Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response.

In 2 experiments, 36 New Zealand albino rabbits received classical conditioning of the nictitating membrane response in a trace conditioning paradigm. In this paradigm, a 250-msec tone conditioned stimulus (CS) occurred, after which there was a 500-msec period of time in which no stimuli occurred (the trace interval), followed by a 100-msec air-puff unconditioned stimulus (UCS). In Exp I, lesions of the hippocampus or cingulate/retrosplenial cortex (CRC) disrupted acquisition of the long-latency or adaptive conditioned response (CR) relative to unoperated controls and Ss that received neocortical lesions that spared the CRC. When Ss with hippocampal or CRC lesions were switched to a standard delay paradigm in which the CS and UCS were contiguous in time, they acquired in about the same number of trials as naive Ss. In Exp II, multiple-unit activity in area CA1 of the hippocampus was examined during acquisition of the trace CR. Ss had a 500-msec trace interval (Group T-500), received explicitly unpaired presentations of the CS and UCS, or underwent conditioning with a 2-sec trace interval. Group T-500 acquired the CR in about 500 trials. Early in training, there was a substantial increase in neuronal activity in the hippocampus that began during the CS and persisted through the trace interval. Later in conditioning as CRs emerged, the activity shifted to later in the trace interval and formed a model of the amplitude–time course of the behavioral CR. (65 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning after cerebellar lesions in humans.

Explored classical conditioning in human Ss who had lesions in their cerebellar circuitry. Seven patients with damage to cerebellar structures and matched control Ss underwent simple delay tone–airpuff conditioning. Eyelid CR acquisition was severely disrupted in the patient group, whereas autonomic CRs and slow cortical potentials developing between the CS and the unconditioned stimulus/stimuli (UCS) were unaffected. Results are consistent with animal studies and earlier case reports indicating that intact cerebellar structures are necessary for the acquisition of classically conditioned motor responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the cerebellar vermis and cerebellar hemispheres: Effects on heart rate conditioning in rats.

The effects of lesions of the cerebellum on the acquisition of heart rate (HR) conditioned responses (CRs) were examined in rats. Large lesions of the cerebellar vermis severely attenuated the acquisition of differentially conditioned bradycardic responses in restrained rats without affecting unconditioned HR responses to the tone conditioned stimuli (CSs) or the shock unconditioned stimulus/stimuli (UCS). In Exp 2, Ss were trained unrestrained, and under these conditions the CR was tachycardia in control Ss. Lesions of the vermis again severely attenuated acquisition of this CR without affecting unconditioned response (UCR) to the CSs or UCS. Bilateral lesions of the cerebellar hemispheres did not affect HR conditioning in either test procedure. The vermis of the cerebellum is an essential component of an HR conditioning circuit in the rat. The cerebellar hemispheres, which are involved in some discrete somatomotor CRs, have no essential functional contribution to HR conditioning. Results are discussed in relation to contributions from a forebrain system involved in HR conditioning and in relation to lateral cerebellar contributions to discrete somatomotor CRs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective hippocampal lesions abolish the contextual specificity of latent inhibition and conditioning.

The contextual specificity of the CR and latent inhibition (LI) was examined in rats with selective hippocampal lesions. Acquisition of the CR to a novel CS was equally rapid in control and hippocampal rats (Exps 1 and 2), and CS preexposure disrupted acquisition (i.e., produced LI) to an equal extent in both groups (Exp 2). In control Ss, however, the CR established in one context transferred incompletely to a 2nd context (Exp 1), and LI was attenuated when CS preexposure and conditioning occurred in different contexts (Exp 3). This context specificity of the CR and LI was not apparent in hippocampal rats; the CR and LI transferred readily from one context to another. In addition, hippocampal rats were impaired in a spatial learning task (Exp 2) but were unimpaired in learning a Pavlovian contextual discrimination (Exp 3). Results suggest that a common contextual retrieval process underlies the contextual dependence of the CR and of LI and that this process is mediated by the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The septohippocampal cholinergic system and classical conditioning of the rabbit's nictitating membrane response.

