The Concentration of Isoflurane Required to Suppress Learning Depends on the Type of Learning

Background Recent reports suggest that one type of learning, fear conditioning to context, requires more neural processing than a related type, fear conditioning to tone. To determine whether these types of learning were differentially affected by anesthesia, the authors applied isoflurane during the training phases of fear conditioning paradigms for freezing to context and freezing to tone. Methods The authors trained seven groups of eight rats to fear tone by administering a tone (conditioned stimulus) while breathing various concentrations of isoflurane from 0.00 to 0.75 minimum alveolar concentration (MAC; one concentration per group) separated by 0.12-MAC steps. On the succeeding day, and in the absence of isoflurane, the authors presented the tone (without shock) in a different context (different cage shape and odor) and measured the time each rat froze (became immobile). Six other groups of eight rats were trained to fear context by applying the shock in the absence of a tone but in the presence of environmental cues such as cage shape, texture, and odor. Fear to context was determined the succeeding day by returning the rat to the training cage (without shock) and measuring duration of freezing. Control groups (16 per group) received 0.75 MAC isoflurane but no foot shocks. Group scores were compared using analysis of variance, and the ED50 values for quantal responses of individual rats were calculated using logistic regression. Results Conditioning to context occurred at 0.00 and 0.13 MAC (P < 0.05 compared with unshocked control) but not 0.25 MAC; the ED50 was 0.25 +/- 0.03 MAC (mean +/- SEM). In contrast, conditioning to tone occurred at 0.48 MAC (P < 0.05) but not 0.62 MAC; the ED50 was 0.47 +/- 0.02 MAC (P < 0.01 for the difference between ED50 values). Conclusions Suppression of fear conditioning to tone required approximately twice the isoflurane concentration that suppressed fear conditioning to context. Thus, the concentration of anesthetic required to suppress learning may depend on the neural substrates of learning. Our results suggest that isoflurane concentrations greater than 0.5 MAC may be needed to suppress both forms of fear conditioning.

Classic conditioning of the ventilatory responses in rats

Nsegbe, Elise, Guy Vardon, Pierre Perruchet, and Jorge Gallego. Classic conditioning of the ventilatory responses in rats. J. Appl. Physiol. 83(4): 1174–1183, 1997.—Recent authors have stressed the role of conditioning in the control of breathing, but experimental evidence of this role is still sparse and contradictory. To establish that classic conditioning of the ventilatory responses can occur in rats, we performed a controlled experiment in which a 1-min tone [conditioned stimulus (CS)] was paired with a hypercapnic stimulus [8.5% CO2, unconditioned stimulus (US)]. The experimental group ( n = 9) received five paired CS-US presentations, followed by one CS alone to test conditioning. This sequence was repeated six times. The control group ( n = 7) received the same number of CS and US, but each US was delivered 3 min after the CS. We observed that after the CS alone, breath duration was significantly longer in the experimental than in the control group and mean ventilation was significantly lower, thus showing inhibitory conditioning. This conditioning may have resulted from the association between the CS and the inhibitory and aversive effects of CO2. The present results confirmed the high sensitivity of the respiratory controller to conditioning processes.

Electroencephalic Audiometry by Cortical Conditioning

Twenty-four normal-hearing adults were conditioned to associate a flash of light (unconditioned stimulus) with a pure tone (conditioned stimulus). The contingent response was used to estimate auditory threshold for 500, 1000, and 2000 Hz. Results showed that 23 of the 24 subjects were conditioned to form the tone-light association, the majority within 10 trials. Conditioned EEG responses varied in form, amplitude, and latency within and among individuals, and were without hemispheric predominance. The evoked EEG response habituated rapidly, whereas the conditioned EEG response was maintained throughout the procedure and transferred readily among the test frequencies. Auditory threshold estimated by this method was within 5 dB of voluntary threshold for at least one of the test frequencies for all 23 of the conditioned subjects.