Article

Anesthesia suppresses nonsynchronous responses to repetitive broadband stimuli

University of Oklahoma, 865 Asp Avenue, Felgar Hall 210, Norman, OK 73019, USA.
Neuroscience (Impact Factor: 3.33). 04/2007; 145(1):357-69. DOI: 10.1016/j.neuroscience.2006.11.043
Source: PubMed

ABSTRACT 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.

Full-text

Available from: Sara E Anderson, Jan 13, 2014
0 Followers
 · 
135 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In auditory cortex, temporal information within a sound is represented by two complementary neural codes: a temporal representation based on stimulus-locked firing and a rate representation, where discharge rate co-varies with the timing between acoustic events but lacks a stimulus-synchronized response. Using a computational neuronal model, we find that stimulus-locked responses are generated when sound-evoked excitation is combined with strong, delayed inhibition. In contrast to this, a non-synchronized rate representation is generated when the net excitation evoked by the sound is weak, which occurs when excitation is coincident and balanced with inhibition. Using single-unit recordings from awake marmosets (Callithrix jacchus), we validate several model predictions, including differences in the temporal fidelity, discharge rates and temporal dynamics of stimulus-evoked responses between neurons with rate and temporal representations. Together these data suggest that feedforward inhibition provides a parsimonious explanation of the neural coding dichotomy observed in auditory cortex.
    PLoS Computational Biology 04/2015; 11(4):e1004197. DOI:10.1371/journal.pcbi.1004197 · 4.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective. An increasing number of deaf individuals are being implanted with central auditory prostheses, but their performance has generally been poorer than for cochlear implant users. The goal of this study is to investigate stimulation strategies for improving hearing performance with a new auditory midbrain implant (AMI). Previous studies have shown that repeated electrical stimulation of a single site in each isofrequency lamina of the central nucleus of the inferior colliculus (ICC) causes strong suppressive effects in elicited responses within the primary auditory cortex (A1). Here we investigate if improved cortical activity can be achieved by co-activating neurons with different timing and locations across an ICC lamina and if this cortical activity varies across A1. Approach. We electrically stimulated two sites at different locations across an isofrequency ICC lamina using varying delays in ketamine-anesthetized guinea pigs. We recorded and analyzed spike activity and local field potentials across different layers and locations of A1. Results. Co-activating two sites within an isofrequency lamina with short inter-pulse intervals (<5 ms) could elicit cortical activity that is enhanced beyond a linear summation of activity elicited by the individual sites. A significantly greater extent of normalized cortical activity was observed for stimulation of the rostral-lateral region of an ICC lamina compared to the caudal-medial region. We did not identify any location trends across A1, but the most cortical enhancement was observed in supragranular layers, suggesting further integration of the stimuli through the cortical layers. Significance. The topographic organization identified by this study provides further evidence for the presence of functional zones across an ICC lamina with locations consistent with those identified by previous studies. Clinically, these results suggest that co-activating different neural populations in the rostral-lateral ICC rather than the caudal-medial ICC using the AMI may improve or elicit different types of hearing capabilities.
    Journal of Neural Engineering 07/2014; 11(4):046021. DOI:10.1088/1741-2560/11/4/046021 · 3.42 Impact Factor
  • Source
    [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