Dopaminergic neuromodulation of high gamma stimulus phase‐locking in gerbil primary auditory cortex mediated by D1/D5‐receptors

Deliano, Matthias; Brunk, Michael G. K.; Tabbal, Mohamed El; Zempeltzi, Marina M.; Happel, Max F. K.; Ohl, Frank W.

doi:10.1111/ejn.13898

Cited by 21 publications

(22 citation statements)

References 42 publications

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“…The CSD thus provides a functional readout of the cortical microcircuitry function, encompassing a wider, mesoscopic field of view than for instance single-or multiunit approaches 55 . Early current sinks in the auditory cortex are, therefore, indicative of thalamic input in granular layers III/IV and infragranular layers Vb/VI 21,[56][57][58][59] . In order to describe the overall columnar processing, the CSD profiles were transformed by averaging the rectified waveforms of each channel:…”

Section: Methodsmentioning

confidence: 99%

Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits

et al. 2020

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The primary auditory cortex (A1) is an essential, integrative node that encodes the behavioral relevance of acoustic stimuli, predictions, and auditory-guided decision-making. However, the realization of this integration with respect to the cortical microcircuitry is not well understood. Here, we characterize layer-specific, spatiotemporal synaptic population activity with chronic, laminar current source density analysis in Mongolian gerbils (Meriones unguiculatus) trained in an auditory decision-making Go/NoGo shuttle-box task. We demonstrate that not only sensory but also task-and choice-related information is represented in the mesoscopic neuronal population code of A1. Based on generalized linear-mixed effect models we found a layer-specific and multiplexed representation of the task rule, action selection, and the animal's behavioral options as accumulating evidence in preparation of correct choices. The findings expand our understanding of how individual layers contribute to the integrative circuit in the sensory cortex in order to code task-relevant information and guide sensorybased decision-making.

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Section: Methodsmentioning

confidence: 99%

Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits

et al. 2020

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“…The surgical procedure for electrophysiological recording has been previously described in detail (Deliano et al 2020). Briefly, ketamine-xylazine was administered as described above -before and throughout the surgery and experiment.…”

Section: Acute Recordings and Pharmacological Silencing Of The Auditomentioning

confidence: 99%

Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

Deane

Brunk

Curran

et al. 2020

The Journal of Physiology

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Ketamine is a common anaesthetic agent used in research and more recently as medication in treatment of depression. It has known effects on inhibition of interneurons and cortical stimulus-locked responses, but the underlying functional network mechanisms are still elusive. r Analysing population activity across all layers within the auditory cortex, we found that doses of this anaesthetic induce a stronger activation and stimulus-locked response to pure-tone stimuli. r This cortical response is driven by gain enhancement of thalamocortical input processing selectively within granular layers due to an increased recurrent excitation. r Time-frequency analysis indicates a higher broadband magnitude response and prolonged phase coherence in granular layers, possibly pointing to disinhibition of this recurrent excitation. r These results further the understanding of ketamine's functional mechanisms, which will improve the ability to interpret physiological studies moving from anaesthetized to awake paradigms and may lead to the development of better ketamine-based depression treatments with lower side effects.

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“…Acute recordings and pharmacological silencing of the auditory cortex. The surgical procedure for electrophysiological recording has been previously described in detail (Deliano et al, 2018). Briefly, ketamine/xylazine was administered during surgery and throughout the experiment to maintain a steady anesthesia level.…”

Section: Methodsmentioning

confidence: 99%

Ketamine anesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

Deane

Brunk

Curran

et al. 2019

Preprint

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The N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, is commonly used as an anesthetic agent and has more recently gained attention as an antidepressant. Ketamine has been linked to increased stimulus-locked excitability, inhibition of interneurons, and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anesthetic network effects may improve upon previous interpretations of seminal studies conducted under anesthesia and have widespread relevance for neuroscience with awake and anesthetized subjects as well as in medicine. Here, we investigated the effects of anesthetic doses of ketamine (15mg kg−1/h i.p.) on the network activity after pure tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This effect on early thalamocortical input processing was not due to changes in cross-trial phase coherence. Rather, the layer-dependent gain enhancement under ketamine was attributed to a broadband increase in amplitude reflecting an increase in recurrent excitation. The time-frequency analysis is further indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits—in line with the common hypothesis of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons.Statement of significanceKetamine is a common anesthetic agent and is known to alter excitability and neuronal synchronicity in the cortex. We reveal here that anesthetic doses of ketamine increase recurrent excitation of thalamic input in the granular layers of the auditory cortex of Mongolian gerbils. This leads to a layer-specific gain enhancement of the time-locked response to external stimuli. Analysis of tone-evoked amplitudes and cross-trial variability of cortical current sources and sinks indicate a mechanism of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons. Our findings might help to understand the functional mechanisms of the clinical effects of ketamine promoting the development of new therapeutic agents with lower side effects.

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Dopaminergic neuromodulation of high gamma stimulus phase‐locking in gerbil primary auditory cortex mediated by D1/D5‐receptors

Cited by 21 publications

References 42 publications

Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits

Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits

Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

Ketamine anesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

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