28 New Zealand albino rabbits received bilateral microinjections of scopolamine (1 μl) or saline into either the dorsal hippocampus (Exp I) or the medial septal nucleus (Exp II). Ss then underwent classical conditioning of the nictitating membrane response in which a light served as a CS and eye shock served as the UCS. Results indicate that whereas hippocampal injections of scopolamine had no effect on conditioning, scopolamine injected into the medial septum retarded acquisition of the response. A 3rd experiment indicated that this retardation of conditioning was not due to changes in sensitivity to either the CS or UCS. Results are discussed in terms of accumulating evidence that manipulations that produce certain patterns of activity in the hippocampus are detrimental to acquisition of the nictitating CR. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of eyeblink conditioned response timing in rats.

Eyeblink conditioned response (CR) timing was assessed in adult and infant rats. In Experiment 1, adult rats were trained with a 150-ms tone conditioned stimulus (CS) paired with a periorbital shock unconditioned stimulus (US; presented at 200- or 500-ms interstimulus intervals [ISIs]). The rats acquired CRs with 2 distinct peaks that occurred just before the US onset times. Experiments 2 and 3 examined developmental changes in CR timing in pups trained on Postnatal Days 24-26 or 32-34. Experiment 3 used a delay conditioning procedure in which the tone CS continued throughout the ISIs. Pups of both ages exhibited robust conditioning. However, there were age-related increases in the percentage of double-peaked CRs and in CR timing precision. Ontogenetic changes in eyeblink CR timing may be related to developmental changes in cerebellar cortical or hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

The role of the hippocampus (HPC) in trace eye-blink conditioning was evaluated using a 100-ms tone conditioned stimulus/stimuli (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus/stimuli (UCS). Rabbits received complete hippocampectomy (dorsal & ventral), sham lesions or neocortical lesions. Hippocampectomy produced differential effects in relation to the trace interval used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did not learn the task (only 22% conditioned responses [CRs] after 25 sessions, whereas controls showed >80% after 10 sessions), and on the few trials in which a CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during or just after the CS and always terminated prior to UCS onset). The authors conclude that the HPC encodes a temporal relationship between CS and UCS, and when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary for associative learning of the conditioned eye-blink response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retention and acquisition of classical trace conditioned responses by rabbits with hippocampal lesions.

Examined the effects of dorsal hippocampal lesions on retention of classical trace conditioned responses (CRs) using the rabbit nictitating membrane preparation. In Exp I, 18 New Zealand albino rabbits were trained to criteria and then lesioned either in the cortex or in the hippocampus and the cortex. Hippocampal damage had no effect on the retention of responses but produced significantly longer onset latencies. A control group of hippocampal Ss acquired CRs at least as quickly as the prelesion Ss and exhibited longer response onset latency. Exp II, with 24 Ss, evaluated the performance of hippocampal-lesioned Ss in classical trace conditioning with either a low-intensity periorbital shock or a corneal air puff as the unconditioned stimulus (UCS). Hippocampal Ss successfully acquired CRs under both conditions but exhibited an alteration of response onset that depended on the form of the UCS. Hippocampal Ss displayed shorter response onset in the air-puff condition and longer response onset in the shock condition. Cortical Ss consistently timed responses regardless of the UCS. Findings suggest that the hippocampus modulates temporal characteristics of learned behavior. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal lesions impair memory of short-delay conditioned eye blink in rabbits.

