Abstract
Brain derived neurotropic factor (BDNF) supports neuronal survival, growth, and differentiation and is involved in forms of hippocampus-dependent and independent learning, as well as hippocampus-dependent learning. Extinction learning comprises active inhibition of no-longer relevant learned information, in conjunction with a decreased response of a previously learned behavior. It is highly dependent on context, and evidence exists that it requires hippocampal activation. The participation of BDNF in memory processing is experience-dependent. For example, BDNF has been associated with synaptic plasticity needed for spatial learning, and it is involved in acquisition and extinction learning of fear conditioning. However, little is known about its role in spatial appetitive extinction learning. In this study, we evaluated to what extent BDNF contributes to spatial appetitive extinction learning in the presence (ABA) or absence (AAA) of exposure to the acquisition context. Daily training, of BDNF+/−-mice or their wildtype (WT) littermates, to reach acquisition criterion in a T-maze, resulted in a similar performance outcome. However, extinction learning was delayed in the AAA, and impaired in the ABA-paradigm compared to performance in WT littermates. Trial-by-trial learning analysis indicated differences in the integration of the context into extinction learning by BDNF+/−-mice compared to WT littermates. Taken together, these results support an important role for BDNF in processes that relate to information updating and retrieval that in turn are crucial for effective extinction learning.
Highlights
Operant behaviors are voluntary actions controlled by their consequences
We report no ostensible deficiencies in task learning in the acquisition context (AAA paradigm), but extinction learning was delayed in this paradigm in Brain derived neurotropic factor (BDNF)+/− mice compared to their WT littermates
That extinction learning in a context that differs from the acquisition context is more sensitive to the reduced availability of BDNF than extinction learning in the acquisition context
Summary
Operant behaviors are voluntary actions controlled by their consequences. Animals readily acquire behaviors (e.g., lever pressing) to obtain a desirable outcome (e.g., food pellet or drug delivery) and learn to suppress or diminish this behavior when the reinforcer is withdrawn, in a process known as extinction learning (Eddy et al, 2016). In opposition, extinguished behavior, the associated responses for which have been abolished, can re-emerge through several mechanisms One of these processes is referred to as renewal, which occurs in the form of a return of the associated response, when an animal is tested in a context different from the one in which extinction learning took place, or when substantial time has elapsed since extinction learning occured (Bouton and Bolles, 1979). Spatial-Appetitive Extinction Learning Requires BDNF extinction learning is accelerated when animals are exposed to a context that differs from the original acquisition context, referred to here as an ABA paradigm, compared to extinction learning in the original acquisition context (AAA paradigm) (Bouton and Bolles, 1979; Bouton, 2004, 2019; Bouton et al, 2006) This reappearance of responding demonstrates that extinction learning does not comprise erasure of the original learning. Evidence exists that extinction learning may be considered to be a new form of learning, involving memory formation whilst preserving the original memory trace (Mendez-Couz et al, 2019)
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