Ketamine: Acquisition and retention of classically conditioned responses during treatment with large doses

Ghoneim, Mohammed M.; Chen, Ping; El-Zahaby, H. M.; Block, Robert I.

doi:10.1016/0091-3057(94)90265-8

Cited by 10 publications

(6 citation statements)

References 25 publications

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“…These results add to the classical conditioning literature about the role of awareness in the acquisition of associative learning (Edeline and Neuenschwander-el Massioui 1988;Ghoneim et al 1994;Pang et al 1996;Weinberger et al 1984). For the first time, we report physiological response to a trace conditioning protocol under anesthesia.…”

Section: Discussionsupporting

confidence: 68%

“…However, less studied are some forms of learning, including motor learning and delay conditioning, that arise in nonawake states. Evidence suggests that the acquisition and maintenance of new associative memories may occur out of awareness, such as sleep (de Lavilléon et al 2015) or under deep anesthesia induced by a variety of agents [pentobarbital with epinephrine (Weinberger et al 1984), ketamine (Edeline and Neuenschwander-el Massioui 1988;Ghoneim et al 1994), and halothane (Pang et al 1996)]. Studying learning mechanisms under anesthesia, when sensory, movement-related, and other extraneous activity are weakened, might provide a robust methodological approach to further our understanding of learning and memory mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Hippocampal and lateral entorhinal cortex physiological activity during trace conditioning under urethane anesthesia

Oliveira

Dickson

Reyes

2020

Journal of Neurophysiology

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Significant evidence shows that the acquisition of delay conditioning can occur in out-of-awareness states, such as under anesthesia. However, it is unclear to what extent and what type of conditioning animals may achieve during non-awake states. Trace conditioning is an appealing protocol to study under anesthesia, given the long empty gap separating the conditioned and unconditioned stimuli, which must be bridged for acquisition to happen. Here, we show evidence that rats display physiological activity during the trace conditioning paradigm under anesthesia. We recorded the activity of the hippocampus (HPC) and lateral entorhinal cortex (LEC) in urethane-anesthetized rats, along with an electromyogram and the electrocardiogram. The protocol consisted of randomly presenting two distinct sound stimuli (CS- and CS+), where only one of them (CS+) was assigned to be trace-paired with a footshock. A trial-average analysis revealed that animals developed a significant climbing heart rate activity initiating at the CS onset and persisting during the trace period. Such climbing arose for both CS- and CS+ with similar slopes, but different intercepts, suggesting CS+ heart rates typically above CS-. The power and coherence of HPC and LEC high frequency bands (> 100 Hz) significantly increased during CS presentation and trace, similarly to both CS- and CS+ and insensitive to either activated or deactivated states. To the best of our knowledge, this is the first attempt to perform a trace conditioning protocol under anesthesia. Confirmation of this procedure acquisition can allow a new preparation for the exploration of brain mechanisms that bind time-discontinuous events.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Hippocampal and lateral entorhinal cortex physiological activity during trace conditioning under urethane anesthesia

Oliveira

Dickson

Reyes

2020

Journal of Neurophysiology

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“…The necessary microcircuit is located in the cerebellar hemispheres, lesions of which permanently prevent and abolish eyeblink conditioning 9 17 . Conditioned motor responses are not expressed under general anesthesia 18 (see also Supplementary Figs 1 and 2a ), and therefore the observed motor responses of the brain-chip hybrids would depend on deep brain stimulation controlled by the on-chip synthetic cerebellar circuit, rather than on biological compensation mechanisms or spared cerebellar function that would be expected in surgical or chemical lesion studies.…”

Section: Resultsmentioning

confidence: 99%

A neuro-inspired model-based closed-loop neuroprosthesis for the substitution of a cerebellar learning function in anesthetized rats

Hogri

Bamford

Taub

et al. 2015

Sci Rep

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Neuroprostheses could potentially recover functions lost due to neural damage. Typical neuroprostheses connect an intact brain with the external environment, thus replacing damaged sensory or motor pathways. Recently, closed-loop neuroprostheses, bidirectionally interfaced with the brain, have begun to emerge, offering an opportunity to substitute malfunctioning brain structures. In this proof-of-concept study, we demonstrate a neuro-inspired model-based approach to neuroprostheses. A VLSI chip was designed to implement essential cerebellar synaptic plasticity rules, and was interfaced with cerebellar input and output nuclei in real time, thus reproducing cerebellum-dependent learning in anesthetized rats. Such a model-based approach does not require prior system identification, allowing for de novo experience-based learning in the brain-chip hybrid, with potential clinical advantages and limitations when compared to existing parametric “black box” models.

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“…11e14 In contrast to studies that show decreased conditioning with ketamine, 62 other studies show successful acquisition of FeC under ketamine anaesthesia. 87,88 An enhanced response to the CS in the auditory thalamus and auditory cortex under ketamine anaesthesia could be retrieved in an alert state, while responses learned in awake animals could be retrieved under ketamine anaesthesia. 89e91 However, learning that occurred under ketamine anaesthesia could be detected only by indirect measures such as improved re-learning of the same task.…”

Section: Implicit Fear Memory Under General Anaesthesiamentioning

confidence: 99%

Implicit aversive memory under anaesthesia in animal models: a narrative review

Samuel

Taub

Paz

et al. 2018

British Journal of Anaesthesia

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Explicit memory after anaesthesia has gained considerable attention because of its negative implications, while implicit memory, which is more elusive and lacks patients' explicit recall, has received less attention and dedicated research. This is despite the likely impact of implicit memory on postoperative long-term well-being and behaviour. Given the scarcity of human data, fear conditioning in animals offers a reliable model of implicit learning, and importantly, one where we already have a good understanding of the underlying neural circuitry in awake conditions. Animal studies provide evidence that fear conditioning occurs under anaesthesia. The effects of different anaesthetics on memory are complex, with different drugs interacting at different stages of learning. Modulatory suppressive effects can be because of context, specific drugs, and dose dependency. In some cases, low doses of general anaesthetics can actually lead to a paradoxical opposite effect. The underlying mechanisms involve several neurotransmitter systems, acting mainly in the amygdala, hippocampus, and neocortex. Here, we review animal studies of aversive conditioning under anaesthesia, discuss the complex picture that arises, identify the gaps in knowledge that require further investigation, and highlight the potential translational relevance of the models.

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Ketamine: Acquisition and retention of classically conditioned responses during treatment with large doses

Cited by 10 publications

References 25 publications

Hippocampal and lateral entorhinal cortex physiological activity during trace conditioning under urethane anesthesia

Hippocampal and lateral entorhinal cortex physiological activity during trace conditioning under urethane anesthesia

A neuro-inspired model-based closed-loop neuroprosthesis for the substitution of a cerebellar learning function in anesthetized rats

Implicit aversive memory under anaesthesia in animal models: a narrative review

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