PMC

The responses of an individual VTA dopamine neuron to an auditory click (left panel) and a light flash (right panel). X axis ranges from 400 msec before to 600 msec after the auditory or visual stimulus (arrow) of 1 msec duration (time 0).

Two-way (Drug X Day) analysis of variance (ANOVA) conducted on days 3, 7, and 17 locomotor scores revealed a main effect of drug (P < 0.000001), a main effect of day (P < 0.05), and no interaction, showing that the drug produced similar locomotor suppression across different stages of learning.

Proportion of missed trials (i.e., trials for which latency to respond to the CS was > 10 sec) as a function of SCH23390 dose on test day 3, 7, and 17. Bars represent the standard error of the mean. On day 3, SCH23390 produced a dose-dependent increase in the proportion of missed trials (P < 0.0005). In contrast, animals that received SCH23390 on either day 7 or 17 of training showed no increase in missed trials. Note that animals in each group received only a single injection of SCH23390.

Performance of each treatment group during day 19, the drug-free test session. The y axis shows mean proportion of trials during which rats’ heads were in the food compartment for each successive 100 msec bin during the 10 sec before tone onset (−10 to 0), the presentation of the tone (0–6), and the 10 sec after tone offset (6–16). As can be seen, rats that had received UNPAIRED presentations of CS and food showed reduced CS period head-in durations compared to paired CS–food controls (P < 0.01). Animals that were under the influence of the highest SCH23390 dose during tone–food pairings also showed a reduced CS head-in probability (P < 0.05). Animals that were under the influence of RAC during the tone–food pairings showed increased CS head-in probabilities compared to vehicle controls on test day (P < 0.01).

(A) Left panels: Raster plot of head entries (horizontal lines) from −16 sec before to 10 sec after CS presentation (x axis). Successive trials 1–28 are represented from the bottom to the top of the y axis. On day 3 of training (after approximately 60 trials) systemic 0.16 mg/kg SCH23390 strongly suppresses head entries during the intertrial interval and in response to the CS (time 0). (B) Right panels: Separate groups of rats receive VEH or SCH23390 on day 17 of training. In animals receiving extended training prior to D1 antagonist challenge, the drug continues to suppress spontaneous head entries emitted during the ITI (−16 to 0), but does not affect the latency to respond to the CS.

Output neurons (B1, B2) in the dorsal and ventral striatum receive GLU inputs (A1, A2) originating in cortical and limbic regions. The informational nature of these GLU inputs varies according to the striatal target region. For the sake of the illustration, we imagine that the inputs (A) carry information about the sensory environment, and the outputs (B) represent behavioral response tendencies. DA activity influences information flow through,, and plasticity (LTP and LTD) of the currently active A→B GLU synapse (bold square). DA binding to receptors on the output cells (stippled squares) does not promote strengthening of nonactive GLU synapses (other squares). The diagram is simplified regarding the nature of the input–output connectivity. There is a large (up to 10,000 to 1) convergence of information from the cortex to striatum; that is, a given striatal neuron receives a large number of cortical and/or limbic GLU inputs (for an examination of corticostriatal mapping, see review; Ref. ). In addition, while dorsolateral striatal cells receive GLU input primarily from sensory-motor cortical regions, many striatal regions receive GLU inputs that carry information regarding sensory inputs, anticipated movements, expected outcomes, as well as information regarding appetitive and aversive valences of current inputs. Often, a single striatal neuron receives a convergence of such information, and responds to a conjunction of sensory, motor, and outcome–expectation conditions (see Ref. ; review).