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Mediodorsal but not anterior thalamic nuclei lesions impair acquisition of a conditional discrimination task

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Highlights

  • MD lesions in rats transiently impair acquisition of a conditional discrimination.

  • ATN lesions are without effect in the same task.

  • MD may help identify relevant dimensions during initial learning.

Abstract

The limbic thalamus is a heterogeneous structure with distinctive cortical connectivity. A recent review suggests that the mediodorsal thalamic nucleus (MD), unlike the anterior thalamic nuclei (ATN), may be involved in selecting relevant information in tasks relying on executive functions. We compared the effects of excitotoxic lesions of the MD or the ATN on the acquisition of a simple conditional discrimination in rats. When required to choose from two levers according to auditory or visual cues, ATN rats and sham-lesioned rats performed to the same levels and displayed similar acquisition curves. Under the same conditions, MD rats’ acquisition of the task was markedly delayed. This group nevertheless attained nearly normal performances after more extensive training. Furthermore, all rats learned reversal of the original discrimination at the same rate. These results highlight functional specialization within the limbic thalamus and support the notion that MD contributes to the identification of relevant dimensions in conditional tasks during the initial stages of acquisition.

Introduction

It is generally admitted that the integrity of the limbic thalamus is necessary for normal cognitive functions. The thalamus is however a heterogeneous structure and the specific roles of its different regions remain imperfectly defined. A recent review of rodent data indicates a major functional dissociation within the limbic thalamus between the anterior (ATN) and mediodorsal (MD) thalamic nuclei, the former supporting essentially hippocampal functions and the latter contributing to prefrontal cortical functions (Wolff, Alcaraz, Marchand, & Coutureau, 2014). At the crossroad between direct and indirect hippocampal and midbrain inputs, the ATN are essential to spatial navigation (Jankowski et al., 2013), but recent experimental data (Dupire et al., 2013, Law and Smith, 2012, Marchand et al., 2013, Wolff et al., 2006) as well as the study of clinical cases (Carlesimo et al., 2011, Gold and Squire, 2006, Harding et al., 2000, Pergola and Suchan, 2013) indicate that this region may play a broader role in cognition. The MD, on the other hand, entertains privileged links with all divisions of the prefrontal cortex, including the OFC and the mPFC (Groenewegen, 1988). Our understanding of the role of this region now shifts from an essentially mnesic to a more “executive” function. MD appears to be involved in the early stages of acquisition of complex tasks (Hunt & Aggleton, 1991; Hunt, Neave, Shaw, & Aggleton, 1994) and in learning new response strategies, particularly when they require differentiating complex stimuli. It has therefore been suggested that MD contributes to prefrontal cortical functions during task acquisition by focusing attention onto relevant sensory dimensions of the current task (Wolff et al., 2014). Still, few studies have directly compared the differential impact of lesion to either MD or ATN (Alcaraz et al., 2014, Chudasama et al., 2001, Corbit et al., 2003). The present study therefore aimed at comparing the respective contributions of the ATN and MD in a relatively simple conditional task relying on auditory and visual discriminative stimuli. Our hypothesis was that MD lesions would delay the identification of the relevant cues needed to successfully solve the discrimination. By contrast, as the task involved few spatial or relational requirements, the involvement of the ATN was expected to be minimal.

Section snippets

Animals and housing conditions

32 male Long Evans rats from Centre d’Elevage Janvier (France) were housed in pairs in polycarbonate cages containing tainted polycarbonate tubing elements as enrichment medium, in accordance with current French (council directive 2013-118, February 1, 2013) and European (directive 2010-63, September 22, 2010, European Community) laws and policies regarding animal experiments. Tests were performed during the light portion of the daily cycle (7 a.m. to 7 p.m.). Protocols received approval #

Histology

Representative examples of MD and ATN lesions, as well as minimal and maximal extent, are shown on Fig. 1. Three MD and one ATN rats had only minimal damage and were discarded from further analysis. In order to avoid unintended damage to the ATN region, the MD lesions were deliberately performed slightly more posterior than usually in conventional MD studies. As a result, the ATN were preserved in all included MD rats. Nonetheless, substantial damage was apparent at the level of the MD,

Discussion/conclusion

During acquisition of the conditional discrimination task, the selective deficit exhibited by MD rats confirmed the existence of a major functional dissociation between the ATN and MD (Wolff et al., 2014). In particular, the lack of any effect of ATN lesions in the present study contrasts with the dramatic impairments observed in tasks with spatial components (Aggleton, 2014, Jankowski et al., 2013), including conditional discrimination tasks where place information is critical for successful

Acknowledgments

This work was supported by the CNRS and the Conseil Régional d’Aquitaine. We thank D. Panzeri, N. Argenta and J. Huard for their help in animal care.

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