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Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats with chronic tinnitus: a direct determination using high resolution point-resolved proton magnetic resonance spectroscopy (H-MRS).

Brozoski T, Odintsov B, Bauer C - Front Syst Neurosci (2012)

Bottom Line: Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB.In the MGB Glu was increased ipsilaterally but decreased contralaterally.The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield IL, USA.

ABSTRACT
Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA), and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu). Because central processing systems are integrated and well-regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high resolution point-resolved proton magnetic resonance spectroscopy ((1)H-MRS) was used to quantify their levels in the dorsal cochlear nucleus (DCN), inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1) of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

No MeSH data available.


Related in: MedlinePlus

Examples of tinnitus in individual rats. (A) A rat with focal narrow-band tinnitus in the vicinity of 20 kHz, and (B) A rat with rather broad-band tinnitus localized between 10 and 24 kHz. Error bars show the standard error of the mean of the unexposed group. Relative rate of lever pressing, as indicated by the suppression ratio (see Text), is shown on the y-axis, and test stimulus across stimulus levels (dB, SPL) is shown on the x-axis.
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Figure 3: Examples of tinnitus in individual rats. (A) A rat with focal narrow-band tinnitus in the vicinity of 20 kHz, and (B) A rat with rather broad-band tinnitus localized between 10 and 24 kHz. Error bars show the standard error of the mean of the unexposed group. Relative rate of lever pressing, as indicated by the suppression ratio (see Text), is shown on the y-axis, and test stimulus across stimulus levels (dB, SPL) is shown on the x-axis.

Mentions: Significant tinnitus was evident in the exposed rats approximately four months after exposure. The protocol in the present experiment (exposure before psychophysical training and testing), reveals tinnitus as a downshift in discrimination functions. This happens because the sensory correlate of speaker-off periods, i.e., tinnitus in exposed animals, is the conditioned stimulus for response suppression. Therefore, stimuli resembling the speaker-off sensation suppress responding. Frequency-specific suppression was evident in both individual (Figure 3) as well as group data (Figure 4), between 16 and 24 kHz. Individual subjects showed some variation in the frequency range of their suppression, from rather narrow (Figure 3A) to broad (Figure 3B). This may reflect the tonality of their tinnitus. In addition, some individuals showed evidence of tinnitus plus hyperacusis. Nevertheless, all of the exposed rats showed some evidence of tinnitus.


Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats with chronic tinnitus: a direct determination using high resolution point-resolved proton magnetic resonance spectroscopy (H-MRS).

Brozoski T, Odintsov B, Bauer C - Front Syst Neurosci (2012)

Examples of tinnitus in individual rats. (A) A rat with focal narrow-band tinnitus in the vicinity of 20 kHz, and (B) A rat with rather broad-band tinnitus localized between 10 and 24 kHz. Error bars show the standard error of the mean of the unexposed group. Relative rate of lever pressing, as indicated by the suppression ratio (see Text), is shown on the y-axis, and test stimulus across stimulus levels (dB, SPL) is shown on the x-axis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285819&req=5

Figure 3: Examples of tinnitus in individual rats. (A) A rat with focal narrow-band tinnitus in the vicinity of 20 kHz, and (B) A rat with rather broad-band tinnitus localized between 10 and 24 kHz. Error bars show the standard error of the mean of the unexposed group. Relative rate of lever pressing, as indicated by the suppression ratio (see Text), is shown on the y-axis, and test stimulus across stimulus levels (dB, SPL) is shown on the x-axis.
Mentions: Significant tinnitus was evident in the exposed rats approximately four months after exposure. The protocol in the present experiment (exposure before psychophysical training and testing), reveals tinnitus as a downshift in discrimination functions. This happens because the sensory correlate of speaker-off periods, i.e., tinnitus in exposed animals, is the conditioned stimulus for response suppression. Therefore, stimuli resembling the speaker-off sensation suppress responding. Frequency-specific suppression was evident in both individual (Figure 3) as well as group data (Figure 4), between 16 and 24 kHz. Individual subjects showed some variation in the frequency range of their suppression, from rather narrow (Figure 3A) to broad (Figure 3B). This may reflect the tonality of their tinnitus. In addition, some individuals showed evidence of tinnitus plus hyperacusis. Nevertheless, all of the exposed rats showed some evidence of tinnitus.

Bottom Line: Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB.In the MGB Glu was increased ipsilaterally but decreased contralaterally.The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield IL, USA.

ABSTRACT
Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA), and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu). Because central processing systems are integrated and well-regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high resolution point-resolved proton magnetic resonance spectroscopy ((1)H-MRS) was used to quantify their levels in the dorsal cochlear nucleus (DCN), inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1) of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

No MeSH data available.


Related in: MedlinePlus