superior Olivary Complex.
The superior olivary complex (SOC) serves as a major computation center in the brainstem auditory system. It participates in a variety of brainstem auditory circuits and is a hub for many ascending and descending auditory pathways. Among the many functions SOC serves in hearing, its roles in sound localization are well known (Harrison and Feldman, 1970; Grothe et al., 2010). Ascending auditory inputs to SOC emerge from the cochlear nucleus (CN; Cant and Casseday, 1986; Kuwabara et al., 1991; Thompson and Schofield, 2000). In turn, ascending projections from the SOC project primarily to nuclei of the lateral lemniscus and the inferior colliculus (IC), with smaller projections to the superior colliculus and auditory thalamus (Schofield et al., 2014; Mellott et al., 2018; Mansour et al., 2021). The SOC neurons that are responsible for computing the location of sound sources in the azimuth plane include medial superior olive (MSO) and lateral superior olive (LSO) neurons (Helfert and Aschoff, 1996). To ensure computational stability and accuracy, these neurons establish a complex and precise neural circuitry (Adams and Mugnaini, 1990; Schofield and Cant, 1991; Smith et al., 1998). In this network, the role of excitation and inhibition in shaping sound-evoked responses are well studied using simple acoustic stimuli (Brugge and Geisler, 1978; Albrecht et al., 2014; Grothe and Pecka, 2014). However, in response to more complex stimuli, the ability to maintain computational stability and accuracy may be challenged. Elevated input intensity or complicated input components causes synaptic depression, and weakened synapses affect the timing and strength of signal transmission among these SOC neurons (Banks and Smith, 1992; Grothe and Sanes, 1993; Song et al., 2005; Kopp-Scheinpflug et al., 2008). In addition to the known excitatory and inhibitory inputs, neuromodulatory mechanisms may be available to modify the SOC network dynamically for optimized performance. Numerous studies have suggested that SOC neurons employ local neuromodulation to regulate synaptic transmission to accommodate the complexity of acoustic inputs. In the MNTB, a number of ion channels and/or receptors are involved in regulating the signal transmission at its large and highly reliable synapse from the calyx of Held (Kopp-Scheinpflug et al., 2011). In the MSO, GABAB receptors modulate binaural synaptic inputs to ensure the precision of neural computation (Pecka et al., 2008; Hassfurth et al., 2010; Fischl et al., 2012). In the LSO, serotonergic modulation induces synaptic suppression of both excitatory and inhibitory inputs (Fitzgerald and Sanes, 1999).
The superior olivary complex (SOC) is a major computation center in the brainstem auditory system. Despite previous reports of high expression levels of cholinergic receptors in the SOC, few studies have addressed the functional role of acetylcholine in the region. The source of the cholinergic innervation is unknown for all but one of the nuclei of the SOC, limiting our understanding of cholinergic modulation. The medial nucleus of the trapezoid body, a key inhibitory link in monaural and binaural circuits, receives cholinergic input from other SOC nuclei and also from the pontomesencephalic tegmentum. Here, we investigate whether these same regions are sources of cholinergic input to other SOC nuclei. We also investigate whether individual cholinergic cells can send collateral projections bilaterally (i.e., into both SOCs), as has been shown at other levels of the subcortical auditory system. We injected retrograde tract tracers into the SOC in gerbils, then identified retrogradely-labeled cells that were also immunolabeled for choline acetyltransferase, a marker for cholinergic cells. We found that both the SOC and the pontomesencephalic tegmentum (PMT) send cholinergic projections into the SOC, and these projections appear to innervate all major SOC nuclei. We also observed a small cholinergic projection into the SOC from the lateral paragigantocellular nucleus of the reticular formation. These various sources likely serve different functions; e.g., the PMT has been associated with things such as arousal and sensory gating whereas the SOC may provide feedback more closely tuned to specific auditory stimuli. Further, individual cholinergic neurons in each of these regions can send branching projections into both SOCs. Such projections present an opportunity for cholinergic modulation to be coordinated across the auditory brainstem.
