Abstract
Attention-deficit hyperactivity disorder (ADHD) and schizophrenia are both associated with prefrontal cortex (PFC) dysfunctions, such as alterations of neural activity and reduced dopaminergic transmission. Furthermore, low dose methylphenidate (Ritalin), which is commonly used to treat ADHD, may improve cognition by increasing dopamine neurotransmission in the PFC. We have recently demonstrated that putative pyramidal neurons in the rat anterior cingulate cortex (ACC) and the medial PFC (mPFC) exhibit phasic excitatory and inhibitory responses prior to an attended cue in the 3-choice serial reaction time task (Totah et al. J Neurosci.20: 6418. 2009). 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. In order to assess the effects of methylphenidate on attention-related neural activity, we recorded both local field potential (LFP) and single unit firing patterns during the 3-choice serial reaction time task before and after acute treatment of methylphenidate or vehicle. 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. We recorded neural activity during 10 min of task performance, followed by i.p. administration of vehicle, 0.25 mg/kg methylphenidate, or 1.0 mg/kg methylphenidate, and then recorded another 30 min of neural activity during the task. We found that low dose (0.25 mg/kg) methylphenidate increased delta and theta oscillations in LFP during preparatory attention compared to vehicle. The analysis of changes in the number of responsive single units and attention-related neural activity is ongoing. Given that individuals with ADHD exhibit abnormal LFP oscillatory activity in the PFC that may be corrected by methylphenidate, these studies provide important translational information about neuronal alterations associated with ADHD. By studying changes in neural activity at a “multi-scale” level (both LFP and single units), we can assess the discrete and distributed networks that are implicated in the mechanism of action of methylphenidate.
