A componential view of configural cues in generalization and discrimination in Pavlovian conditioning.

This paper describes three theoretical approaches to the representation of configural cues in generalization and discrimination in Pavlovian conditioning: that of the Rescorla-Wagner model, the Pearce model, and the authors' 'replaced elements' model. We summarize the results of a generalization experiment using the rabbit Pavlovian conditioned eyeblink response where animals were trained with cues A, AB, or ABC, and tested with A, AB, and ABC. The pattern of generalization decrement in testing supported the replaced elements model.

Modulation of the acquisition of the rabbit eyeblink conditioned response by conditioned contextual stimuli.

Three experiments were conducted to ask if conditioned emotional responses (CERs) controlled by contextual cues modulate the acquisition of eyelid conditioned responses (CRs) to discrete conditioned stimuli (CSs). Experiment 1 showed that 30-s auditory stimuli that were paired with aversive shocks to one paraorbital region or the other controlled discriminated CERs, as measured by potentiation of a startle response. In Experiments 2 and 3, similarly trained 30-s stimuli served as contexts in which 1.050-ms CSs were paired with a paraorbital unconditioned stimulus (US). Reinforced contexts both impaired (Experiments 2A and 2B) and facilitated (Experiment 3B) acquisition of the eyeblink CR, depending on the locus of the USs involved. The data are consistent with the interpretation that CERs controlled by contextual cues facilitate CR acquisition, but do so in the face of blocking effects of CR tendencies also conditioned to the contextual cues.

Discriminated lateralized eyeblink conditioning in the rabbit: an experimental context for separating specific and general associative influences.

Four experiments are reported that demonstrate discriminated lateralized eyeblink conditioning in rabbits and show how the phenomenon may be used to differentiate between the reflexive and emotive consequences of Pavlovian conditioning. Experiments 1, 2, and 3 characterized how 2 conditioned stimuli (CSs), contemporaneously trained with left vs. right paraorbital unconditioned stimuli (USs), can produce different conditioned reflexes (CRs), each involving predominant closure of the eye ipsilateral to its US. Experiment 4 showed how the associative tendencies controlled by additional stimuli could be evaluated by presentations in compound with such discriminanda: A 30-s stimulus, presumed to acquire a conditioned emotional response but no eyeblink CR, equally potentiated the eyelid CRs elicited by both CSs; a 1,050-ms CS that evoked an eyeblink CR in isolation also increased the responding to both CSs but biased it toward its own lateralized CR.

Modulation of a discrete Pavlovian conditioned reflex by a putative emotive Pavlovian conditioned stimulus.

Three experiments showed the modulation of a rabbit eyeblink conditioned response (CR) to a Pavlovian conditioned stimulus (CS) by 30-s stimuli (A & B) that had been differentially paired with paraorbital shock. The CS (Y) was a 1,050-ms cue that had been paired with paraorbital shock outside A or B. In testing, the amplitude of CRs was greater when Y was presented within A than within B. Differential modulation occurred whether shock in A had been preceded by another 1,050-ms cue, X(AX+,BX-;Experiment 1) or not (A+B-;Experiment 2). Experiment 3 compared the technique of Experiment 1 (AX+) with that of Experiment 2 (A+) and found the latter to be advantageous for facilitation of CRs to Y by A. These data are consistent with the predictions of a model of Pavlovian conditioning (AESOP, Wagner & Brandon, 1989) that distinguishes between emotive and sensory conditioning as did Konorski (1967).

Modulation of unconditioned defense reflexes by a putative emotive Pavlovian conditioned stimulus.

Four experiments showed differential modulation of defensive unconditioned responses (URs) in rabbits by contextual stimuli that Brandon and Wagner (1991) have shown similarly to modulate conditioned eyeblink responses. Two 30-s auditory cues, A and B, were differentially paired with shock. Tests were presentations of a response-eliciting probe stimulus within A, B, or a comparable blank interval, Experiments 1 and 2 demonstrated that A and B differentially facilitated eyeblink URs, and Experiments 3 and 4 showed that A and B similarly differentially facilitated startle responses elicited by airpuffs to the ear. These data are consistent with a characterization of Pavlovian conditioning that distinguishes between emotive and sensory conditioning and assumes that conditioned emotional responses similarly modulate specific conditioned and unconditioned defensive reflexes (Konorski, 1967; Wagner & Brandon, 1989).

Modulation of a conditioned eyeblink response by a putative emotive stimulus conditioned with hindleg shock.

Two experiments with rabbits showed that the differential modulation of a conditioned eyeblink response (CR) by 30-s auditory stimuli previously paired with shock was independent of the locus of shock application. In Experiment 1, the modulation occurred when the CR was trained with paraorbital shock and the 30-s stimuli were trained with either hindleg or paraorbital shock. Experiment 2 replicated the observed adequacy of hindleg shock for modulation training, under 2 different conditions of eyeblink conditioning. The data, along with the findings that the same 30-s stimuli similarly facilitate the unconditioned eyeblink and the airpuff-elicited startle response (Brandon, Bombace, Falls & Wagner, 1991), were viewed as supporting the notion that the CR-modulation is dependent upon a conditioned fear response elicited by the 30-s cues (Wagner & Brandon, 1989).

Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein.

Vertebrate cells synthesize two forms of the 82- to 90-kilodalton heat shock protein that are encoded by distinct gene families. In HeLa cells, both proteins (hsp89 alpha and hsp89 beta) are abundant under normal growth conditions and are synthesized at increased rates in response to heat stress. Only the larger form, hsp89 alpha, is induced by the adenovirus E1A gene product (M. C. Simon, K. Kitchener, H. T. Kao, E. Hickey, L. Weber, R. Voellmy, N. Heintz, and J. R. Nevins, Mol. Cell. Biol. 7:2884-2890, 1987). We have isolated a human hsp89 alpha gene that shows complete sequence identity with heat- and E1A-inducible cDNA used as a hybridization probe. The 5'-flanking region contained overlapping and inverted consensus heat shock control elements that can confer heat-inducible expression on a beta-globin reporter gene. The gene contained 10 intervening sequences. The first intron was located adjacent to the translation start codon, an arrangement also found in the Drosophila hsp82 gene. The spliced mRNA sequence contained a single open reading frame encoding an 84,564-dalton polypeptide showing high homology with the hsp82 to hsp90 proteins of other organisms. The deduced hsp89 alpha protein sequence differed from the human hsp89 beta sequence reported elsewhere (N. F. Rebbe, J. Ware, R. M. Bertina, P. Modrich, and D. W. Stafford (Gene 53:235-245, 1987) in at least 99 out of the 732 amino acids. Transcription of the hsp89 alpha gene was induced by serum during normal cell growth, but expression did not appear to be restricted to a particular stage of the cell cycle. hsp89 alpha mRNA was considerably more stable than the mRNA encoding hsp70, which can account for the higher constitutive rate of hsp89 synthesis in unstressed cells.

Modulation of behavioral and insulin responses by contextual stimuli paired with food.

A context-like conditioned stimulus (CS) previously paired with a food unconditioned stimulus (US) enhanced both food-related activity and insulin secretion in rats. Experiment 1 documented the effectiveness of an appetitive conditioning procedure in which a 10 sec visual CS ("x") was followed by food when embedded within one 35 sec auditory CS ("A"), but not another ("B"). Approach to a food magazine during x was enhanced (facilitated) when x was within A, as compared to within B or alone. Experiment 2 documented the adequacy of blood sampling and insulin assay procedures that could be accommodated to the conditioning procedure. Plasma insulin was observably different after unconditioned deliveries of glucose solutions of different intensities. In Experiment 3, training as in Experiment 1 was followed by testing for food magazine approach and changes in insulin levels following x alone or in the presence of A or B. It was demonstrated that the A cue enhanced both responses. The results support the view [e.g., (18,19)] that insulin secretion is in part under the control of environmental cues, and findings (22) that show that conditioned context-like cues can modulate consummatory responding to punctate CSs.

Sequence and organization of genes encoding the human 27 kDa heat shock protein.

The 27 kDa human heat shock protein (hsp27) is encoded by a gene family of 4 members. Two genomic fragments hybridizing to cDNA encoding hsp27 have been isolated, characterized, and sequenced. One clone is a member of a cluster of three genes linked within a 14-18 kb region of the genome and encodes a transcript interrupted by two intervening sequences. A single open reading frame encodes a polypeptide of 22,300 deduced molecular weight. The 5' flanking region contains two transcription start sites and sequences homologous to the Drosophila consensus heat inducible control element. Induction of both potential transcripts follows heat shock in vivo. Accurate heat inducible transcription occurs at both start sites after injection into Xenopus oocytes. The second genomic clone is a processed pseudogene lacking promoter elements and is unlinked with the other members of the hsp27 gene family. The amino acid sequence of human hsp27 shows striking homology with mammalian alpha crystallin, and contains a region towards the carboxy terminus which shares homology with the small hsp of Drosophila and other organisms.

Molecular cloning of sequences encoding the human heat-shock proteins and their expression during hyperthermia.

Plasmids containing cDNA copies of mRNAs induced in HeLa cells by heat shock have been isolated and characterized. In vitro translation of RNAs selected by hybridization to plasmid DNAs identified sequences representing the three major classes (89, 70 and 27-kDa) of heat-shock proteins (hsp) and a 60-kDa minor hsp. Plasmids with inserts specific for the 27, 60, and 70-kDa hsp each hybridize with a single discrete size class of heat-inducible mRNA. Plasmids specific for the 89-kDa protein, however, hybridize with either a 2.7- or 2.95-kb mRNA species. Both mRNAs are coordinately induced during heat shock. We show that the characteristic pattern of induction and repression of each class of hsp during sustained hyperthermia is the result of changes in the steady state level of each mRNA.