Beebe NL; Zhang C; Burger RM; Schofield BR
Frontiers in Neural Circuits
2021
2021-07-15
Journal Article
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Multiple Sources of Cholinergic Input to the Superior Olivary Complex.
acetylcholine; arousal; collateral; gerbil; hearing; modulation; plasticity; pontomesencephalic tegmentum
The superior olivary complex (SOC) is a major computation center in the brainstem auditory system. Despite previous reports of high expression levels of cholinergic receptors in the SOC, few studies have addressed the functional role of acetylcholine in the region. The source of the cholinergic innervation is unknown for all but one of the nuclei of the SOC, limiting our understanding of cholinergic modulation. The medial nucleus of the trapezoid body, a key inhibitory link in monaural and binaural circuits, receives cholinergic input from other SOC nuclei and also from the pontomesencephalic tegmentum. Here, we investigate whether these same regions are sources of cholinergic input to other SOC nuclei. We also investigate whether individual cholinergic cells can send collateral projections bilaterally (i.e., into both SOCs), as has been shown at other levels of the subcortical auditory system. We injected retrograde tract tracers into the SOC in gerbils, then identified retrogradely-labeled cells that were also immunolabeled for choline acetyltransferase, a marker for cholinergic cells. We found that both the SOC and the pontomesencephalic tegmentum (PMT) send cholinergic projections into the SOC, and these projections appear to innervate all major SOC nuclei. We also observed a small cholinergic projection into the SOC from the lateral paragigantocellular nucleus of the reticular formation. These various sources likely serve different functions; e.g., the PMT has been associated with things such as arousal and sensory gating whereas the SOC may provide feedback more closely tuned to specific auditory stimuli. Further, individual cholinergic neurons in each of these regions can send branching projections into both SOCs. Such projections present an opportunity for cholinergic modulation to be coordinated across the auditory brainstem. (Copyright © 2021 Beebe, Zhang, Burger and Schofield.)
Beebe NL; Zhang C; Burger RM; Schofield BR
Frontiers in Neural Circuits
2021
2021-07-15
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.3389/fncir.2021.715369" target="_blank" rel="noreferrer noopener">10.3389/fncir.2021.715369</a>
Cholinergic projections from the pedunculopontine tegmental nucleus contact excitatory and inhibitory neurons in the inferior colliculus
rat; acetylcholine; auditory; brain-stem; plasticity; cells; modulation; neuromodulation; pathways; midbrain; hearing; arousal; acetylcholine-receptors; auditory input; choline acetyltransferase; gabaergic neurons; viral tracing; volume transmission; viral tracing
The inferior colliculus processes nearly all ascending auditory information. Most collicular cells respond to sound, and for a majority of these cells, the responses can be modulated by acetylcholine (ACh). The cholinergic effects are varied and, for the most part, the underlying mechanisms are unknown. The major source of cholinergic input to the inferior colliculus is the pedunculopontine tegmental nucleus (PPT), part of the pontomesencephalic tegmentum known for projections to the thalamus and roles in arousal and the sleep-wake cycle. Characterization of PPT inputs to the inferior colliculus has been complicated by the mixed neurotransmitter population within the PPT. Using selective viral-tract tracing techniques in a ChAT-Cre Long Evans rat, the present study characterizes the distribution and targets of cholinergic projections from PPT to the inferior colliculus. Following the deposit of viral vector in one PPT, cholinergic axons studded with boutons were present bilaterally in the inferior colliculus, with the greater density of axons and boutons ipsilateral to the injection site. On both sides, cholinergic axons were present throughout the inferior colliculus, distributing boutons to the central nucleus, lateral cortex, and dorsal cortex. In each inferior colliculus (IC) subdivision, the cholinergic PPT axons appear to contact both GABAergic and glutamatergic neurons. These findings suggest cholinergic projections from the PPT have a widespread influence over the IC, likely affecting many aspects of midbrain auditory processing. Moreover, the effects are likely to be mediated by direct cholinergic actions on both excitatory and inhibitory circuits in the inferior colliculus.
