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     

Latent inhibition in the developing rat: an examination of context-specific effects

Latent inhibition (LI) refers to the reduction in conditioned responding when the conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor-shock pairings markedly reduced conditioned freezing in 25-day-old rats; however, this LI effect was observed only if odor preexposure and odor-shock pairings occurred in the same context (i.e., LI was context-specific at this age). The results of Experiment 1b showed that 18-day-olds also exhibited LI, but this effect was not context-specific at this age. In Experiment 2, rats were preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days of age. These rats exhibited context-specific latent inhibition, suggesting that 18-day-old rats encoded the preexposure context. In Experiment 3, all parameters were identical to Experiment 2, with the exception that odor-shock pairings were given at approximately PN18 and testing occurred at approximately PN25. These rats exhibited latent inhibition at test, but this effect was not context-specific. The results of this study suggest that (a) PN18 rats can exhibit latent inhibition, and (b) the expression of context-specific latent inhibition depends on the age at which conditioning occurs.     

Hippocampal control of cingulate cortical and anterior thalamic information processing during learning in rabbits

Summary Past studies of the neural determinants of discriminative avoidance conditioning in rabbits have fostered a theoretical model that describes the interactive functioning of the cingulate cortex (Brodmann's Areas 24 and 29), the anterior ventral and medial dorsal thalamic nuclei (AVN and MDN) and the hippocampus. Here we test hypotheses of the model concerning the influence of the hippocampus on cortical and thalamic information processing. The rabbits learned to perform locomotory conditioned responses (CRs) in an activity wheel in response to an acoustic (pure tone) positive conditional stimulus (CS+). A shock unconditional stimulus (US) was given 5 s after CS+ onset, but locomotion during the CS+ -US interval prevented the US. The rabbits also learned to ignore a second tone (a negative conditional stimulus, CS-) of different auditory frequency than the CS+, that did not predict the US. Multi-unit activity and intracranial macropotentials were recorded in the cingulate cortex and the AVN uring acquisition, overtraining, extinction, reacquisition and reversal training. Data were obtained in intact rabbits and in rabbits with bilateral lesions of the subicular complex, the origin of projections of the hippocampal formation to the cingulate cortex and AVN. In addition, the activity in the AVN was recorded in a separate group of rabbits with posterior cingulate cortical (Area 29) lesions. Subicular and Area 29 lesions were associated with an enhancement of the training-induced CS+ elicited neuronal response in the AVN. The frequency of CRs was enhanced in animals with subicular lesions. CS elicited unit responses in the cingulate cortices were attenuated in rabbits with subicular lesions. Both of the lesions were associated with significantly increased amplitudes of the CS elicited average cortical and thalamic macropotentials. These results suggested the following conclusions: a) subiculocortical afferents provide an enabling influence that is essential for CS elicited excitation in the cingulate cortex; b) the cingulate cortical excitatory response in intact animals exerts a limiting influence on the activity in the AVN; c) the enhanced AVN neuronal response in rabbits with lesions is due to the absence of the limiting influence and it contributes to the increased CR frequency in those animals. It is hypothesized that the hippocampus via subiculocortical projections, governs the flow of CR-inducing thalamocortical excitatory volleys. This governance determines the timing of CR output. The results of hippocampal processing of contextual information acting through the subiculocortical projection determines the moment most appropriate for the CR.     

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.     

Novel factors contributing to the expression of latent inhibition

Behavioral and neural correlates of latent inhibition (LI) during eyeblink conditioning were studied in 2 experiments. In Experiment 1, rabbits (Oryctolagus cuniculus) were conditioned after 8 days of tone conditioned stimulus (CS) presentations or 8 days of context-alone experience. LI was seen in the CS-preexposed rabbits when a relatively intense (5 psi) airpuff unconditioned stimulus was paired with the CS. In Experiment 2, rabbits were given 0, 4, or 8 days of CS preexposures or context-alone experience. Hippocampal activity was monitored from the 8-day CS- or context-exposure rabbits. The LI effect was seen only in rabbits given 4 days of CS preexposure, thus suggesting that LI depended largely on the rate of acquisition in the context-preexposed control group. The neural recordings showed that the hippocampus was sensitive to the relative novelty of the stimuli and the overall context, regardless of whether exposure to stimuli and context promoted LI.     

