Whole body hyperthermia selectively induces heat shock protein 72 in neurons of the rat spinal cord

Rabbits with lesions of either medial prefrontal cortex (mPFC) or amygdala central nucleus (ACN) were compared with sham-lesioned animals during differential and reversal classical conditioning of the eyeblink (EB) and heart rate (HR) response. Lesions of the mPFC, but not ACN, produced a severe impairment in EB reversal conditioning, but neither lesion affected original discrimination. However, both mPFC and ACN lesions produced a severe attenuation of accompanying HR decelerations during both initial differentiation and reversal. These results suggest that mPFC processing of Pavlovian conditioning contingencies affects not only the autonomic component of learning but preservative somatomotor conditioning as well, whereas ACN processing affects only the autonomic component.     

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)     

Prefrontal control of trace eyeblink conditioning in rabbits: Role in retrieval of the CR?

Rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink (EB) conditioning task to a criterion of 10 consecutive EB conditioned responses (CRs). One week later, ibotenic acid or sham lesions were made in the mPFC centered on the prelimbic region (Brodmann's area 32) or the cingulate cortex (Brodmann's area 24). Following a 1-week postoperative recovery period, all animals were retrained for 4 consecutive days using the same parameters as during acquisition, given 1 week off, and retrained for another 4 days. Mean EB conditioning deficits in the group with area 32 lesions occurred on the first and second days of each retraining period. However, by the third and fourth days of retraining, these lesioned animals were performing at a level comparable to that of the sham group. Lesions of area 24 did not produce deficits at either retesting period. These findings were interpreted to indicate that area 32, but not area 24, is involved in retrieval processes, rather than consolidation or storage, in that the animals were impaired at both retesting times, but were able to relearn the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuronal activity in the medial prefrontal cortex during Pavlovian eyeblink and nictitating membrane conditioning

The present study assessed Pavlovian eyeblink (EB) conditioning, using tones and periorbital shock as the conditioned and unconditioned stimuli (CS and US), and nictitating membrane (NM) conditioning, using tones and airpuffs as the CS and US. During each experiment, CS-evoked changes in multiple-unit activity (MUA) in the medial prefrontal cortex (mPFC) were recorded. Concomitant heart rate (HR) conditioned responses (CRs) were also recorded. A nonassociative control group received explicitly unpaired presentations of the CS and US in each experiment. Increases in both NM and EB CRs occurred over sessions in the paired, but not the unpaired, groups. Decelerative HR CRs also occurred in the eyeshock, but not the airpuff, group. Although tone-evoked increases in neuronal activity were obtained during 10 initial tone-alone presentations in all groups, this activity habituated over trials. CS-evoked increases in neuronal activity also occurred, but this activity was considerably greater in the group that received periorbital shock as the US. During subsequent extinction trials, decreases in tone-evoked neuronal activity occurred in this group, compared with the previous CS/US paired trials. CS-evoked MUA increases were minimal during all except the pretraining phase of the study in the CS/US unpaired control groups and in the paired airpuff group. These findings show that neuronal activity during associative learning occurs in the mPFC during Pavlovian EB, as well as HR conditioning, but this activity apparently reflects an affective component to learning that is only indirectly related to skeletal conditioning.     

Prefrontal control of trace versus delay eyeblink conditioning: Role of the unconditioned stimulus in rabbits (Oryctolagus cuniculus).

The conditioned eyeblink (EB) response was studied with trace conditioning procedures in rabbits (Oryctolagus cuniculus) with lesions to the medial prefrontal cortex (mPFC) or sham lesions. Three experiments were performed in which either periorbital shock or a corneal airpuff served as the unconditioned stimulus (US) in separate groups of sham or mPFC-lesioned rabbits. Acquisition of the EB conditioned response (CR) was faster and reached a higher asymptote with the eyeshock US than with the airpuff US. However, mPFC lesion-induced trace conditioning deficits were obtained only in the groups that received the airpuff US. All rabbits showed normal delay conditioning and extinction. These results suggest that mPFC mediates trace EB conditioning when emotional arousal is low. However, in circumstances when emotional arousal may be high (i.e., during exposure to aversive periorbital shock), other structures (such as amygdala) may be activated to permit learning even in the absence of input from mPFC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial prefrontal cortex and Pavlovian conditioning: Trace versus delay conditioning.

