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Differences in responses to 70 dB clicks of cerebellar units with simple versus complex spike activity: (i) in medial and lateral ansiform lobes and flocculus; and (ii) before and after conditioning blink conditioned responses with clicks as conditioned stimuli.

Activity was recorded from 554 cerebellar units in eleven conscious cats to determine if responses to 70 dB clicks differed in units with simple and complex spike discharges. Effects of region of recording and behavioral state (with click used as a conditioned stimulus for conditioning) were also assessed. Cells with only simple spikes were distinguished from cells that had the following types of complex spike events: Type I-simple or initial spike followed > 1 ms by multiple spikes with baseline displacement (classical complex spikes), Type II--followed < or = 1 ms by spikes with or without baseline displacement (spikes in the absolute refractory period should arise from a separate site of initiation), and Type III-followed by spikes and displacement too close to the baseline noise to distinguish as Type I or II. Among the groups mean baseline activity was greatest in cells with Type I complex spikes, least in cells with Type III complex spikes, and greater in Type II cells than simple cells. Significant increases in activity within 32 ms of presenting clicks were found in the groups of Type II cells and simple cells. These appear to be the main auditory responsive cells of the cerebellar regions studied. Activity of Type II cells best reflected the temporal properties of the click; responses of simple cells had slower onsets (except in flocculus) and longer durations. Responses to click in Type II and simple cells differed in recordings from: (i) lateral ansiform lobe (lateral crus I and portions of crus II), (ii) medial ansiform lobe (medial crus I), and (iii) flocculus. The largest mean responses above baseline in the first 32 ms after click were found in Type II cells of the lateral ansiform lobe with onsets of 8-16 ms. Magnitudes of response differed before and after conditioning and backward conditioning. In the lateral ansiform lobe, the < 32 ms response to click was greater in Type II than simple cells in each state, but showed a greater increase above baseline after backward conditioning when conditioned responses were not produced than after conditioning. The onset of increased activity to click conditioned stimuli in Type II cells of the lateral ansiform region preceded the onset of the blink conditioned response after conditioning, consisted almost entirely of simple spikes, and reflected an increase in magnitude of response as opposed to an increased number of responsive units. After conditioning, an increased number of units in the flocculus responded to click conditioned stimuli in the 16-24 ms post stimulus period. Of the 16 cells with an onset of increased activity at this time, eight showed only simple spike activity. Seven of the remaining eight cells (all Type II) showed a significant increase in conditioned stimulus-evoked complex spiking above the low (usually < 1/s) baseline level of complex spike discharges. The findings support the conclusions that cerebellar units can respond rapidly enough to acoustic stimuli to play a role in auditory as well as motor processing and that the responses to 70 dB clicks differ among cells with simple and complex spike discharges. The differences are influenced substantially by the region of cerebellar recording and the behavioral state. The findings in cells of the flocculus offer the first evidence that complex as well as simple spike activity can contribute to an increased probability of discharge to click as a conditioned stimulus after conditioning.

Acoustic Stimulation↗

Interoceptive Pavlovian conditioning with nicotine as the conditional stimulus varies as a function of the number of conditioning trials and unpaired sucrose deliveries.

In rats, the pharmacological (interoceptive) effects of nicotine can serve as a signal (conditional stimulus) in a Pavlovian (classical) conditioning task. In this task, nicotine administration (0.4 mg base/kg, subcutaneous) is typically paired with intermittent access to a liquid sucrose unconditional stimulus; sucrose is withheld on saline sessions. An increase in sucrose receptacle entries (goal tracking) on nicotine sessions indicates conditioning. Given our limited understanding of the functional relationships controlling conditioned responding to a nicotine conditional stimulus, the present research examined nicotine's sensitivity to several manipulations shown to affect the conditioned responding in more widely studied Pavlovian conditioning tasks that use exteroceptive conditional stimuli: number of nicotine conditional stimulus-sucrose unconditional stimulus pairings per session (0, 3, 9, 18, or 36) and the impact of sucrose deliveries in saline sessions. Differential goal tracking developed in fewer sessions and asymptotic conditioned responding magnitude was greater with more nicotine-sucrose pairings. Further, goal tracking was more resistant to extinction (unconditional stimulus withheld) with more conditional-unconditional stimulus pairings during the acquisition phase. The discrimination was not acquired when sucrose presentations (9 or 18) also occurred during saline sessions. Furthermore, expression of the discrimination was disrupted when sucrose was presented in saline sessions; this disruption resulted from goal tracking in saline sessions. These results are consistent with the notion that nicotine-evoked goal tracking results from interoceptive conditioning processes.

