Background & Aims

The mediodorsal thalamus (MD) is a higher-order thalamic nucleus projecting to the prefrontal cortex (PFC). In rats, MD is formed by three segments, the medial, the central, and the lateral subdivisions, with distinct anatomical and functional properties. Each MD subdivision projects to a single and specific region of the PFC. This differential neuroanatomy and connectivity patterns suggest that these three subdivisions might be differentially involved in pain processing. Previous studies have provided evidence for a differential implication in the cognitive process. However, in pain processing, the exact contribution of MD and each of its subdivisions have not been explored yet. Therefore, the present study was designed to explore the role of the MD thalamus in pain processing, with a specific focus on the contribution of each of its subdivisions to the transmission and processing of nociceptive information in its two dimensions, sensory-discriminative and affective-emotional.

Methods

Our study is a behavioral assessment of the outcomes of excitotoxic bilateral lesions, of the total MD (MDtot), the medial-central (MDmc), and the lateral (MDL) subdivisions in adult rats. The Von Frey filaments and the “hot/cold” plate were used to evaluate the sensory component of pain, while the place escape avoidance paradigm (PEAP) was performed to dissect the affective component of pain. Using the Golgi-Cox impregnation method we also examined the morphological changes of the prefrontal cortical neurons. Finally, the prefrontal glial cell reactivity was evaluated by analyzing the profiles of GFAP and iba1 markers.

Results

Our findings revealed a significant increase in both mechanical and thermal nociception following the three MD lesions, demonstrating a filtering role for the MD in the sensory-discriminative component of pain. However, the PEAP paradigm exclusively exhibited an attenuation of the aversive nature of noxious stimuli following MDL lesions, implicating this subdivision in the emotional dimension of pain. In addition, control female rats displayed increased sensitivity to pain compared to control male rats. Interestingly, this sex difference was no longer reported following MD lesions. The morphological analysis showed a clear disruption in the dendritic arborization of pyramidal neurons of the ACC and prelimbic cortex following the different lesions of the MD. This PFC morphology disturbance was accompanied by an increase in microglial and astrocytic activation. Microglial activation was exclusively observed in MDL-lesioned females, while astrocytic activation was observed in both sexes.

Conclusions

The MD thalamus is a key structure in several neurological and psychiatric disorders. Our study is the first that underlines the differential intervention of MD subdivisions and the importance of considering each subdivision of the MD as an independent nucleus, distinct in its function and its contribution to different processes, notably nociception. Additionally, our findings provide compelling evidence that pain processing occurs within the MD, before reaching the PFC.

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Presenting Author

Hanane Iben Daoudi

Poster Authors

HANANE IBEN DAOUDI

PhD

Lab of Pharmacology, Neurobiology, Anthropobiology & Environment, FSSM.

Lead Author

Zakaria OUHAZ

Lab of Pharmacology, Neurobiology, Anthropobiology & Environment, FSSM, Cadi Ayyad University.

Lead Author

Franck ABY

Lab of Pharmacology, Neurobiology, Anthropobiology & Environment, FSSM.

Lead Author

Saadia BAMHAMED

Lab of Pharmacology, Neurobiology, Anthropobiology & Environment, FSSM, Cadi Ayyad University.

Lead Author

Mohamed BENNIS

Lab of Pharmacology, Neurobiology, Anthropobiology & Environment, FSSM, Cadi Ayyad University.

Lead Author

Fatima-Zahra LAMGHARI MOUBARRAD

Lab of Pharmacology, Neurobiology, Anthropobiology & Environment, FSSM.

Lead Author

Marc LANDRY

University of Bordeaux IMN, CNRS UMR 5293

Lead Author

Topics

  • Assessment and Diagnosis