scholarly journals Different Serotonin Receptor Agonists Have Distinct Effects on Sound-Evoked Responses in Inferior Colliculus

2006 ◽  
Vol 96 (5) ◽  
pp. 2177-2188 ◽  
Author(s):  
Laura M. Hurley

The neuromodulator serotonin has a complex set of effects on the auditory responses of neurons within the inferior colliculus (IC), a midbrain auditory nucleus that integrates a wide range of inputs from auditory and nonauditory sources. To determine whether activation of different types of serotonin receptors is a source of the variability in serotonergic effects, four selective agonists of serotonin receptors in the serotonin (5-HT) 1 and 5-HT2 families were iontophoretically applied to IC neurons, which were monitored for changes in their responses to auditory stimuli. Different agonists had different effects on neural responses. The 5-HT1A agonist had mixed facilitatory and depressive effects, whereas 5-HT1B and 5-HT2C agonists were both largely facilitatory. Different agonists changed threshold and frequency tuning in ways that reflected their effects on spike count. When pairs of agonists were applied sequentially to the same neurons, selective agonists sometimes affected neurons in ways that were similar to serotonin, but not to other selective agonists tested. Different agonists also differentially affected groups of neurons classified by the shapes of their frequency-tuning curves, with serotonin and the 5-HT1 receptors affecting proportionally more non-V-type neurons relative to the other agonists tested. In all, evidence suggests that the diversity of serotonin receptor subtypes in the IC is likely to account for at least some of the variability of the effects of serotonin and that receptor subtypes fulfill specialized roles in auditory processing.

2005 ◽  
Vol 94 (2) ◽  
pp. 1143-1157 ◽  
Author(s):  
Sarah M. N. Woolley ◽  
John H. Casseday

The avian auditory midbrain nucleus, the mesencephalicus lateralis, dorsalis (MLd), is the first auditory processing stage in which multiple parallel inputs converge, and it provides the input to the auditory thalamus. We studied the responses of single MLd neurons to four types of modulated sounds: 1) white noise; 2) band-limited noise; 3) frequency modulated (FM) sweeps, and 4) sinusoidally amplitude-modulated tones (SAM) in adult male zebra finches. Responses were compared with the responses of the same neurons to pure tones in terms of temporal response patterns, thresholds, characteristic frequencies, frequency tuning bandwidths, tuning sharpness, and spike rate/intensity relationships. Most neurons responded well to noise. More than one-half of the neurons responded selectively to particular portions of the noise, suggesting that, unlike forebrain neurons, many MLd neurons can encode specific acoustic components of highly modulated sounds such as noise. Selectivity for FM sweep direction was found in only 13% of cells that responded to sweeps. Those cells also showed asymmetric tuning curves, suggesting that asymmetric inhibition plays a role in FM directional selectivity. Responses to SAM showed that MLd neurons code temporal modulation rates using both spike rate and synchronization. Nearly all cells showed low-pass or band-pass filtering properties for SAM. Best modulation frequencies matched the temporal modulations in zebra finch song. Results suggest that auditory midbrain neurons are well suited for encoding a wide range of complex sounds with a high degree of temporal accuracy rather than selectively responding to only some sounds.


1988 ◽  
Vol 60 (6) ◽  
pp. 1823-1840 ◽  
Author(s):  
C. E. Schreiner ◽  
G. Langner