Noftz WA; Beebe NL; Mellott JG; Schofield BR
Frontiers in Neural Circuits
2020
2020-07-16
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.3389/fncir.2020.00043" target="_blank" rel="noreferrer noopener">10.3389/fncir.2020.00043</a>
VISUAL DEPRIVATION DECREASES LONG-TERM POTENTIATION IN RAT VISUAL CORTICAL SLICES
cortex; rat; plasticity; depression; period; Neurosciences & Neurology; pathways; induction; long-term potentiation; organization; nmda receptors; evoked-potentials; visual cortex; critical; current source density; dark rearing; monocular deprivation; source density analysis
A major finding in the visual plasticity literature is that visual deprivation is effective only during an early 'sensitive' period, which is lengthened by dark rearing. Unresolved is whether the visual cortex is in a normally plastic state prior to light stimulation. This cannot be addressed using paradigms employing light exposure to assess plasticity. Several developmental studies have investigated a plastic phenomenon termed long-term potentiation (LTP) in slices from cat (J. Neurophysiol., 59 (1988) 124-141) and rat (Brain Res., 439 (1988) 222-229) visual cortex. Susceptibility to the induction of LTP parallels the period of sensitivity to visual deprivation. This suggests that slices can be used to assay visual cortical plasticity, avoiding light exposure. In the present study, field potentials were recorded from slices of the primary visual cortices of dark-reared (DR) and control (CONT) Long Evans hooded rats (17 to 21 days). Field potential profiles recorded before and 90 min following tetanic electrical stimulation were subjected to current source density analysis, yielding extracellular current sink amplitudes. Tetanus resulted in LTP in both CONT and DR slices, but DR slices were significantly less potentiated. These results indicate that the primary visual cortex of DR animals is not fully plastic, indicating a role for light stimulation in inducing visual cortical plasticity.
Berry R L; Perkins A T; Teyler T J
Brain Research
1993
1993-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0006-8993(93)90943-h" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(93)90943-h</a>
Differences in kinematic plasticity between freshwater turtle species underlie differences in swimming performance in response to varying flow conditions.
ANIMAL swimming; behavioural plasticity; Biomechanics; HYDRAULICS; locomotion; LOGGERHEAD turtle; plasticity; reptile; SPECIES; TETRAPODS; TURTLES
The distribution and performance of aquatic vertebrates can be linked strongly to their ability to perform in variable conditions of flowing water. Performance in these variable conditions can be affected by both morphology and behaviour, and animals that experience more variable environments often show greater behavioural plasticity that improves performance in those environments. One common metric of performance is swimming stability, which can constitute a majority of the daily energy budget of swimming animals. We compared the body oscillations arising from recoil forces of the limbs of two species of freshwater turtles as they swam in different flow conditions: the lentic specialist Emydura subglobosa and the habitat generalist Chrysemys picta. We found that E. subglobosa experienced more limited oscillations in still water than C. picta , but that C. picta had a greater kinematic response to increased flow speed that might contribute to their improved performance in flowing water. These results provide insight into how secondarily aquatic tetrapods respond to the functional demands of variation in flow, helping to build understanding of the relationship between energetics, kinematics and performance of such lineages in different environments. [ABSTRACT FROM AUTHOR]
Mayerl Christopher J; Hicks Kirsten E; Blob Richard W
Biological Journal of the Linnean Society
2019
2019-08
<a href="http://doi.org/10.1093/biolinnean/blz051" target="_blank" rel="noreferrer noopener">10.1093/biolinnean/blz051</a>
Perineuronal nets and GABAergic cells in the inferior colliculus of guinea pigs.
GABA; auditory; plasticity; extracellular matrix; inhibition; midbrain
Perineuronal nets (PNs) are aggregates of extracellular matrix that have been associated with neuronal plasticity, critical periods, fast-spiking cells and protection from oxidative stress. Although PNs have been reported in the auditory system in several species, there is disagreement about the distribution of PNs within the inferior colliculus (IC), an important auditory hub in the midbrain. Furthermore, PNs in many brain areas are preferentially associated with GABAergic cells, but whether such an association exists in the IC has not been addressed. We used Wisteria floribunda agglutinin staining and immunohistochemistry in guinea pigs to examine PNs within the IC. PNs are present in all IC subdivisions and are densest in the central portions of the IC. Throughout the IC, PNs are preferentially associated with GABAergic cells. Not all GABAergic cells are surrounded by PNs, so the presence of PNs can be used to subdivide IC GABAergic cells into "netted" and "non-netted" categories. Finally, PNs in the IC, like those in other brain areas, display molecular heterogeneity that suggests a multitude of functions.
Foster Nichole L; Mellott Jeffrey G; Schofield Brett R
Frontiers in neuroanatomy
2014
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3389/fnana.2013.00053" target="_blank" rel="noreferrer noopener">10.3389/fnana.2013.00053</a>
Extracellular Molecular Markers and Soma Size of Inhibitory Neurons: Evidence for Four Subtypes of GABAergic Cells in the Inferior Colliculus.
