Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of differential hippocampal lesions and pre- and postoperative training on extinction.

Examined resistance to extinction of a food-motivated response in a total of 78 male albino Wistar rats with sham operations or bilateral dorsal hippocampal, ventral hippocampal, or combined dorsal and ventral hippocampal lesions in 2 experiments. Surgery occurred either before or after acquisition of the to-be-extinguished response. Ss with combined hippocampal lesions showed greater resistance to extinction than controls if acquisition occurred preoperatively, but less resistance if acquisition occurred postoperatively. Ss with ventral hippocampal lesions were affected in a similar manner but to a lesser degree by differential prior experience. In contrast, dorsal hippocampal-lesioned Ss exhibited no change in approach latency during extinction, irrespective of the timing of surgery. It is suggested that both ventral and combined hippocampal lesions interfere with the changing of an established approach "set." (French summary) (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Studies of the limbic comparator: Limbic circuit training-induced unit activity and avoidance behavior in rabbits with anterior dorsal thalamic lesions.

Multiunit activity of cingulate cortex and the anterior ventral (AntV) thalamic nucleus was recorded as rabbits learned to avoid a shock by locomoting in response to a tone (CS+) and to ignore a nonpredictive tone (CS–). Rabbits with anterior dorsal (AntD) thalamic lesions avoided shock more often than controls during the first training session and the first session of extinction training given after the completion of acquisition. Training-induced neuronal changes in cingulate cortex and in components of the AntV nucleus were lost in the rabbits with lesions. These effects were comparable to previously observed effects of subicular lesions. It is proposed that interactions of AntD thalamic, subicular, and cingulate cortical neurons yield a stable mnemonic representation of the associative significance of the CS. The representation is used in a comparator circuit, which inhibits behavior when unexpected events occur. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociations between medial prefrontal cortical subregions in the modulation of learning and action.

The medial prefrontal cortex (mPFC) has been implicated in various attentional functions. This experiment examined the involvement of mPFC subregions in the allocation of attention in learning and action as a function of the predictive accuracy of cues. Rats with dorsal (encompassing anterior cingulate, prelimbic, and infralimbic cortices) or ventral (encompassing mainly infralimbic and dorsopeduncular cortices and tenia tecta) mPFC lesions were trained in a multiple-choice discrimination task in which operant nosepoke responses to some visual cues were consistently (100%) reinforced (CRF) with food, whereas responses to other visual cues were partially (50%) reinforced (PRF). In challenge tests designed to assess attention in the control of action, responding was directed more to CRF cues than to PRF cues in sham and dorsal mPFC-lesioned rats, but ventral mPFC-lesioned rats showed similar levels of responding to both CRF and PRF cues. Nevertheless, when given a choice between simultaneously presented CRF and PRF cues in a cue competition test, all groups responded more to CRF cues. In a subsequent Pavlovian overshadowing phase designed to assess attention in the acquisition of new learning, previously trained CRF cues overshadowed conditioning to novel auditory cues more than did PRF cues in dorsal mPFC-lesioned rats, whereas the opposite pattern was observed in sham and ventral mPFC-lesioned rats. These results suggest a dissociation within the mPFC in the use of reinforcement prediction information to allocate attention for new learning and for the control of action. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Promoter/repressor system of Lactobacillus plantarum phage og1e: characterization of the promoters pR49-pR-pL and overproduction of the cro-like protein cng in Escherichia coli

Previous studies have shown that extensive damage to the medial prefrontal cortex (mPFC) of rats causes reversal learning deficits. The mPFC of rats, however, consists of several subareas that are different from each other in both cytoarchitecture and neural connectivity, suggesting a functional dissociation among the mPFC subareas. In the present study, selective lesions of the mPFC of rats were made with a specially designed microknife whose intracranial placement could be controlled stereotaxically. Restricted lesions were made to each of the 3 parts of the mPFC: the anterior cingulate area (AC) (including the medial precentral area, PrCm), the prelimbic area (PL), and the infralimbic area (IL). One week after surgery, rats were trained in an aversively motivated visual discrimination task in a novel rotating T-maze. After reaching the acquisition criterion, rats were trained in a reversal task in the same maze. No difference was found in acquisition between control and mPFC lesioned rats. However, lesions of either the PL or the IL produced a marked deficit in the reversal task. This behavioral deficit was not found in rats with lesions of the AC. The results indicate that the mPFC of rats is not essential for discrimination learning, but that each of the 2 ventral subareas of the mPFC, PL, and IL, plays a critical role in reversal learning.     

Dissociable effects of lesions to the dorsal or ventral noradrenergic bundle on the acquisition, performance, and extinction of aversive conditioning.

