Douglas A. Weldon

Posttraining D1 receptor blockade impairs odor conditioning in neonatal rats.

Rat pups that were exposed to a novel anise odor paired with tactile stimulation (stroking the skin with a paint brush) received injections of either saline or the dopamine D1 receptor antagonist (+/-)-SKF 83566 (0.1 mg/kg) before conditioning or immediately after conditioning. Animals that received the drug either before or after training showed less approach to the conditioned odor during the testing period 24 hr later than did animals that received the vehicle. Posttraining administration of the D2 receptor antagonist spiperone (0.1 mg/kg) did not affect subsequent approach to the conditioned odor, suggesting a selective effect of D1 receptor blockade. The impairment in learning by the administration of (+/-)-SKF 83566 before conditioning was reversed by the injection of the dopamine receptor agonist apomorphine (0.1 mg/kg) immediately after conditioning. Posttraining D1 receptor activation appears necessary for normal odor conditioning in rat pups.

Superior colliculus lesions and environmental experience: Nonvisual effects on problem solving and locomotor activity ☆

Bilateral lesions of the superior colliculus were produced in rats reared in either a restricted or complex environment. Problem solving ability in a Hebb-Williams closed field and activity in an open field were subsequently observed in conditions of either bright or dim illumination. Animals with superior colliculus lesions were deficient in problem solving ability and were hyperactive in the open field. Complex environment exposure during development increased problem solving ability and initial ambulation scores in all groups. Extent of pretectal damage and behavioral measures were significantly related for animals reared in the complex, but not in the restricted environment. There were no interactions with illumination level, suggesting that the deficits resulting from collicular lesions are not dependent upon the availability of visual cues.

Task-specific deficits in reversal performance following superior colliculus lesions in rats ☆

Rats with lesions of the superior colliculus or control operations were tested in acquisition, extinction and reversal performance of operant visual tasks in four experiments. The tasks used in the experiments were: a simultaneous choice task (Experiment 1), a successive choice task (Experiment 2), a simultaneous go/no-go task (Experiment 3) and a successive go/no-go task (Experiment 4). Acquisition discrimination performance was affected by lesions only in Experiment 3, where in contrast with previous reports animals with lesions performed better than controls. Reversal performance of animals with lesions was impaired in Experiments 1 through 3, but not in Experiment 4. Effects on extinction performance were minimal in all experiments. The data are interpreted to indicate a role o the superior colliculus in the processing of spatial information.

Olfactory Conditioning Impairment Following Posttraining NMDA Receptor Blockade in Neonatal Rats

Six-day-old Sprague-Dawley rat pups were exposed to peppermint odor paired with tactile stimulation (stroking the skin with a paint brush) for twenty 10-s conditioning trials, and their olfactory preference was tested the next day. In Experiment 1, pups that had received an injection of the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 (0.1 mg/kg, i.p.) either 30 min before or immediately after conditioning spent less time over the conditioned odor than saline-treated controls. In Experiment 2, pups received an injection of either MK-801 or saline 0, 30, or 60 min after the training period. There was a reduction in the preference for the conditioned odor in the animals receiving MK-801 immediately following training, but treatment with the drug at the other intervals did not produce a performance impairment. The impairment following immediate posttraining injection occurred with either 0.05 or 0.1, but not with 0.01 mg/kg of MK-801 (Experiment 3). Experiment 4 provided control data to confirm that pups that had experienced the procedures used in Experiments 1-3 showed greater preference for the conditioned odor than did naive pups or those receiving exposure to the odor without stroking. The data indicate that immediate posttraining activation of N-methyl-D-aspartate receptors is required for normal olfactory learning in neonatal rats.

Development of rotorod performance in normal and congenitally hypothyroid mutant mice

Balancing behavior on a rotating cylinder was measured in genetically hypothyroid (hyt/hyt) mutant mice and their phenotypically normal littermates (hyt/+) at 10 different ages between Day 12 and Day 55. Normal mice showed competent balancing behavior in this task by 23 days of age, but mutant hypothyroid mice were incapable of balancing throughout the period of testing. Similar results were found with animals initially tested as adults, indicating that the developmental effects are probably not attributable to different rates of learning. These results are discussed in terms of documented central nervous system abnormalities in animals deprived of thyroid hormone early in life.