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.     

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.     

Latent Inhibition and Conditioning in Rat Strains Which Show Differential Prepulse Inhibition

Latent inhibition (LI) is the retardation of associative conditioning resulting from preexposure of the conditioned stimulus (CS) alone prior to conditioning. Schizophrenic patients show deficient prepulse inhibition (PPI) and, at least acutely, deficient LI as well. We recently found that Brown Norway (BN) rats show a PPI deficit compared to Wistar-Kyoto (WKY) rats. If PPI and LI depend on neural processes with common genetic substrates, then LI should be deficient in BN rats as well. Here, LI of a conditioned taste aversion was examined in BN and WKY rats. One group from each strain was preexposed to a saccharin-flavored solution (CS) the day prior to conditioning. For taste aversion conditioning, these two groups again consumed saccharin and were injected with lithium chloride (unconditioned stimulus) 10 min later. A second group from each strain was not preexposed to the CS and was treated identically during conditioning, while a third group was not conditioned (injected with sodium chloride). To test for taste aversion conditioning, saccharin was offered for 20 min/day for 3 days. Nonconditioned BN and WKY rats consumed equal amounts of saccharin on test days. In both strains, conditioned rats showed a saccharin aversion. However, conditioning was less robust in BN than in WKY rats. WKY rats showed good LI of the conditioned taste aversion in that preexposed WKY rats consumed significantly more saccharin on test days than conditioned, nonpreexposed WKY rats. Preexposed BN rats did not consume significantly more saccharin on test days than conditioned, nonpreexposed BN rats. The previously reported deficiency in PPI in the BN rats was confirmed here 1 week after the taste aversion experiment. These results suggest that BN rats show deficient LI as well as PPI and display poor associative learning, a trait also reported in schizophrenia.     

Age-related differences in avoidance behavior in rats following CS preexposure

Weanling and adult rats were exposed to either 0 or 10 conditioned stimulus (CS) presentations prior to 1-way active-avoidance (AA) training. Although CS exposure retarded avoidance acquisition in the adults, it produced no effect in the pups during avoidance learning. Neither adult nor young rats demonstrated preexposure effects in extinction. A general extinction analysis showed that pups had less resistance to extinction than the adults, despite a comparable avoidance learning criterion between age groups. The lack of preexposure influences on performance by the pups was compared to previous findings of response inhibitory deficits in immature rats. The results were considered in light of selective attention interpretations of latent inhibition.     

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.     

Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus

The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing.     

Neural activation and memory for natural scenes: Explicit and spontaneous retrieval

Stimulus repetition elicits either enhancement or suppression in neural activity, and a recent fMRI meta‐analysis of repetition effects for visual stimuli (Kim, 2017) reported cross‐stimulus repetition enhancement in medial and lateral parietal cortex, as well as regions of prefrontal, temporal, and posterior cingulate cortex. Repetition enhancement was assessed here for repeated and novel scenes presented in the context of either an explicit episodic recognition task or an implicit judgment task, in order to study the role of spontaneous retrieval of episodic memories. Regardless of whether episodic memory was explicitly probed or not, repetition enhancement was found in medial posterior parietal (precuneus/cuneus), lateral parietal cortex (angular gyrus), as well as in medial prefrontal cortex (frontopolar), which did not differ by task. Enhancement effects in the posterior cingulate cortex were significantly larger during explicit compared to implicit task, primarily due to a lack of functional activity for new scenes. Taken together, the data are consistent with an interpretation that medial and (ventral) lateral parietal cortex are associated with spontaneous episodic retrieval, whereas posterior cingulate cortical regions may reflect task or decision processes.     

Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder

BACKGROUND: In the conditioned fear paradigm, repeated pairing of an aversive unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned stimulus (CS) (e.g. bright light) results in a conditioned fear response to the light alone. Animal studies have shown that the amygdala plays a critical role in acquisition of conditioned fear responses, while the medial prefrontal cortex (including anterior cingulate), through inhibition of amygdala responsiveness, has been hypothesized to play a role in extinction of fear responses. No studies have examined neural correlates of fear conditioning and extinction in patients with post-traumatic stress disorder (PTSD). METHOD: Women with early childhood sexual-abuse-related PTSD (n = 8) and women without abuse or PTSD (n = 11) underwent measurement of psychophysiological (skin conductance) responding as well as positron emission tomographic (PET) measurement of cerebral blood flow during habituation, acquisition and extinction conditions. During habituation subjects were repeatedly exposed to a blue square on a screen. During acquisition, exposure to the blue square (CS) was paired with an electric shock to the forearm (US). With extinction, subjects were again exposed to the blue squares without shock. On a different day subjects went through the same procedure with electric shocks administered randomly in the absence of the blue square. RESULTS: Skin conductance responding to the CS was consistent with the development of conditioned responses with this paradigm. PTSD patients had increased left amygdala activation with fear acquisition, and decreased anterior cingulate function during extinction, relative to controls. CONCLUSIONS: These findings implicate amygdala and anterior cingulate in the acquisition and extinction of fear responses, respectively, in PTSD.     

Lesions to the basolateral amygdala and the orbitofrontal cortex but not to the medial prefrontal cortex produce an abnormally persistent latent inhibition in rats

Repeated nonreinforced preexposure to a stimulus interferes with the establishment of conditioned responding to this stimulus when it is subsequently paired with reinforcement. This stimulus-preexposure effect is known as latent inhibition (LI). Rather remarkably, LI appears to be resistant to the effects of numerous lesions, including the prefrontal cortex (PFC) and the basolateral amygdala (BLA). However, intact behavioral expression of LI following damage to given brain regions does not preclude the possibility that such regions participate in the regulation of LI expression in the intact brain. The present study showed that lesions of the BLA and the orbitofrontal cortex (OFC) but not of the medial PFC (mPFC) led to an abnormally persistent LI which emerged under conditions that disrupted LI in control rats. LI was measured in a thirst motivated conditioned emotional response procedure by comparing suppression of drinking in response to a tone in rats which received 0 (nonpreexposed) or 40 tone presentations (preexposed) followed by either two or five tone-shock pairings. Control rats showed LI with 40 preexposures and two conditioning trials, but raising the number of conditioning trials to five disrupted LI. OFC- and BLA-lesioned rats showed LI under the former condition but in addition persisted in exhibiting LI under the latter condition. Rats with lesion of the mPFC did not show persistent LI. Thus, although LI does not depend on the integrity of BLA and OFC (because it is present in BLA- and OFC- lesioned rats even under conditions disrupting the phenomenon in normal rats), these regions play an important role in the modulation of its expression, more specifically, in the control of the non-expression of LI when the impact of conditioning increases beyond a certain level.     

Modification of auditory and somatosensory system activity during pupillary conditioning in the paralyzed cat.

