Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus.

Maximiliano Rapanelli,Luciana Romina Frick,Bonifacio Silvano Zanutto

doi:10.1371/journal.pone.0014713

Abstract

Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC) and the hippocampus (HIPP) during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU) injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task) when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task) when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC) in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and neuronal maturation depending on the learning phase in the mPFC-HIPP circuit.

Highlights

Learning a task implies remodeling of neural circuits in the brain, these changes could be achieved by synaptic plasticity events as well as neurogenesis [1]
Behavioral results To study if learning a goal directed behavior could induce cell proliferation, neurogenesis, astrogliogenesis and neuronal maturation in the medial prefrontal cortex (mPFC)-HIPP circuit, we trained two groups of animals in an operant conditioning task
It was found that astrogliogenesis, neurogenesis and neuronal maturation occurred in the mPFC-HIPP circuit during learning an operant conditioning task

Summary

Introduction

Learning a task implies remodeling of neural circuits in the brain, these changes could be achieved by synaptic plasticity events as well as neurogenesis [1]. The operant conditioning task is one of the most important learning paradigms used in rodents for studying goal directed behaviors. Two of the areas involved in learning an operant conditioning task are the medial Prefrontal Cortex (mPFC) and the Hippocampus (HIPP). The aim was to study if learning an operant conditioning task promotes cellular proliferation in the mPFCHIPP circuit, if it is associated to the degree of acquisition of the task and to identify the phenotype of these new cells. These results would bring better insights into the mechanisms of circuit modification during learning an operant conditioning task

Methods

Results

Conclusion