Involvement of hippocampus in short-delay eye blink conditioning was reexamined during conditioned response (CR) consolidation. Rabbits received bilateral hippocampectomy, removal of overlying neocortex, or sham lesions and were trained with tone/puff pairings to early acquisition (consolidation) or well trained (overtraining); retention was tested. Two effects were observed: (1) Rabbits with hippocampal lesions showed less retention in the consolidation experiment than controls. Previous studies may not have found this because initial training was more complete. Overtrained hippocampal rabbits showed more retention, which agrees with this suggestion. (2) Hippocampectomized rabbits showed larger CR amplitudes in the overtraining experiment. The complementary roles of hippocampus in the consolidation process during early learning and in modulating the expression of the amplitude/time course of behavioral CRs after associations are well learned are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal modulation of cingulo-thalamic neuronal activity and discriminative avoidance learning in rabbits

Two experiments assessed the effects of 1) combined subicular complex and posterior cingulate cortical lesions on training-induced neuronal activity (TIA) in the anterior ventral (AV) and medial dorsal (MD) thalamic nuclei; 2) hippocampal (Ammon's horn and dentate gyrus) lesions on TIA in cingulate cortex and in the AV and MD thalamic nuclei. The rabbits acquired a conditioned avoidance response (CR), stepping in an activity wheel upon hearing a 0.5-s tone (CS+), in order to prevent a foot-shock scheduled 5 s after tone onset. No response was required after a different, safety-predictive tone (CS-). In experiment 1 the combined subicular and cingulate cortical lesions enhanced thalamic TIA during acquisition and increased CR incidence in the first session of acquisition. These results confirmed the hypothesis that subicular and cingulate cortical efferents are not essential for thalamic TIA or for avoidance learning. Hippocampal lesions (experiment 2) also enhanced thalamic TIA. However, unlike subicular lesions, hippocampal lesions enhanced posterior cingulate cortical TIA as well, especially during extinction training. Hippocampal lesions did not affect CR performance. The results suggested that subicular excitatory efferents are responsible for incrementing cingulate cortical TIA, which is viewed as subserving associative attention. Activity from hippocampus downregulates the cue-elicited neuronal activity of the cingulo-thalamic circuits by suppressing the excitatory influence of the subiculum. The hippocampal influence reduces cingulo-thalamic cue-elicited activation in particular circumstances, such as the onset of CR extinction, when an expected reinforcer is omitted.     

Age-related disruption of trace but not delay classical conditioning of the rabbit's nictitating membrane response.

16 6-mo-old and 15 36–60 mo old New Zealand albino rabbits underwent classical conditioning of the nictitating membrane response in either a delay conditioning (Exp I) or a trace conditioning (Exp II) paradigm. There was no difference between old and young Ss in the acquisition of the CR in the delay paradigm, nor were there any age-related differences in generalization to the tone CS or in sensitivity to the tone CS or eyeshock UCS. However, in the trace conditioning paradigm, old Ss acquired the CR significantly more slowly than young Ss. Because the same stimulus parameters and the same response were used in both experiments, it is unlikely that age-related differences in trace conditioning were due to stimulus sensitivity, motivation, or fatigue. Results are discussed in terms of how brain changes that accompany aging could differentially affect these 2 types of classical conditioning. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the middle cerebellar peduncle disrupt acquisition and retention of the rabbit's classically conditioned nictitating membrane response.

Rabbits were classically conditioned to emit a nictitating membrane response (NMR) to either a light or tone conditioned stimulus (CS) paired with an eye shock unconditioned stimulus (UCS). They then received lesions of the middle cerebellar peduncle (MCP) or served as unoperated controls. Following surgery, they were given separate presentations of tone, light, and vibratory CSs, each paired with the eye shock UCS. In this way, conditioned responses (CR) to the previously trained light or tone served as a test of retention, whereas CRs to the remaining two conditioned stimuli (tone and vibratory or light and vibratory) served as a test of acquisition. The results of the study revealed that rabbits with complete lesions of the MCP showed disrupted acquisition and retention of the conditioned NMR to all stimuli, rabbits with partial MCP lesions also showed disrupted acquisition and retention to all CSs, but to a lesser degree, and animals with lesions that missed the MCP and unoperated controls both showed normal acquisition and retention of the conditioned NMR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following hippocampal ablation.

