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

Past studies of the neuronal correlates of avoidance conditioning in rabbits have led to a model of information flow among structures of the limbic system. A hypothesis of the model is that unexpected stimuli activate certain hippocampal and cingulate cortical neurons. This activity in turn suppresses or "limits" the firing of limbic thalamic neurons. This hypothesis is tested in relation to stimuli classified as unexpected or expected on the basis of their incidence or "probability." Multi-unit and field potential responses in the anterior and posterior cingulate cortices (AC and PC), the dentate gyrus (DG), and the anterior ventral (AV) and medial dorsal (MD) thalamic nuclei were recorded during the acquisition and performance of a locomotor conditioned response (CR). The CR, stepping in an activity wheel in response to a 0.5-s tone (CS+), prevented the occurrence of a shock US scheduled 5 s after CS+ onset. The rabbits also learned to ignore a different tone (CS-), not predictive of the US. Training was given daily (120 trials, 60 with each CS in an irregular sequence) until behavioral discrimination reached criterion. After criterion, asymmetric probability (AP) sessions were given, in which the CS+/CS- proportions were .2/.8 or .8/.2. The AP sessions were the same as conditioning sessions except for the probability manipulation. A significant discriminative response, i.e., a greater neuronal discharge to the CS+ than to the CS-, developed in all regions during behavioral acquisition. The unit response in the AP sessions 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 cortical areas (AC, PC, and DG), but it suppressed the firing of limbic thalamic (AV and MD) neurons. These results were supportive of the model. Rare CS+ presentations did not alter AV and PC neuronal activity in rabbits with subicular lesions, a result suggesting that an intact hippocampus is essential for normal neuronal responses to stimulus probability in the cingulate cortex and limbic thalamus.     

Effects of cingulate cortical lesions on avoidance learning and training-induced unit activity in rabbits

Summary This study extends an ongoing analysis of the neural mediation of discriminative avoidance learning in rabbits. Electrolytic lesions encompassing anterior and posterior cingulate cortex (area 24 and 29) or ibotenic acid lesions in area 24 only were made prior to avoidance conditioning wherein rabbits learned to step in response to a tone conditional stimulus (CS+) in order to avoid a brief, response-terminated 1.5 mA. foot-shock unconditional stimulus (US). The US was presented 5 s after CS+ onset, in the absence of a prior stepping response. The rabbits also learned to ignore a different tone (CS-) not followed by the US. Multi-unit activity of the caudate and medial dorsal (MD) thalamic nuclei, projection targets of the cingulate cortex, was recorded during learning in all rabbits. Activity was also recorded in area 29 in the rabbits with area 24 lesions. Learning in rabbits with combined lesions was severely impaired and it was moderately retarded after lesions in area 24. MD thalamic and caudate training-induced neuronal discharge increments elicited by the CS+ were enhanced in rabbits with lesions, suggesting a suppressive influence of cingulate cortical projections on this activity. Early-, but not late-developing training-induced unit activity in area 29c/d was absent in rabbits with area 24 lesions, indicating that area 24 is a source of early-developing area 29 plasticity. These results are consistent with hypotheses of a theoretical working model, stating that: a) learning depends on the integrity of two functional systems, a mnemonic recency system comprised by circuitry involving area 24 and the MD nucleus and a mnemonic primacy system comprised by circuitry involving area 29 and the anterior thalamic nuclei; b) corticothalamic information flow in these systems suppresses thalamic CS elicited activity in trained rabbits; c) corticostriatal information flow is involved in avoidance response initiation. An absence of rhythmic theta-like neuronal bursts in area 29b in rabbits with area 24 lesions is attributable to passing fiber damage.     

Lesions of the entorhinal cortex disrupt behavioral and neuronal responses to context change during extinction of discriminative avoidance behavior