Female; GABA; Male; Animals; auditory; Guinea Pigs; plasticity; Auditory Pathways/cytology/*physiology; Biomarkers; Cell Size; Extracellular Space/*physiology; gamma-Aminobutyric Acid/*physiology; Glutamate Decarboxylase/metabolism; Inferior Colliculi/cytology/*physiology; inhibition; Neuronal Plasticity/physiology; Neurons/*physiology/ultrastructure; perineuronal net; Vesicular Glutamate Transport Protein 2/metabolism; VGLUT2
UNLABELLED: Inhibition plays an important role in shaping responses to stimuli throughout the CNS, including in the inferior colliculus (IC), a major hub in both ascending and descending auditory pathways. Subdividing GABAergic cells has furthered the understanding of inhibition in many brain areas, most notably in the cerebral cortex. Here, we seek the same understanding of subcortical inhibitory cell types by combining staining for two types of extracellular markers–perineuronal nets (PNs) and perisomatic rings of terminals expressing vesicular glutamate transporter 2 (VGLUT2)–to subdivide IC GABAergic cells in adult guinea pigs. We found four distinct groups of GABAergic cells in the IC: (1) those with both a PN and a VGLUT2 ring; (2) those with only a PN; (3) those with only a VGLUT2 ring; and (4) those with neither marker. In addition, these four GABAergic subtypes differ in their soma size and distribution among IC subdivisions. Functionally, the presence or absence of VGLUT2 rings indicates differences in inputs, whereas the presence or absence of PNs indicates different potential for plasticity and temporal processing. We conclude that these markers distinguish four GABAergic subtypes that almost certainly serve different roles in the processing of auditory stimuli within the IC. SIGNIFICANCE STATEMENT: GABAergic inhibition plays a critical role throughout the brain. Identification of subclasses of GABAergic cells (up to 15 in the cerebral cortex) has furthered the understanding of GABAergic roles in circuit modulation. Inhibition is also prominent in the inferior colliculus, a subcortical hub in auditory pathways. Here, we use two extracellular markers to identify four distinct groups of GABAergic cells. Perineuronal nets and perisomatic rings of glutamatergic boutons are present in many subcortical areas and often are associated with inhibitory cells, but they have rarely been used to identify inhibitory subtypes. Our results further the understanding of inhibition in the inferior colliculus and suggest that these extracellular molecular markers may provide a key to distinguishing inhibitory subtypes in many subcortical areas.
Beebe Nichole L; Young Jesse W; Mellott Jeffrey G; Schofield Brett R
The Journal of neuroscience : the official journal of the Society for Neuroscience
2016
2016-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1523/JNEUROSCI.0217-16.2016" target="_blank" rel="noreferrer noopener">10.1523/JNEUROSCI.0217-16.2016</a>
Perineuronal nets in subcortical auditory nuclei of four rodent species with differing hearing ranges.
guinea pig; inferior colliculus; mouse; naked mole-rat; plasticity; rat; RRID: AB141637; RRID: AB1500687; RRID: AB2336066; RRID: AB2336874; RRID: AB2336881; RRID: AB90460; superior olive; thalamus
Perineuronal nets (PNs) are aggregates of extracellular matrix molecules that surround some neurons in the brain. While PNs occur widely across many cortical areas, subcortical PNs are especially associated with motor and auditory systems. The auditory system has recently been suggested as an ideal model system for studying PNs and their functions. However, descriptions of PNs in subcortical auditory areas vary, and it is unclear whether the variation reflects species differences or differences in staining techniques. Here, we used two staining techniques (one lectin stain and one antibody stain) to examine PN distribution in the subcortical auditory system of four different species: guinea pigs (Cavia porcellus), mice (Mus musculus, CBA/CaJ strain), Long-Evans rats (Rattus norvegicus), and naked mole-rats (Heterocephalus glaber). We found that some auditory nuclei exhibit dramatic differences in PN distribution among species while other nuclei have consistent PN distributions. We also found that PNs exhibit molecular heterogeneity, and can stain with either marker individually or with both. PNs within a given nucleus can be heterogeneous or homogenous in their staining patterns. We compared PN staining across the frequency axes of tonotopically organized nuclei and among species with different hearing ranges. PNs were distributed non-uniformly across some nuclei, but only rarely did this appear related to the tonotopic axis. PNs were prominent in all four species; we found no systematic relationship between the hearing range and the number, staining patterns or distribution of PNs in the auditory nuclei.
Beebe Nichole L; Schofield Brett R
The Journal of comparative neurology
2018
2018-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/cne.24383" target="_blank" rel="noreferrer noopener">10.1002/cne.24383</a>