Pavlovian eyeblink (EB) conditioning was studied in both trace and delay paradigms in rabbits (Oryctolagus cuniculus) with either medial prefrontal cortex (mPFC) lesions or sham lesions. mPFC lesions of prelimbic cortex (Brodmann's Area 32) retarded EB conditioning in the trace but not the delay paradigm. However, this effect was significant only when the conditioned stimulus (CS) was 500 rather than 100 ms in duration. Lesions of the anterior cingulate cortex (Area 24) did not affect EB conditioning in a trace paradigm. Accompanying CS-evoked heart rate slowing was attenuated under all conditions by the mPFC lesions, although this result was not always statistically significant. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the substantia nigra retard Pavlovian eye-blink but not heart rate conditioning in the rabbit.

Bilateral radio-frequency (RF) lesions of the substantia nigra retarded Pavlovian eye-blink (EB) conditioning without affecting concurrent heart rate (HR) conditioning. Dopamine (DA) depletion occurred only in the caudate nucleus, whereas norepinephrine (NE) depletion was limited to the hypothalamus. Bilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra retarded acquisition of both EB and HR responses. Six-OHDA lesions produced significant NE depletion in the nucleus acumbens/septi, frontal cortices, and hypothalamus, as well as DA depletion in the caudate nucleus. Trials required to reach EB conditioning criterion were significantly correlated to the caudate DA levels. The magnitude of conditioned bradycardia was on the other hand significantly correlated with hypothalamic NE levels. Results suggest that interruption of the nigro-striatal dopaminergic pathway retards Pavlovian somatomotor learning without affecting concurrent autonomic learning, although the latter may depend on an intact ascending NE pathway to the hypothalamus, which passes through the tegmentum and thus is also destroyed in some cases by substantia nigra lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial Prefrontal Lesions and Pavlovian Eyeblink and Heart Rate Conditioning: Effects of Partial Reinforcement on Delay and Trace Conditioning in Rabbits (Oryctolagus cuniculus).

Effects of continuous (100%) versus partial (25%) reinforcement were studied on Pavlovian delay and trace eyeblink conditioning in rabbits (Oryctolagus cuniculus) with either lesions to the medial prefrontal cortex (mPFC) or sham lesions. Concomitant heart rate changes evoked by the conditioned stimulus were also assessed. Partial reinforcement retarded eyeblink conditioning in both the trace and delay paradigm, but this impairment was greater during trace conditioning and in rabbits with mPFC lesions. Accompanying conditioned stimulus-evoked heart rate slowing was attenuated under all conditions by the mPFC lesions, although this result was not always statistically significant. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraseptal scopolamine has differential effects on Pavlovian eye blink and heart rate conditioning.

Evaluated the effects of intraseptal scopolamine hydrobromide (40 μg) injections on Pavlovian (classical) conditioning, with tones used as the CS and a periorbital electric shock train as the UCS, using New Zealand albino rabbits. Eyeblink (EB) and heart rate (HTR) CRs were concomitantly recorded. Although injections of scopolamine into the medial septum impaired the acquisition of the Pavlovian conditioned eyelid reflex, these injections enhanced the magnitude of accompanying Pavlovian conditioned HTR decelerations. However, scopolamine applied to the lateral septal area had no effect on EB conditioning, relative to the vehicle; like medial injections, scopolamine also enhanced the magnitude of the accompanying HTR decelerations. Results are compatible with those of previous investigations indicating that medial septal dysfunction impairs somatomotor conditioning but leaves autonomic conditioning intact and that septal dysfunction produces a parasympathetic bias of the cardiovascular system. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peripheral autonomic mechanisms and Pavlovian conditioning in the rabbit (Oryctolagus cuniculus).