 Rabbits given either electrolytic lesions of the entorhinal cortex or sham-lesions were trained to prevent a foot-shock by stepping in an activity wheel after one tone, a positive conditioned stimulus (CS+), and to ignore a different tone, a negative conditioned stimulus (CS–). Neuronal activity was recorded simultaneously in the basolateral nucleus of the amygdala, the CA1 cell field of hippocampus, anterior cingulate cortical area 24b and posterior cingulate cortical area 29c/d. The activity of neurons in the entorhinal cortex was recorded in the controls. Acquisition of conditioned avoidance responses (CRs) was not affected by lesions of the entorhinal cortex. Discriminative neuronal activity (greater neuronal responses to the CS+ than to the CS–) during CR acquisition was significantly enhanced in hippocampal area CA1 and attenuated in the basolateral amygdala in rabbits with lesions. Following acquisition to a criterion, two counterbalanced extinction tests were administered, one in the original context and the other in the presence of novel contextual stimuli. CR frequency was significantly reduced in controls but not in rabbits with lesions, during extinction with novel contextual stimuli, relative to performance in the original context. The rabbits with lesions also showed fewer inter-trial responses than controls during extinction in the original context but inter-trial response frequency in rabbits with lesions did not differ from the frequency in controls during extinction in the novel context. Neurons in the basolateral amygdala in controls showed discriminative activity during extinction in the original context but not in the novel context. Amygdalar neurons in the rabbits with lesions did not show discriminative activity during extinction in either context. Posterior cingulate cortical neurons in control rabbits did not show discriminative activity during extinction in the original context but these neurons exhibited robust discriminative activity in the novel context. Posterior cingulate cortical neurons in rabbits with lesions showed discriminative activity in both extinction sessions. The results indicated that the entorhinal cortex does not play a significant role in the acquisition of discriminative avoidance behavior, under the employed conditions of training. However, the interactions of neurons in the entorhinal cortex, amygdala and cingulate cortex are essential for contextual modulation of CRs during extinction. Received: 17 September 1996 / Accepted: 14 January 1997     

Anterior and medial thalamic lesions,discriminative avoidance learning,and cingulate cortical neuronal activity in rabbits

Summary Four groups of male albino rabbits were trained to perform a conditioned response (CR, stepping in an activity wheel) to an acoustic (pure tone) conditional stimulus (CS+). A 1.5–2.0 mA shock unconditional stimulus (US) delivered through the grid floor of the wheel was administered 5 s after CS + onset, but stepping during the CS-US interval prevented the US. The rabbits were also trained to ignore a second tone (a negative conditional stimulus or CS-) of different auditory frequency than the CS+, that was presented in an irregular order on half of the conditioning trials but never followed by the US. One group had bilateral electrolytic lesions in the medial dorsal (MD) thalamic nucleus, a second group had combined bilateral lesions in the MD and the anterior thalamic nuclei, and a third group had no lesions. The fourth group was composed of rabbits with combined lesions that resulted in only partial damage in the anterior and MD nuclei. In all rabbits, multi-unit activity and field potentials were recorded from the cingulate cortical projection targets of the MD and anterior nuclei. The average rate of acquisition in rabbits with MD and partial lesions was not significantly different from that in controls, but the asymptotic performance in rabbits with lesions was significantly impaired, relative to that in controls. None of the rabbits that had the combined MD and anterior thalamic lesions reached the acquisition criterion. The average proportion of trials in which these rabbits performed avoidance responses during their final training sessions was 0.3, compared to 0.8 in controls. The unconditioned response was not significantly affected by the lesions, nor was there any indication that the lesions impaired the sensory processing of the CSs. These results and the massive traininginduced neuronal discharges shown in past studies to occur in the limbic thalamic neurons indicate that these neurons are importantly involved in the circuitry that mediates discriminative avoidance conditioning in rabbits. The training-induced neuronal activity in cingulate cortex was dramatically attenuated in rabbits with lesions. Differences in the degree of this attenuation between lesion conditions and with respect to training stages were discussed in relation to a theoretical working model of limbic thalamic and cingulate cortical associative functions.     

