Event-related oscillations in the parietal cortex of adult alcohol-preferring (P) and alcohol-nonpreferring rats (NP)

Abstract

The selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines were developed from Wistar rats to model high and low voluntary alcohol consumption and have been demonstrated to exhibit many of the characteristics of human alcohol dependence. Electrophysiologic studies have shown P rats exhibit more electroencephalographic fast frequency activity and reduced P3 amplitude in the parietal cortex than NP rats, findings that are more common in alcohol-dependent individuals. Event-related oscillations (EROs) have been suggested to be good endophenotypes associated with ethanol dependence in clinical studies. Recently EROs have also been demonstrated to occur in rodents in response to stimuli that are similar to that used in human clinical studies. The objective of the present study was to characterize EROs in adult P and NP rats. A time-frequency representation method was used to determine delta, theta, and alpha/beta ERO energy and the degree of phase variation in the parietal cortex of adult P and NP rats. The present results suggest that the decrease in P3 amplitudes previously shown in P rats were not associated with changes in ERO energy but were significantly associated with decreases in evoked delta and alpha/beta phase locking. These studies demonstrate ERO measures may also be good endophenotypes in animal models of alcoholism.

Introduction

Genetic selection studies have resulted in a number of high-drinking lines of mice and rats (see Bell et al., 2006, Green and Grahame, 2008). The alcohol-preferring (P) and -nonpreferring (NP) rat lines are one of the most extensively examined animal models of alcoholism (Li et al., 1993). These rats were developed for differences in home cage ethanol consumption to study ethanol-drinking behaviors and their consequences (Bell et al., 2006, Lumeng et al., 1977). Selectively bred P rats have been shown to voluntarily consume levels of 10% ethanol of more than 5 g/kg/d, with an ethanol preference ratio (vs. water) of greater than 2:1. The NP rats generally consume levels of 10% ethanol of less than 1.5 g/kg/d, with an ethanol preference ration of less than 0.2:1. These lines have been the focus of intensive study of the behavioral, neurobiological, and neurophysiologic factors that contribute to ethanol consumption (for reviews, see Bell et al., 2006, Li et al., 1993, McBride and Li, 1998).

Electrophysiologic differences between the rat lines have also been demonstrated (Breen and Morzorati, 1996, Ehlers et al., 1991, Ehlers et al., 1992, Ehlers et al., 1999, Morzorati et al., 1994, Robledo et al., 1993, Robledo et al., 1994). The study of neurophysiologic endophenotypes in P and NP rats with well-differentiated ethanol-related phenotypes could be an additional tool for identifying susceptibility genes for ethanol dependence. We have previously characterized the electrophysiologic profile of P and NP rats and found that P rats have significantly lower amplitude of the P3 component of the event-related potential (ERP), when compared with NP rats (Ehlers et al., 1999). This finding is similar to what has been reported for human subjects at differing risk for ethanol dependence (for review, see Porjesz et al., 2005).

There is evidence to suggest that ERPs may originate from an additive evoked activation of neural assemblies independent of ongoing electroencephalogram (EEG) as well as by the phase resetting of ongoing EEG oscillations in response to sensory input (for review, see Rangaswamy and Porjesz, 2008, Sauseng et al., 2007). Considerable efforts have been made in understanding how these models may potentially explain the generation of human ERPs. For instance, it has been proposed that the P3 component arises from a series of superimposed event-related oscillations (EROs) that are induced by sensory or cognitive processes that influence the dynamics of EEG rhythms (e.g., Demiralp et al., 2001, Karakas et al., 2000, Yordanova and Kolev, 1996). EROs are estimated by performing a decomposition of the EEG signal into phase and magnitude information over a range of frequencies and then the changes in those frequencies are characterized over a millisecond time scale with respect to task events. EROs have been demonstrated to be sensitive measures of both normal and abnormal cognitive functioning in humans (see Basar et al., 1999, Basar et al., 2001, Gevins et al., 1998, Klimesch et al., 1997, Schurmann et al., 2001). Additionally, these oscillations have been linked to several relevant genes associated with ethanol dependence phenotypes (Begleiter and Porjesz, 2006, Edenberg et al., 2004, Jones et al., 2004).

Studies have further demonstrated that delta and theta EROs are the primary contributors to the human P3 ERP component (Basar et al., 1999, Basar-Eroglu et al., 1992, Demiralp et al., 2001, Karakas et al., 2000, Schurmann et al., 2001). Reductions in P3 amplitude have been related to decreased cortical ERO energy and also to higher phase variability and weaker phase locking. For instance, it has been shown that the reduction of P3 amplitude during retrieval of a working memory task is associated with a decrease in delta ERO power and an increase in phase variability (Schack and Klimesch, 2002). In addition to their role in generating the P3 ERP component, evoked oscillations have also been shown to play a role in the generation of other ERP components, including the P1–N1 complex. There is evidence to suggest that alpha and theta evoked power and phase locking (PL) plays an important role in the generation of the P1–N1 complex (Klimesch et al., 2004). However, whether differences in ERO energy and phase variability play a role in the different neurophysiologic profiles identified in animal models has been less studied.

In view of the evidence from human studies of the link between alcohol dependence and ERO energy (Porjesz et al., 2005), characterizing the relationship between an ethanol preference phenotype and changes in EROs, translating this information to an animal model may provide valuable information on the mechanisms underlying these measures. The present study extended our initial analyses of neurophysiologic endophenotypes in P and NP rats to EROs generated in cortical sites in response to an auditory oddball paradigm (standard, rare, and noise tones). In this study, we investigated oscillatory activity in the delta, theta, and alpha/beta frequency ranges in the parietal cortex of P and NP rats within the temporal window of the P3 ERP response. ERO and PL analyses were accomplished from the same datasets that were used to generate the ERP data reported in a previous publication (Ehlers et al., 1999). We hypothesize that differences in hippocampal P3 amplitudes previously reported in P and NP rats (Ehlers et al., 1999) are associated to differences in delta and theta ERO oscillatory activity.