Three experiments examined the effects of peripheral administration of 0–50 mg/kg atropine methyl nitrate and 6-hydroxydopamine hydrobromide on differential classical conditioning of eye-blink (EB) and heart rate (HR) responses in 102 New Zealand albino rabbits. Atropine decreased HR CR magnitude and increased baseline HR, although the latter declined somewhat over the 1st few sessions of the experiment. As baseline HR declined, EB CRs increased in Ss treated with atropine. However, the acquisition of the EB response was impaired in these Ss compared with Ss treated with saline. The administration of 6-hydroxydopamine produced an impairment of the HR response early and late during acquisition but had no effect on EB conditioning. Control experiments suggested that the impairments produced by methyl atropine were not due to general somatomotor deficits or to a differential sensitivity to the electric shock UCS. The conditioning data are consistent with B. C. Lacey and J. I. Lacey's (1974) peripheral afferent feedback hypothesis of autonomic-somatic relations. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motor cortex lesions do not affect learning or performance of the eyeblink response in rabbits.

The possible modulatory role of motor cortex in classical conditioning of the eyeblink response was examined by ablating anterior neocortex in rabbits and training them with an auditory conditioned stimulus (CS) and an airpuff unconditioned stimulus (US) in either a delay (Experiment 1) or a trace (Experiment 2) conditioning paradigm. Topographic measures such as amplitude and onset latency were assessed during conditioning sessions for conditioned responses (CRs) and on separate test days for unconditioned responses (URs) by using a range of US intensities. No lesion effects were observed for learning or performance measures in acquisition or retention of either delay or trace conditioning. During trace conditioning, lesioned rabbits did, however, exhibit a trend toward impairment and demonstrated significantly longer CR latencies. Damage to motor and frontal cortex does not significantly affect eyeblink response performance or learning in either a delay or a trace conditioning paradigm. (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)     

Feasibility of an immunoassay for mevalonolactone

Trace eyeblink classical conditioning was assessed in patients with bilateral medial-temporal amnesia and matched control participants who had previously shown equivalent delay eyeblink conditioning (J. D. E. Gabrieli et al., 1995). The silent trace interval varied for durations of 500, 750, or 1,000 ms in successive sessions separated by at least 2 weeks; extinction trials followed each session. Patients with amnesia produced significantly fewer conditioned responses (CRs) than did control participants at all trace intervals. Both groups produced fewer CRs as the trace interval lengthened. Thus, the temporal lobe memory system in humans makes an essential contribution to normal acquisition in trace, but not delay, classical eyeblink conditioning.     

Cortical involvement in acquisition and extinction of trace eyeblink conditioning.

Previous studies have implicated 2 cortical regions interconnected with the hippocampal formation, the retrosplenial cortex (RSQ and the medial prefrontal cortex (mPFC), as loci important for the acquisition of hippocampally dependent trace eyeblink conditioning. These loci have also been proposed to serve as long-term storage sites of task critical information. This study used lesions made prior to training to investigate the roles of the RSC, as well as the caudal and rostral subdivisions of the mPFC, in the acquisition and subsequent extinction of trace eyeblink conditioning in the rabbit. The caudal mPFC and rostral were shown to be critical for acquisition and extinction of the conditioned reflex, respectively. The data indicate that the RSC is not critical for acquisition or extinction of the trace conditioned reflex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the mediodorsal nucleus of the thalamus and classical eyeblink conditioning under less-than-optimal stimulus conditions: Role of partial reinforcement and interstimulus interval.

Rabbits received lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions and were subjected to classical eyeblink (EB) and heart rate (HR) conditioning. Separate groups of sham and lesioned animals received either 50% or 25% reinforcement with a periorbital shock unconditioned stimulus. Other groups received an interstimulus interval (ISI) of either 1.0 or 1.5 s. Animals with MD lesions acquired the EB conditioned response (CR) more slowly than sham-lesioned animals with either the 1.5-s ISI or with the 25% reinforcement schedule. The lesions had no significant effect on the HR CR, however. Results suggest that information processed by MD is relayed to the prefrontal cortex and is required for somatomotor response selection under nonoptimal learning conditions. (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)     

Ethanol enhancement of Pavlovian conditioning.

