Information is needed concerning the role of various neuroregulators in the mediation of neural responses associated with conditioned stimuli. Such information will aid in developing a more complete understanding of the function of these substances in the cellular mechanisms of conditioning. It is likely that acetylcholine has an important role in cognitive function, and disruption of cholinergic activity is associated with Alzheimer's disease and aging. However, the specific actions of acetylcholine in the mediation of neural responses to conditioned stimuli are not defined at the level of the single neuron. The overall goal of this project is to define those actions of acetylcholine. The long-term goal of this research program is to examine the function of several neuroregulators in conditioned unit activity.
The specific aims of this project are: 1) To investigate the function of acetylcholine in rat frontal cortex unit responses associated with discrimination conditioning. 2) To determine the type(s) of cholinergic receptor involved in the acetylcholine effect. 3) To compare three different cortical regions which receive nucleus basalis innervation (frontal, parietal, anteromedial cortex) in order to assess the generality of involvement of acetylcholine in conditioning-related single unit responses. Microiontophoretic techniques will be employed to examine the effects of cholinergic agents on rat cortical neurons which demonstrate differential responses to reinforced and non-reinforced tone stimuli. Medial forebrain bundle stimulation will be used as reinforcement, and cortical slow potential responses will be monitored to confirm that the discrimination has been learned. The studies will be performed in urethane anesthetized rats, which have been shown to demonstrate conditioned slow potential and single unit responses similar to those observed in unanesthetized animals. This preparation offers the advantage of providing a stable recording condition, thereby increasing the likelihood of accomplishing the objectives with the microiontophoretic approach. Cortical units will be characterized regarding response to conditioned stimuli, response to iontophoretic acetylcholine, response to nucleus basalis stimulation, the effect of muscarinic and nicotinic antagonists on the various responses, and the effect of acetylcholine on the conditioned responses.
| Pirch, J H (1993) Basal forebrain and frontal cortex neuron responses during visual discrimination in the rat. Brain Res Bull 31:73-83 |
| Pirch, J H; Turco, K; Rucker, H K (1992) A role for acetylcholine in conditioning-related responses of rat frontal cortex neurons: microiontophoretic evidence. Brain Res 586:19-26 |
| Pirch, J; Rigdon, G; Rucker, H et al. (1991) Basal forebrain modulation of cortical cell activity during conditioning. Adv Exp Med Biol 295:219-31 |