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

Rabbits received classical conditioning of the nictitating membrane response (NMR) in a trace conditioning paradigm. In this paradigm, a 250-ms tone conditioned stimulus (CS) occurs, after which there is a 500-ms period of time in which no stimuli occur (the trace interval), followed by a 100-ms air puff unconditioned stimulus (UCS). In Experiment 1, lesions of the hippocampus or cingulate/retrosplenial cortex disrupted acquisition of the long-latency or adaptive conditioned response relative to unoperated controls and animals that received neocortical lesions that spared the cingulate/retrosplenial areas. When animals with hippocampal or cingulate/retrosplenial 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 rabbits. In a second experiment multiple-unit activity in area CA1 of the hippocampus was examined during acquisition of the trace conditioned response (CR). Three groups of animals were tested: animals that had a 500-ms trace interval (Group T-500), animals that received explicitly unpaired presentations of the CS and UCS (Group UP), and animals that underwent conditioning with a 2,000-ms trace interval (Group T-2000). Animals in Group T-500 acquired the CR in about 500 trials. Early in training, and well before any CRs occurred, there was a substantial increase in neuronal activity in the hippocampus that began during the CS and persisted through the trace interval. There was also an increase in the UCS period that modeled the amplitude-time course of the behavioral unconditioned response. Later in conditioning as CRs emerged, there was no longer neuronal bursting throughout the CS + trace period. Rather, the activity shifted to later in the trace interval and formed a model of the amplitude-time course of the behavioral CR. Activity during the UCS period was similar to that seen earlier in conditioning. Animals in Group UP showed no behavioral conditioning and no increase in neuronal activity. Animals in Group T-2000 showed no long-latency behavioral conditioning and no increase in neuronal activity. The data are discussed in terms of the role of the hippocampus in conditioning during situations in which the CS and UCS are not contiguous in time.     

Neuronal encoding of conditional stimulus duration in the cingulate cortex and the limbic thalamus of rabbits

Neuronal activity in cingulate cortex was recorded during discriminative active avoidance conditioning of rabbits. In one subpopulation of neurons, brief (200 and 500 ms) conditional stimuli (CSs) elicited greater average cingulate cortical training-induced neuronal discharges during conditioned response acquisition than did a long (5,000 ms) CS, and the amount of neuronal discrimination between CS+ and CS- was greater in response to the brief CSs than to the long CS. Neurons in a different subpopulation did not encode CS duration per se but were sensitive to the novelty of the CS duration. Medial dorsal and anteroventral thalamic neurons were suppressed by novel CS durations that activated novelty-sensitive neurons in related cingulate cortical areas. These results are discussed in relation to a theoretical model of the neural mediation of avoidance conditioning.     

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.     

Cingulate cortical coding of context-dependent latent inhibition

Neuronal activity of the auditory thalamus, amygdala, cingulate cortex, and substantia nigra was recorded during the administration of a behavioral test for latent inhibition (LI) or the retardation of behavioral conditioning because of preexposure of the conditional stimulus (CS). Following CS preexposure, both the preexposed CS and a control CS predicted avoidable footshock. LI occurred as significantly fewer avoidance conditioned avoidance responses after the preexposed CS than after the control CS. Attenuation of neuronal responses to the preexposed CS, or neural LI, occurred in all monitored areas. One group of subjects (Oryctolagus cuniculus) then received context extinction, and additional groups experienced novel context exposure or handling. Context extinction enhanced behavioral responding to the preexposed CS, eliminating LI. Context extinction also eliminated cingulate cortical neural LI by enhancing posterior cingulate cortical responses to the preexposed CS and attenuating anterior cingulate cortical responses to the control CS. Present and past results are interpreted to indicate that LI is (a) a failure of response retrieval and/or expression mediated by interfering CS-context associations and (b) a product of interactions of the posterior cingulate cortex and the hippocampus.     

Conditioned eyeblink response consists of two distinct components

The aim of these experiments was to obtain a detailed knowledge of how the orbicularis oculi muscle is activated during the execution of a conditioned eyeblink response (CR). This is the first critical step to understand the underlying neural mechanisms involved in the control of the CR. Decerebrate ferrets were trained in a classical conditioning paradigm. The conditioned stimulus (CS) was a train of electrical stimuli (15 pulses, 50 Hz, 1 mA) applied to the forelimb, and the unconditioned stimulus (US) was a train of electrical stimuli (3 pulses, 50 Hz, 3-4 mA) to the periorbital region. The CRs were studied by recording electromyograms (EMGs) from the orbicularis oculi muscle. The eyeblink CR in all animals showed a similar topography with at least two different components, CR1 and CR2, which were expressed at different rates. CR1 appeared first during acquisition, had a shorter onset latency, and was more phasic and more resistant to extinction than CR2. A marked pause in the muscle activity separated the two components. To control that the two-component CR were not species, paradigm or preparation specific, awake rabbits were trained with a tone CS (300 ms, 4 kHz, 64 dB) and a train of periorbital stimuli as US (3 pulses, 50 Hz, 3 mA). CR1 and CR2 were present in the rabbit eyeblink CR. The cerebellum is implicated in the control of CRs and to study whether separate neural pathways were responsible for CR1 and CR2, direct brachium pontis stimulation was used to replace the forelimb CS. CR1 and CR2 were present in the CR elicited by the brachium pontis CS. The presence of CR1 and CR2 after a unilateral lesion of the brachium conjunctivum shows that output from the contralateral cerebellar hemisphere was not the cause for any of the components. Other mechanisms that might be involved in the separation of the CR into two components are discussed. The results show that the eyeblink CR consists of at least two components, CR1 and CR2, which most likely originate either as a direct central command from the cerebellum or in the output pathway before the facial nucleus.     

