Differential Implications of the mediodorsal thalamic nucleus subdivisions in regulating prefrontal cortex GAD67 and GABAB receptors expression: behavioral and cognitive outcomes.
Neuroscience. 2026-02-01; 594: 203-223
DOI: 10.1016/j.neuroscience.2025.12.024
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https://www.bordeaux-neurocampus.fr/12402
Iben-Daoudi H(1), Bennis M(2), Landry M(3), Lamrghari FZ(1), Ba-M’hamed S(1),
Ouhaz Z(4).
Author information:
(1)Lab. Pharmacology, Neurobiology, Anthropobiology & Environment, Faculty of
Sciences Semlalia, Cadi Ayyad University, Marrakech, Morocco.
(2)Lab. Pharmacology, Neurobiology, Anthropobiology & Environment, Faculty of
Sciences Semlalia, Cadi Ayyad University, Marrakech, Morocco. Electronic
address: .
(3)University of Bordeaux, Institute of Neurodegenerative disease, IMN, UMR
5293, Bordeaux, France.
(4)Higher Institute of Nursing and Health Technology Professions, Marrakech,
Morocco.
The mediodorsal thalamus plays a pivotal role in cognitive and emotional
processes. Its heterogeneous subdivisions, medial, central, and lateral, exhibit
distinct connectivity with prefrontal regions. However, their specific
contributions to behavior and cortical inhibition remain unclear. NMDA-induced
excitotoxic lesions in adult male and female Sprague-Dawley rats were made to
selectively disrupt specific subdivisions of the MD (total MD, MDmc, and MDl).
Subsequently, we evaluated changes in behavioral outcomes using the open field,
elevated plus maze, social interaction, Y-maze, and passive avoidance tests.
Alterations in GABAergic markers were also assessed by quantifying
GAD67-expressing interneurons and GABAB receptor densities across cortical
layers of the anterior cingulate cortex and prelimbic cortex using
immunohistochemical procedures. MD lesions significantly impaired working
memory, associative learning, and social behaviors. Specifically, MDl lesions
induced significant hyperactivity, particularly in females. MDmc and total MD
lesions increased anxiety-like behaviors, whereas MDl lesions decreased anxiety
in males. Neurochemically, all MD lesions increased GAD67 expression and
decreased GABAB receptor densities in layers 2/3 and 5 of the anterior cingulate
cortex and the prelimbic cortex, with marked sex-dependent effects. These
findings illustrate the functional specificity of MD subdivisions in modulating
prefrontal circuits critical for behavior, providing novel insights into
thalamocortical mechanisms and their relevance to neuropsychiatric disorders
characterized by GABAergic dysfunction.
Copyright © 2025 International Brain Research Organization (IBRO). Published by
Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuroscience.2025.12.024
PMID: 41391737
Conflict of interest statement: Declaration of competing interest The authors
declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this
paper.