In six experiments, we studied the effects of lesions to either the dorsal or ventral noradrenergic bundle on the acquisition and extinction of the conditioned emotional response (CER) as measured in a conditioned suppression paradigm. Infusions of the neurotoxin 6-hydroxy-dopamine (6-OHDA) into the trajectory of the dorsal noradrenergic ascending bundle (DNAB) impaired the acquisition of on-the-baseline and off-the-baseline conditioned suppression. The acquisition impairment for on-the-baseline conditioning was also shown to still be present when training did not commence until 8 weeks following central noradrenergic depletion. However, in rats previously trained on the CER, DNAB lesions did not affect performance. There was also a small resistance to extinction following on-, but not off-the-baseline conditioning. The acquisition impairment was shown not to be because of an altered sensitivity to the footshock. In contrast, infusions of 6-OHDA into the ventral noradrenergic ascending bundle (VNAB) had no effect upon the acquisition of the CER in an on-the-baseline procedure, but retarded its extinction to a much greater extent. The results here are discussed in terms of other acquisition deficits shown by rats with DNAB lesions and with reference to Gray's "anxiety" and Mason's "selective attention" theories of locus coeruleus function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential role of the medial and lateral prefrontal cortices in fear and anxiety.

In the rat, both the medial and lateral prefrontal. cortices (PFC; mPFC and lPFC, respectively) have direct connections with limbic structures that are important in the expression of fear and anxiety. The present study investigated the behavioral effects of excitotoxic lesions of either the mPFC or the lPFC on conditioned and unconditioned fear paradigms. In both unconditioned fear paradigms (open field, elevated plus-maze), lesions of the mPFC decreased anxiety. In fear conditioning, lPFC lesions substantially increased freezing throughout the different phases of the experiment, whereas mPFC lesions increased freezing to contextual cues and showed reduced freezing to discrete cues. These results support the functional role of the PFC in mediating or modulating central states of fear and anxiety and suggest a functional dissociation between the lPFC and mPFC in their role in fear and anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diversity of capsular polysaccharide synthesis gene clusters in Streptococcus pneumoniae

Echoplanar functional magnetic resonance imaging (fMRI) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction. A simple discrimination procedure was employed in which activation to a visual cue predicting shock (CS+) was compared with activation to another cue presented alone (CS-). CS+ and CS- trial types were intermixed in a pseudorandom order. Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala. Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction. The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects. Consistent with a recent electrophysiological recording study in the rat (Quirk et al., 1997), the profile of the amygdala response was temporally graded, although this dynamic was only statistically reliable during extinction. These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks.     

Cortical involvement in acquisition and extinction of trace eyeblink conditioning.

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

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

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

Fear conditioning to tone, but not to context, is attenuated by lesions of the insular cortex and posterior extension of the intralaminar complex in rats.

C. Shi and M. Davis (see record 1999-00012-009) recently reported that combined lesions of the posterior extension of the intralaminar complex (PINT) and caudal insular cortex (INS) block acquisition but not expression of fear-potentiated startle to discreet conditioned stimuli (CSs) and a footshock unconditioned stimulus (US) and proposed that PINT-INS projections to the amygdala constitute the essential US pathways involved in fear conditioning. The present study further tested this hypothesis by examining whether PINT-INS lesions block fear conditioning (as measured by freezing) to diffuse-context and discrete-tone CSs, and whether posttraining lesions with continued CS–US training result in extinction to the CSs. Posttraining lesions resulted in a selective attenuation of tone conditoning, but context conditioning was unaffected by pre-and posttraining lesions. These results do not support the view that the PINT-INS represent the essential US pathway in fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hippocampal stimulation on acquisition, extinction, and generalization of conditioned suppression in the rat.

In 6 experiments, a total of 142 male Holtzman rats implanted with electrodes in the dorsal or ventral hippocampus received posttrial stimulation in training sessions with footshock reinforcement. Afterdischarges without overt seizures were consistently without effect on the rate of acquisition of suppression of licking during an auditory CS, although conditioning was retarded by the delivery of distracting stimuli following footshock. The rate of conditioning remained insensitive to elicitation of dorsal hippocampal afterdischarges (DHAD) despite subsequent alterations of session length, intertrial interval, and preexposure to the CS. However, faster extinction of suppression occurred following DHAD, suggesting a limited but essential role of the hippocampus in addressing stored information. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Observational fear conditioning in the acquisition and extinction of attentional bias for threat: An experimental evaluation.