Cerebellar cortex and eyeblink conditioning: bilateral regulation of conditioned responses

We examined the role of the cerebellum in classical conditioning of the nictitating membrane response (NMR) of rabbits by comparing the effects of unilateral and bilateral cerebellar cortical lesions. Using extended preoperative conditioning to ensure high levels of learning, we confirmed that unilateral lesions of lobules HVI and ansiform lobe impaired conditioned responses (CRs) previously established to an auditory conditioned stimulus, but did not prevent some relearning with post-operative retraining. Bilateral lesions of HVI and ansiform lobe produced similar impairments of CRs, but also prevented subsequent relearning. Unilateral cortical lesions produced significant enhancement of unconditioned response (UR) amplitudes to periorbital electrical stimulation. Bilateral cortical lesions enhanced UR amplitudes to a lesser extent. Because there was no correlation between the degree of CR impairment and UR enhancement across the unilateral and bilateral lesion groups, the suggestion that the lesions impaired CRs due to general effects upon performance, rather than due to losses of learning, is not supported. Both sides of the cerebellar cortex contribute towards learning a unilaterally trained CR. This finding is important for the re-interpretation of unilateral, reversible inactivation studies that have found no involvement of the cerebellar deep nuclei in the acquisition of NMR conditioning. In addition, we found conditioning-dependent modifications of unconditioned responses that were particularly apparent at low intensities of periorbital electrical stimulation. This finding is important for the re-interpretation of studies that have found apparent changes in the UR of conditioned subjects after cerebellar lesions.     

Activity profiles of single neurons in caudal anterior cingulate cortex during trace eyeblink conditioning in the rabbit

Acquisition of trace eyeblink conditioning involves the association of a conditioned stimulus (CS) with an unconditioned stimulus (US) separated by a stimulus-free trace interval. This form of conditioning is dependent upon the hippocampus and the caudal anterior cingulate cortex (AC), in addition to brain stem and cerebellar circuitry. Hippocampal involvement in trace eyeblink conditioning has been studied extensively, but the involvement of caudal AC is less well understood. In the present study, we compared neuronal responses from rabbits given either paired (trace conditioning) or unpaired (pseudoconditioning) presentations of the CS and US. Presentation of the CS elicited significant increases in neuronal activity at the onset of both trace conditioning and pseudoconditioning. A robust CS-elicited neuronal response persisted throughout the first 2 days of trace conditioning, declining gradually across subsequent training sessions. In contrast, the magnitude of the CS-elicited excitatory response during pseudoconditioning began to decline within the first 10 trials. Neurons exhibiting excitatory responses to the CS during trace conditioning also exhibited excitatory responses to the US that were significantly greater in magnitude than US-elicited responses during pseudoconditioning. CS-elicited decreases in neuronal activity became more robust over the course of trace conditioning compared to pseudoconditioning. Reductions in activity during the CS interval consistently preceded excitation in both training groups, suggesting that the CS-elicited decreases in neuronal activity may serve to increase the signal-to-noise ratio of the excitatory response to the tone. Taken together, these data suggest that the caudal AC is involved early in trace eyeblink conditioning and that maintenance of the CS-elicited excitatory response may serve to signal the salience of the tone.     

Kinetic and frequency-domain properties of reflex and conditioned eyelid responses in the rabbit

