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PubMed2004

AX+, BX- discrimination learning in the fear-potentiated startle paradigm: possible relevance to inhibitory fear learning in extinction.

The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear inhibition, a great deal of behavioral work suggests that postextinction training conditioned stimuli are both excitatory and inhibitory, making it difficult to determine whether a neural manipulation affects inhibition, excitation, or some combination thereof. For this reason we sought to develop a behavioral procedure that would render a stimulus primarily inhibitory while at the same time avoiding some of the issues raised by the traditional conditioned inhibition paradigm, namely second-order conditioning, external inhibition, and configural learning. Using the fear-potentiated startle paradigm, we adapted an AX+, BX- training procedure in which stimuli A and X were presented simultaneously and paired with shock, and stimuli B and X were presented simultaneously in the absence of shock. In testing, high levels of fear-potentiated startle were seen in the presence of A and AX and much lower levels were seen in the presence of B and AB, as would be predicted if stimulus B were a conditioned inhibitor. We believe this method is a viable alternative to the traditional conditioned inhibition training procedure and will be useful for studying the neural mechanisms of fear inhibition.

Acoustic Stimulation↗
PubMed1999

Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation.

Cognitive decline is apparent in the early stages of Huntington's disease and progressively worsens throughout the course of the disease. Expression of the human Huntington's disease mutation in mice (R6/2 line) causes a progressive neurological phenotype with motor symptoms resembling those seen in Huntington's disease. Here we describe the cognitive performance of R6/2 mice using four different tests (Morris water maze, visual cliff avoidance, two-choice swim tank, and T-maze). Behavioral testing was performed on R6/2 transgenic mice and their wild-type littermates between 3 and 14.5 weeks of age, using separate groups of mice for each test. R6/2 mice did not show an overt motor phenotype until approximately 8 weeks of age. However, between 3.5 and 8 weeks of age, R6/2 mice displayed progressive deterioration in specific aspects of learning in the Morris water maze, visual cliff, two-choice swim tank, and T-maze tasks. The age of onset and progression of the deficits in the individual tasks differed depending on the particular task demands. Thus, as seen in humans with Huntington's disease, R6/2 mice develop progressive learning impairments on cognitive tasks sensitive to frontostriatal and hippocampal function. We suggest that R6/2 mice provide not only a model for studying cognitive and motor changes in trinucleotide repeat disorders, but also a framework within which the functional efficacy of therapeutic strategies aimed at treating such diseases can be tested.

Animals↗
PubMed1990

The role of information about the response-outcome relation in instrumental discrimination learning.

In 4 instrumental learning experiments, the hierarchical organization among responses (R), outcomes (O), and stimuli (S) was examined. Each experiment explored the possibility that S becomes associated with the R-O relation by providing information about that relation. In each case, an analogy was developed to a paradigm that has been important for concluding that informational relations affect Pavlovian conditioning. Experiments 1 and 2 found an effect of the information that S provides about the R-O relation, using paradigms analogous to blocking and contingency experiments. Experiments 3 and 4 demonstrated a similar result, using a paradigm like that of relative validity. In each case, the experiments pointed to the importance of the information that S gives about the R-O relation, rather than about the individual R and O elements.

Animals↗