The role of sensory systems in the development of behavioral conditioned responses was investigated by recording multiple-unit activity in the auditory and somatosensory pathways during Pavlovian conditioning of the pupillary-dilation responses of paralyzed cats. Establishment of conditioned pupillary-dilation responses to a white noise CS+, pupillary discrimination between the CS+ and a tone CS-, and subsequent discrimination reversal provided the behavioral foundation for examining neural changes related to behavioral learning. Multiple-unit responses to the acoustic CS+ were significantly enhanced in the auditory cortex, cochlear nucleus, and somatic cortex, but not in the cuneate nucleus. The possibility that these effects could be due to changes in stimulus intensity at the sensory receptor, to mo-ement artifacts, or to feedback from skeletal responses were ruled out because the animals were immobilized. Nor could these neural changes be attributable to sensitization, as those brain areas which showed conditioned enhancement to the CS+ exhibited significantly larger responses to the CS+ than to the CS-. Furthermore, the changes in neural activity followed the significance of the CS; after reversal of the reinforcement contingencies, the amount of multiple-unit activity evoked by the stimuli gradually reversed too. Although the somatic cortex showed conditioning and discrimination, greater stimulus specificity was found in the auditory system. Only in the somatic cortex was there a significant increase in responses to the CS- as well as the CS4. Furthermore, both somatosensory loci exhibited enhanced responses to those tactile probes presented during the acoustic CS, suggesting a phasic increase in neural excitability to all stimuli. Analysis of the number of trials required to attain an acquisition criterion indicated that the neural changes occurred first in the auditory cortex, then the cochlear nucleus, followed in turn by the somatic cortex, and finally the cuneate nucleus. However, none of these neural changes preceded acquisition of conditioned pupillary dilations. These results suggest that sensory system changes are not essential for the initial associative process. These findings indicate that the study of autonomic conditioned responses may prove beneficial in seeking the critical neural events which underlie the initial association between two stimuli. A hypothetical model, which explains the development of pupillary and sensory system conditioned responses, was also presented.     

Ontogeny of context-specific latent inhibition of conditioned fear: Implications for configural associations theory and hippocampal formation development

Latent inhibition of fear conditioning to an auditory cue, as measured by behavioral freezing, was examined in 18- and 23-day-old rats. In Experiment 1, CS preexposure and conditioning occurred in the same context for some rats but in a different context for other rats, and 24 hr separated CS preexposure and conditioning. The 23-day-old rats showed a context-specific latent inhibition effect, but the 18-day-old rats showed no latent inhibition. In Experiment 2, CS preexposure and conditioning occurred in the same trainining session and both 18- and 23-day-old rats showed latent inhibition. These results were discussed in relation to Wagner's (1976) theory of information processing, hippocampal formation maturation, and function, and Sutherland and Rudy's (1989) configural association theory.©1994 John Wiley & Sons, Inc.     

Early handling and latent inhibition in the conditioned suppression paradigm

Latent inhibition (LI) is a behavioral paradigm in which repeated exposure to stimuli not followed by meaningful consequences renders these stimuli ineffective for subsequent learning. The development of LI is considered to reflect learning not to attend, to ignore, or tune out irrelevant stimuli. The present study investigated the differences in the development of LI between handled and nonhandled males and females. Infantile handled (days 1-22) and nonhandled, male and female Wistar rats were tested in maturity in the LI paradigm, using a conditioned emotional response (CER) procedure. The procedure consisted of three stages: preexposure, in which the to-be-conditioned stimulus, tone, was presented without being followed by reinforcement; acquisition, in which the preexposed tone was paired with shock; and test, in which LI was indexed by animals' suppression of licking during tone presentation. Handled animals exhibited less conditioned suppression as compared to nonhandled animals. LI was obtained in both the handled and the nonhandled females, but only the handled males showed the LI effect. Nonhandled males failed to develop LI. These results replicate our previous findings on LI in conditioned avoidance in demonstrating that: the effects of handling are evident in learning tasks that do not involve motivational-emotional variables, i.e., learning to ignore irrelevant stimuli; handling differentially affects males and females; the nonhandling procedure has deleterious consequences on adult behavior.     

Differential extinction of 2-way active avoidance in young and adult rats.

