A Sensorimotor Pathway via Higher-Order Thalamus

Abstract

We now know that sensory processing in cortex occurs not only via direct communication between primary to secondary areas, but also via their parallel cortico-thalamo-cortical (i.e., trans-thalamic) pathways. Both corticocortical and trans-thalamic pathways mainly signal through glutamatergic class 1 (driver) synapses, which have robust and efficient synaptic dynamics suited for the transfer of information such as receptive field properties, suggesting the importance of class 1 synapses in feedforward, hierarchical processing. However, such a parallel arrangement has only been identified in sensory cortical areas: visual, somatosensory, and auditory. To test the generality of trans-thalamic pathways, we sought to establish its presence beyond purely sensory cortices to determine whether there is a trans-thalamic pathway parallel to the established primary somatosensory (S1) to primary motor (M1) pathway. We used transsynaptic viral tracing, optogenetics in slice preparations, and bouton size analysis in the mouse (both sexes) to document that a circuit exists from layer 5 of S1 through the posterior medial nucleus of the thalamus to M1 with glutamatergic class 1 properties. This represents a hitherto unknown, robust sensorimotor linkage and suggests that the arrangement of parallel direct and trans-thalamic corticocortical circuits may be present as a general feature of cortical functioning.

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

“…As a result, mitochondria-rich synapses are capable of maintaining a high release probability over a wide range of firing rates 34 . Our observations of larger mitochondrial concentration near the VPM S1 synapses seems thus consistent with electrophysiological evidence that VPM synapses produce relatively large (∼4.8mV) excitatory postsynaptic potentials 9 or currents 10 with low failure rates 11, 12 , while Po synapses in S1-L5a produce smaller postsynaptic currents 10, 15, 16 , that have slower rise and decay times 14 .…”

“…7; Table 1), despite the fact that these two synapse populations arise from different thalamic nuclei and are located in widely separated cortical domains. Such overall resemblance is consistent with electrophysiological observations that both Po MC and VPM S1 synapses elicit similarly large EPSCs 9, 16 , exhibit paired-pulse depression and involve only ionotropic receptors 3, 16 . Remarkably, however, the size of the Po MC-L3/4 synapse PSDs is 60% larger than that of the VPM L4 synapses, suggesting that the former may have even greater high synaptic strength and release probability.…”

“…Likewise, the presence of large vesicle pools and extensive and complex PSDs is associated with higher neurotransmitter release probabilities and synaptic efficacy 17, 18, 19, 35 and to the number and distribution of postsynaptic receptors 20, 22, 23 . The striking differences in these parameters between Po MC-L3/4 and S1-L5a boutons thus imply that the first may readily keep a high release probability at high-frequency firing rates, which is consistent with the observed capacity of MC Po synapses to transmit signals with higher efficacy and temporal acuity than Po S1 synapses 3, 16 . Besides the structural differences, specific ionotropic and metabotropic receptor distributions may contribute to the temporal profile divergence of MC and S1 neuron responses to the repetitive activation of Po synapses 3 .…”

“…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 .…”

“…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.…”