1. The topographical distributions of single-unit and multiple-unit responses to amplitude-modulated tones--and to other relevant parameters of simple tonal stimuli--were defined across the main frequency representational gradient and within narrow frequency ranges represented in "frequency band laminae" in the principal midbrain auditory nucleus, the central nucleus of the inferior colliculus (ICC), in adult, barbiturate-anesthetized cats. 2. Responses to amplitude-modulated tones with the carrier set at the characteristic frequency (CF) of recorded neurons were obtained at many ICC locations in each experiment. The best modulation frequency (BMF) of neurons was defined at each site as that modulation frequency producing the highest neural discharge rate. Encountered BMFs ranged from approximately 10 to 1,000 Hz. A significant range of BMFs were recorded for neurons with any given characteristic frequency. BMF ranges varied as a systematic function of CF and of ICC recording depth. 3. Recorded BMFs were distributed topographically within functionally defined ICC frequency band laminae. Highest BMFs were found clustered in an ICC sector roughly between the middle and lateral third of its frequency band laminae. Progressively lower BMFs were recorded with increasing distance across the laminae in any direction away from the highest-BMF cluster. That is, "iso-BMF contours" were arrayed concentrically around the highest-BMF region. 4. Within frequency band laminae centered at approximately 3 and 12 kHz, quality factors (Q10 dBS) of frequency tuning curves were found to be between 0.8 and 8. Q10 dB values were distributed topographically within given frequency band laminae. Responses with narrow tuning curves (high Q10 dB values) were clustered in the middle third of the mediolateral extent of laminae; sharpness of tuning declined systematically away from this focus of highest Q10 dB values. The center of this distribution did not coincide with the center of the BMF distribution within the same lamina. 5. For neurons at greater than 90% of the ICC loci studied in these experiments, onset latencies to CF tones defined approximately 60 dB above response threshold fell within a range between 5 and 18 ms. Across a given frequency band lamina, onset latencies varied systematically, with longest response latencies recorded medially, and progressively shorter latencies recorded progressively more laterally. 6. Binaural interaction types were systematically distributed within frequency-band laminae. A cluster of excitatory-excitatory (EE) was seen, covering approximately one-third of the mapped area.(ABSTRACT TRUNCATED AT 400 WORDS)


1992 ◽  
Vol 68 (5) ◽  
pp. 1760-1774 ◽  
Author(s):  
L. Yang ◽  
G. D. Pollak ◽  
C. Resler

1. The influence of bicuculline on the tuning curves of 65 neurons in the inferior colliculus of the mustache bat was investigated. Single units were recorded with multibarrel electrodes where one barrel contained bicuculline, an antagonist specific for gamma-amino-butyric acid (GABA)A receptors. Fifty-nine tuning curves were recorded from units that were sharply tuned to 60 kHz, the dominant frequency of the bat's orientation call, but six tuning curves were also recorded from units tuned to lower frequencies and whose tuning curves were broader than the 60 kHz cells. Tuning curves were constructed from peristimulus time (PST) histograms obtained over a wide range of frequency-intensity combinations. Thus tuning curves, PST histograms evoked by frequencies within the tuning curve, and rate-level functions at the best frequency were obtained before iontophoresis of bicuculline and compared with the tuning curves and response properties obtained during the administration of bicuculline. 2. Three general types of tuning curves were obtained: 1) open tuning curves that broadened on both the high- and low-frequency sides with increasing sound level; 2) level-tolerant tuning curves in which the width of the tuning curve remained uniformly narrow with increasing sound level; and 3) upper-threshold tuning curves, which did not discharge to high-intensity tone bursts at the best frequency, thereby creating closed or folded tuning curves. 3. One major finding is that GABAergic inhibition plays an important role in sharpening frequency tuning properties of many neurons in the mustache bat inferior colliculus. In response to blocking GABAergic inputs with bicuculline, the tuning curves broadened in 42% of the neurons that were sharply tuned to 60 kHz. The degree of change in most units varied with sound level: tuning curves were least affected, or not affected at all, within 10 dB of threshold and showed progressively greater changes at higher sound levels. These effects were seen in units that had open, level-tolerant, and upper-threshold tuning curves. 4. A second key result is that bicuculline affected rate-level functions and/or temporal discharge patterns in many units. Bicuculline transformed the rate-level functions of 13 cells that originally had nonmonotonic rate level functions, from strongly nonmonotonic into weakly nonmonotonic or monotonic functions. It also changed the temporal discharge patterns in 22 cells, and the changes were often frequency specific.(ABSTRACT TRUNCATED AT 400 WORDS)


