Properties of neurons in the superficial laminae of trigeminal nucleus caudalis

Abstract

The trigeminal nucleus caudalis ( TN c) receives extensive afferent innervation from peripheral sensory neurons of the trigeminal ganglion (TG), and is the first central relay in the circuitry underpinning orofacial pain. Despite the initial characterization of the neurons in the superficial laminae, many questions remain. Here we report on electrophysiological properties of 535 superficial lamina I/ II TN c neurons. Based on their firing pattern, we assigned these cells to five main groups, including (1) tonic, (2) phasic, (3) delayed, (4) H‐current, and (5) tonic‐phasic neurons, groups that exhibit distinct intrinsic properties and share some similarity with groups identified in the spinal dorsal horn. Driving predominantly nociceptive TG primary afferents using optogenetic stimulation in TRPV 1/ChR2 animals, we found that tonic and H‐current cells are most likely to receive pure monosynaptic input, whereas delayed neurons are more likely to exhibit inputs that appear polysynaptic. Finally, for the first time in TN c neurons, we used unsupervised clustering analysis methods and found that the kinetics of the action potentials and other intrinsic properties of these groups differ significantly from one another. Unsupervised spectral clustering based solely on a single voltage response to rheobase current was sufficient to group cells with shared properties independent of action potential discharge pattern, indicating that this approach can be effectively applied to identify functional neuronal subclasses. Together, our data illustrate that cells in the TN c with distinct patterns of TRPV 1/ChR2 afferent innervation are physiologically diverse, but can be understood as a few major groups of cells having shared functional properties.

Excitatory Effects of Calcitonin Gene-Related Peptide (CGRP) on Superficial Sp5C Neurons in Mouse Medullary Slices

“…Most of these neurons were not spontaneously active and had a resting membrane potential of −65.90 ± 0.77 mV ( n = 61). When the membrane potential of Sp5C laminae I/II neurons was held at −70 mV, depolarizing current pulses (20–200 pA for 500 ms) elicited action potentials (APs) with characteristic discharge patterns, namely tonic, phasic and delayed spikes, or single spike ( Figure 1 B), consistent with previous studies [ 23 , 24 , 25 , 26 ]. Interestingly, we identified a fifth class of Sp5C neurons that responded to depolarizing pulses in a burst-like manner.…”

“…Neurons in the superficial laminae of Sp5C are known to be composed of heterogeneous groups with diverse morphological and electrophysiological properties. Using whole-cell recordings from laminae I/II neurons in transverse brainstem slices of juvenile C57BL/6 mice, our classification of Sp5C superficial neurons regarding their response characteristics as action potentials conformed well to those from the literature in in vitro preparations from rats [ 23 , 25 ] and mice [ 24 , 26 ]. Among the patterns of tonic, phasic, delayed and single spiking that have been well-described in P14–35 rodent slices, we have sampled a prevalent population with tonic spiking among 175 neurons in P8–14 mice (77%).…”

“…Without knowledge about the connectivity and transmitter identity of the tonic firing neurons we recorded from in the superficial laminae of mouse Sp5C slices, the functional implications of their strong responsiveness to CGRP under physiological and pathological conditions remain to be determined. By taking advantage of genetic reporter lines, Pradier et al [ 26 ] reported recently that tonic firing neurons are among the neuronal population labelled with GABA/glycine vesicular transporter (exclusively inhibitory neurons), but not among that labelled with somatostatin (mostly co-expressed in excitatory neurons).…”

“…Excitatory drives onto the Sp5C superficial neurons have been detected in few studies [ 23 , 24 , 25 , 62 ]. More recently, however, an elegant study using optogenetic tools was able to selectively activate a nociceptor-enriched subset of primary afferents and characterized long-term plasticity at excitatory synapses onto second-order neurons in superficial laminae of the trigeminal nucleus [ 26 ]. The presence of glutamate vesicles in the presynaptic nerve terminals [ 63 ] and the strong CGRP immunoreactivity of nerve fibers in the superficial laminae of Sp5C [ 3 ] argue for a cooperative effect of this neuromodulator and glutamate in synaptic transmission.…”

The fifth cranial nerve in headaches

“…Pradier and McCormick reported in their study, based on electrophysiological characteristics of neurons of the TNC, that there are five main groups of neurons, including; tonic, phasic, delayed, H-current and tonic-phasic neurons, groups that exhibit distinct intrinsic properties and share some similarity with groups identified in the spinal dorsal horn [59]. The primary function of the TNC is to carry information on temperature, deep or crude touch (PO and PI), and pain from the portion of the face (PC) [54].…”