Postnatal development of cholinergic input to the thalamic reticular nucleus of the mouse

• Published in: The European journal of neuroscience Vol. 49; no. 8; pp. 978 - 989
• Main Authors: Sokhadze, Guela, Campbell, Peter W., Guido, William
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01-04-2019
• Subjects: acetylcholine; Acetylcholine receptors (muscarinic); Arousal; Axon collaterals; Basal forebrain; Brain stem; brainstem; Cerebral cortex; Cortex (somatosensory); Forebrain; Innervation; muscarinic; Neural networks; Neurons; nicotinic; Sleep and wakefulness; Synaptogenesis; Thalamic reticular nucleus; Thalamus; Visual cortex; Visual pathways; γ-Aminobutyric acid; muscarinic; brainstem; acetylcholine; nicotinic; basal forebrain
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.13942

The thalamic reticular nucleus (TRN), a shell‐like structure comprised of GABAergic neurons, gates signal transmission between thalamus and cortex. While TRN is innervated by axon collaterals of thalamocortical and corticothalamic neurons, other ascending projections modulate activity during different behavioral states such as attention, arousal, and sleep‐wake cycles. One of the largest arise from cholinergic neurons of the basal forebrain and brainstem. Despite its integral role, little is known about how or when cholinergic innervation and synapse formation occurs. We utilized genetically modified mice, which selectively express fluorescent protein and/or channelrhodopsin‐2 in cholinergic neurons, to visualize and stimulate cholinergic afferents in the developing TRN. Cholinergic innervation of TRN follows a ventral‐to‐dorsal progression, with nonvisual sensory sectors receiving input during week 1, and the visual sector during week 2. By week 3, the density of cholinergic fibers increases throughout TRN and forms a reticular profile. Functional patterns of connectivity between cholinergic fibers and TRN neurons progress in a similar manner, with weak excitatory nicotinic responses appearing in nonvisual sectors near the end of week 1. By week 2, excitatory responses become more prevalent and arise in the visual sector. Between weeks 3–4, inhibitory muscarinic responses emerge, and responses become biphasic, exhibiting a fast excitatory, and a long‐lasting inhibitory component. Overall, the development of cholinergic projections in TRN follows a similar plan as the rest of sensory thalamus, with innervation of nonvisual structures preceding visual ones, and well after the establishment of circuits conveying sensory information from the periphery to the cortex.
We examined the postnatal development of cholinergic projections to the mouse thalamic reticular nucleus (TRN) and found that both anatomical and functional patterns of connectivity follow a ventral‐to‐dorsal gradient, with nonvisual sectors innervated prior to the visual sector of TRN. These results also indicate that modulation of TRN activity by cholinergic input emerges during postnatal week 2, with adult‐like biphasic responses seen during week 4.