1991 ◽  
Vol 159 (S12) ◽  
pp. 7-14 ◽  
Author(s):  
P. J. Cowen

Serotonin (5-HT) interacts with multiple brain 5-HT receptor subtypes to influence a wide range of behaviours. Three main families of 5-HT receptors (5-HT1, 5-HT2 and 5-HT3) have been described which differ in their binding affinity for selective ligands, their receptor-effector coupling mechanisms, and the behavioural processes they regulate. Nevertheless, manipulation of several different 5-HT receptor subtypes (5-HT1A, 5-HT1c, 5-HT2 and 5-HT3) may produce anxiolytic effects; 5-HT1A and 5-HT2 receptors may be involved in the aetiology of major depression and the therapeutic effects of antidepressant treatment; and 5-HT3 receptors have been linked to reward mechanisms and cognitive processes. These advances offer therapeutic possibilities, the value of which can only be satisfactorily assessed by controlled clinical trials.


2014 ◽  
Vol 11 (1) ◽  
pp. 96-101 ◽  
Author(s):  
B Suvarna

Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer. DOI: http://dx.doi.org/10.3126/kumj.v11i1.11054 Kathmandu University Medical Journal Vol.11(1) 2013: 96-101


2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Laura Cristina Berumen ◽  
Angelina Rodríguez ◽  
Ricardo Miledi ◽  
Guadalupe García-Alcocer

Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.


2007 ◽  
Vol 98 (6) ◽  
pp. 3461-3472 ◽  
Author(s):  
Lars Holmstrom ◽  
Patrick D. Roberts ◽  
Christine V. Portfors

Neurons in the inferior colliculus (IC) of the mustached bat integrate input from multiple frequency bands in a complex fashion. These neurons are important for encoding the bat's echolocation and social vocalizations. The purpose of this study was to quantify the contribution of complex frequency interactions on the responses of IC neurons to social vocalizations. Neural responses to single tones, two-tone pairs, and social vocalizations were recorded in the IC of the mustached bat. Three types of data driven stimulus-response models were designed for each neuron from single tone and tone pair stimuli to predict the responses of individual neurons to social vocalizations. The first model was generated only using the neuron's primary frequency tuning curve, whereas the second model incorporated the entire hearing range of the animal. The extended model often predicted responses to many social vocalizations more accurately for multiply tuned neurons. One class of multiply tuned neuron that likely encodes echolocation information also responded to many of the social vocalizations, suggesting that some neurons in the mustached bat IC have dual functions. The third model included two-tone frequency tunings of the neurons. The responses to vocalizations were better predicted by the two-tone models when the neuron had inhibitory frequency tuning curves that were not near the neuron's primary tuning curve. Our results suggest that complex frequency interactions in the IC determine neural responses to social vocalizations and some neurons in IC have dual functions that encode both echolocation and social vocalization signals.


2005 ◽  
Vol 93 (1) ◽  
pp. 71-83 ◽  
Author(s):  
Jun Yan ◽  
Yunfeng Zhang ◽  
Günter Ehret

Plasticity of the auditory cortex can be induced by conditioning or focal cortical stimulation. The latter was used here to measure how stimulation in the tonotopy of the mouse primary auditory cortex influences frequency tuning in the midbrain central nucleus of the inferior colliculus (ICC). Shapes of collicular frequency tuning curves (FTCs) were quantified before and after cortical activation by measuring best frequencies, FTC bandwidths at various sound levels, level tolerance, Q-values, steepness of low- and high-frequency slopes, and asymmetries. We show here that all of these measures were significantly changed by focal cortical activation. The changes were dependent not only on the relationship of physiological properties between the stimulated cortical neurons and recorded collicular neurons but also on the tuning curve class of the collicular neuron. Cortical activation assimilated collicular FTC shapes; sharp and broad FTCs were changed to the shapes comparable to those of auditory nerve fibers. Plasticity in the ICC was organized in a center (excitatory)-surround (inhibitory) way with regard to the stimulated location (i.e., the frequency) of cortical tonotopy. This ensures, together with the spatial gradients of distribution of collicular FTC shapes, a sharp spectral filtering at the core of collicular frequency-band laminae and an increase in frequency selectivity at the periphery of the laminae. Mechanisms of FTC plasticity were suggested to comprise both corticofugal and local ICC components of excitatory and inhibitory modulation leading to a temporary change of the balance between excitation and inhibition in the ICC.