Eyelid position and the electromyographic activity of the orbicularis oculi muscle were recorded unilaterally in rabbits during reflex and conditioned blinks. Air-puff-evoked blinks consisted of a fast downward phase followed sometimes by successive downward sags. The reopening phase had a much longer duration and slower peak velocity. Onset latency, maximum amplitude, peak velocity, and rise time of reflex blinks depended on the intensity and duration of the air puff-evoking stimulus. A flashlight focused on the eye also evoked reflex blinks, but not flashes of light, or tones. Both delayed and trace classical conditioning paradigms were used. For delayed conditioning, animals were presented with a 350-ms, 90-dB, 600-Hz tone, as conditioned stimulus (CS). For trace conditioning, animals were presented with a 10-ms, 1-k/cm(2) air puff, as CS. The unconditioned stimulus (US) consisted of a 100-ms, 3-k/cm(2) air puff. The stimulus interval between CS and US onsets was 250 ms. Conditioned responses (CRs) to tones were composed of downward sags that increased in number through the successive conditioning sessions. The onset latency of the CR decreased across conditioning at the same time as its maximum amplitude and its peak velocity increased, but the time-to-peak of the CR remained unaltered. The topography of CRs evoked by short, weak air puffs as the CS showed three different components: the alpha response to the CS, the CR, and the reflex response to the US. Through conditioning, CRs showed a decrease in onset latency, and an increase in maximum amplitude and peak velocity. The time-to-peak of the CR remained unchanged. A power spectrum analysis of reflex and conditioned blink acceleration profiles showed a significant approximately 8-Hz oscillation within a broadband of frequencies between 4 and 15 Hz. Nose and mandible movements presented power spectrum profiles different from those characterizing reflex and conditioned blinks. It is concluded that eyelid reflex responses in the rabbit present significant differences from CRs in their profiles and metric properties, suggesting different neural origins, but that a common approximately 8-Hz neural oscillator underlies lid motor performance. According to available data, the frequency of this putative oscillator seems to be related to the species size.     

Classically Conditioned Blood Pressure Decreases Induced by Electrical Stimulation of Posterior Lateral Hypothalamus in Rabbits

An experimental group of 5 rabbits received 5 acquisition sessions during which repeated presentation of a 550 Hz tone for 10 sec as the conditioned stimulus (CS) was always followed immediately by 25 pulse per sec, 10 sec train-duration stimulation of the posterior lateral hypothalamus as the unconditioned stimulus (US). A control group of 5 rabbits received random presentations of the CS and US. The unconditioned responses (URs) to intracranial stimulation consisted of tachycardia and a depressor response; conditioned responses (CRs) consisted of depressor responses unaccompanied by systematic changes in heart rate. Neither systematic heart rate nor blood pressure responses occurred to the CS in the control group. The present results contrast with those of previous studies in rabbits in which higher frequency, shorter pulse-train hypothalamic stimulation as US induced a pressor response and reflexive bradycardia as URs, and bradycardia unaccompanied by blood pressure changes as CRs. It is concluded that hypothalamic stimulation as US permits more than one cardiovascular response pattern to be studied under controlled conditions during classical conditioning.     

Contextual modulation of conditioned responses: role of the ventral subiculum and nucleus accumbens

The performance of conditioned responses (CRs) is diminished when trained subjects are tested in a novel context. This study tested the hypothesis that the flow of contextual information along the disynaptic "ESA" (entorhinal cortex-ventral subiculum-nucleus accumbens) pathway is responsible for context-related modulation of CRs. Rabbits received electrolytic or sham lesions of the ventral subiculum followed by discriminative avoidance conditioning and counterbalanced extinction sessions in the original training context, a novel context, and the original training context with a novel cue. Neuronal activity was recorded simultaneously in the nucleus accumbens, cingulate cortex, and basolateral amygdala. The lesions did not affect the acquisition of avoidance behavior or prevent the reduction of CRs in response to a novel cue. However, the lesions did reduce CR incidence during extinction, and they did eliminate a further novel-context-induced CR reduction found in controls. In addition, lesions disrupted context-dependent neuronal responses in the nucleus accumbens but not in the cingulate cortex or amygdala. These findings are interpreted as supportive of the hypothesis that the ESA pathway mediates contextual modulation of CRs during extinction.     

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. The 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.     

Widespread cortical projections of the hippocampal formation in the cat

Efferent projections from the hippocampal formation to the cat's cortex were traced with the retrograde horseradish peroxidase technique. Different areas of the cortex of 31 cats were injected with small amounts of horseradish peroxidase. All subregions of the hippocampal formation were screened for labeled cells. It was found that, with the exception of the entorhinal injections, only subicular areas of the hippocampal formation contain labeled neurons. When HRP was injected into the entorhinal cortex, labeled cells are also found in the hippocampus proper. The most dense projection from the subicular cortex is directed to the medial part of the cortical hemisphere. Here, cingulate, retrosplenial and medial prefrontal fields receive a substantial number of subicular efferents. Furthermore, the entorhinal cortex is reached by a number of axons originating in the subicular area. Scarce projections from the subicular cortex terminate in the dorsal prefrontal, temporal, parietal and prepiriform cortex. It is suggested that the projection from the subicular cortex to the neocortical areas of the frontal pole (medial prefrontal cortex) is of special importance as it may constitute a link between the association areas of the neocortex and those regions of the limbic system thought to play a role in memory (subicular cortex, mamillary bodies, anterior thalamus, cingulate gyrus).     

