scholarly journals Serotonin Transporter Defect Disturbs Structure and Function of the Auditory Cortex in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Wenlu Pan ◽  
Jing Pan ◽  
Yan Zhao ◽  
Hongzheng Zhang ◽  
Jie Tang

Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.

2002 ◽  
Vol 87 (1) ◽  
pp. 305-321 ◽  
Author(s):  
Jos J. Eggermont

We present here a comparison between the local field potentials (LFP) and multiunit (MU) responses, comprising 401 single units, in primary auditory cortex (AI) of 31 cats to periodic click trains, gamma-tone and time-reversed gamma-tone trains, AM noise, AM tones, and frequency-modulated (FM) tones. In a large number of cases, the response to all six stimuli was obtained for the same neurons. We investigate whether cortical neurons are likely to respond to all types of repetitive transients and modulated stimuli and whether a dependence on modulating waveform, or tone or noise carrier, exists. In 97% of the recordings, a temporal modulation transfer function (tMTF) for MU activity was obtained for gamma-tone trains, in 92% for periodic click trains, in 83% for time-reversed gamma-tone trains, in 82% for AM noise, in 71% for FM tones, and only in 53% for AM tones. In 31% of the cases, the units responded to all six stimuli in an envelope-following way. These particular units had significantly larger onset responses to each stimulus compared with all other units. The overall response distribution shows the preference of AI units for stimuli with short rise times such as clicks and gamma tones. It also shows a clear asymmetry in the ability to respond to AM noise and AM tones and points to a strong effect of the frequency content of the carrier on the subcortical processing of AM stimuli. Yet all temporal response properties were independent of characteristic frequency and frequency-tuning curve bandwidth. We show that the observed differences in the tMTFs for different stimuli are to a large extent produced by the different degree of phase locking of the neuronal firings to the envelope of the first stimulus in the train or first modulation period. A normalization procedure, based on these synchronization differences, unified the tMTFs for all stimuli except clicks and allowed the identification of a largely stimulus-invariant, low-pass temporal filter function that most likely reflects the properties of synaptic depression and facilitation. For nonclick stimuli, the low-pass filter has a cutoff frequency of ∼10 Hz and a slope of ∼6 dB/octave. For nonclick stimuli, there was a systematic difference between the vector strength for LFPs and MU activity that can likely be attributed to postactivation suppression mechanisms.


Author(s):  
Joshua D Downer ◽  
James Bigelow ◽  
Melissa Runfeldt ◽  
Brian James Malone

Fluctuations in the amplitude envelope of complex sounds provide critical cues for hearing, particularly for speech and animal vocalizations. Responses to amplitude modulation (AM) in the ascending auditory pathway have chiefly been described for single neurons. How neural populations might collectively encode and represent information about AM remains poorly characterized, even in primary auditory cortex (A1). We modeled population responses to AM based on data recorded from A1 neurons in awake squirrel monkeys and evaluated how accurately single trial responses to modulation frequencies from 4 to 512 Hz could be decoded as functions of population size, composition, and correlation structure. We found that a population-based decoding model that simulated convergent, equally weighted inputs was highly accurate and remarkably robust to the inclusion of neurons that were individually poor decoders. By contrast, average rate codes based on convergence performed poorly; effective decoding using average rates was only possible when the responses of individual neurons were segregated, as in classical population decoding models using labeled lines. The relative effectiveness of dynamic rate coding in auditory cortex was explained by shared modulation phase preferences among cortical neurons, despite heterogeneity in rate-based modulation frequency tuning. Our results indicate significant population-based synchrony in primary auditory cortex and suggest that robust population coding of the sound envelope information present in animal vocalizations and speech can be reliably achieved even with indiscriminate pooling of cortical responses. These findings highlight the importance of firing rate dynamics in population-based sensory coding.


2006 ◽  
Vol 96 (6) ◽  
pp. 2972-2983 ◽  
Author(s):  
Gabriel Soto ◽  
Nancy Kopell ◽  
Kamal Sen

Two fundamental issues in auditory cortical processing are the relative importance of thalamocortical versus intracortical circuits in shaping response properties in primary auditory cortex (ACx), and how the effects of neuromodulators on these circuits affect dynamic changes in network and receptive field properties that enhance signal processing and adaptive behavior. To investigate these issues, we developed a computational model of layers III and IV (LIII/IV) of AI, constrained by anatomical and physiological data. We focus on how the local and global cortical architecture shape receptive fields (RFs) of cortical cells and on how different well-established cholinergic effects on the cortical network reshape frequency-tuning properties of cells in ACx. We identify key thalamocortical and intracortical circuits that strongly affect tuning curves of model cortical neurons and are also sensitive to cholinergic modulation. We then study how differential cholinergic modulation of network parameters change the tuning properties of our model cells and propose two different mechanisms: one intracortical (involving muscarinic receptors) and one thalamocortical (involving nicotinic receptors), which may be involved in rapid plasticity in ACx, as recently reported in a study by Fritz and coworkers.


