Cortical evoked potential changes during classical conditioning of morphine dependence in rats.

A classical conditioning experiment was designed to determine if a conditioned neural response would develop and persist in cortical evoked potentials elicited by a foreleg stimulus (CS+) that was paired with morphine administration during the development of dependence and subsequent withdrawal. A stimulus to the other foreleg (CS-) was presented explicitly unpaired with morphine delivery. After dependence was established, the rats were taken from the experimental chamber and withdrawn from morphine for 6 days in their home cages. Finally, during the testing phase, the animals were returned to the experimental chamber and the foreleg stimuli were presented. The CS+ was paired with either morphine or saline injections. Changes due to both morphine effects only and conditioning were observed. The conditioned response, however, was present only in the cortical evoked potentials recorded from those animals receiving contralateral foreleg stimulation as the CS+. The conditioned neural response persisted after withdrawal and was present in both the drug-free and morphine-intoxicated animals. These results provide support for the relapse theory that a nonextinguished conditioned response is retained after withdrawal. However, further experiments are necessary to determine if these conditioned responses can elicit drug-seeking behavior.

Cortical motor neuron activity in the cat during classical conditioning with central stimulation as the CS and the US.

The neuronal basis of associative conditioning in the cat was investigated by pairing stimulation of thalamocortical pathways as the conditioned stimulus (CS) with antidromic activation of pericruciate pyramidal tract (PT) cells as the unconditioned stimulus in a differential classical conditioning paradigm. Contrary to expectations, based both on the available literature and on theoretical considerations (i.e., a pairing or activation hypothesis), thalamic stimulation was not an effective CS. The response of PT cells to thalamic stimulation did not change as a function of reinforcement with PT stimulation. These results led to a reconsideration of the hypothesis that the simple pairing of any two neural events is the essential mechanism underlying associative conditioning changes. The results did suggest that the combined activation of specific and nonspecific thalamic nuclei may be important in producing increases in responsiveness of PT neurons.

P300 wave elicited by a stimulus-change paradigm in acutely prepared rats.

Presentation of a long sequence of stimuli in one modality followed by infrequent substitution of stimuli in a different modality produced a very large P300 wave in the evoked potential to the infrequent stimulus. The P300 wave was never observed in a repetitive train of stimuli in one modality or to the background stimuli during the stimulus change procedure. This phenomenon was observed in cortical recordings from anesthetized rats. This P300 wave corresponds in latency to that observed in human cognitive studies, and the use of this paradigm in animal studies could greatly facilitate work to determine the neural basis of the P300 wave.

Influence of thalamic cooling on sensory responses in association cortex.

Evoked responses to light flash, click, and paw stimuli were recorded in the four cortical association areas in the acutely prepared cat. Average evoked responses (AEP) for 100 trials were formed before, during, and after localized cooling in the midline thalamus. Cooling of the midline thalamus reduced the magnitude of responses to click and paw stimuli, and increased or did not change the responses to light flash. There was very little similarity in trial-to-trial fluctuations of EP magnitude across cortical areas, and cooling did not reduce the similarity that existed. Waveform similarity was reduced by cooling for responses across the cortex to a single stimulus modality, whereas similarity of responses in a single cortical area to all three stimuli was not changed. The temporal components of the AEP influenced by thalamic cooling were different for different stimuli and cortical locations. It was concluded that the midline thalamo-cortical projection through the centromedian area to association cortices is particularly well-differentiated for multisensory responses in a single cortical region, and that the system should not be thought of as nonspecific but as convergent or multisensory.

Isotherm of alcohol-cooled cryoprobe.

The spread of cooling from the tip of a cryoprobe placed in the ventral posterior lateral nucleus of the thalamus in 10 cats was determined. A 20 degrees C isotherm was described as having a diameter of 4 mm and extending 2 mm below the tip of the cryoprobe and tapering up along the shaft of the cryoprobe for a distance of 2 mm, when the cryoprobe tip temperature was maintained at 3 degrees C.

Conditioning of cortical neurons in cats with antidromic activation as the unconditioned stimulus.

Single-cell activity was recorded from the postcruciate cortex of acutely prepared cats during a differential classical conditioning procedure. The conditioned stimuli (CS) were hind paw stimuli, and the unconditioned stimulus (US) was pyramidal tract stimulation that produced an antidromic response in the recorded cortical neuron. A control group was also examined in which the pyramidal stimulus was set below the threshold to produce an antidromic response. Clear differential conditioning was found for the experimental group, with antidromic activation of the neuron as the US. There was no evidence of differential conditioning in the control group without antidromic activation. Any activation of orthodromic pathways should have been the same in the control and experimental groups. The absence of conditioning in the control group demonstrated that orthodromic pathways were not contributing to the differential conditioning observed in the experimental group. This indicates that it was activation of the neuron produced by antidromic firing which was important for conditioning. All the evidence suggests that the site of learning was in the cortex. It is concluded that the the role of the US in conditioning may be simply to activate the neuron at an appropriate interval following the CS.

Trial development of unit response changes during conditioning in cats.

Single-cell and evoked potential (EP) activity in the postcruciate cortex of acutely prepared cats was recorded during a classical conditioning procedure. The temporal pattern of response (PSH) of the neuron was separated into three components, and the trial development of learning changes for these components was examined individually. Changes over trials in the similarity of the EP waveform and the unit PSH were also examined. The unit response components showed changes in response at different trial periods; these changes could not be accounted for by changes at lower brain levels that projected to the cortex. This suggests that local learning changes were taking places in the cortex. The EP-PSH similarity decreased for neurons showing the largest changes in response during conditioning. Since the EP reflects the response of the whole population of neurons and a majority did not show learning changes, this could account for the observed decrease.