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 (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus (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 greater than 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.     

Neuronal activity in rabbit neostriatum during classical eyelid conditioning

Extracellular multiple- and single-unit recordings were made from the neostriatum of rabbits during classical eyelid conditioning. Neostriatal neurons processed information regarding the conditioned auditory stimulus (CS) and conditioned eyelid response (CR) as well as the unconditioned stimulus/response (US/UR). These data are consistent with previous reports that neostriatal neurons respond to movement and movement-related sensory stimuli. In most cases, neostriatal neurons increased activity to the US during the early phase of training, but to the CR as training progressed. A close temporal correlation was found between neuronal activity and CR onset with unit discharges typically preceding CR onset by 10–50 ms. The activity of some multiple and single units was monitored after injection of haloperidol, a neuroleptic and dopamine antagonist known to disrupt neostriatal function. Interestingly, haloperidol caused a greater disruption of CRs at low-intensity than at high-intensity CSs, but conditioning-related neuronal activity was disrupted equally at both intensities. These data are discussed in terms of a possible role for the neostriatum in eyelid conditioning.     

A comparison of multiple-unit activity in the medial prefrontal and agranular insular cortices during Pavlovian heart rate conditioning in rabbits

Summary Multiple-unit activity (MUA) was recorded from chronically implanted electrodes in the medial prefrontal cortex (PFCm) and the agranular insular cortex (Iag) in separate groups of rabbits during habituation training, followed by aversive Pavlovian conditioning and subsequent extinction training. Control animals received explicitly unpaired presentations of the tone conditioned stimulus (CS) and eye-shock unconditioned stimulus (US). Both the cardiac orienting reflex and the conditioned heart rate response (HR CR) consisted of bradycardia, whereas tone-evoked tachycardia was observed in animals that received unpaired stimuli. Short-latency (<20–60 ms), tone-evoked increases in PFCm MUA were observed during the initial trials of habituation training, with their magnitude declining predictably across repeated tonealone presentations. Subsequent CS/US pairings, however, served systematically to reinstate and enhance this CS-evoked MUA, while both non-associative (unpaired CS/US) and extinction (CS alone) training resulted in significant attenuation of such activity. Unconditioned tone-evoked increases in MUA were also observed in the Iag during habituation; however, such unit responses appeared to be more variable than their PFCm counterparts and were of considerably lesser magnitude. Moreover, in striking contrast to the above PFCm findings, conditioning and non-associative training did not differentially affect overall mean evoked MUA in the Iag, although different post-tone patterns of activity were obtained with the two procedures. The contrasting training effects observed in animals with PFCm vs. Iag electrode placements did not appear to be attributable to differences in regional sensitivity to the US, since excitatory patterns of MUA were elicited by unsignalled presentations of eye-shock at most placements within each cortical field. Accordingly, the present findings are consistent with our previous lesion data in suggesting that, although training-induced changes in PFCm neuronal activity may contribute to the initial events in aversive Pavlovian conditioning, an involvement of the Iag in such processes, if any, remains to be demonstrated.     

Temporally specific extinction of conditioned responses in the rabbit (Oryctolagus cuniculus) nictitating membrane preparation

Extinguishing a conditioned response (CR) has entailed separating the conditioned stimulus (CS) from the unconditioned stimulus (US). This research reveals that elimination of the rabbit (Oryctolagus cuniculus) nictitating membrane response occurred during continuous CS-US pairings. Initial training contained a mixture of 2 CS-US interstimulus intervals (ISIs): 200 ms and 1,200 ms. The CRs showed double peaks, one for each ISI. When 1 ISI was removed, its CR peak showed the hallmarks of extinction: a decline across sessions, spontaneous recovery between sessions, and rapid reacquisition when the absent ISI was reintroduced. These results support real-time models of conditioning that segment the CS into microstimuli while challenging theories that rely on contextual control, US representations, CS processing, and response inhibition.