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.


2000 ◽  
Vol 83 (4) ◽  
pp. 1856-1863 ◽  
Author(s):  
Syed A. Chowdhury ◽  
Nobuo Suga

In a search phase of echolocation, big brown bats, Eptesicus fuscus, emit biosonar pulses at a rate of 10/s and listen to echoes. When a short acoustic stimulus was repetitively delivered at this rate, the reorganization of the frequency map of the primary auditory cortex took place at and around the neurons tuned to the frequency of the acoustic stimulus. Such reorganization became larger when the acoustic stimulus was paired with electrical stimulation of the cortical neurons tuned to the frequency of the acoustic stimulus. This reorganization was mainly due to the decrease in the best frequencies of the neurons that had best frequencies slightly higher than those of the electrically stimulated cortical neurons or the frequency of the acoustic stimulus. Neurons with best frequencies slightly lower than those of the acoustically and/or electrically stimulated neurons slightly increased their best frequencies. These changes resulted in the over-representation of repetitively delivered acoustic stimulus. Because the over-representation resulted in under-representation of other frequencies, the changes increased the contrast of the neural representation of the acoustic stimulus. Best frequency shifts for over-representation were associated with sharpening of frequency-tuning curves of 25% of the neurons studied. Because of the increases in both the contrast of neural representation and the sharpness of tuning, the over-representation of the acoustic stimulus is accompanied with an improvement of analysis of the acoustic stimulus.


1995 ◽  
Vol 73 (5) ◽  
pp. 1876-1891 ◽  
Author(s):  
M. B. Calford ◽  
M. N. Semple

1. Several studies of auditory cortex have examined the competitive inhibition that can occur when appropriate sounds are presented to each ear. However, most cortical neurons also show both excitation and inhibition in response to presentation of stimuli at one ear alone. The extent of such inhibition has not been described. Forward masking, in which a variable masking stimulus was followed by a fixed probe stimulus (within the excitatory response area), was used to examine the extent of monaural inhibition for neurons in primary auditory cortex of anesthetized cats (barbiturate or barbiturate-ketamine). Both the masking and probe stimuli were 50-ms tone pips presented to the contralateral ear. Most cortical neurons showed significant forward masking at delays beyond which masking effects in the auditory nerve are relatively small compared with those seen in cortical neurons. Analysis was primarily concerned with such components. Standard rate-level functions were also obtained and were examined for nonmonotonicity, an indication of level-dependent monaural inhibition. 2. Consistent with previous reports, a wide range of frequency tuning properties (excitatory response area shapes) was found in cortical neurons. This was matched by a wide range of forward-masking-derived inhibitory response areas. At the most basic level of analysis, these were classified according to the presence of lateral inhibition, i.e., where a probe tone at a neuron's characteristic frequency was masked by tones outside the limits of the excitatory response area. Lateral inhibition was a property of 38% of the sampled neurons. Such neurons represented 77% of those with nonmonotonic rate-level functions, indicating a strong correlation between the two indexes of monaural inhibition; however, the shapes of forward masking inhibitory response areas did not usually correspond with those required to account for the "tuning" of a neuron. In addition, it was found that level-dependent inhibition was not added to by forward masking inhibition. 3. Analysis of the discharges to individual stimulus pair presentations, under conditions of partial masking, revealed that discharges to the probe occurred independently of discharges to the preceding masker. This indicates that even when the masker is within a neuron's excitatory response area, forward masking is not a postdischarge habituation phenomenon. However, for most neurons the degree of masking summed over multiple stimulus presentations appears determined by the same stimulus parameters that determine the probability of response to the masker.(ABSTRACT TRUNCATED AT 400 WORDS)


2000 ◽  
Vol 84 (3) ◽  
pp. 1453-1463 ◽  
Author(s):  
Jos J. Eggermont

Responses of single- and multi-units in primary auditory cortex were recorded for gap-in-noise stimuli for different durations of the leading noise burst. Both firing rate and inter-spike interval representations were evaluated. The minimum detectable gap decreased in exponential fashion with the duration of the leading burst to reach an asymptote for durations of 100 ms. Despite the fact that leading and trailing noise bursts had the same frequency content, the dependence on leading burst duration was correlated with psychophysical estimates of across frequency channel (different frequency content of leading and trailing burst) gap thresholds in humans. The duration of the leading burst plus that of the gap was represented in the all-order inter-spike interval histograms for cortical neurons. The recovery functions for cortical neurons could be modeled on basis of fast synaptic depression and after-hyperpolarization produced by the onset response to the leading noise burst. This suggests that the minimum gap representation in the firing pattern of neurons in primary auditory cortex, and minimum gap detection in behavioral tasks is largely determined by properties intrinsic to those, or potentially subcortical, cells.


