Reduction of Prelimbic Inhibitory Gating of Auditory Evoked Potentials After Fear Conditioning Ryan P. Mears and Nash N. Boutros Wayne State University School of Medicine Howard C. Cromwell Bowling Green State University Inhibitory gating (IG) is a basic central nervous system process for filtering repetitive sensory informa- tion. Although IG deficits coincide with cognitive and emotional dysfunction in a variety of neuropsy- chiatric disorders, limited research has been completed on the basic, functional nature of IG. Persistent IG occurs in rat prelimbic medial prefrontal cortex (mPFC), a crucial site for modulating emotional learning. To investigate the interaction of affect and IG, we recorded local field potentials (LFP) directly from prelimbic mPFC and examined the influence of tone-shock fear conditioning (FC) on IG. Behav- ioral reactions during IG were observed before and after FC, and increase of orienting response after FC indicated induction of tone-shock association. After FC, some components of LFP response exhibited short-term weakening of IG. On a subsequent day of recording, IG strengthened for all LFP components, but individual components differed in their particular changes. Affective regulation of IG represents an important factor influencing within-subject IG variability, and these results have implications for understanding the role of rapid, implicit neural coding involved in emotional learning and affective disruption in psychiatric disease. Keywords: evoked potentials, prefrontal cortex, sensory gating, negative affect, acute stress Inhibitory gating (IG) is a neurophysiological mechanism pro- posed to be involved in elemental information filtering (Adler et al., 1982; Boutros & Belger, 1999). Neurophysiological assays that gauge IG have been used in basic science fields (Bock & Goode, 2002; Eccles, 1969) and in clinical neurophysiology (Adler et al., 1990; Boutros, Korzyukov, Jansen, Feingold, & Bell, 2004). Clin- ical research has indicated that IG could be used as a marker or potential neuroendophenotype for specific psychiatric disorders (Cadenhead, Light, Shafer, & Braff, 2005; Gottesman & Gould, 2003). It is well known that IG when tested in an elemental fashion is disrupted in patients from a diverse set of disorders including schizophrenia (Adler et al., 2001; Boutros et al., 2004; Freedman et al., 1996), Alzheimer’s disease (Jessen et al., 2001), obsessive– compulsive disorder (OCD; Rossi et al., 2005), addiction (Adler et al., 2001; Boutros et al., 2002; Boutros, Uretsky, Lui, & Millana, 1997), panic disorder (Ghisolfi et al., 2006), and posttraumatic stress disorder (PTSD; Ghisolfi et al., 2004; Neylan et al., 1999; Skinner et al., 1999). IG is typically tested in clinical settings using a standard two-tone paradigm in which two identical tones are presented with a 500-ms interstimulus interval (Adler et al., 1982). Normally, the neural response to the second or “test” tone is reduced relative to initial or “conditioning” tone. IG is similar to habituation or adaptation except that the response to the initial tone is preserved whereas the main impact reflects the “inhibitory trace” that bridges the two stimuli and inhibits subsequent infor- mation. A “gating ratio” is usually calculated by dividing the test tone response by the conditioning tone response: scores approach- ing 0 or 1 reflect respectively greater or less inhibition. Patients with diverse neuropsychiatric illnesses have been found to have potential impairment of the typical degree of inhibition reflecting disruption of basic inhibitory circuits (Freedman et al., 1994, 1996), and gating of auditory evoked potentials (AEPs) at various stages of auditory processing (i.e., P1, N1, and P2) are indepen- dently affected in neuropsychiatric disease (Boutros et al., 2004, 2006). Complications in interpretation can arise for multiple rea- sons with changes in the computed gating ratio observed in clinical (Patterson et al., 2000) and preclinical studies (Hajos, 2006). Alterations in gating ratios might be due to changes primarily in the response to the second tone, to the first tone, or to inverse or parallel changes in both responses (Mears, Klein, & Cromwell, 2006). A second major issue in the clinical studies of IG includes the influence of state alteration on IG (Boutros & Kwan, 1998; Boutros, Overall, & Zouridakis, 1991; Smith, Boutros, & Schwar- zkopf, 1994). These state changes can involve arousal, sleep- wakefulness, attention, and emotion. These diverse state-related influences on IG are only beginning to be analyzed (Kisley, Olincy, & Freedman, 2001). It is known that all of the disorders in which IG is altered are characterized by emotional alterations. However, unaccounted within-subject variability is an obstacle to establishing the reliability of gating as an assessment tool, regard- Ryan P. Mears and Nash N. Boutros, Department of Psychiatry and Brain Research and Imaging Neuroscience, Wayne State University School of Med- icine; Howard C. Cromwell, Department of Psychology and J. P. Scott Center for Neuroscience, Mind, and Behavior, Bowling Green State University. Ryan P. Mears is now affiliated with Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. This work was partially supported by the J. P. Scott graduate fellowship and Joe Young Sr. Research in Psychiatry funds. We thank Holly Moore and Matthew Galloway for helpful comments and guidance on this article. Andrew Klein, Dorcie Gray, Sarah Echols, and Nick Baldwin assisted with some behavioral assessments and histological preparations. Correspondence concerning this article should be addressed to Ryan P. Mears, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, CLS 07M1, Boston, MA 02215. E-mail: rmears@bidmc.harvard.edu Behavioral Neuroscience © 2009 American Psychological Association 2009, Vol. 123, No. 2, 315–327 0735-7044/09/$12.00 DOI: 10.1037/a0014364 315 This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.