Posterior thalamic nucleus axon terminals have different structure and functional impact in the motor and somatosensory vibrissal cortices

Abstract

Rodents extract information about nearby objects from the movement of their whiskers through dynamic computations that are carried out by a network of forebrain structures that includes the thalamus and the primary sensory (S1BF) and motor (M1wk) whisker cortices. The posterior nucleus (Po), a higher order thalamic nucleus, is a key hub of this network, receiving cortical and brainstem sensory inputs and innervating both motor and sensory whisker-related cortical areas. In a recent study in rats, we showed that Po inputs differently impact sensory processing in S1BF and M1wk. Here, in C57BL/6 mice, we measured Po synaptic bouton layer distribution and size, compared cortical unit response latencies to "in vivo" Po activation, and pharmacologically examined the glutamatergic receptor mechanisms involved. We found that, in S1BF, a large majority (56%) of Po axon varicosities are located in layer (L)5a and only 12% in L2-L4, whereas in M1wk this proportion is inverted to 18% and 55%, respectively. Light and electron microscopic measurements showed that Po synaptic boutons in M1wk layers 3-4 are significantly larger (~ 50%) than those in S1BF L5a. Electrical Po stimulation elicits different areaspecific response patterns. In S1BF, responses show weak or no facilitation, and involve both ionotropic and metabotropic glutamate receptors, whereas in M1wk, unit responses exhibit facilitation to repetitive stimulation and involve ionotropic NMDA glutamate receptors. Because of the different laminar distribution of axon terminals, synaptic bouton size and receptor mechanisms, the impact of Po signals on M1wk and S1BF, although simultaneous, is likely to be markedly different.

Area-specific synapse structure in branched axons reveals a subcellular level of complexity in thalamocortical networks

“…Our FIB-SEM analysis is based on sampling 2,435 µm 3 of cortical neuropil. At high magnification FIB-SEM, the axonal BDA axonal segments were few and widely scattered.…”

“…Two thalamocortical pathways lay at the core of these loops: Ventral Posteromedial thalamic nucleus (VPM) axons arborizing focally on L4 in the vibrissal “barrel” domain of the primary somatosensory cortex (S1); and Posterior thalamic nucleus (Po) axons arborizing mainly in L5a but also L1 of S1 2; 3 . Importantly, Po axons may target, in addition, the motor cortex (MC) middle layers 3, 4, 5 (L5-L3). The VPM axons relay time-locked mechanoreceptive single-whisker trigeminal signals, crucial for computing object location.…”

“…The Po S1 synapses involve both ionotropic and metabotropic glutamate conductances, show paired-pulse facilitation 10, 15 and rapidly increase their efficacy in response to learned reward even in the adult 13 . Recent data about the Po MC synapses indicate that, surprisingly, they elicit large currents, depress upon repetitive activation 5, 16 and involve only ionotropic receptors 3 .…”

“…Furthermore, the PSD surface area is proportional to the number of postsynaptic receptors 20–23 . Thus, given the markedly divergent effect observed in S1 vs. MC Po synapses, and recent light microscope evidence that Po S1 axon varicosities are relatively small 3 we aimed to determine whether Po synapses in MC and S1 were different in their ultrastructural composition. Moreover, as studies in rat have reported that MC and S1 can be simultaneously targeted by branches of the same individual Po axons 4, 24 , we also set out to elucidate if structural differences occur between boutons on separate branches of the same Po cell axon.…”

“…In addition, we report similarly sharp differences between Po and VPM axon synapses in S1. Along with recent parallel functional observations 3, 16 differences in synapse structure both between axons originated in diverse thalamic nuclei, and between the branches of the same individual axons targeting separate cortical areas/layers, call into question current models of thalamocortical interaction.…”