Dissociable contributions of mediodorsal and anterior thalamic nuclei in visual attentional performance: A comparison using nicotinic and muscarinic cholinergic receptor antagonists

Abstract

Background: Thalamic subregions mediate various cognitive functions, including attention, inhibitory response control and decision making. Such neuronal activity is modulated by cholinergic thalamic afferents and deterioration of such modulatory signaling has been theorised to contribute to cognitive decline in neurodegenerative disorders. However, the thalamic subnuclei and cholinergic receptors involved in cognitive functioning remain largely unknown. Aims: We investigated whether muscarinic or nicotinic receptors in the mediodorsal thalamus and anterior thalamus contribute to rats’ performance in the five-choice serial reaction time task, which measures sustained visual attention and impulsive action. Methods: Male Long-Evans rats were trained in the five-choice serial reaction time task then surgically implanted with guide cannulae targeting either the mediodorsal thalamus or anterior thalamus. Reversible inactivation of either the mediodorsal thalamus or anterior thalamus were achieved with infusions of the γ-aminobutyric acid-ergic agonists muscimol and baclofen prior to behavioural assessment. To investigate cholinergic mechanisms, we also assessed the behavioural effects of locally administered nicotinic (mecamylamine) and muscarinic (scopolamine) receptor antagonists. Results: Reversible inactivation of the mediodorsal thalamus severely impaired discriminative accuracy and response speed and increased omissions. Inactivation of the anterior thalamus produced less profound effects, with impaired accuracy at the highest dose. In contrast, blocking cholinergic transmission in these regions did not significantly affect five-choice serial reaction time task performance. Conclusions/interpretations: These findings show the mediodorsal thalamus plays a key role in visuospatial attentional performance that is independent of local cholinergic neurotransmission.

Time to retire the serial Papez circuit: Implications for space, memory, and attention

“…Importantly, evidence that the human anterior thalamic nuclei have similar roles in attention emerges from clinical and imaging data ( Bourbon-Teles et al, 2014 , Leszczyński and Staudigl, 2016 ), albeit at lower anatomical resolution to that from animal studies. Meanwhile, other animal lesion studies help to show that the anterior thalamic nuclei are not needed for all aspects of attention ( Chudasama and Muir, 2001 , Mantanona et al, 2020 ). Findings from human fMRI research support the view that the anterior thalamic nuclei have diverse cognitive actions.…”