Animals↗

Behaviorally conditioned suppression of mitogen-induced proliferation and immunoglobulin production: effect of time span between conditioning and reexposure to the conditioning stimulus.

Rats were subjected to taste aversion conditioning using the immunosuppressive drug cyclophosphamide (CY) as the unconditioned stimulus (UCS) paired with saccharin, the conditioned stimulus (CS), and were reexposed to the CS at 2, 5, or 10 days after a single conditioning trial. Twenty-four hours after reexposure the rats were sacrificed and spleen cells assayed for mitogen-induced proliferation and immunoglobulin production. A robust conditioned taste aversion (CTA) was observed irrespective of the day of CS reexposure. However, only conditioned rats reexposed to the CS 2 days after training displayed a conditioned reduction in proliferative responses to PHA and PWM. These rats also exhibited a reduction in the synthesis of IgM, but not IgG or IgA, by spleen cells cultured with PWM. These effects were not observed in conditioned rats reexposed 5 or 10 days after conditioning. In another experiment, rats were subjected to a backward conditioning (UCS prior to CS) training trial, tested 2 days later for the presence of CTA, and sacrificed 24 h later for assessment of immune function as described above. The results of this experiment demonstrated that rats do not develop an aversion to saccharin when it is first presented 4 h after CY, and no alterations in spleen cell proliferation and immunoglobulin production were noted. The data show that the CTA response established by explicit association between CY and saccharin depresses in vitro spleen cell proliferation and IgM production only when elicited shortly after the conditioning trial.

Animals↗

Time of conditioning selectively influences contextual fear conditioning: further support for a multiple-memory systems view of fear conditioning.

Time of conditioning influences long-term retention of contextual but not auditory-cue fear conditioning. Long-Evans rats (Rattus norvegicus) conditioned at 12 noon displayed reduced contextual fear conditioning compared to rats conditioned at 8 a.m. or 4 p.m. This effect was eliminated by exposure to the context 24 hr prior to conditioning and by a posttrial injection of corticosterone (1.0 mg/kg). Time of conditioning did not influence short-term retention of contextual fear. These results suggest that time of conditioning influences the posttrial processes that construct a memory representation of the context. They also support the view that contextual and auditory-cue fear conditioning depend on different processes. These results are discussed in relation to the concept of memory storage modulators.

Animals↗

Colchicine-induced lesion of rat hippocampal granular cells prevents conditioned active avoidance with perforant path stimulation as conditioned stimulus, but not conditioned emotion.

Successful acquisition of active avoidance by rats with low frequency (15 cps) stimulation of the perforant path as a conditioning stimulus is correlated with a slowly developing long-term enhancement of perforant path-granular cell synapses. After selective destruction of granular cells of the stimulated side by unilateral microinjection of 1.6 micrograms/0.2 microliter colchicine into the dentate area, field potentials could no longer be evoked by test stimuli and animals subsequently failed to acquire the conditioned active avoidance with perforant path stimulation as a CS. However, colchicine-treated animals showed the same development of conditioned emotional responses as saline controls and they could also successfully be conditioned with light and tone as the CS. These results suggest that the granular cells are necessarily involved in the conditioning pathway for the active avoidance with perforant path stimulation as the CS. Other targets of the perforant path, e.g., ipsi- and contralateral CA1 pyramidal cells and contralateral granular cells, or antidromic activation of the entorhinal cortex seem an insufficient substitute for granular cells in the pathway for this conditioned active avoidance, but would probably participate in the conditioned emotional responses. The results additionally support our hypothesis, that post-conditioning LTP in granular cell synapses contribute to the acquisition and/or the storage of a memory trace.

