Early and late acquisition of discriminative neuronal activity during differential conditioning in rabbits: Specificity within the laminae of cingulate cortex and the anteroventral thalamus.

Recorded multiple-unit activity of the circulate cortex and the anteroventral (AV) nucleus of the thalamus during discriminative conditioning of an avoidance response (locomotion) in 50 New Zealand White rabbits. Results indicate a greater unit response in cingulate cortex to the positive conditional stimulus (CS+; a tone paired with a footshock UCS) relative to the negative conditional stimulus (CS–; a tone randomly interspersed with the positive stimuli but never paired with the UCS). The majority of neuronal records obtained from the deep laminae of cingulate cortex manifested 1st neuronal discrimination in the session of 1st exposure to conditioning. However, the majority of neuronal records of the superficial laminae showed 1st discrimination at a late stage of training, during the session in which the criterion of behavioral discrimination was met. The late developing discriminative activity of the superficial laminae was coincident with the late developing discriminative activity of the AV thalamus. Once acquired, neuronal discrimination in cortex persisted throughout 600 msec after CS onset, and during 6 sessions of training of overtraining. Analysis of individual neuronal records suggested that the persistence during overtraining resulted from replacement of early fading neuronal discriminations by late neuronal discriminations. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain stem reticular formation neuronal correlates of stimulus significance and behavior during discriminative avoidance conditioning in rabbits.

Recorded multiple-unit activity in the reticular formation (RF) of the midbrain and pons in 14 New Zealand white rabbits during discriminative conditioning of locomotor (wheel-running) avoidance behavior, to examine whether discriminative neuronal activity develops in the RF during discriminative avoidance conditioning, and, if so, what its relation is to the activity in the limbic cortical structures and to the behavior. The positive and negative conditional stimuli (CS+ and CS–) were pure tones of different auditory frequency, and the unconditioned stimulus/stimuli (UCS) was a constant-current footshock (1.5–2.5 mA) delivered through the grid floor of the wheel. The pontine, but not the midbrain, sites manifested development during behavioral acquisition, of brief-latency (10–40 msec) discriminative neuronal discharges (i.e., greater discharges to the CS+ than to the CS–). The greatest magnitude of the discriminative discharges in the rostral pontine loci occurred in the 1st conditioning session. The discriminative response in the caudal loci developed more slowly, and it persisted to the criterial stage of training. Both rostral and caudal pontine loci, during the interval from CS onset to UCS onset, manifested a progressive build-up of neuronal firing in anticipation of the behavioral response. (59 ref) (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)     

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.     

Discriminative conditioning with different CS–US intervals produces temporally differentiated conditioned responses in the two eyes of the rabbit (Oryctolagus cuniculus).

The conditioned eyeblink response (CR) in rabbits is lateralized to the eye targeted by the unconditioned stimulus (US). However, a contralateral component has been reported during concurrent discriminative conditioning of the two eyes. The authors investigated CRs produced by both eyes during conditioning with 2 different interstimulus intervals (ISIs) in which a short conditioned stimulus (CS) was paired with a US to the left eye and a long CS was paired with a US to the right eye. Whether the 2 CSs were more or less similar (or identical), the short CS produced short-latency CRs in the left eye, whereas the long CS produced long-latency CRs in the right eye. The contralateral responses to a CS trained at one ISI were separable into temporal corollaries of the ipsilateral response (suggesting a bilaterality of the CR) versus those to a CS trained at another ISI (indicating generalization between the CSs). The results indicate that the neuronal substrates subserving CRs of the two eyes involve not only a dominant lateralization but also some avenue of bilaterality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cingulate cortical and anterior thalamic neuronal correlates of reversal learning in rabbits.

Recorded unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in 48 New Zealand White rabbits during reversal training following differential conditioning of a locomotory avoidance response. The positive and negative conditional stimuli (CS+ and CS–) were pure tones (1 kHz and 8 kHz), and the UCS was footshock (1.5 mA). During the 1st session, activity appropriate to the original task (i.e., a greater neuronal response to the CS– than to the CS+) occurred in the deep cortical laminae, but the superficial laminae manifested the original discrimination in certain records and the reverse discrimination in others. All discriminative effects diminished during subsequent sessions except the short-latency deep laminar original discrimination, which persisted throughout reversal training. Activity of the AV nucleus underwent gradual transition, in parallel with the behavior, from the original to the reverse discrimination. Arousal-producing footshocks given after behavioral reversal reduced the original and reverse discriminations in the deep and superficial laminae, respectively. These data indicate the role of cingulate cortex and anterior thalamus for encoding the associative significance of the CS (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anterior thalamic lesions and neuronal activity in the cingulate and retrosplenial cortices during discriminative avoidance behavior in rabbits.

Bilateral electrolytic lesions of the anteroventral nucleus of the thalamus given after training impaired retention performance (extinction and reacquisition) of 12 male New Zealand White rabbits in a differential avoidance conditioning task. In addition, the lesions abolished the excitatory, discriminative multiple-unit discharges that had developed in the cingulate and retrosplenial cortices to the auditory CSs during the course of behavioral acquisition, prior to the induction of the lesions. The excitatory discharges were supplanted in the Ss with lesions by CS-elicited reduction of neuronal firing to levels below the prestimulus baseline. Lesions given to 8 Ss before training did not disrupt behavioral acquisition, but they did eliminate the excitatory tone-elicited neuronal discharges that normally occur in the cortex before and during training. The CS-elicited reduction of neuronal firing did not occur at the beginning of training in the Ss given lesions before training, but it developed during the course of training. The lesions did not eliminate the excitatory and discriminative neuronal activity of the prefrontal cortex. Results demonstrate the excitatory and discriminative neuronal discharges in the cingulate and retrosplenial cortices are critically dependent on the connections of these areas with the anterior thalamic nuclei. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial geniculate lesions block amygdalar and cingulothalamic learning-related neuronal activity

This study assessed the role of the thalamic medial geniculate (MG) nucleus in discriminative avoidance learning, wherein rabbits acquire a locomotory response to a tone [conditioned stimulus (CS)+] to avoid a foot shock, and they learn to ignore a different tone (CS-) not predictive of foot shock. Limbic (anterior and medial dorsal) thalamic, cingulate cortical, or amygdalar lesions severely impair acquisition, and neurons in these areas develop training-induced activity (TIA): more firing to the CS+ than to the CS-. MG neurons exhibit TIA during learning and project to the amygdala. The MG neurons may supply afferents essential for amygdalar and cingulothalamic TIA and for avoidance learning. To test this hypothesis, bilateral electrolytic or excitotoxic ibotenic acid MG nuclear lesions were induced, and multiunit recording electrodes were chronically implanted into the anterior and posterior cingulate cortex, the anterior-ventral and medial-dorsal thalamic nuclei, and the basolateral nucleus of the amygdala before training. Learning was severely impaired and TIA was abolished in all areas in rabbits with lesions. Thus learning and TIA require the integrity of the MG nucleus. Only damage in the medial MG division was significantly correlated with the learning deficit. The lesions abolished the sensory response of amygdalar neurons, and they attenuated (but did not eliminate) the sensory response of cingulothalamic neurons, suggesting the existence of extra geniculate sources of auditory transmission to the cingulothalamic areas.     

Summation of reinforcement rates when conditioned stimuli are presented in compound.

Three experiments used delay conditioning of magazine approach in rats to examine the summation of responding when two conditioned stimuli (CSs) are presented together as a compound. The duration of each CS varied randomly from trial-to-trial around a mean that differed between the CSs. This meant that the rats' response rate to each CS was systematically related to the reinforcement rate of that CS, but remained steady as time elapsed during the CS (Harris & Carpenter, 2011; Harris, Gharaei, & Pincham, 2011). When the rats were presented with a compound of two CSs that had been conditioned separately, they responded more during the compound than during either of the CSs individually. More significantly, however, in all three experiments, the rats responded to the compound at the same rate as they responded to a third CS that had been reinforced at a rate equal to the sum of the reinforcement rates of the two CSs in compound. We discuss the implications of this finding for associative models (e.g., Rescorla & Wagner, 1972) and rate-based models (Gallistel & Gibbon, 2000) of conditioning. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

In utero cocaine, discriminative avoidance learning with low-salient stimuli and learning-related neuronal activity in rabbits (Oryctolagus cuniculus).

Daily injections of cocaine administered to pregnant rabbits (Oryctolagus cuniculus) throughout gestation were associated with neural and behavioral changes during development and in adulthood, including altered neuron structure and function in areas receiving dopaminergic projections and retarded Pavlovian eyeblink conditioning with low-salient conditional stimuli. Studies of discriminative avoidance learning have shown changes in learning-related cingulothalamic neuronal activity, but no behavioral learning impairment in cocaine-exposed offspring. Here, low-salient stimuli were used during discriminative avoidance conditioning. Impairments early in behavioral acquisition were found, as well as alterations of anterior cingulate and medial prefrontal cortical, medial dorsal thalamic, and amygdalar neuronal response profiles and learning-related neuronal activity. These results elucidate the neural processes, impaired by prenatal cocaine, that support conditioning with low-salient stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning.

During Pavlovian fear conditioning a conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (UCS). In many studies the CS and UCS are paired on every trial, whereas in others the CS and UCS are paired intermittently. To better understand the influence of the CS-UCS pairing rate on brain activity, the experimenters presented continuously, intermittently, and non-paired CSs during fear conditioning. Amygdala, anterior cingulate, and fusiform gyrus activity increased linearly with the CS-UCS pairing rate. In contrast, insula and left dorsolateral prefrontal cortex responses were larger during intermittently paired CS presentations relative to continuously and non-paired CSs. These results demonstrate two distinct patterns of activity in disparate brain regions. Amygdala, anterior cingulate, and fusiform gyrus activity paralleled the CS-UCS pairing rate, whereas the insula and dorsolateral prefrontal cortex appeared to respond to the uncertainty inherent in intermittent CS-UCS pairing procedures. These findings may further clarify the role of these brain regions in Pavlovian fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal dynamics of the rabbit's nictitating membrane response in serial compound conditioned stimuli.

Two experiments, with 88 female albino rabbits, investigated conditioning of the nictitating membrane response to a reinforced serial compound stimulus. The serial compound was composed of a 400-msec CS (CSA), a trace interval of at least 2 sec, and a brief 2nd CS (CSB) prior to the UCS. The CSB duration was either 150, 250, or 400 msec in Exp I, and the CSB duration in Exp II was 400 msec. Exp I compared serial compound training to an "uncoupled" condition, which contained intermixed CSA–UCS trials and CSB–UCS trials. Exp II compared serial compound training with uncoupled training, 2nd-order conditioning (CSA–CSB/CSB–UCS), trace conditioning (CSA–UCS), and generalization testing that entailed CSB–UCS training and unreinforced tests with CSA. The serial compound, uncoupled, and 2nd-order conditioning procedures all produced high levels of responding during CSA, but only the reinforced serial compound procedure yielded an appreciable likelihood of CR initiation during the trace interval between CSA and CSB. The CRs during the trace interval were temporally distinct from the CRs during CSA and did not appear to be belated CRs to CSA itself. Results are discussed in connection with stimulus selection phenomena, for example, overshadowing and potentiation of toxicosis conditioning. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unit activity in cingulate cortex and anteroventral thalamus of the rabbit during differential conditioning and reversal

Multiple-unit activity was recorded from the rabbit anterior cingulate cortical area (AC) and from the anteroventral nucleus of the thalamus (AV) during differential avoidance conditioning and reversal. The positive and negative conditioned stimuli were tones of different frequency, and the unconditioned stimulus (UCS) was shock delivered through the grid floor of a rotating-wheel conditioning apparatus. Conditioning was preceded by pretraining with tones and noncontingent presentations of the shock UCS. The results showed associative (differential) neuronal activity in both AC and AV during differential conditioning. The effect in AC occurred in the intermediate and final sessions of conditioning. A very large differential effect appropriate to original conditioning occurred in AC in the first two sessions of reversal training. The differential effect in AV occurred in the final session of conditioning when the behavioral response was well learned. There was no clear neuronal reversal in AC or AV.     

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)     

Physiological plasticity of single neurons in auditory cortex of the cat during acquisition of the pupillary conditioned response: II. Secondary field (AII).

Recorded the discharges of 22 single neurons in the secondary auditory cortical field (AII) during acquisition of the pupillary dilation conditioned defensive response in 12 chronically prepared cats. All 22 neurons developed discharge plasticity in background activity, and 21 of 22 cells developed plasticity in their responses to the acoustic CS. Decreases in background activity developed at the time that Ss began to display CRs. Increases in background activity developed in Ss that became more tonically aroused during conditioning. However, both increases and decreases in evoked activity developed independently of the rate of pupillary learning, tonic arousal level, or changes in background activity. Findings indicate that changes in background activity are closely related to behavioral processes of learning and arousal, whereas stimulus-evoked discharge plasticity develops solely as a consequence of stimulus pairing. Comparison with data obtained by the 2nd author and colleagues (see record 1985-03305-001) for the primary auditory cortical field (AI) indicates that both regions developed neuronal discharge plasticity early in the conditioning phase and that increases in background activity in primary auditory cortex were also associated with elevated levels of tonic arousal. The incidence of single neurons developing learning-related discharge plasticity was significantly greater in AII than in AI. Findings are discussed in terms of parallel processing in sensory systems and multiple sensory cortical fields. (69 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frequency-specific receptive field plasticity in the medial geniculate body induced by Pavlovian fear conditioning is expressed in the anesthetized brain.

Fear conditioning modifies the processing of frequency information; receptive fields (RFs) in the auditory cortex and the medial geniculate body (MGB) are altered to favor processing the frequency of the conditioned stimulus/stimuli (CS) over the pretraining best frequency (BF) and other frequencies. This experiment was designed to determine whether brief conditioning in the waking state produces RF plasticity that is expressed under general anesthesia. Guinea pigs bearing electrodes in the MGB received 20 trials on tone-shock pairing in a single training session. RFs were determined with animals under ketamine anesthesia before conditioning and 1–3 hrs and 24 hrs after conditioning. Frequency-specific RF plasticity was evident for both postconditioning periods: The BF shifted toward or to the CS frequency, responses to the BF decreased, and responses to the CS increased. Broadly tuned cells developed greater RF plasticity than narrowly tuned neurons. Results demonstrate that the specific neuronal results of brief learning experiences can be expressed in the anesthetized brain. (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)     

Effects of bed nucleus of the stria terminalis lesions on conditioned anxiety: Aversive conditioning with long-duration conditional stimuli and reinstatement of extinguished fear.

Four experiments investigated the effects of lesions of the bed nucleus of the stria terminalis (BNST) on conditioned fear and anxiety. Though BNST lesions did not disrupt fear conditioning with a short-duration conditional stimulus (CS; Experiments 1 and 3), the lesion attenuated conditioning with a longer duration CS (Experiments 1 and 2). Experiment 3 found that lesions attenuated reinstatement of extinguished fear, which relies on contextual conditioning. Experiment 4 confirmed that the lesion reduced unconditioned anxiety in an elevated zero maze. The authors suggest that long-duration CSs, whether explicit cues or contexts, evoke anxiety conditioned responses, which are dissociable from fear responses to shorter CSs. Results are consistent with behavioral and anatomical distinctions between fear and anxiety and with a behavior-systems view of defensive conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Conditioning During Amygdalar Inactivation on Training-Induced Neuronal Plasticity in the Medial Geniculate Nucleus and Cingulate Cortex in Rabbits (Oryctolagus cuniculus).

This study addressed the amygdala's role in avoidance conditioning in rabbits (Oryctolagus cuniculus). Intra-amygdalar muscimol infusion before 60 or 120 conditioning trials blocked training-induced neuronal activity (TIA) in the medial geniculate (MG) nucleus. One hundred twenty trials with muscimol blocked TIA permanently, during conditioning with muscimol and then later without muscimol; 60 trials with muscimol blocked TIA only when muscimol was present. Cingulate cortical TIA was blocked only when muscimol was present. Behavioral learning did not occur with muscimol, but later learning was facilitated (i.e., savings occurred) in rabbits initially given muscimol plus training. These results define the time period wherein amygdalar processes initiate TIA in the MG nucleus and suggest that distinct forms of amygdalar processes induce TIA in the MG nucleus and cingulate cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)