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)     

Cigarette smoking predicts development of depressive symptoms among U.S. adolescents

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its nonreinforced preexposure. LI is impaired in acute schizophrenic patients and in rats treated with amphetamine. Neuroleptic drugs enhance LI, and this effect is selective and specific for this class of drugs. The present experiments tested the proposition that neuroleptic-induced enhancement of LI stems from decreased capacity of stimulus-preexposed animals to switch responding according to the new stimulus-reinforcement contingency in the conditioning stage. LI was assessed using an off-baseline conditioned emotional response (CER) procedure in rats licking for water, consisting of three stages: preexposure to the-to-be conditioned stimulus, tone; conditioning, in which the preexposed stimulus was paired with a foot-shock; and test, in which LI was indexed by animals' degree of suppression of licking during tone presentation. Whereas in previous studies that demonstrated LI enhancement by neuroleptics, preexposure consisted of 10 to 40 tones, and conditioning included two tone-shock pairings, the present experiments used 40 tone preexposures, followed by an extended conditioning stage with five tone-shock pairings. It was expected that under these conditions no LI effect would be evident in untreated animals, but that animals treated with a neuroleptic drug, either during the entire LI procedure or only in conditioning, would show LI. Experiments 1 and 2 showed that LI was obtained in rats treated with haloperidol (0.1 mg/kg in experiment 1, 0.03 and 0.2 mg/kg in experiment 2) but not in the untreated controls. Experiment 3 showed that the same outcome was obtained when haloperidol (0.1 mg/kg) administration was confined to the conditioning stage. Experiment 4 showed that clozapine (5 mg/kg)-treated animals showed LI when the drug was confined to conditioning, but not to the preexposure stage. The implications of these results for the mechanism of action of neuroleptic drugs are discussed.     

Haloperidol reinstates latent inhibition impaired by hippocampal lesions: Data and theory.

The effect of haloperidol administration on the impairment of latent inhibition produced by aspirative lesions of the hippocampus was examined in the rat eyeblink response preparation. During the preexposure phase, rats with hippocampal or control lesions were either exposed to a tone or allowed to sit in the training apparatus. During the conditioning phase, the tone was paired with an airpuff to the eye after the rats were injected with either saline or haloperidol. Although saline-injected rats with hippocampal lesions did not show latent inhibition, the phenomenon was reinstated in rats that received haloperidol injections. A possible locus of the interaction between hippocampal lesions and haloperidol is the nucleus accumbens. The reported data are well described by a neural network model of classical conditioning. This study contributes to the understanding of the neurophysiology of latent inhibition as well as the neuropsychological bases of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Latent inhibition: A neural network approach.

A formal theory of latent inhibition (LI) is offered in the context of a real-time, neural network model of classical conditioning. The network assumes that the effectiveness of a CS in establishing associations with the unconditioned stimulus/stimuli (UCS) is proportional to total novelty, defined as the sum of the absolute value of the difference between the predicted and observed amplitudes of all environmental events. CS effectiveness controls both the rate of storage (formation, or read-in) and the retrieval (activation, or read-out) of CS-CS and CS-UCS associations. The model describes LI because total novelty and, therefore, CS effectiveness decrease during CS preexposure. Computer simulations demonstrate that the neural network correctly describes, and sometimes predicts, the effects on LI of experimental manipulations before and during CS preexposure and during and after conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Latent inhibition in rats is abolished by NMDA-induced neuronal loss in the retrohippocampal region, but this lesion effect can be prevented by systemic haloperidol treatment.

Latent inhibition (LI) refers to the retardation in learning about the significance of a neutral stimulus that results from its nonreinforced preexposure. There is evidence that electrolytic or aspiration lesions of the hippocampal formation can disrupt LI (I. Weiner, see record 1991-06652-001). It has been suggested that this effect may stem from the interruption of a projection from the retrohippocampal region to the nucleus accumbens (A. J. M. Clark et al, 1992). The present experiment assessed this possibility by comparing LI in rats with retrohippocampal N-methyl-D-aspartate (NMDA) lesions extending from the entorhinal cortex to the ventral subiculum to that seen in vehicle controls and unoperated controls. LI was abolished by the retrohippocampal lesion. The effect of the lesion on LI was prevented by treatment with systemic haloperidol (0.2 mg/kg). The results are discussed with respect to an animal model of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural substrates of latent inhibition: The switching model.

