Classical conditioning of tone-signaled bradycardia modifies 2-deoxyglucose uptake patterns in cortex, thalamus, habenula, caudate-putamen and hippocampal formation.

The 2-[14C]deoxyglucose (2-DG) autoradiographic method was used to map metabolic activity in all telencephalic and diencephalic structures of the rat brain during and after classical conditioning. A trial was made of a 4-5 KHz frequency modulated tone (CS) paired with midbrain reticular stimulation (US). The unconditioned response was a rapid bradycardia elicited by the US. Alert rats were injected with 2-DG, placed in a sound-proof chamber, and subjected during 90 min to a given treatment: (1) the CS before conditioning, (2) the US alone, (3) the paired CS-US (acquisition), (4) the CS after conditioning (extinction), (5) the US prior to the CS (sensitization), (6) the unpaired CS-US (pseudoconditioning), (7) the CS after pseudoconditioning and (8) no stimulation. The prefrontal cortex showed discrete regions with enhanced 2-DG uptake during conditioning and pseudoconditioning. A columnar organization was well-defined in the posterior parietal cortex of rats subjected to CS-US pairing. The medial thalamus was greatly activated in all groups subjected to reticular stimulation. The dorsomedial nucleus showed its largest activation during conditioning. The lateral habenula and a caudal portion of caudate-putamen showed an overall increase in 2-DG uptake during conditioning. The hippocampal formation showed a specific pattern of metabolic activation during conditioning and after conditioning. A laminar densitometric analysis showed that 2-DG uptake was concentrated in a central band along the sides of the hippocampal fissure which corresponded to the molecular layers. Only this neuropil band of greater metabolic activity showed the learning-related changes. In addition, the hippocampal formation was the only nonauditory structure in the forebrain which clearly responded to the acquired signal value of the tone CS after conditioning. These changes revealed by 2-DG provide a first demonstration of forebrain substrates with localized metabolic alterations related to learning and reticular sensitization.