Effects of apomorphine on appetitive conditioning in 6-hydroxydopamine treated rat pups

Rat pups were treated on postnatal day 5 either with the combination of desmethylimipramine (DMI) and 6-hydroxydopamine (6-OHDA) to produce depletion of brain dopamine, or with control injections of saline. Two days later they were presented a novel anise odor paired with intraoral baby formula, and on the next day were tested for preference for the novel odor. Before conditioning and testing, animals were treated with either apomorphine (0.05 mg/kg) or isotonic saline. Performance of the conditioned appetitive response was impaired in dopamine depleted animals. In DMI/6-OHDA treated pups, apomorphine administration prior to conditioning produced an improvement in performance, but drug treatment prior to testing had no effect. In normal pups, apomorphine administration either before conditioning or testing produced impaired performance at testing.

Reward-related neuronal activity in the rat superior colliculus

The activity of single units in the intermediate and deep layers of the superior colliculus was recorded while rats performed an operant conditioning task. On all trials, each animal pressed a bar and then inserted his snout into a food cup; on half of the trials, food reinforcement was available. To test for tactile sensitivity, on half of the trials the rats received a puff of air to the face when the snout entered the food cup. Activity of most cells was correlated with the motor activity of inserting the snout into the food cup, even when reinforcement was not available. For many cells, a larger burst of activity was seen on the reinforced trials than on trials when rats made the same movements without the presence of reward. There was no evidence that an increase in tactile sensitivity occurred when the animal retrieved the reinforcement. These results suggest that cells in the superior colliculus have an increase in activity associated with reward retrieval, which for some neurons is not dependent on simple sensory or motor factors.

Rotational behavior following cholinergic stimulation of the superior colliculus in rats

Rate which received microinjections of carbachol into the superior colliculus exhibited pronounced dose-dependent rotational behavior contralateral to the site of injection (Experiment 1). Wet dog shakes were also observed in some animals. Similar injections in the midbrain reticular formation produced immobility with slight contralateral flexion of the neck. Convulsions were observed in some rats after injections into either anatomical location. In Experiment 2, circling induced by carbachol in the superior colliculus was blocked by prior injection of either the muscarinic receptor antagonist scopolamine or the nicotinic receptor antagonist mecamylamine, suggesting that both nicotinic and muscarinic receptors are involved in the effect. In Experiment 3 contralateral rotational behavior was induced by intracollicular microinjections of the combination of acetylcholine chloride and physostigmine. The results suggest that collicular mediation of contralateral rotational behavior, and perhaps orientation, might involve cholinergic receptors.

Changes in sensory responsivity in deep layer neurons of the superior colliculus of behaving rats

Neurons in the deep layers of the superior colliculus in behaving hooded rats were tested for responsivity to visual, auditory, or somesthetic stimuli. Some sensory cells, particularly those responsive to tactile stimuli, showed a change in responsivity (and sometimes an abolishment in firing rate or change in receptive field size) when the animal was gently restrained or placed onto an elevated platform. Thus, sensory neurons in the superior colliculus of the behaving rat have response properties that vary according to the conditions of testing.

Cortical evoked responses to synonyms and antonyms

The brain’s processing of synonymity and antonymy was explored by examining the cortical evoked responses to correct judgments that a test word was a synonym or an antonym of a standard word presented 1 sec previously. Each of five subjects judged 256 pairs of words in each of two sessions. The evoked response to the second word was averaged separately for synonym and antonym pairs. Presentation of each test word as a synonym or an antonym, the order of presentation of each pair, and the side of the “synonym” response key were counter-balanced within subjects. The difference between the averaged response to antonym test words and that to synonym test words differed biphasically over the interval 250-650 msec after the stimulus. The demonstration of an evoked response difference between synonyms and antnyms extends the applicability of evoked potentials from attributes of individual word meaning to the semantic relationships between words.