Spontaneous firing patterns in the medial geniculate nucleus in a guinea pig model of tinnitus

Cook, Jennifer; Barry, Kristin; Zimdahl, Jack W; Leggett, Kerry; Mulders, Wilhelmina

doi:10.1016/j.heares.2021.108190

Cited by 7 publications

(12 citation statements)

References 44 publications

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“…However, the increased activity in the MGN following iTBS was unexpected: first, in view of the pathway outlined above and second, because an increase in firing rates in the auditory pathway is associated with the presence of tinnitus (Kalappa et al, 2014;Wu et al, 2016). Indeed, we have shown in our animal model that there is an increased tonic spontaneous firing in the MGN of animals with tinnitus compared to animals without tinnitus (Cook et al, 2021) and hence we expected reduced spontaneous firing rates in the MGN following both active protocols alongside the attenuation of tinnitus.…”

Section: Discussionmentioning

confidence: 61%

“…ECG was expressed by measurements of the interval between QRS complexes (ECG interval) which were continuously displayed during the experiment on an oscilloscope. In a previous experiment (Cook et al, 2021) we have demonstrated that spontaneous firing rates in MGN significantly decrease with ECG intervals > 300 ms. Therefore, recordings were only included and analyzed while the ECG intervals were under 300 ms. At the conclusion of the experiment, animals were euthanized via an injection of fixed dose of 0.3 ml Lethabarb (sodium pentobarbitone 325 mg/ml; Virbac, Milperra, Australia).…”

Section: Electrophysiological Recordings and Burst Firing Analysismentioning

confidence: 81%

“…The possibility exists that we recorded from different subdivisions in the MGN, however it is unlikely that there would be a consistent bias toward one subdivision in one group of animals and not in the other groups. It also seems unlikely that it is linked to the use of anesthesia, although our anesthesia protocol is likely to have resulted in lower overall spontaneous activity as we have discussed previously using our animal model (Cook et al, 2021).…”

Section: Discussionmentioning

confidence: 93%

“…In the present study, we implemented our guinea pig model of acoustic trauma (AT) and tinnitus (Mulders et al, 2014a(Mulders et al, , 2016 to investigate the effects of two excitatory rTMS protocols, 20 Hz and intermittent theta burst stimulation (iTBS) applied over PFC, and assessed neuronal firing patterns in MGN as well as behavioral signs of tinnitus. The MGN was selected as a target to measure neuronal activity as we have previously shown that it shows increased spontaneous firing rates in the presence of tinnitus (Cook et al, 2021) and electrical stimulation of PFC evokes changes in MGN neuronal firing patterns (Barry et al, 2017). Modeling of the rTMS coil was used to assess the extent and strength of the electric fields (E-fields) and to investigate whether the MGN could be directly activated.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

et al. 2021

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Tinnitus, a phantom auditory perception that can seriously affect quality of life, is generally triggered by cochlear trauma and associated with aberrant activity throughout the auditory pathways, often referred to as hyperactivity. Studies suggest that non-auditory structures, such as prefrontal cortex (PFC), may be involved in tinnitus generation, by affecting sensory gating in auditory thalamus, allowing hyperactivity to reach the cortex and lead to perception. Indeed, human studies have shown that repetitive transcranial magnetic stimulation (rTMS) of PFC can alleviate tinnitus. The current study investigated whether this therapeutic effect is achieved through inhibition of thalamic hyperactivity, comparing effects of two common clinical rTMS protocols with sham treatment, in a guinea pig tinnitus model. Animals underwent acoustic trauma and once tinnitus developed were treated with either intermittent theta burst stimulation (iTBS), 20 Hz rTMS, or sham rTMS (10 days, 10 min/day; weekdays only). Tinnitus was reassessed and extracellular recordings of spontaneous tonic and burst firing rates in auditory thalamus made. To verify effects in PFC, densities of neurons positive for calcium-binding proteins, calbindin and parvalbumin, were investigated using immunohistochemistry. Both rTMS protocols significantly reduced tinnitus compared to sham. However, spontaneous tonic firing decreased following 20 Hz stimulation and increased following iTBS in auditory thalamus. Burst rate was significantly different between 20 Hz and iTBS stimulation, and burst duration was increased only after 20 Hz treatment. Density of calbindin, but not parvalbumin positive neurons, was significantly increased in the most dorsal region of PFC indicating that rTMS directly affected PFC. Our results support the involvement of PFC in tinnitus modulation, and the therapeutic benefit of rTMS on PFC in treating tinnitus, but indicate this is not achieved solely by suppression of thalamic hyperactivity.

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Section: Discussionmentioning

confidence: 61%

Section: Electrophysiological Recordings and Burst Firing Analysismentioning

confidence: 81%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

et al. 2021

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“…A tungsten in a glass recording electrode was used to record single neuron activity in the MGN of the thalamus ( Merrill and Ainsworth, 1972 ). Entry into the right (contralateral to noise stimulus) MGN was verified by the presence of a robust cluster response to broadband noise stimulus (50 ms duration, 1 ms rise and fall times, sample rate of 96 kHz) ( Cook et al, 2021 ; Zimdahl et al, 2021 ). Electrophysiological recordings of single neuron activity were recorded in MGN in response to stimulation of the right (ipsilateral to MGN) PFC.…”

Section: Methodsmentioning

confidence: 99%

Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus

Vis

Barry

Mulders

2022

Front. Synaptic Neurosci.

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Sensory gating is the process whereby irrelevant sensory stimuli are inhibited on their way to higher cortical areas, allowing for focus on salient information. Sensory gating circuitry includes the thalamus as well as several cortical regions including the prefrontal cortex (PFC). Defective sensory gating has been implicated in a range of neurological disorders, including tinnitus, a phantom auditory perception strongly associated with cochlear trauma. Recently, we have shown in rats that functional connectivity between PFC and auditory thalamus, i.e., the medial geniculate nucleus (MGN), changes following cochlear trauma, showing an increased inhibitory effect from PFC activation on the spontaneous firing rate of MGN neurons. In this study, we further investigated this phenomenon using a guinea pig model, in order to demonstrate the validity of our finding beyond a single species and extend data to include data on sound evoked responses. Effects of PFC electrical stimulation on spontaneous and sound-evoked activity of single neurons in MGN were recorded in anaesthetised guinea pigs with normal hearing or hearing loss 2 weeks after acoustic trauma. No effect, inhibition and excitation were observed following PFC stimulation. The proportions of these effects were not different in animals with normal hearing and hearing loss but the magnitude of effect was. Indeed, hearing loss significantly increased the magnitude of inhibition for sound evoked responses, but not for spontaneous activity. The findings support previous observations that PFC can modulate MGN activity and that functional changes occur within this pathway after cochlear trauma. These data suggest hearing loss can alter sensory gating which may be a contributing factor toward tinnitus development.

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Acoustic trauma increases inhibitory effects of amygdala electrical stimulation on thalamic neurons in a rat model

Zimdahl,

Rodger,

Mulders

2023

Hearing Research

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Spontaneous firing patterns in the medial geniculate nucleus in a guinea pig model of tinnitus

Cited by 7 publications

References 44 publications

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus

Acoustic trauma increases inhibitory effects of amygdala electrical stimulation on thalamic neurons in a rat model

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