Animals↗

When pentobarbital is the conditioned stimulus and amphetamine is the unconditioned stimulus, conditioning depends on the type of conditioned response.

Injections of drugs into rats were used as conditioned stimuli (CSs) and as unconditioned stimuli (USs). With heart rate (HR) conditioning, the pentobarbital CS produces a higher HR than under control conditions. With avfail (aversion failure) conditioning, the pentobarbital CS loses much of its capacity to induce a conditioned taste aversion. HR conditioning was obtained with forward delays of up to 30 min and backward delays of up to 270 min, where the delays are defined by the interinjection interval. Avfail was obtained with forward delays of up to 270 min but not with backward delays. Neither HR conditioning nor avfail were context specific but could be demonstrated in a test apparatus after pairings that occurred in the home cage. This indicated that the external environment was not an important part of the effective stimulus complex. When HR conditioning was obtained, its latency and duration was not related to the delay between the CS and US injections or whether they were forward or backward.

Animals↗

Conditioned stimulus determinants of conditioned response form in Pavlovian fear conditioning.

Four experiments using barpress conditioned suppression in rats found that tone evoked more freezing (immobility) than did light. Still, tone and light appeared to have similar conditioned value as assessed by suppression in Experiments 1, 2, and 3, and by blocking, second-order conditioning, and overconditioning assays in Experiments 1, 2, and 3, respectively. Experiment 4 arranged for tone to evoke less suppression than light but more freezing. Results suggest that in fear conditioning, the nature of the conditioned stimulus affects the form of conditioned responding (strong vs. weak freezing). This conclusion extends one drawn by P. C. Holland (1977) on the basis of his work in appetitive conditioning.

Animals↗

Odor-guided fear conditioning in rats: 2. Lesions of the anterior perirhinal cortex disrupt fear conditioned to the explicit conditioned stimulus but not to the training context.

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS-unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning.

Animals↗

Classical conditioning, differential conditioning, and second-order conditioning of the Aplysia gill-withdrawal reflex in a simplified mantle organ preparation.

Nonassociative learning was previously examined in a simplified preparation consisting of the isolated mantle organs and abdominal ganglion of Aplysia californica that is advantageous for relating cellular events to behavior (T. E. Cohen, S. W. Kaplan, E. R. Kandel, & R. D. Hawkins, 1997). Results of the current study show that the gill-withdrawal reflex in that preparation also underwent 2 associative forms of learning: classical conditioning and differential conditioning. In addition, the reflex underwent second-order conditioning with either forward or simultaneous pairing of a novel conditioned stimulus (CS2) and a previously conditioned stimulus (CS1). Moreover, extinction of CS1 after simultaneous second-order conditioning was accompanied by a decrease in responding to CS2, suggesting that the conditioning might have involved formation of an association between the CSs. In each of these paradigms, learning in the Aplysia mantle organ preparation resembled learning in vertebrates.

Analysis of Variance↗

Effects of bed nucleus of the stria terminalis lesions on conditioned anxiety: aversive conditioning with long-duration conditional stimuli and reinstatement of extinguished fear.

Four experiments investigated the effects of lesions of the bed nucleus of the stria terminalis (BNST) on conditioned fear and anxiety. Though BNST lesions did not disrupt fear conditioning with a short-duration conditional stimulus (CS; Experiments 1 and 3), the lesion attenuated conditioning with a longer duration CS (Experiments 1 and 2). Experiment 3 found that lesions attenuated reinstatement of extinguished fear, which relies on contextual conditioning. Experiment 4 confirmed that the lesion reduced unconditioned anxiety in an elevated zero maze. The authors suggest that long-duration CSs, whether explicit cues or contexts, evoke anxiety conditioned responses, which are dissociable from fear responses to shorter CSs. Results are consistent with behavioral and anatomical distinctions between fear and anxiety and with a behavior-systems view of defensive conditioning.

Analysis of Variance↗

The comparator hypothesis of conditioned response generation: manifest conditioned excitation and inhibition as a function of relative excitatory strengths of CS and conditioning context at the time of testing.