60 New Zealand albino rabbits were tested for Pavlovian conditioning and extinction of eye-blink (EB) and heart-rate (HR) responses following water or various doses of oral ethanol (375–2,500 mg/kg). The highest dose suppressed both EB and HR conditioning during training, whereas the lowest dose enhanced HR responses during training and increased EB responses during later extinction in a symmetrically state-dependent manner. An intermediate dose (750 mg/kg) administered during training enhanced HR responses and suppressed EB responses but increased EB responses during later extinction following either ethanol or water. Ethanol treatments also suppressed unconditioned responses (UCRs) to shock and increased locomotor activity; however, these effects differed qualitatively from those that ocurred during Pavlovian training and extinction. Results suggest that very low doses of ethanol can enhance the ability of stimuli to elicit Pavlovian conditioned reflexes and impair the ability to adaptively modify these reflexes when stimulus contingencies later change. (55 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired trace eyeblink conditioning in bilateral, medial-temporal lobe amnesia.

Trace eyeblink classical conditioning was assessed in patients with bilateral medial-temporal amnesia and matched control participants who had previously shown equivalent delay eyeblink conditioning (J. D. E. Gabrieli et al., 1995). The silent trace interval varied for durations of 500, 750, or 1,000 ms in successive sessions separated by at least 2 weeks; extinction trials followed each session. Patients with amnesia produced significantly fewer conditioned responses (CRs) than did control participants at all trace intervals. Both groups produced fewer CRs as the trace interval lengthened. Thus, the temporal lobe memory system in humans makes an essential contribution to normal acquisition in trace, but not delay, classical eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of autonomic and behavioral components of conditioned fear during development in the rat.

Examined classical conditioning of heart rate (HR) in unrestrained preweanling and weanling Sprague-Dawley rats (aged 16, 19, 21, 25, and 28 days old), with tone and light as the conditioned stimulus/stimuli (CS) and electric shock as the unconditioned stimulus/stimuli (UCS). The conditioned cardiac response was a sustained deceleration in HR that did not emerge until Day 21 for the tone CS and until Day 28 for the light CS. In contrast, when suppression of a behavioral response (running in a straight alley for dry suckling as reward) was used as the index of conditioning, the suppressive effects of the CS were evident around Day 16 for the tone and around Day 19 for the light. Findings indicate that during ontogenesis (a) the behavioral and autonomic responses to the same CS do not develop at the same pace; (b) the emergence of conditioned responses (CRs) to tone and light stimuli parallel the sequential order in which the relevant sensory modalities achieve maturity (first audition, next vision); and (c) there is no clear-cut interdependence between development of the HR orienting response and conditionability of HR because unconditioned cardiac deceleration to both auditory and visual stimuli first appears about Day 16 in the developing rat, well before conditioned HR responses can be established to either stimulus. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lateral septal lesions enhance conditioned bradycardia in the rabbit.

52 New Zealand albino rabbits received sham lesions or complete, medial, lateral, or posterior septal lesions and were subjected to differential conditioning in which tones of different frequencies served as CSs, and paraorbital electric shock was the UCS. EMG, heart rate (HR), blood pressure (BP) CRs, and hippocampal rhythmic slow wave activity (RSA) were recorded. Lateral or complete septal lesions enhanced the bradycardiac HR CR but had no effect on the BP depressor response. Both unconditioned and conditioned EMG responses occurred infrequently and were unaffected by any lesion. Unconditioned HR responses and somatomotor threshold determinations to unsignaled electric shock were also unaffected by the lesions. Complete septal lesions increased locomotor activity relative to sham or other septal lesions. Little hippocampal RSA was detected in Ss with medial lesions, but the HR CR was unimpaired in these Ss. Data implicate the septo-hippocampal circuit in classical conditioning of cardiovascular changes and further suggest that diencephalic forebrain structures may modulate forebrain processing of sensory stimulation, perhaps in terms of assessing its biological significance. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)