Three experiments examined age-related differences in extinction of active avoidance in rats through manipulation of the stimulus context. In Experiment I, 36 weanlings and 36 adults acquired comparable avoidance levels to a tonal conditioned stimulus (CS), and novel stimuli consisting of either the presence of a naive rat or a light were presented during 2 tests in extinction. Results indicated more pronounced disruption of extinction in the pups, compared to adults, with the animate novel stimulus having the greater effect. Eighteen pups of 22 days of age and 18 adults in Experiment II were trained to avoid shock with a CS consisting of simultaneous tone and light onset. During extinction responses did not terminate 1 of the CS elements, but rather produced continuation of either the tone or light for an additional 5 sec. Continuation of the tonal element resulted in greater disruption of extinction trials than the light in the adults, although the pups had faster, but nondifferential, extinction rates. A 3rd experiment presented 36 pups and adults with either 0-, 5-, or 10-sec delays of tonal CS reactivation after extinction responses. Both 5- and 10-sec delays resulted in increased numbers of extinction trials in the adults, but the pups failed to respond differentially to any of the delay intervals. Results of all of the experiments were considered in light of species-specific behaviors in avoidance extinction relative to environmental and associative saliencies between ages.     

Ontogenetic differences in the effects of unpaired stimulus preexposure on eyeblink conditioning in the rat

Learned irrelevance (LIr) is a Pavlovian conditioning phenomenon in which random or unpaired preexposure to a conditional stimulus (CS) and to an unconditional stimulus (US) retards subsequent paired conditioning involving these stimuli. A previous developmental study of eyeblink conditioning in the rat suggested that LIr is not present on postnatal Day 20. Stanton, Fox, and Carter (1998) showed that unpaired preexposure to a CS and a US on postnatal Day 17 failed to retard (and, in fact, facilitated) subsequent paired conditioning involving these stimuli on postnatal Day 20. The present experiments were designed to further characterize the ontogeny of this phenomenon. In Experiment 1, LIr was observed when rat pups were tested for eyeblink conditioning as described in Stanton et al. (1998), except that preexposure occurred on postnatal Day 27, and acquisition testing occurred on postnatal Day 30. In Experiment 2, preexposure and acquisition both occurred on postnatal Day 30, and four types of preexposure were compared: chamber only, CS alone, US alone, or unpaired presentation of CS and US. Unpaired preexposure impaired acquisition relative to that of the remaining three groups, which did not differ. Experiment 3, showed that under the conditions of Experiment 2, LIr failed to appear on postnatal Day 20, but was observed on postnatal Days 25 and 30. These findings suggest that learning that events are unrelated emerges between postnatal Days 20 and 25 in the rat. Possible behavioral and neural mechanisms underlying this effect are discussed.     

Trial sequence of changed unit activity in auditory system of alert rat during conditioned response acquisition and extinction.

1. The activity of units in the auditory system of alert, freely moving rats was studies during the acquisition and extinction of a tone-signaled, appetitive classically conditioned response. Responses of neurons in inferior colliculus (N = 28), medial geniculate (N = 32), posterior nucleus of thalamus (N = 28), pretectal region (N = 19), and cortex (N = 100) were studies in 74 rats across 10-trial blocks. 2. During behavioral acquisition, neurons in posterior nucleus of thalamus were the first to show response increments to CS+ onset. They were followed by neurons in cortex, pretectal region, medial geniculate, inferior colliculus and by movement behavior. 3. Prestimulus background rates during acquisition showed significant decrements in cortical neurons. These background decrements began to be evidenced in the trial series before the response increases in posterior nucleus. These data strengthened the suggestion of a previous study that posterior nucleus responses could be dependent on tonic modulation from cortex. 4. Extinction appeared to be largely a reverse of acquisition. Cortex and behavior showed response decrements first in the trial series. They were followed by medial geniculate, pretectal region, posterior nucleus, and inferior colliculus neurons. 5. The hypothesis was advanced that the auditory lemniscal adjunct afferent system may play a primary role in the early phases of auditory conditioned-response acquisition.