Anxious persons show automatic and strategic attentional biases for threatening information. Yet, the mechanisms and processes that underlie such biases remain unclear. The central aim of the present study was to elucidate the relation between observational threat learning and the acquisition and extinction of biased threat processing by integrating emotional Stroop color naming tasks within an observational differential fear conditioning procedure. Forty-three healthy female participants underwent several consecutive observational fear conditioning phases. During acquisition, participants watched a confederate displaying mock panic attacks (UCS) paired with a verbal stimulus (CS+), but not with a second nonreinforced verbal stimulus (CS-). As expected, participants showed greater magnitude electrodermal and verbal-evaluative (e.g., distress, fear) conditioned responses to the CS+ over the CS- word. Participants also demonstrated slower color-naming latencies to CS+ compared to the CS- word following acquisition and showed attenuation of this preferential processing bias for threat following extinction. Findings are discussed broadly in the context of the interplay between fear learning and processing biases for threat as observed in persons suffering from anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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

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

Neurotoxic or electrolytic lesions of the ventral subiculum produce deficits in the acquisition and expression of Pavlovian fear conditioning in rats.

The effects of neurotoxic or electrolytic ventral subicular (vSUB) lesions on the acquisition and expression of Pavlovian fear conditioning in rats were examined. Conditioning consisted of the delivery of tone–footshock trials in a novel observation chamber, and freezing served as the measure of conditional fear. Pretraining vSUB lesions produced a severe tone freezing deficit and a modest context freezing deficit, whereas posttraining lesions produced severe deficits in freezing to both a tone -and a context conditional stimulus (CS). Similar impairments were produced by neurotoxic and electrolytic lesions. Increases in motor activity associated with the lesions could not account for freezing deficits. These results reveal that neurons in the vSUB have an important role in both the acquisition and expression of Pavlovian fear conditioning to contextual and acoustic CSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Counterconditioning versus forced exposure in extinction of avoidance responding and conditioned fear in rats.

Conducted 2 experiments using 64 and 32 male Long-Evans hooded rats, respectively. Exp. I investigated the extinction of the conditioned avoidance response (CAR) by response prevention and counterconditioning methods. Response prevention was most effective in extinguishing both the CAR and associated conditioned fear, although counterconditioning produced greater extinction than the regular extinction procedure. Exp. II equated the counterconditioning and response-prevention conditions for duration of CS exposure and demonstrated the superiority of the latter in extinguishing the CAR; both methods were equally effective in decreasing conditioned fear as compared to the regular extinction procedure. Extinction of the CAR was facilitated to the extent to which different procedures eliminated response-contingent feedback by reducing escape-avoidance responses. Conditioned fear was a function of the amount of nonreinforced exposure to the CS during extinction. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extinction of conditioned fear in rats as a function of several parameters of CS exposure.

Employed Pavlovian fear acquisition and extinction procedures in a factorial design which varied conditioned-stimulus (CS) duration in acquisition, the number and duration of CS exposures in extinction, and total CS exposure across extinction trials. Ss were 128 female Blue Spruce hooded rats. Suppression of licking for water served as the measure of residual fear. The data revealed that suppression of licking was an inverse function of total nonreinforced CS exposure irrespective of the number and duration of extinction exposures used to amass that total. The effect of total nonreinforced CS exposure was not significantly influenced by the duration of the CS utilized in acquisition training. The discrepancy between the obtained results and predictions derived from several theories of extinction is discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

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

Temporally massed CS presentations generate more fear extinction than spaced presentations.

Rodent fear conditioning models both excitatory learning and the pathogenesis of human anxiety, whereas extinction of conditional fear is a paradigm of inhibitory learning and the explicit model for behavior therapy. Many studies support a general learning rule for acquisition: Temporally spaced training is more effective than massed training. The authors asked whether this rule applies to extinction of conditional fear in mice. The authors find that both short- and long-term fear extinction are greater with temporally massed presentations of the conditional stimulus (CS). The data also indicate that once CS presentations are sufficiently massed to initiate, or "induce," extinction learning, further CS presentations are more effective when spaced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampus and Pavlovian Fear Conditioning in Rats: Muscimol Infusions Into the Ventral, but Not Dorsal, Hippocampus Impair the Acquisition of Conditional Freezing to an Auditory Conditional Stimulus.

The authors compared the effects of pharmacological inactivation of the dorsal hippocampus (DH) or ventral hippocampus (VH) on Pavlovian fear conditioning in rats. Freezing behavior served as the measure of fear. Pretraining infusions of muscimol, a GABAA receptor agonist, into the VH disrupted auditory, but not contextual, fear conditioning; DH infusions did not affect fear conditioning. Pretesting inactivation of the VH or DH did not affect the expression of conditional freezing. Pretraining electrolytic lesions of the VH reproduced the effects of muscimol infusions, whereas posttraining VH lesions disrupted both auditory and contextual freezing. Hence, neurons in the VH are importantly involved in the acquisition of auditory fear conditioning and the expression of auditory and contextual fear under some conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)