30 male and female New Zealand albino rabbits received 0 to 450 exposures of a tone CS prior to classical defensive conditioning of the nictitating membrane response based on an infraorbital eye shock UCS. Tone preexposure resulted in retarded conditioning in normal Ss, but was not present in Ss with bilateral dorsal hippocampectomy produced by aspiration. Controls with bilateral neocortical and callosal aspiration lesions demonstrated a latent inhibition effect similar to that shown by normal nonoperated Ss. The failure of CS preexposure to retard conditioning in hippocampal Ss was not due to differences in threshold of the conditioned response to the CS or to differences in response mechanisms as determined by tests of habituation and dishabituation of the UCR. A subsequent experiment with 24 Ss used combined-cue summation tests to confirm the fact that preexposure did not endow the tone with conditioned as well as latent inhibitory properties. Finally, tests of stimulus generalization along the auditory frequency dimension indicated flatter relative gradients for hippocampals than for nonoperated controls, with cortical controls in between. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overshadowing and summation in compound stimulus conditioning of the rabbit's nictitating membrane response.

Examined acquisition of the rabbit's nictitating membrane response to a light?+?tone simultaneous compound stimulus and its components as a function of the intensity of the tone. In Exp I, the tone intensity was varied across the values of 85, 89, and 93 db, and the CS–UCS interval was 400 msec. In Exp II, the tone intensities were 73, 85, and 93 db, and the CS–UCS interval was 800 msec. Exps III and IV further examined the effects of the 73-db CS–UCS tone at CS–UCS intervals of 400 and 800 msec. All experiments included control groups, which were trained with either a light or a tone CS. Overall results show repeated instances of overshadowing: the impairment of CR acquisition to one or both of the components of a compound. Two types of summation were obtained: within-Ss summation, in which Ss trained with a compound showed a higher level of responding to the compound than to either of its component CSs; and between-groups summation, in which a group trained with a compound showed faster CR acquisition than either of its corresponding control groups trained with a single CS. Results are discussed in terms of perceptual and distributive processing models of compound stimulus conditioning. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal activity during classical discrimination—Reversal eyeblink conditioning in rabbits.

Multiple-unit neuronal recordings were taken from the hippocampi of 10 male, New Zealand white rabbits during classical discrimination and reversal eyeblink conditioning using 2 tones as the conditioned stimuli (CS+ and CS–) and an air-puff unconditioned stimulus. During discrimination training, characteristic learning-related activity was seen in the hippocampus on trials when a conditioned response (CR) was executed. During early phases of reversal training, however, when high numbers of CRs were evident to both the new CS+ (the former CS–) and the new CS– (the former CS+), no learning-related activity was observed. Characteristic CR-related hippocampal activity to the CS+ was observed only after the rabbits began to learn the reversal response. These results suggest that the hippocampus may encode different features of eyeblink conditioning during discrimination and reversal learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditional stimulus probability and activity of hippocampal, cingulate cortical, and limbic thalamic neurons during avoidance conditioning in rabbits.

Multi-unit and field potential responses in the anterior (AC) and posterior cingulate cortices (PC), dentate gyrus (DG), and anterior ventral (AV) and medial dorsal (MD) thalamic nuclei of rabbits were recorded during acquisition and performance of a locomotor conditioned response (CR). The CR, stepping in an activity wheel in response to a tone (conditioned stimulus [CS+]), prevented the occurrence of a shock unconditioned stimulus (UCS) scheduled 5 sec after CS+ onset. Ss also learned to ignore a different tone (CS–), not predictive of the UCS. Training was given daily until behavioral discrimination reached criterion. After criterion, asymmetric probability (AP) sessions were given that were the same as the conditioning session except for probability manipulation. A significant discriminative response developed in all regions during behavioral acquisition. The unit response in the AP session was enhanced in all areas by rare presentation of the CS–, compared with the equal and frequent CS– conditions. Rare presentation of the CS+ enhanced the unit response in the AC, PC, and DG, but it suppressed the firing of AV and MD neurons. Rare CS+ presentations did not alter AV and PC neuronal activity in Ss with subicular lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Element pretraining influences the content of appetitive serial compound conditioning in rats.