Latent inhibition (LI) refers to decrement in conditioning to a stimulus as a result of its prior nonreinforced preexposure. This robust phenomenon has been shown in classical and instrumental conditioning procedures and in many mammalian species, including humans. Development of LI reflects decreased associability of, or attention to, stimuli that predict no significant outcome. The fact that LI reflects attentional processes has become important to neuroscientists who see LI as a convenient tool for measuring the effects of drug treatments and lesions on attention. Data on brain systems studied for their involvement in LI are surveyed. These are presented in sections on noradrenergic, cholinergic, dopaminergic, serotonergic, and septo-hippocampal manipulations. It is concluded that the neural substrates of LI include the mesolimbic dopaminergic system (MDS), the mesolimbic serotonergic system (MSS), and the hippocampus. The preexposed stimulus loses its capacity to affect behavior in conditioning, even though it predicts reinforcement, because the hippocampus inhibits the switching mechanism of the nucleus accumbens via the subiculum-accumbens pathway. This hippocampal action is modulated by the MSS via its interactions with the hippocampal system or MDS, or both. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA processes mediate anterograde amnesia of contextual fear conditioning induced by hippocampal damage: Immunization against amnesia by context preexposure.

Hippocampal lesions in rats produce both a retrograde and an anterograde amnesia of contextual fear conditioning. The present experiments examined the anterograde deficit in context conditioning involving a total of 113 rats in 4 experiments. The deficit produced by electrolytic hippocampal lesions was apparent when training occurred on 7, 14, or 28 days following surgery, confirming the durability of the amnesia. The role of the hippocampus in context conditioning may be related to an N-methyl-D-aspartate (NMDA) receptor-mediated process. Both NMDA hippocampal lesions and intrahippocampal administration of an NMDA antagonist produced anterograde amnesia. Ss preexposed to the conditioning context 28 days prior to hippocampal lesioning were protected from the deficit normally produced by the lesions. Thus, the hippocampus must form a contextual representation during preexposure that is subsequently stored elsewhere. Once formed this representation of the context can be associated with an unconditioned stimulus/stimuli (UCS). (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)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine manipulations limited to preexposure are sufficient to modulate latent inhibition.

Four experiments are reported that demonstrated that dopamine (DA) transmission is involved in the acquisition of latent inhibition (LI) of a conditioned taste aversion. LI refers to weaker conditioning as a consequence of nonreinforced preexposure (PE) of the future conditioned stimulus. Although it is known to depend on DA transmission during the conditioning phase, it is usually thought that the cognitive processes involved in the establishment of LI (during the PE phase) are DA independent. Either amphetamine (AMPH; 0.5 or 1.0 mg/kg) or haloperidol (HAL; 0.1 mg/kg) were injected before 1 or all of the 3 PE sessions. AMPH blocked the acquisition of LI if it was injected before each or before only the last PE session and HAL potentiated LI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fimbria-fornix cut affects spontaneous activity, two-way avoidance and delayed non matching to sample, but not latent inhibition

Latent inhibition (LI) consists of a decrement in conditioning to a stimulus as a result of its prior nonreinforced preexposure. Based on evidence pointing to the involvement of the hippocampus and the nucleus accumbens (NAC) in LI disruption, it has been proposed that LI depends on the integrity of the subicular input to the NAC. Since fibers originating in the subiculum and destined for the NAC run through the fimbria-fornix, we assessed the effects of fimbria-fornix lesion, made using a knife cut, on LI. In addition, we assessed the effects of the fimbria-fornix cut in three tests known to be sensitive to lesions to the hippocampal region, namely, spontaneous activity, two-way active avoidance and delayed-non-matching-to-sample. In accord with previously documented effects of lesions to the hippocampus and related structures, the fimbria-fornix cut increased spontaneous activity (Experiment 1), facilitated the acquisition of two-way active avoidance (Experiment 3), and produced a delay-dependent deficit in the delayed-non-match-to-sample task (Experiment 4), demonstrating that it disrupted hippocampal functioning. In contrast, LI remained unaffected by the fimbria-fornix cut (Experiment 2), indicating that disruption of subicular input to the NAC is not responsible for the attenuation of LI following non-selective hippocampal lesions. The implications of these results for the neural circuitry of LI are discussed.     

Amygdala central nucleus lesions disrupt increments, but not decrements, in conditioned stimulus processing.

The effects of neurotoxic lesions of the amygdala central nucleus (CN) on changes in the associability of a CS in appetitive Pavlovian conditioning were examined in 2 experiments with rats. In Exp 1, CN lesions had no effect on the reduction in the associability of a CS produced by preexposure to that cue (latent inhibition). In Exp 2, CN lesions prevented the enhancement of the associability of a CS that is normally observed when an inconsistent predictive relation is arranged between that CS and another cue. Results support previous claims that the amygdala CN is involved in broad-based incremental, but not decremental, changes in the processing of CSs in Pavlovian conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blocking of a CS–US association by a US–US association.

