Stimulus-Specific Adaptation and Deviance Detection in the Rat Auditory Cortex Nevo Taaseh1, Amit Yaron1, Israel Nelken1,2* 1 Department of Neurobiology, Silberman Institute of Life Sciences, Hebrew University, Jerusalem, Israel, 2 The Edmond and Lily Safra Center for Brain Sciences and Interdisciplinary Center for Neural Computation, Hebrew University, Jerusalem, Israel Abstract Stimulus-specific adaptation (SSA) is the specific decrease in the response to a frequent (‘standard’) stimulus, which does not generalize, or generalizes only partially, to another, rare stimulus (‘deviant’). Stimulus-specific adaptation could result simply from the depression of the responses to the standard. Alternatively, there may be an increase in the responses to the deviant stimulus due to the violation of expectations set by the standard, indicating the presence of true deviance detection. We studied SSA in the auditory cortex of halothane-anesthetized rats, recording local field potentials and multi- unit activity. We tested the responses to pure tones of one frequency when embedded in sequences that differed from each other in the frequency and probability of the tones composing them. The responses to tones of the same frequency were larger when deviant than when standard, even with inter-stimulus time intervals of almost 2 seconds. Thus, SSA is present and strong in rat auditory cortex. SSA was present even when the frequency difference between deviants and standards was as small as 10%, substantially smaller than the typical width of cortical tuning curves, revealing hyper-resolution in frequency. Strong responses were evoked also by a rare tone presented by itself, and by rare tones presented as part of a sequence of many widely spaced frequencies. On the other hand, when presented within a sequence of narrowly spaced frequencies, the responses to a tone, even when rare, were smaller. A model of SSA that included only adaptation of the responses in narrow frequency channels predicted responses to the deviants that were substantially smaller than the observed ones. Thus, the response to a deviant is at least partially due to the change it represents relative to the regularity set by the standard tone, indicating the presence of true deviance detection in rat auditory cortex. Citation: Taaseh N, Yaron A, Nelken I (2011) Stimulus-Specific Adaptation and Deviance Detection in the Rat Auditory Cortex. PLoS ONE 6(8): e23369. doi:10.1371/journal.pone.0023369 Editor: Izumi Sugihara, Tokyo Medical and Dental University, Japan Received February 24, 2011; Accepted July 15, 2011; Published August 10, 2011 Copyright: 2011 Taaseh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by an EU FP6 grant (NOVELTUNE consortium, http://cordis.europa.eu/fp6), by grants from the Israel Science Foundation (219/ 05 and 72/09) to I.N. (http://www.isf.org.il/), and by a grant from the Gatsby Charitable Foundation to the Interdisciplinary Center for Neural Computation at the Hebrew University (http://www.gatsby.org.uk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: Israel@cc.huji.ac.il Introduction The auditory system processes a continuously changing auditory scene. The detection of violations to regularities in the sound stream may be critical for survival, and may play an important role in the formation of auditory objects (e.g. [1,2]). Neural mechanisms of deviance detection have been extensively investi- gated, mainly using the oddball paradigm [3,4]. In this paradigm, deviance is typically produced by presenting a rare (‘deviant’) stimulus against a background of a frequent (‘standard’) stimulus. In cat auditory cortex [5,6], rat inferior colliculus [7], barn owl midbrain and forebrain [8], mouse and rat auditory thalamus [9,10] and rat auditory cortex [11,12], the responses of neurons to a tone are larger when that tone is deviant than when it is standard. This effect, called stimulus-specific adaptation (SSA), depends on the physical difference between the standard and the deviant stimuli, on the probability of appearance of the deviant tone, and on the inter-stimulus time interval [5,6,7]. SSA shares many properties with, (but is probably not identical to, [12,13]) mismatch negativity (MMN), a component of the auditory event- related potentials (ERPs) that is elicited by deviant tones in humans [14]. Current research is somewhat ambiguous regarding the definition of SSA. The term itself emphasizes the adaptation of the responses to the standard tone. However, the hallmark of SSA is the large response to the deviant. This large response could be due to the fact that the deviant is rare and, therefore, the response it evokes is not adapted. But the deviant also represents a violation of the expectation to hear a standard. Indeed, the MMN literature emphasizes the responses to the deviant tone, and a substantial effort has been made to demonstrate that MMN is not (or not only) due to the rarity of the deviant, but is at least partially due to the violation of the regularity of the tone sequence caused by the presentation of the deviant [15,16,17]. Two types of sound sequence have been used to uncover the factors contributing to the responses to deviants. The first is the ‘deviant-alone’ control, in which the tone sequence consists of mainly silent trials, broken by the occasional deviant tone at the same probability as in the oddball paradigm (but otherwise in random positions) [15]. In these sequences, there is presumably no regularity to break, and therefore the response should reflect rarity alone, in contrast with the response to deviants with standards, that includes a potential contribution of deviance as well. However, the response to the deviant in the deviant-alone PLoS ONE | www.plosone.org 1 August 2011 | Volume 6 | Issue 8 | e23369