1999 ◽  
Vol 82 (5) ◽  
pp. 2327-2345 ◽  
Author(s):  
Jagmeet S. Kanwal ◽  
Douglas C. Fitzpatrick ◽  
Nobuo Suga

Mustached bats, Pteronotus parnellii parnellii,emit echolocation pulses that consist of four harmonics with a fundamental consisting of a constant frequency (CF1-4) component followed by a short, frequency-modulated (FM1-4) component. During flight, the pulse fundamental frequency is systematically lowered by an amount proportional to the velocity of the bat relative to the background so that the Doppler-shifted echo CF2 is maintained within a narrowband centered at ∼61 kHz. In the primary auditory cortex, there is an expanded representation of 60.6- to 63.0-kHz frequencies in the “Doppler-shifted CF processing” (DSCF) area where neurons show sharp, level-tolerant frequency tuning. More than 80% of DSCF neurons are facilitated by specific frequency combinations of ∼25 kHz (BFlow) and ∼61 kHz (BFhigh). To examine the role of these neurons for fine frequency discrimination during echolocation, we measured the basic response parameters for facilitation to synthesized echolocation signals varied in frequency, intensity, and in their temporal structure. Excitatory response areas were determined by presenting single CF tones, facilitative curves were obtained by presenting paired CF tones. All neurons showing facilitation exhibit at least two facilitative response areas, one of broad spectral tuning to frequencies centered at BFlowcorresponding to a frequency in the lower half of the echolocation pulse FM1 sweep and another of sharp tuning to frequencies centered at BFhigh corresponding to the CF2 in the echo. Facilitative response areas for BFhigh are broadened by ∼0.38 kHz at both the best amplitude and 50 dB above threshold response and show lower thresholds compared with the single-tone excitatory BFhigh response areas. An increase in the sensitivity of DSCF neurons would lead to target detection from farther away and/or for smaller targets than previously estimated on the basis of single-tone responses to BFhigh. About 15% of DSCF neurons show oblique excitatory and facilitatory response areas at BFhigh so that the center frequency of the frequency-response function at any amplitude decreases with increasing stimulus amplitudes. DSCF neurons also have inhibitory response areas that either skirt or overlap both the excitatory and facilitatory response areas for BFhigh and sometimes for BFlow. Inhibition by a broad range of frequencies contributes to the observed sharpness of frequency tuning in these neurons. Recordings from orthogonal penetrations show that the best frequencies for facilitation as well as excitation do not change within a cortical column. There does not appear to be any systematic representation of facilitation ratios across the cortical surface of the DSCF area.


1993 ◽  
Vol 70 (5) ◽  
pp. 1988-2009 ◽  
Author(s):  
S. P. Dear ◽  
J. Fritz ◽  
T. Haresign ◽  
M. Ferragamo ◽  
J. A. Simmons

1. In Eptesicus the auditory cortex, as defined by electrical activity recorded from microelectrodes in response to tone bursts, FM sweeps, and combinations of FM sweeps, encompasses an average cortical surface area of 5.7 mm2. This area is large with respect to the total cortical surface area and reflects the importance of auditory processing to this species of bat. 2. The predominant pattern of organization in response to tone bursts observed in each cortex is tonotopic, with three discernible divisions revealed by our data. However, although cortical best-frequency (BF) maps from most of the individual bats are similar, no two maps are identical. The largest division contains an average of 84% of the auditory cortical surface area, with BF tonotopically mapped from high to low along the anteroposterior axis and is part of the primary auditory cortex. The medium division encompasses an average of 13% of the auditory cortical surface area, with highly variable BF organization across bats. The third region is the smallest, with an average of only 3% of auditory cortical surface area and is located at the anterolateral edge of the cortex. This region is marked by a reversal of the tonotopic axis and a restriction in the range of BFs as compared with the larger, tonotopically organized division. 3. A population of cortical neurons was found (n = 39) in which each neuron exhibited two BF threshold minima (BF1 and BF2) in response to tone bursts. These neurons thus have multipeaked frequency threshold tuning curves. In Eptesicus the majority of multipeaked frequency-tuned neurons (n = 27) have threshold minima at frequencies that correspond to a harmonic ratio of three-to-one. In contrast, the majority of multipeaked neurons in cats have threshold minima at frequencies in a ratio of three-to-two. A three-to-one harmonic ratio corresponds to the "spectral notches" produced by interference between overlapping echoes from multiple reflective surfaces in complex sonar targets. Behavioral experiments have demonstrated the ability of Eptesicus to use spectral interference notches for perceiving target shape, and this subpopulation of multipeaked frequency-tuned neurons may be involved in coding of spectral notches. 4. The auditory cortex contains delay-tuned neurons that encode target range (n = 99). Most delay-tuned neurons respond poorly to tones or individual FM sweeps and require combinations of FM sweeps. They are combination sensitive and delay tuned.(ABSTRACT TRUNCATED AT 400 WORDS)


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