Increased pyramidal and VIP neuronal excitability in rat primary auditory cortex directly correlates with tinnitus behaviour

Ghimire, Madan; Cai, Rui; Ling, Lynne; Brownell, Kevin A; Hackett, Troy A.; Llano, Daniel A.; Caspary, Donald M.

doi:10.1113/jp284675

Cited by 5 publications

(2 citation statements)

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“…Ghimere et al ( 2023), provided the physiology/ pathology basis for the present study, included recordings from ENT rats (Ghimire et al, 2023). ENT animals were not included in the present study since for the tinnitus-related functional changes tested in the present study, ENT A1 neurons' PN group data from Ghimire et al (2023) found no statistical differences in physiological characteristics between ENT and control animals. A total of 24 Control and 18 tinnitus animals were used for in vitro studies as detailed in Table 1.…”

Section: Resultsmentioning

confidence: 86%

“…Exposed animals that showed control-like psychophysical behavior, with near control ability to distinguish silence from tone, were categorized as ENT ( Figsures 2B,C ) ( F (1, 75) = 2.6, p = 0.11, Two-way ANOVA, followed by a Bonferroni post-hoc test). Ghimere et al (2023), provided the physiology/pathology basis for the present study, included recordings from ENT rats ( Ghimire et al, 2023 ). ENT animals were not included in the present study since for the tinnitus-related functional changes tested in the present study, ENT A1 neurons’ PN group data from Ghimire et al (2023) found no statistical differences in physiological characteristics between ENT and control animals.…”

Section: Resultsmentioning

confidence: 99%

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Desensitizing nicotinic agents normalize tinnitus-related inhibitory dysfunction in the auditory cortex and ameliorate behavioral evidence of tinnitus

et al. 2023

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Tinnitus impacts between 10–20% of the population. Individuals most troubled by their tinnitus have their attention bound to and are distracted by, their tinnitus percept. While numerous treatments to ameliorate tinnitus have been tried, no therapeutic approach has been clinically accepted. The present study used an established condition-suppression noise-exposure rat model of tinnitus to: (1) examine tinnitus-related changes in nAChR function of layer 5 pyramidal (PNs) and of vasoactive intestinal peptide (VIP) neurons in primary auditory cortex (A1) and (2) examine how the partial desensitizing nAChR agonists, sazetidine-A and varenicline, can act as potential therapeutic agents in the treatment of tinnitus. We posited that tinnitus-related changes in layer 5 nAChR responses may underpin the decline in attentional resources previously observed in this animal model (Brozoski et al., 2019). In vitro whole-cell patch-clamp studies previously revealed a significant tinnitus-related loss in nAChR-evoked excitatory postsynaptic currents from A1 layer 5 PNs. In contrast, VIP neurons from animals with behavioral evidence of tinnitus showed significantly increased nAChR-evoked excitability. Here we hypothesize that sazetidine-A and varenicline have therapeutic benefits for subjects who cannot divert their attention away from the phantom sound in their heads. We found that sazetidine-A or varenicline normalized tinnitus-related reductions in GABAergic input currents onto A1 layer 5 PNs. We then tested sazetidine-A and varenicline for the management of tinnitus using our tinnitus animal model. Subcutaneous injection of sazetidine-A or varenicline, 1 h prior to tinnitus testing, significantly decreased the rat’s behavioral evidence of tinnitus in a dose-dependent manner. Collectively, these results support the need for additional clinical investigations of partial desensitizing nAChR agonists sazetidine-A and varenicline for the treatment of tinnitus.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%