Examined the effects of prior pairings of conditioned stimulus/stimuli (CS)2 with the unconditioned stimulus/stimuli (UCS) on the nature of the associations formed in CS1?→?CS2?→?UCS serial compound conditioning, in 4 experiments with 72 male and 32 female albino rats. In Exps I and II, prior training of CS2 prevented the acquisition of stimulus–stimulus (S–S) associations between CS1 and stimulus features of CS2 but enhanced the acquisition of stimulus–response (S–R) associations between CS1 and the emotional conditioned response (CR) evoked by CS2. In Exps III and IV, the effects of CS2 pretraining were not due to CS2 training itself, but rather to its endowing CS2 with the ability to evoked a strong CR during the early stages of serial compound conditioning. In Exp III, suppression of the CR to a pretrained CS2 during serial compound conditioning permitted the establishment of S–S associations. In Exp IV, the induction of a CR in the presence of an untrained CS2 during serial compound conditioning prevented the acquisition of S–S associations. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of conditioned associations in Hermissenda: Additive effects of contiguity and the forward interstimulus interval.

Examined conditioned suppression of photokinesis (CSPK) by the marine mollusc in 3 experiments. In each experiment, groups of Ss received light (conditioned stimulus, CS) paired with high-speed orbital rotation (unconditioned stimulus, UCS), light and rotation explicitly unpaired, or no exposure to these stimuli. 24 hrs after training, all Ss were tested for CSPK in the presence of the light. 50 CS–UCS pairings resulted in a marginal CSPK, whereas 100 and 150 pairings produced strong CSPK. In Exp 2, delay between CS onset and UCS onset was varied between 1 and 10 s. The 10-s interstimulus interval (ISI) did not support conditioning, whereas 1-s and 2-s ISIs were effective. In Exp 3, CS–UCS pairings in which the CS preceded the onset of the UCS and ended with the offset of the UCS evoked stronger CSPK than either a CS that preceded the UCS and ended with its onset or a CS that was paired in simultaneous compound with the UCS. CS–UCS contiguity and the forward ISI act additively to establish the CS–UCS association. No differences were observed between groups that were untreated and that received the CS and UCS unpaired. Similarities are noted in the temporal characteristics of associative learning in these Ss and vertebrate species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bilateral cerebellar lesions disrupt conditioned eyelid responses in unrestrained rats.

Electromyographic eyelid responses in unrestrained rats were classically conditioned in a Pavlovian delay paradigm by using a tone conditioned stimulus (CS) and periorbital shock unconditioned stimulus (US). After eyelid conditioning was complete, bilateral electrolytic lesions were made in the dentate-interpositus region of the cerebellar nuclei. Initial eyelid conditioning was reliable and very similar to that previously observed in the rabbit, although the asymptotic eyelid responses contained a short-latency startle response in addition to the usual conditioned and unconditioned responses (CR and UR). Substantial decrements in CRs were observed in 13 of the 14 rats with accurately placed lesions. In contrast, startle responses and URs were unaffected. Results replicate the effects of cerebellar lesions on eyelid CRs in the rabbit and suggest that the anatomical basis of eyelid conditioning in both species is similar. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of classically conditioned-related activity in the hippocampus is affected by lesions of the cerebellar interpositus nucleus.

Rabbits were first given left cerebellar interpositus nucleus lesions followed by classical nictitating membrane (NM) conditioning using paired presentations of a tone conditioned stimulus (CS) and an air puff unconditioned stimulus (UCS). Multiple-unit hippocampal activity was monitored over the course of training. In rabbits with anterior interpositus lesions, the acquisition of learned responses and significant increases in training-related hippocampal activity were prevented when paired training was given to the left NM but not when training was switched to the right NM. Rabbits with lesions anterior to the interpositus or in surrounding cerebellar regions failed to show deficits in behavioral responding or hippocampal activity. These results indicate that acquisition of conditioning-related activity in the hippocampus depends on an intact interpositus nucleus of the cerebellum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)