In the present research water-deprived rats were used in a conditioned lick suppression paradigm to test and further develop Rescorla's (1968) contingency theory, which posits that excitatory associations are formed when a conditioned stimulus (CS) signals an increase in unconditioned stimulus (US) likelihood and that inhibitory associations develop when the CS signals a decrease in US likelihood. In Experiment 1 we found that responding to a CS varied inversely with the associative status of the context in which the CS was trained and that this response was unaltered when testing occurred in a distinctively dissimilar context with a different conditioning history, provided associative summation with the test context was minimized. These results suggest that manifest excitatory and inhibitory conditioned responding is modulated by the associative value of the training context rather than that of the test context. In Experiment 2 it was demonstrated that postconditioning decreases in the associative value of the CS training context reduced the effective inhibitory value of the CS even when testing occurred outside of the training context. Moreover, this contextual deflation effect was specific to the CS training context as opposed to any other excitatory context. Collectively, these studies support the comparator hypothesis, which states that conditioned responding is determined by a comparison of the associative strengths of the CS and its training context that occurs at the time of testing rather than at the time of conditioning. This implies that all associations are excitatory and that responding indicative of conditioned inhibition reflects a CS-US association that is below (or near) the associative strength of its comparator stimulus. It is suggested that response rules which go beyond a monotonic relation between associative value and response strength can partially relieve learning theories of their explanatory burdens, thereby allowing for simpler models of acquisition.

Animals↗

Reevaluating evaluative conditioning: a nonassociative explanation of conditioning effects in the visual evaluative conditioning paradigm.

In 2 studies, the authors investigated whether evaluative conditioning (EC) is an associative phenomenon. Experiment 1 compared a standard EC paradigm with nonpaired and no-treatment control conditions. EC effects were obtained only when the conditioned stimulus (CS) and unconditioned stimulus (UCS) were rated as perceptually similar. However, similar EC effects were obtained in both control groups. An earlier failure to obtain EC effects was reanalyzed in Experiment 2. Conditioning-like effects were found when comparing a CS with the most perceptually similar UCSs used in the procedure but not when analyzing a CS rating with respect to the UCS with which it was paired during conditioning. The implications are that EC effects found in many studies are not due to associative learning and that the special characteristics of EC (conditioning without awareness and resistance to extinction) are probably nonassociative artifacts of the EC paradigm.

Adolescent↗

Hippocampus and Pavlovian fear conditioning in rats: muscimol infusions into the ventral, but not dorsal, hippocampus impair the acquisition of conditional freezing to an auditory conditional stimulus.

The authors compared the effects of pharmacological inactivation of the dorsal hippocampus (DH) or ventral hippocampus (VH) on Pavlovian fear conditioning in rats. Freezing behavior served as the measure of fear. Pretraining infusions of muscimol, a GABAA receptor agonist, into the VH disrupted auditory, but not contextual, fear conditioning; DH infusions did not affect fear conditioning. Pretesting inactivation of the VH or DH did not affect the expression of conditional freezing. Pretraining electrolytic lesions of the VH reproduced the effects of muscimol infusions, whereas posttraining VH lesions disrupted both auditory and contextual freezing. Hence, neurons in the VH are importantly involved in the acquisition of auditory fear conditioning and the expression of auditory and contextual fear under some conditions.

Acoustic Stimulation↗

Comparator mechanisms and conditioned inhibition: conditioned stimulus preexposure disrupts Pavlovian conditioned inhibition but not explicitly unpaired inhibition.

Three conditioned lick-suppression experiments with rats examined the effects of pretraining exposure to the conditioned stimulus (CS) on behavior indicative of conditioned inhibition. After CS-preexposure treatment, subjects received either Pavlovian conditioned inhibition training or explicitly unpaired inhibition training with the preexposed CS. The inhibitory status of the CS was then assessed with a retardation (Experiment 1) or a summation (Experiment 2) test. Experiment 3 controlled for the unconditioned stimulus-preexposure effect being a potential confound in Experiments 1 and 2. As predicted by the comparator hypothesis (R. R. Miller & L. D. Matzel, 1988), the CS-context association that developed during the CS-preexposure phase disrupted the expression of Pavlovian conditioned inhibition but not the expression of explicitly unpaired inhibition.

