Neuronal activity of the prefrontal cortex is reduced in rats selectively bred for deficient sensorimotor gating Mesbah Alam, Svilen Angelov, Meike Stemmler, Christof von Wrangel, Joachim K. Krauss, Kerstin Schwabe ⁎ Department of Neurosurgery, Hannover Medical School, Carl-Neuberg-Str.1, D- 30625 Hannover, Germany abstract article info Article history: Received 1 October 2013 Received in revised form 8 August 2014 Accepted 15 August 2014 Available online 16 September 2014 Keywords: Entopeduncular nucleus Local field potentials Neuropsychiatric disorders Nucleus accumbens Prepulse inhibition Rats selectively bred for deficient prepulse inhibition (PPI), an operant measure of sensorimotor gating in which a weak prepulse stimulus attenuates the response to a subsequent startling stimulus, may be used to study certain pathophysiological mechanisms and therapeutic strategies for neuropsychiatric disorders with abnormalities in information processing, such as schizophrenia and Tourette's syndrome (TS). Little is known about neuronal activity in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), which are involved in the modulation of PPI. Here, we examined neuronal activity in these structures, and also in the entopeduncular nucleus (EPN), since lesions of this region alleviate the PPI deficit. Male rats with breeding-induced high and low expression of PPI (n = 7, each) were anesthetized with urethane (1.4 mg/kg). Single-unit activity and local field potentials were recorded in the mPFC, the NAC and in the EPN. In the mPFC discharge rate, measures of irregularity and burst activity were significantly reduced in PPI low com- pared to PPI high rats (P b 0.05), while analysis in the NAC showed approximately inverse behavior. In the EPN no difference between groups was found. Additionally, the oscillatory theta band activity (4–8 Hz) was enhanced and the beta band (13–30 Hz) and gamma band (30–100 Hz) activity was reduced in the NAC in PPI low rats. Reduced neuronal activity in the mPFC and enhanced activity in the NAC of PPI low rats, together with altered oscillatory behavior are clearly associated with reduced PPI. PPI low rats may thus be used to study the patho- physiology and therapeutic strategies for neuropsychiatric disorders accompanied by deficient sensorimotor gating. © 2014 Elsevier Inc. All rights reserved. 1. Introduction Neuropsychiatric disorders are increasingly recognized as network disorders with abnormal neuronal activity in cortico-subcortical loops. Understanding the abnormalities in the firing patterns and synchrony of neuronal activity that underlie specific behavioural disturbances would be useful to develop and improve therapeutics to attenuate such pathological processes (Carlson et al., 2006; Kopell and Greenberg, 2008). Sensorimotor gating mechanisms, which allow the nervous system to suppress or “gate” responding to external stimuli and internally generated signals or impulses, are disturbed in certain neuropsychiatric disorders (Swerdlow and Geyer, 1998; Braff et al., 2001). Such gating mechanisms have been operationalized in measures of prepulse inhibition (PPI) of the acoustic startle response (ASR), i.e., the reduction of the ASR when the startling noise pulse is shortly preceded by a weak prepulse (Koch et al., 2000; Swerdlow et al., 2001). Deficient PPI has been demonstrated in schizophrenia, Tourette's syndrome (TS), and obsessive compulsive disorder (Swerdlow and Sutherland, 2006; Braff et al., 2001; Kohl et al., 2013), and experimentally-induced PPI deficits in rodents are used as a common endophenotype to model this basic deficiency in these disorders (Cadenhead et al., 2002; Braff and Light, 2005). Selective breeding in Wistar rats for high and low PPI leads to a segregation of two rat lines with significantly different PPI (Schwabe et al., 2007). The antipsychotic dopamine (DA) receptor antagonist haloperidol alleviated the breeding-induced PPI-deficit (Hadamitzky et al., 2007). Additionally, behavioral deficits and epigenetic factors in PPI low rats corroborate clinical findings seen in clinical practice (Dieckmann et al., 2007; Freudenberg et al., 2007; Rhein et al., 2013). Within the neuronal circuitry that regulates PPI, the medial prefron- tal cortex (mPFC) and the nucleus accumbens (NAC) play key roles (Swerdlow et al., 2001; Pothuizen et al., 2005). Abnormal neurofunctional coupling of the mPFC and NAC has been found in differ- ent animal models for deficient sensorimotor gating (Miller et al., 2010; Arime et al., 2012; Li et al., 2013; Swerdlow et al., 2013). Lesions or deep Progress in Neuro-Psychopharmacology & Biological Psychiatry 56 (2015) 174–184 Abbreviations: ASR, acoustic startle response; AP, anterior-posterior; AU, arbitrary units; DA, dopamine; ECG, electrocardiographic; EEG, electroencephalogram; EPN, entopeduncular nucleus; LFPs, local field potentials; mPFC, medial prefrontal cortex; ML, mediolateral; NAC, nucleus accumbens; PPTg, pedunculopontine tegmental nucleus; PPI, prepulse inhibition; SU, single unit; SPL, sound pressure level; TS, Tourette's syn- drome; V, ventral. ⁎ Corresponding author. Tel.: +49 511 532 2862; fax: +49 511 532 3960. E-mail address: schwabe.kerstin@mh-hannover.de (K. Schwabe). http://dx.doi.org/10.1016/j.pnpbp.2014.08.017 0278-5846/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry