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A Poremba

Publications and source records attributed to A Poremba.

At least 19 recordsLinked to original sources

Amygdalar efferents initiate auditory thalamic discriminative training-induced neuronal activity.

It is well known that neurons of the medial geniculate (MG) nucleus of the thalamus send axonal projections to the amygdala. It has been proposed that these projections supply information that supports amygdalar associative processes underlying acquisition of acoustically cued conditioning and learning. Here we demonstrate the reverse direction of influence. Temporary inactivation of the amygdala using the GABA(A) receptor agonist muscimol just before the onset of discriminative avoidance conditioning permanently blocked the development of training-induced discriminative neuronal activity in the MG nucleus of rabbits. No discriminative activity developed when the amygdala was inactivated or during later training to criterion without muscimol. Thus, amygdalar processing at the outset of training is necessary for the development of training-induced discriminative activity of neurons in the MG nucleus.

Acoustic Stimulation↗

Congenital helpless rats as a genetic model for cortex metabolism in depression.

The validity of congenital helplessness as a genetic rat model for human depression was investigated in cortical regions of the rat brain thought to be analogous to those showing abnormalities in human neuroimaging studies. Cortex metabolism was analyzed using quantitative cytochrome oxidase histochemistry. Congenital helpless rats showed changes in frontal and cingulate regions comparable to those that have demonstrated metabolic differences in human depression. Significant metabolic decreases were found in dorsal frontal, medial orbital, and anterior cingulate, whereas a significant increase was found in infraradiata (subgenual) cingulate. The direction of these changes were the same as those seen in human studies. These findings support the validity of congenital helplessness as a model for human depression.

Animals↗

Amygdala neurons mediate acquisition but not maintenance of instrumental avoidance behavior in rabbits.

Whereas the amygdala is generally understood to be involved in aversively motivated learning, the specific associative function of the amygdala remains controversial. This study addressed the amygdalar role in mediation of discriminative instrumental avoidance learning of rabbits. Bilateral microinjection of the GABA receptor agonist muscimol centered in the basolateral nucleus of the amygdala was given to inactivate amygdalar neurons at each of three stages of acquisition. The absence of behavioral learning in rabbits trained immediately after amygdalar inactivation confirmed previous results with electrolytic lesions. The absence of savings during training after muscimol had become ineffective indicated an amygdalar role in the establishment of acquisition-relevant neural plasticity, not simply in the expression of the learned response. A time-limited role of the amygdala in instrumental avoidance learning was indicated by the finding that intra-amygdalar muscimol failed to disrupt performance of the well-established avoidance response. The passage of time alone (with no training trials) was sufficient to reduce amygdalar involvement in response performance. These results and demonstrations that other limbic system areas make time-limited contributions to learning indicate that the amygdala is part of a larger intermediate memory system that supports learning and performance before habit consolidation.

Amygdala↗

Classical conditioning modifies cytochrome oxidase activity in the auditory system.

The effects of excitatory classical conditioning on cytochrome oxidase activity in the central auditory system were investigated using quantitative histochemistry. Rats in the conditioned group were trained with consistent pairings of a compound conditional stimulus (a tone and a light) with a mild footshock, to elicit conditioned suppression of drinking. Rats in the pseudorandom group were exposed to pseudorandom presentations of the same tone, light and shock stimuli without consistent pairings. Untrained rats in a naive group did not receive presentations of the experimental stimuli. The findings demonstrated that auditory fear conditioning modifies the metabolic neuronal responses of the auditory system, supporting the hypothesis that sensory neurons are responsive to behavioural stimulus properties acquired by learning. There was a clear distinction between thalamocortical and lower divisions of the auditory system based on the differences in metabolic activity evoked by classical conditioning, which lead to an overt learned behavioural response versus pseudorandom stimulus presentations, which lead to behavioural habituation. Increases in cytochrome oxidase activity indicated that tone processing is enhanced during associative conditioning at upper auditory structures (medial geniculate nucleus and secondary auditory cortices). In contrast, metabolic activation of lower auditory structures (cochlear nuclei and inferior colliculus) in response to the pseudorandom presentation of the experimental stimuli suggest that these areas may be activated during habituation to tone stimuli. Together these findings show that mapping the metabolic activity of cytochrome oxidase with quantitative histochemistry can be successfully used to map regional long-lasting effects of learning on brain systems.

Acoustic Stimulation↗

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.

Acoustic Stimulation↗

Amygdalar lesions block discriminative avoidance learning and cingulothalamic training-induced neuronal plasticity in rabbits.

Learning to fear dangerous situations requires the participation of neurons of the amygdala. Here it is shown that amygdalar neurons are also involved in learning to avoid dangerous situations. Amygdalar lesions severely impaired the acquisition of acoustically cued, discriminative instrumental avoidance behavior of rabbits. In addition, the development of anterior cingulate cortical and medial dorsal thalamic training-induced neuronal plasticity in the early stages of behavioral acquisition was blocked in rabbits with lesions. The development of training-induced neuronal plasticity in the medial dorsal and anterior thalamic nuclei in late stages of behavioral acquisition was also blocked in rabbits with lesions. These results indicate that the integrity of the amygdala is essential for the establishment of both early and late training-induced cingulothalamic neuronal plasticity. It is hypothesized that amygdalar training-induced neuronal plasticity in the initial trials of conditioning represents a substrate of learned fear, essential for the early and late cingulothalamic plasticity that is involved in mediation of acquisition of the instrumental avoidance response.

Amygdala↗

Metabolic effects of blocking tone conditioning on the rat auditory system.

The Kamin blocking phenomenon occurs when behavioral expression of conditioning to a novel stimulus fails in the presence of a previously conditioned stimulus (CS). Neural metabolic effects of a tone conditioned as an excitor were compared to the effects of the same physical tone when excitatory conditioning was blocked by previous conditioning with a light. We examined the metabolic activity of the auditory system to test the hypothesis that auditory processing of a tone CS changes during blocking. Quantitative histochemistry of cytochrome oxidase (C.O.), the final mitochondrial enzyme for oxidative metabolism, was used to evaluate cumulative changes in the metabolic capacity of the auditory system resulting from blocking. Rats (Long-Evans) in the Blocking group received pairings of a light CS with a mild footshock unconditioned stimulus (US) during Phase 1 training. Rats in the Control group received random presentations of the same stimuli during Phase 1. Both groups then received the same Phase 2 training consisting of simultaneous tone and light presentations paired with footshock. The Control group exhibited significant suppression of drinking to tone alone presentations after training, whereas the Blocking group did not. Metabolic mapping results demonstrated that blocking effects were localized to auditory regions receiving direct US somatosensory projections. Significantly greater C.O. activity in the inferior colliculus and the dorsal cochlear nucleus was found for the Blocking group relative to the Control group. Input cell layers of secondary auditory cortex also demonstrated a group difference, in that layers II/III and IV had lower levels of C.O. activity in the Blocking group. These specific changes in C.O. activity linked to behavioral training demonstrated that the blocking phenomenon produced distinct neural metabolic changes in CS processing in the auditory system localized to regions with CS-US interactions.

Animals↗

The nomadic engram: overtraining eliminates the impairment of discriminative avoidance behavior produced by limbic thalamic lesions.

Combined lesions of the medial dorsal and anterior thalamic nuclei severely impair the acquisition of discriminative avoidance behavior, wherein rabbits learn to prevent foot-shock by stepping after a tone conditional stimulus (CS+), and they learn to ignore a different tone (CS-) that does not signal foot-shock. Neurons in these thalamic nuclei exhibit training-induced firing pattern changes during behavioral acquisition to asymptotic performance levels. However, the changes decline in magnitude during the course of post-asymptotic training (overtraining), suggesting a declining participation of the thalamic neurons in task mediation. In order to test this hypothesis, electrolytic or sham limbic thalamic lesions were induced either immediately after asymptotic performance was reached, or after the administration of training to asymptote and ten additional overtraining sessions. Retention after the lesions was assessed using an extinction procedure (CS presentation without foot-shock) followed by re-acquisition. Rabbits given lesions after criterion attainment exhibited a significant retention deficit during both the extinction and re-acquisition tests. However, no significant retention deficit was found in rabbits given 10 days of overtraining prior to the lesions. These results support the prediction derived from the neuronal data, of a time-limited involvement of limbic thalamic neurons in mediation of discriminative avoidance behavior.

Animals↗

Stimulus-related and movement-related single-unit activity in rabbit cingulate cortex and limbic thalamus during performance of discriminative avoidance behavior.

Neuronal discharges related to acoustic conditional stimuli and locomotive behavioral responses of 152 anterior and medial dorsal (MD) thalamic and cingulate cortical single-units sorted from multi-unit activity were recorded as rabbits performed in a discriminative avoidance task. The goals were: (1) to document the single-unit constituents of multi-site, multi-unit activity recorded previously in response to the conditional stimuli used for avoidance training; and (2) to document neuronal activity related to the onset of the behavioral avoidance response. Ninety-five units showed discriminative discharges: significantly different firing rates 90-700 ms after a foot shock-predictive conditional stimulus (CS+) than to a safety-predictive conditional stimulus (CS-). In accord with the multi-unit data, a majority of these units discharged at higher rates after the CS+ than after the CS-. The discharge rates of 87 units were greater during the 2-s period preceding the onset of avoidance responses than during comparable trial periods after CS-presentations followed by no response. Fifty-six of the 87 avoidance-related units exhibited a progressive ramp-like firing increase 2 s before the avoidance response, with the maximal discharge rate occurring 200 ms before the response. These dynamic pre-avoidance discharges occurred first in limbic thalamus then in cingulate cortex, suggesting that cortical pre-motor processing may confer temporal specificity upon a more generalized command volley relayed from thalamus. Unlike the multi-unit data, 24 neurons exhibited inverse discrimination, i.e., significantly greater discharges in response to the CS-than to the CS+. Also 27 neurons showed significantly more firing in the 2-s period before the end of CS-trials in which no behavioral response occurred, than in the 2-s pre-avoidance period on CS+ trials with responses. This "inverse' CS-related and pre-avoidance activity occurred at low incidence (< 15%) in all areas except the MD nucleus, wherein it was exhibited by 45% of the recorded units. The inverse activity may reflect the operation of local inhibitory neurons which suppress the discharges of other neurons in response to the CS-. The prevalence of inverse activity in the MD nucleus suggested an involvement of this area in behavioral inhibition.

Acoustic Stimulation↗

Neural substrates of discriminative avoidance learning and classical eyeblink conditioning in rabbits: a double dissociation.

In a previous study, lesions of the deep cerebellar nuclei blocked classical eyeblink conditioning, but did not impair discriminative avoidance learning in rabbits. Here, was also found previously, lesions of the anterior and medial dorsal thalamic nuclei severely impaired discriminative avoidance learning. However, these lesions had no impact on discriminative eyeblink conditioning or reversal learning. These results complete the demonstration of a double dissociation, indicating distinct neural substrates for the acquisition of these learned behaviors. It is proposed that the two learning circuits identified by these studies mediate, respectively, acquisition of specific adaptive reflexes and whole-body, voluntary goal-directed movements.

Animals↗

Afferent connections of the anterior thalamus in rabbits.

This study was designed to determine whether axons of cholinergic dorsal tegmental neurons terminate on cells in the anterior thalamus in rabbits as in other species, and to localize projecting tegmental cells for future studies of their contributions to anterior thalamic learning-relevant neuronal activity. The distribution of retrogradely labeled neurons was examined following injections of wheat germ agglutinin horseradish peroxidase (WGA-HRP) centered in the anterior ventral (AV) thalamic nucleus. The results confirm past findings in rabbits indicating projections to anterior thalamus from the mammillary nuclei, the posterior cingulate cortex, presubiculum and postsubiculum. Demonstrated for the first time in rabbits were projections from the lateral dorsal and the pedunculopontine tegmental nuclei, locus coeruleus, dorsal raphe nucleus, Gudden's dorsal tegmental nucleus, pretectum and reticular thalamic nucleus.

Afferent Pathways↗

Training-stage related neuronal plasticity in limbic thalamus and cingulate cortex during learning: a possible key to mnemonic retrieval.

This study is part of an ongoing project concerned with the analysis of the neural substrates of discriminative avoidance learning in rabbits. Multi-unit activity was recorded in 5 anterior and lateral thalamic nuclei and in 4 layers of 2 posterior cingulate cortical areas (29c/d and 29b) during learning. The rabbits learned to step in response to a warning tone to avoid a foot-shock, and to ignore a different tone not followed by shock. Excitatory training-induced unit activity (TIA, increased tone-elicited activity during training relative to a pretraining session with unpaired tone-shock presentations) and/or discriminative TIA (greater discharges to the warning than to the safe tone) developed during training in 11 of the 13 areas. Discriminative TIA in the thalamic nuclei increased monotonically as learning occurred. Anterodorsal (AD) thalamic excitatory TIA peaked in an early stage (the first session of training), laterodorsal thalamic and parvocellular anteroventral (AVp) excitatory TIA peaked in an intermediate stage (the session of the first behavioral discrimination), and magnocellular anteroventral (AVm) and anteromedial (AM) thalamic excitatory TIA peaked in a late stage (the session in which asymptotic behavioral discrimination first occurred). The excitatory TIA in these nuclei declined as training continued beyond the stage in which the peak occurred. Peaks of excitatory TIA developed in area 29c/d of posterior cingulate cortex in the early (layer IV), intermediate (layers I-III and V) and late (layer IV) training stages, as just defined. Only layer IV in area 29b of posterior cingulate cortex exhibited a peak of excitatory TIA, which occurred in the early and intermediate training stages. As in limbic thalamus, discriminative TIA increased monotonically over training stages in layers V and VI of areas 29c/d and in layer VI of area 29b. However, layers I-III and IV in area 29c exhibited peak discriminative TIA in the intermediate and late training stages, respectively. Lesion studies indicate that limbic thalamus and cingulate cortex are essential for learning. The peaks represent a unique topographic pattern of thalamic and cortical excitation elicited by the CS+. It is proposed that the peaks constitute a retrieval pattern, i.e. a unique topographic array of excitation. This pattern encodes the spatio-temporal context which defines the learning situation and is necessary for recall and output of the learned response.

Animals↗

Cerebellar interpositus nucleus lesions disrupt classical nictitating membrane conditioning but not discriminative avoidance learning in rabbits.

Cerebellar interpositus nucleus lesions were given to 14 rabbits trained in two behavioral paradigms; discriminative avoidance conditioning of locomotor behavior and classical nictitating membrane conditioning. Bilateral lesions that prevented acquisition of the classically conditioned response on both the left and right side failed to affect the acquisition or performance of the conditioned discriminative avoidance response. The results are discussed in terms of differences in neural substrates that apparently subserve the two forms of learning.

Animals↗

Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits.

Basolateral (BL) amygdaloid multi-unit activity was recorded as male albino rabbits learned to avoid a foot-shock unconditioned stimulus (US) by stepping in an activity wheel to an acoustic (pure tone) warning stimulus (CS+). A second tone (CS-) of different auditory frequency than the CS+ was presented in an irregular order on half of the conditioning trials but was never followed by the US. BL amygdaloid neurons developed, in the first session of conditioning, enhanced CS-elicited discharges relative to discharges recorded during pretraining with tones and noncontingent US presentations (excitatory plasticity), and greater discharges to the CS+ than to the CS- (discriminative plasticity). The discriminative plasticity attained maximal magnitude as the rabbits reached the asymptote of behavioral discrimination, and persisted during post-asymptotic training. Peak excitatory plasticity occurred in the session of the first significant behavioral discrimination and declined during the asymptotic and post-asymptotic stages of training. Similar patterns of excitatory and discriminative plasticity in structures directly interconnected with the BL nucleus (anterior cingulate cortex; medial dorsal thalamic nucleus) and effects of lesions suggest that the neurons in these areas participate in a circuit involved in mediation of avoidance learning.

Amygdala↗

Muscarinic receptor binding increases in anterior thalamus and cingulate cortex during discriminative avoidance learning.

Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OXO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OXO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early in training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OXO-M/PZ binding progressively increased throughout training, reached a peak at the criterion stage of performance, and returned to control values during extinction sessions. Peak OXO-M/PZ binding in AVp was significantly elevated over that for cases yoked to criterion performance. In the magnocellular division of the anteroventral nucleus (AVm), OXO-M/PZ binding was elevated only during criterion performance of the task, and it was unaltered in any other limbic thalamic nuclei. Specific OXO-M/PZ binding was also elevated in most layers in rostral area 29c when subjects first performed a significant behavioral discrimination. Training-induced alterations in OXO-M/PZ binding in AVp and layer Ia of area 29c were similar and highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assessing the quality of pharmacist answers to telephone drug information questions.

A quality assurance (QA) program is described in which frontline pharmacists were asked test drug information questions via anonymous telephone calls. The program was instituted at a university hospital that began providing decentralized pharmaceutical services in 1985. Questions were developed on the basis of a pilot study conducted to determine the types and complexity of drug information questions received by frontline pharmacists at the hospital. Data on departmental clinical productivity were used to determine the number of questions that would be posed during each shift in the various service areas. The questions were posed during a 10-day period; the pharmacists were aware of the program, but the callers did not identify their affiliation with it. In response to 105 questions asked, 86 were judged to have been answered correctly, 13 answers were deemed incomplete, and 6 were judged incorrect. Pharmacists were more likely to respond incorrectly to complex questions and questions posed during the night shift. As a result of the audit, staff members with advanced clinical knowledge were asked to help less experienced pharmacists, the position of assistant director for drug information and staff development was created, and educational programs were instituted. The QA audit has been repeated twice. Posing test drug information questions via anonymous telephone calls is effective in assessing the quality of drug information provided by pharmacists in patient-care areas.

Drug Information Services↗