Pigeons were autoshaped with a keylight as the conditioned stimulus (CS) and food as the unconditioned stimulus (US). Preexposure to repeated US presentations was followed by training sessions in which a single US preceded a single CS–US pairing. Preexposure blocked conditioning to the CS only when the interval between the prior US and the US in the US–CS pairing (critical interval) was equal to the US–US interval in preexposure. Blocking was examined as a function of the length of the critical interval and the amount of preexposure. The hypothesis that blocking occurs because prior US predicts the time of arrival of the US in the CS–US pairing was supported by a reduction in blocking when USs separated by intervals longer than the critical interval were added to preexposure sessions. Certain other interpretations of these results were tested and rejected. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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

[Correction Notice: An erratum for this article was reported in Vol 114(2) of Behavioral Neuroscience (see record 2007-17251-001). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4.] 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unilateral asymptomatic carotid disease does not require surgery

If a stimulus (e.g. tone or light) is repeatedly pre-exposed without consequences, it subsequently shows retarded conditioning when paired with a reinforcer (e.g. footshock) compared with a non-pre-exposed stimulus. This is latent inhibition (LI). Haloperidol-treated animals show potentiated LI, and it has been suggested that this is due to retarded switching to respond according to the stimulus-reinforcer contingency. Recently, it has been argued that the slowed control of behaviour by the stimulus-reinforcement contingency is due to a haloperidol-induced decrease in the impact, or salience, of the reinforcer, and thus should be antagonized by increasing the impact of reinforcement. Two experiments tested this prediction. In both, LI was assessed using an off-baseline conditioned emotional response procedure in rats licking for water. In Experiment 1, rats were given 10 light pre-exposures and conditioned with two footshocks of either a low (0.5 mA) or a high (1 mA) intensity. In Experiment 2, rats were given 30 pre-exposures and conditioned with either two or five footshocks of 1 mA. In Experiment 1, no-drug controls did not show LI at both shock intensities. Haloperidol (0.1 mg/kg) was ineffective in potentiating LI at low-intensity shock, but produced LI when shock level was increased. In Experiment 2, no-drug controls showed LI with two but not five conditioning trials. Haloperidol was ineffective in potentiating LI with two conditioning trials, but produced LI with five conditioning trials. Although the effect of haloperidol on LI could thus be modified by manipulating shock intensity or the number of conditioning trials, the direction of such modification indicates that the potentiating effect of haloperidol on LI is not in general antagonized by increasing the impact of reinforcement.     

Contextual control over conditioned responding in a latent inhibition paradigm.

We used 1-, 2-, and 3-context designs to study the control exerted by contexts over freezing in rats exposed to a conditioned stimulus (CS) in advance of its pairing with a shock unconditioned stimulus. The latent inhibition observed when preexposure, conditioning, and testing occurred in the same context was attenuated if preexposure occurred in a different context to conditioning and testing. Latent inhibition (i.e., attenuated performance) was restored in a CS-specific manner if preexposure and testing occurred in the same context and conditioning in a different one. Latent inhibition was also reduced by a long retention interval but remained specific for a particular context–CS relation. Finally, CS preexposure resulted in contextual control over the expression of excitatory conditioned performance. The results are discussed in terms of memory, associative, and associative-performance models of CS-preexposure effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus": Correction to McNish et al (2000).

Reports an error in "Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus" by Kenneth A. McNish, Jonathan C. Gewirtz and Michael Davis (Behavioral Neuroscience, 2000[Feb], Vol 114[1], 64-76). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4. (The following abstract of the original article appeared in record 2000-13470-005.) 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the rat hippocampal system in several effects of context in extinction.

The effect of fornix lesions on some effects of manipulating the context on performance in extinction were studied. In renewal, subjects' responding to an extinguished CS recovered when the CS was presented in the context in which it had been conditioned after extinction in a different context. In reinstatement, it recovered when the CS was tested after independent presentation of the unconditioned stimulus (UCS; an effect mediated by contextual conditioning.) In spontaneous recovery, it recovered after the passage of time, that is, when the CS was tested in a new temporal context. In the conditioned suppression method, fornix lesions had no effect on conditioning, extinction, renewal, or spontaneous recovery; however, they abolished the reinstatement effect. The results suggest that the hippocampal system may be important in the formation of context–UCS associations, but not in other types of learning about the context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)