Anesthesia suppresses nonsynchronous responses to repetitive broadband stimuli

University of Oklahoma, 865 Asp Avenue, Felgar Hall 210, Norman, OK 73019, USA.
Neuroscience (Impact Factor: 3.36). 04/2007; 145(1):357-69. DOI: 10.1016/j.neuroscience.2006.11.043
Source: PubMed


Although many aspects of sensory processing are qualitatively similar in awake and anesthetized subjects, important state-dependent differences are known to exist. To investigate the effects of anesthesia on temporal processing in rat auditory cortex, multi-unit neural responses to trains of broadband clicks were recorded prior to, 15 min following, and 5 h following the administration of a ketamine-based anesthetic. While responses to clicks in isolation were relatively stable between states, responses to subsequent clicks exhibited increases in latency, peak latency, response duration, and post-onset suppression under anesthesia. Ketamine anesthetic reduced the maximum rate at which multi-unit clusters entrained to repeated clicks. No multi-unit clusters entrained to stimulus presentation rates greater than 33 Hz under anesthesia, compared with 85% and 81% in the pre- and post-anesthetic condition, respectively. Anesthesia also induced oscillatory activity that was not present in awake subjects. Finally, ketamine anesthesia abolished all tonic excitatory and suppressive nonsynchronous responses to click trains. The results of this study suggest that ketamine-based anesthesia significantly alters neural coding of broadband click trains in auditory cortex.

Download full-text


Available from: Sara E Anderson, Jan 13, 2014
  • Source
    • "Apart from its amplitude effects, ketamine robustly suppressed and delayed the latency of ERPs, especially at the first time point (~10 min post-injection), suggesting a relative slowing of signal processing and delay in peak synchrony of the neural oscillators generating the ERP response. Ketamine-induced slowing of ERPs has been reported both in clinical (30, 83) as well as in experimental subjects previously (56, 84, 85). Apart from its effects on N1 amplitude and latency, Ketamine impacted other ERP components as well. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia patients exhibit a decreased ability to detect change in their auditory environ-ment as measured by auditory event-related potentials (ERP) such as mismatch negativity. This deficit has been linked to abnormal NMDA neurotransmission since, among other observations, non-selective channel blockers of NMDA reliably diminish automatic deviance detection in human subjects as well as in animal models. Recent molecular and functional evidence links NR2B receptor subtype to aberrant NMDA transmission in schizophrenia. However, it is unknown if NR2B receptors participate in pre-attentive deviance detec-tion. We recorded ERP from the vertex of freely behaving rats in response to frequency mismatch protocols. We saw a robust increase in N1 response to deviants compared to standard as well as control stimuli indicating true deviance detection. Moreover, the increased negativity was highly sensitive to deviant probability. Next, we tested the effect of a non-selective NMDA channel blocker (ketamine, 30 mg/kg) and a highly selective NR2B antagonist, CP-101,606 (10 or 30 mg/kg) on deviance detection. Ketamine attenu-ated deviance mainly by increasing the amplitude of the standard ERP. Amplitude and/or latency of several ERP components were also markedly affected. In contrast, CP-101,606 robustly and dose-dependently inhibited the deviant's N1 amplitude, and as a consequence, completely abolished deviance detection. No other ERPs or components were affected. Thus, we report first evidence that NR2B receptors robustly participate in processes of automatic deviance detection in a rodent model. Lastly, our model demonstrates a path forward to test specific pharmacological hypotheses using translational endpoints relevant to aberrant sensory processing in schizophrenia.
    Frontiers in Psychiatry 08/2014; 5. DOI:10.3389/fpsyt.2014.00096
  • Source
    • "The difference in the persistence of adaptation in the results of Eggermont (2000) and our results may be due to the fact that Eggermont (2000) used anesthesia. Anesthesia would be expected to diminish or even abolish the ongoing response to the adapter (e.g., Cheung et al. 2001; Rennaker et al. 2007), allowing synapses to recover from depression and abolishing sAHP (Schwindt 1988a). Anesthesia may also be expected to affect the processes involved in the reuptake of neurotransmitter after its release into the synaptic cleft and thus shorten the recovery from synaptic depression (Richards 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study investigates the temporal properties of adaptation in the late auditory-evoked potentials in humans. The results are used to make inferences about the mechanisms of adaptation in human auditory cortex. The first experiment measured adaptation by single adapters as a combined function of the adapter duration and the stimulus onset asynchrony (SOA) and inter-stimulus interval (ISI) between the adapter and the adapted sound ("probe"). The results showed recovery from adaptation with increasing ISI, as would be expected, but build up of adaptation with increasing adapter duration, and thus SOA. This suggests that adaptation in auditory cortex is caused by the ongoing, rather than the onset, response to the adapter. Quantitative modeling indicated that the rate of build-up of adaptation is almost an order of magnitude faster than the recovery rate of adaptation. The recovery rate suggests that cortical adaptation is caused by synaptic depression and slow afterhyperpolarization. The P2 was more strongly affected by adaptation than the N1, suggesting that the two deflections originate from different cortical generators. In the second experiment, the single adapters were replaced by trains of two or four identical adapters. The results indicated that adaptation decays faster after repeated presentation of the adapter. This increase in the recovery rate of adaptation might contribute to the elicitation of the auditory mismatch negativity (MMN) response. It may be caused by top-down feedback, or by local processes, such as the build-up of residual Ca(2+) within presynaptic neurons.
    Journal of Neurophysiology 05/2013; 110(4). DOI:10.1152/jn.00547.2012 · 2.89 Impact Factor
  • Source
    • "The auditory cortex is known to be highly sensitive to preceding activity, with periods of synchronized states exhibiting larger, lower frequency waves (Harris et al. 2011). Strong oscillatory responses have also been observed in ketamine-anesthetized preparations (Eggermont 1992; Kisley and Gerstein 1999; Rennaker et al. 2007) and are strongest in medium anesthesia depths (Kisley and Gerstein 1999). To reduce variability in the LFP area calculation, we removed trials that exhibited large sporadic activity preceding our stimulus-driven activity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: While the cochlear implant has successfully restored hearing to many deaf patients, it cannot benefit those without a functional auditory nerve or an implantable cochlea. As an alternative, the auditory midbrain implant (AMI) has been developed and implanted into deaf patients. Consisting of a single-shank array, the AMI is designed for stimulation along the tonotopic gradient of the inferior colliculus (ICC). Although the AMI can provide frequency cues, it appears to insufficiently transmit temporal cues for speech understanding because repeated stimulation of a single site causes strong suppressive and refractory effects. Applying the electrical stimulation to at least two sites within an isofrequency lamina can circumvent these refractory processes. Moreover, co-activation with short inter-site delays (<5 ms) can elicit cortical activation which is enhanced beyond the summation of activity induced by the individual sites. The goal of our study was to further investigate the role of the auditory cortex in this enhancement effect. In guinea pigs, we electrically stimulated two locations within an ICC lamina or along different laminae with varying inter-pulse intervals (0-10 ms) and recorded activity in different locations and layers of primary auditory cortex (A1). Our findings reveal a neural mechanism that integrates activity only from neurons located within the same ICC lamina for short spiking intervals (<6 ms). This mechanism leads to enhanced activity into layers III-V of A1 that is further magnified in supragranular layers. This integration mechanism may contribute to perceptual coding of different sound features that are relevant for improving AMI performance.
    Journal of Neurophysiology 05/2013; 110(4). DOI:10.1152/jn.00022.2013 · 2.89 Impact Factor
Show more