2020 ◽  
Author(s):  
Shawn M. Willett ◽  
Jennifer M. Groh

AbstractHow we distinguish multiple simultaneous stimuli is uncertain, particularly given that such stimuli sometimes recruit largely overlapping populations of neurons. One hypothesis is that tuning curves might change to limit the number of stimuli driving any given neuron when multiple stimuli are present. To test this hypothesis, we recorded the activity of neurons in the inferior colliculus while monkeys localized either one or two simultaneous sounds differing in frequency. Although monkeys easily distinguished simultaneous sounds (∼90% correct performance), the frequency tuning of inferior colliculus neurons on dual sound trials did not improve in any obvious way. Frequency selectivity was degraded on dual sound trials compared to single sound trials: tuning curves broadened, and frequency accounted for less of the variance in firing rate. These tuning curve changes led a maximum-likelihood decoder to perform worse on dual sound trials than on single sound trials. These results fail to support the hypothesis that changes in frequency response functions serve to reduce the overlap in the representation of simultaneous sounds. Instead these results suggest alternative theories, such as recent evidence of alternations in firing rate between the rates corresponding to each of the two stimuli, offer a more promising approach.


1996 ◽  
Vol 76 (2) ◽  
pp. 1059-1073 ◽  
Author(s):  
Z. M. Fuzessery ◽  
J. C. Hall

1. We examined the role of gamma-aminobutyric acid (GABA)-mediated inhibition in shaping excitatory tuning curves and creating selectivity for frequency-modulated (FM) sweeps in 29 neurons in the central nucleus of the inferior colliculus (ICC) of the pallid bat, with the use of single-unit recording coupled with the iontophoretic application of bicuculline methiodide (BIC), an antagonist of GABAA receptors. 2. BIC increased response magnitude 2 to 6 times over pretreatment levels in > 80% of neurons tested, and converted > 50% of nonmonotonic intensity-rate functions to monotonic or plateaued functions, demonstrating that GABAergic input normally limited response magnitude and inhibited responses at higher intensities. BIC typically had little effect on response thresholds, except in more specialized neurons that normally responded poorly to tones. In these cases, BIC disinhibited the neurons' responses to tones and lowered excitatory thresholds as much as 25 dB. 3. We examined the effects of BIC application on both excitatory and inhibitory tuning curves (measured with simultaneous 2-tone inhibition) to determine whether inhibitory curves were GABA mediated and whether removal of this inhibition was accompanied by an expansion of the excitatory curve. BIC had variable effects on the width of excitatory curves. In most cases, excitatory curves were at least slightly broadened, and expanded into regions previously occupied by inhibitory curves. In most cases, excitatory curves were at least slightly broadened, and expanded into regions previously occupied by inhibitory curves. However, in a few cases, inhibitory curves could be eliminated without an expansion of the excitatory curve. The greatest effect was seen in neurons with closed excitatory tuning curves; blocking GABAergic input caused the curves to open, allowing the neurons to respond at higher intensities. 4. Approximately 50% of the neurons in the ICC tuned to the spectrum of the bat's downward FM sweeping biosonar pulse respond preferentially to downward FM sweeps and not to upward sweeps, tones, or noise. In all neurons tested, BIC at least partially destroyed selectivity for sweep direction. This destruction could occur, however, without a loss of response exclusivity; in some cases, the neurons still did not respond to tones or noise. These results suggest that response selectivity for a species-specific signal is created by GABAergic input to ICC neurons. These results are used to suggest a mechanism that creates selectivity for FM sweep direction.


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