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Abstract

Background: Impaired attention to behaviorally-relevant stimuli and impaired ability to use that information to plan behavior are hallmark impairments observed in individuals with schizophrenia. These cognitive impairments are associated with abnormal neural oscillations in the prefrontal cortex. Electrophysiology studies suggest that the rat anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) are both involved in attention and planning behavior. In this study, we sought to characterize local field potential oscillations and their relationship with neuronal firing in the rat ACC and mPFC during a sustained attention task. Methods: Rats were implanted with 8 wire electrode arrays in the ACC and mPFC. Single unit firing and local field potentials (LFPs) were recorded from the same wires during performance of the 3-choice serial reaction time task. The 3-choice task requires a rat to orient toward and divide attention between 3 brief (300 msec duration) light stimuli presented in random order across nose poke holes in an operant conditioning chamber. LFPs were analyzed with a fast fourier transform and multi-taper analysis. A sliding window was used to observe changes in the power of frequencies, such as theta (3-8 Hz) and beta (12-30 Hz) during preparatory attention (before cue onset). Results: We have demonstrated that putative pyramidal neurons in the aCC and mPFC exhibit phasic excitatory and inhibitory responses prior to the attended cue. These responses are related to the level of preparatory (precue) attention and subsequent correct or incorrect choices, in that the magnitude of the single units' response to the cue was lower on incorrect trials and was not different than baseline on unattended trials. Preliminary analysis of LFP activity has indicated an increase in the power of theta and beta frequency range oscillations during preparatory attention (on correct trials). The analysis of single unit phase-locking to LFP theta and beta oscillations is ongoing. Discussion: Given that individuals with schizophrenia exhibit abnormal LFP oscillatory activity in the PFC, these studies provide important translational information about neuronal alterations associated with this disease. By studying attention-related neural activity at the level of both LFP and single units, we can assess the discrete and distributed networks that are implicated in normal cognitive functioning and in the pathophysiology of schizophrenia.