Animals↗

Unbiased cocaine conditioned place preferences (CPP) obscures conditioned locomotion, and nimodipine blockade of cocaine CPP is due to conditioned place aversions.

The effect of nimodipine (0, 0.1, 1.0 and 10 mg/kg, SC), a dihydropyridine L-type Ca2+ channel antagonist, on the establishment of cocaine-(10 mg/kg IP) conditioned place preferences (CPP) was investigated. Nimodipine produced conditioned place aversions (CPA) on its own; reductions in cocaine CPP are apparently due to this CPA. There is a high negative correlation between time spent in the CS+ compartment and the difference in locomotion rates between the CS+ and the non-drug (CS-) compartments, independent of drug effects. This relationship is responsible for an increased rate of locomotion observed in the CS- compartment in cocaine-conditioned rats. Analysis of covariance indicated that cocaine CPP occurred independently of cocaine's effects on locomotion. Furthermore, cocaine produces an increase in the rate of locomotion in the CS+ compartment when time spent in this compartment is equated with time spent in the CS- compartment. This suggests that cocaine's effects on CPP and "conditioned" locomotion are due to separate mechanisms of action. On the other hand, nimodipine-induced place aversions and locomotor rates are not independent of each other, indicating a common mechanism of action, or that one is a consequence of the other. It is concluded that place preferences and place aversions can sometimes be secondary to compartment-specific locomotor changes, and locomotion effects can be confounded by differential times spent in each compartment. The relationships between these two behaviours must be controlled for before conclusions of CPP or CPA can be drawn in drug conditioning studies.

Animals↗

Amygdalar unit activity during three learning tasks: eyeblink classical conditioning, Pavlovian fear conditioning, and signaled avoidance conditioning.

Neural activity in central and basolateral amygdala nuclei (CeA and BLA, respectively) was recorded during delay eyeblink conditioning, Pavlovian fear conditioning, and signaled barpress avoidance. During paired training, the CeA exhibited robust learning-related excitatory activity during all 3 tasks. By contrast, the BLA exhibited minimal activity during eyeblink conditioning, while demonstrating pronounced increases in learning-related excitatory responsiveness during fear conditioning and barpress avoidance. In addition, the relative amount of amygdalar activation observed appeared to be related to the relative intensity of the unconditioned stimulus and somatic requirements of the task. Results suggest the CeA mediates the Pavlovian association between sensory stimuli and the BLA mediates the modulation of instrumental responding through the assignment of motivational value to the unconditioned stimulus.

Action Potentials↗

Blocking in Pavlovian conditioning: effect of prior excitatory conditioning to a stimulus extraneous to compound conditioning.

The effect of prior excitatory conditioning to a stimulus not included in the compound conditioning phase of the typical blocking experiment was assessed in three CER studies. The first experiment, in which rat subjects received A+, C+, or a combination of A+/C+ trials prior to AB+ conditioning, showed that A+/C+ or C+ training produced as robust blocking as A+ training relative to a control group with no prior conditioning. A second experiment which was designed to assess the role of background cues in mediating the blocking effect indicated that background cues were not responsible for the A+ or C+ effects, while a third experiment showed these same effects were not mediated by stimulus generalization. The findings of these experiments are interpreted in the context of pseudoconditioning-induced rehearsal of a US representation in short-term memory.

Animals↗

Inactivation of the interpositus nucleus blocks the conditioned response acquired by a somatosensory conditioned stimulus in rabbit eyeblink conditioning.

1. Earlier studies suggest that the memory trace for the conditioned eyeblink reflex is formed and maintained in the interpositus nucleus (IPN) in the deep cerebellar nuclei when either an auditory or visual stimulus is used as a conditioned stimulus (CS). 2. In the present study, the eyeblink reflex of the rabbit was conditioned to a somatosensory CS (an airpuff onto the back). 3. In well-trained animals, the IPN was reversibly inactivated by local cooling and the existence of the learned responses to the CS was then tested. 4. The reversible IPN inactivation blocked the memory trace the somatosensory CS. The finding further supports the view that IPN-mediated memory trace formation is not dependent on the modality of the CS.

Animals↗