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.
Highlights
The thalamus is segregated into many distinct nuclei based on neural connectivity, as well as functional and neurochemical attributes
In addition to causing mnemonic deficits (Dalrymple-Alford et al, 2015; Leszczyński and Staudigl, 2016), lesions affecting the thalamus result in a range of executive deficits associated with attention, working memory, cognitive flexibility and decision making (Linley et al, 2016; Parnaudeau et al, 2018; Wright et al, 2015), with these functions likely to depend on distinct subregions of the thalamus
Representative cresyl fast violet (CFV)-stained sections are depicted in Figure 2(a) and (b) to illustrate placement of cannulation and injection needle tracks for targeting the anterior thalamic (AT) and MD in the rats
Summary
The thalamus is segregated into many distinct nuclei based on neural connectivity, as well as functional and neurochemical attributes. These subnuclei contribute to large-scale networks associated with specific aspects of cognitive function. Thalamic subregions mediate various cognitive functions, including attention, inhibitory response control and decision making. 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. Conclusions/interpretations: These findings show the mediodorsal thalamus plays a key role in visuospatial attentional performance that is independent of local cholinergic neurotransmission
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