Synaptic properties of the lemniscal and paralemniscal pathways to the mouse somatosensory thalamus

Abstract

Somatosensory information is thought to arrive in thalamus through two glutamatergic routes called the lemniscal and paralemniscal pathways via the ventral posterior medial (VPm) and posterior medial (POm) nuclei. Here we challenge the view that these pathways functionally represent parallel information routes. Using electrical stimulation and an optogenetic approach in brain slices from the mouse, we investigated the synaptic properties of the lemniscal and paralemniscal input to VPm and POm. Stimulation of the lemniscal pathway produced class 1, or "driver," responses in VPm relay cells, which is consistent with this being an informationbearing channel. However, stimulation of the paralemniscal pathway produced two distinct types of responses in POm relay cells: class 1 (driver) responses in 29% of the cells, and class 2, or "modulator," responses in the rest. Our data suggest that, unlike the lemniscal pathway, the paralemniscal one is not homogenous and that it is primarily modulatory. This finding requires major rethinking regarding the routes of somatosensory information to cortex and suggests that the paralemniscal route is chiefly involved in modulatory functions rather than simply being an information route parallel to the lemniscal channel.driver | modulator | glutamatergic | ventral posterior medial nucleus | posterior medial nucleus B efore reaching the cortex, all sensory information except olfaction is relayed by the thalamus. For somatosensory information, there appear to be two potential routes of such information flow, which have been termed "lemniscal" and "paralemniscal." Regarding the trigeminal components of these, the lemniscal route is represented by the pathway from the principal and spinal nuclei of the Vth nerve (PrV and SpV, respectively) via the medial lemniscus (ML) through VPm, whereas the paralemniscal route is represented by the pathway originating mostly from SpV through POm. However, exactly how these circuits function depends critically on the nature of the underlying synapses. These inputs to thalamus and from thalamus to cortex are glutamatergic, meaning that they use glutamate as a neurotransmitter. Recent work has made it clear that glutamatergic inputs in thalamus and cortex are heterogeneous and can be divided into at least two types, known as class 1 (or driver) and class 2 (or modulator) (1-3). It has been suggested that the class 1 inputs carry the main information between neuronal regions and that the class 2 inputs provide a modulatory role, mainly affecting how class 1 inputs are processed (reviewed in refs. 4-6; see also Discussion). Thus, identifying which type of glutamatergic synapses are involved in the lemniscal and paralemniscal pathways could help clarify whether they represent parallel information routes or whether some other functional explanation is more plausible.To this end, we used slice preparations in which we could use a combination of electrical stimulation and optogenetics to activate lemniscal or paralemniscal inputs to patched cells in VPm and P...

A Sensorimotor Pathway via Higher-Order Thalamus

“…Sherman, 2016). For example, in the mouse somatosensory system, the feedforward projections carrying whisker information from the principal nucleus of the fifth nerve (PrV) to the ventral posterior nucleus (VPm) to S1 and S1 to M1 are all mediated by class 1 synapses (Viaene et al, 2011a,b;Petrof et al, 2015;Mo et al, 2017). The presence of class 1 synapses in trans-thalamic pathways suggests that they are also well suited to carry basic information between cortical areas.…”

“…The size of presynaptic terminals has also been used to help classify a synapse as class 1 or class 2 (Sherman and Guillery, 2013; Sherman, 2016). Class 2 modulatory synapses are composed of small presynaptic terminations and class 1 driver synapses are composed of both large and small terminations (Li et al, 2003;Viaene et al, 2011a,b;Petrof and Sherman, 2013;Petrof et al, 2015;Mo et al, 2017). We injected the same eYFP-tagged AAV used in the electrophysiology experiments ( Fig.…”

“…We injected the same eYFP-tagged AAV used in the electrophysiology experiments ( Fig. 4) and measured the area of boutons in the POm to M1 synapse, comparing it with bouton sizes of synapses previously classified as class 1 or class 2: S1 to VPm (class 2), POm to S1 layer 5 (class 2), and S1 to POm (both class 1 and 2) (Viaene et al, 2011a;Petrof et al, 2015;Mo and Sherman, 2017;Fig. 5).…”

My prolonged collaboration with Ray Guillery

“…However, there is evidence that nuclei designated as higher order may also contain first order circuits. For instance, some relay cells in pulvinar appear to receive driver inputs from the superior colliculus (Kelly et al ., ), and some in the posterior medial nucleus are driven by inputs from the spinal nucleus of the fifth nerve (Mo et al ., ). In these cases, it still appears that most relay cells of these nuclei are higher order in terms of their driving inputs, but this proviso must be clear, and for this reason, we often refer to higher order thalamic “relays” (which relates to relay cells) rather than higher order thalamic “nuclei.”…”

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

“…In turn, Po axons convey information mainly about timing/amplitude differences between ongoing cortical outputs and multi-whisker sensory signals, which may be important for computing whisker position 1, 6, 7 . Po cells are primarily driven by heavy and highly effective L5 cortico-thalamic inputs, while ascending trigeminal inputs to Po are sparser and largely modulatory in character 7, 8 .…”