Observational learning in mice can be prevented by medial prefrontal cortex stimulation and enhanced by nucleus accumbens stimulation

Abstract

The neural structures involved in ongoing appetitive and/or observational learning behaviors remain largely unknown. Operant conditioning and observational learning were evoked and recorded in a modified Skinner box provided with an on-line video recording system. Mice improved their acquisition of a simple operant conditioning task by observational learning. Electrical stimulation of the observer's medial prefrontal cortex (mPFC) at a key moment of the demonstration (when the demonstrator presses a lever in order to obtain a reward) cancels out the benefits of observation. In contrast, electrical stimulation of the observer's nucleus accumbens (NAc) enhances observational learning. Ongoing cognitive processes in the demonstrator could also be driven by electrical stimulation of these two structures, preventing the proper execution of the ongoing instrumental task (mPFC) or stopping pellet intake (NAc). Long-term potentiation (LTP) evoked in these two cortical structures did not prevent the acquisition or retrieval process-namely, mPFC and/or NAc stimulation only prevented, or modified, the ongoing behavioral process. The dorsal hippocampus was not involved in either of these two behavioral processes. Thus, both ongoing observational learning and performance of an instrumental task require the active contribution of the mPFC and/or the NAc.

Functional basis of associative learning and its relationships with long-term potentiation evoked in the involved neural circuits: Lessons from studies in behaving mammals

“…When evoked in behaving mice, most LTPs presented profiles similar to those already described for the CA3-CA1 synapse in the same species (Gruart et al, 2006;Madroñal et al, 2007). However, and as reported recently (Jurado-Parras et al, 2012), the CA1-mPFC synapse displayed a characteristic delayed building up of the expected synaptic potentiation, a fact that has also been reported recently in behaving mice (Eleore, López-Ramos, Guerra-Narbona, & Delgado-García, 2011;López-Ramos, Guerra-Narbona, & Delgado-García, 2015). Surprisingly, the thalamic reuniens nucleus (REU)-CA1 synapse showed an evident and significant long-term depression in response to the presentation of the HFS protocol (Fig.…”

Alterations in microglial phenotype and hippocampal neuronal function in transgenic mice with astrocyte-targeted production of interleukin-10

“…The step-through latency (in seconds) was determined automatically by the passive avoidance device (Ugo Basile, Comerio, Italy). For the associative learning task training and testing were performed in six Skinner box operant chambers (Jurado-Parras et al, 2012;Madronal et al, 2010). Before training, mice were handled daily for 7 days and food-deprived to 80% of their free-feeding weight.…”

Multisynaptic State Functions Characterizing the Acquisition of New Motor and Cognitive Skills

“…At that moment, it was assumed that other synapses present in the intrinsic hippocampal circuit and the many other related to its main inputs (perforant pathway) and outputs (other cortical structures) should present similar changes in synaptic strength [2]. Indeed, we have addressed this question in a recently published study [4] and with different ongoing experiments being carried out in our laboratory. As illustrated in Fig.…”

“…Indeed, our experimental approach is susceptible of being used in different types of associative learning as classical and instrumental conditioning, as well in other types of non-associative learning tasks as object recognition and spatial orientation [1][2][3][4].…”

“…Thus, each neuronal type in a selected cortical circuit plays a specific role that can only be determined by the use of experimental models allowing its study in the best physiological conditions and during the acquisition of new motor or cognitive abilities. We have developed the basic technology for the study of activitydependent changes in synaptic strength at a given relay site [1][2][3][4]. In this paper, we have extended this information to many different synapses located in hippocampal and prefrontal circuits (see Figs.…”