Comparative analysis of the chemical neuroanatomy of the mammalian trigeminal ganglion and mesencephalic trigeminal nucleus

Abstract

A characteristic peculiarity of the trigeminal sensory system is the presence of two distinct populations of primary afferent neurons. Most of their cell bodies are located in the trigeminal ganglion (TG) but part of them lie in the mesencephalic trigeminal nucleus (MTN). This review compares the neurochemical content of central versus peripheral trigeminal primary afferent neurons. In the TG, two subpopulations of primary sensory neurons, containing immunoreactive (IR) material, are identified: a number of glutamate (Glu)-, substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)-, cholecystokinin (CCK)-, somatostatin (SOM)-, vasoactive intestinal polypeptide (VIP)- and galanin (GAL)-IR ganglion cells with small and medium-sized somata, and relatively less numerous larger-sized neuropeptide Y (NPY)- and peptide 19 (PEP 19)-IR trigeminal neurons. In addition, many nitric oxide synthase (NOS)- and parvalbumin (PV)-IR cells of all sizes as well as fewer, mostly large, calbindin D-28k (CB)-containing neurons are seen. The majority of the large ganglion cells are surrounded by SP-, CGRP-, SOM-, CCK-, VIP-, NOS- and serotonin (SER)-IR perisomatic networks. In the MTN, the main subpopulation of large-sized neurons display Glu-immunoreactivity. Additionally, numerous large MTN neurons exhibit PV- and CB-immunostaining. On the other hand, certain small MTN neurons, most likely interneurons, are found to be GABAergic. Furthermore, NOS-containing neurons can be detected in the caudal and the mesencephalic-pontine junction portions of the nucleus. Conversely, no immunoreactivity to any of the examined neuropeptides is observed in the cell bodies of MTN neurons but these are encircled by peptidergic, catecholaminergic, serotonergic and nitrergic perineuronal arborizations in a basket-like manner. Such a discrepancy in the neurochemical features suggests that the differently fated embryonic migration, synaptogenesis, and peripheral and central target field innervation can possibly affect the individual neurochemical phenotypes of trigeminal primary afferent neurons.

Introduction

Primary sensory neurons, whose cell bodies normally lie in aggregations called ganglia, transmit somatosensory information to central neurons from a variety of sensory receptors in the periphery. Unlike spinal or most of the cranial sensory ganglia, a striking peculiarity of the trigeminal sensory system is that the cell bodies of trigeminal primary afferents are located in the TG and in the brain (see Ramon y Cajal, 1896, Ramon y Cajal, 1909, Scharf, 1958, Brodal, 1981, Usunoff et al., 1997, Marani and Usunoff, 1998, Lazarov, 2000 for reviews). The TG represents a cranial analog of the DRG in the PNS (Darian-Smith, 1973). The MTN is the only known nucleus situated within the CNS that contains the cell bodies of primary afferent neurons (Johnston, 1909, Freeman, 1925). It is also unique in that these constitute one distinct functional class of trigeminal sensory neurons, i.e. proprioceptive neurons.

The TG neurons innervate mainly mechanoreceptors, thermoreceptors and nociceptors in the face, oral cavity and nasal cavity (Dubner et al., 1978, Davies, 1988). It is well established that pseudounipolar cells in the TG supply both the jaw-closing and jaw-opening muscles (Shigenaga et al., 1988b). Their central processes terminate on several groups of second-order neurons, whose impulses are conveyed to the somatosensory cortex via the thalamus (Kruger and Young, 1981, Pfaller and Arvidsson, 1988), but some second-order neurons belong to local-circuit neurons (Yoshida et al., 1994, Yoshida et al., 1998). The MTN neurons mostly innervate muscle spindles in the masticatory and extraocular muscles (Alvarado-Mallart et al., 1975, Capra et al., 1985, Shigenaga et al., 1988a), and other types of receptors in the periodontal ligaments (Jerge, 1963, Byers and Holland, 1977, Byers, 1985, Byers et al., 1986, Shigenaga et al., 1988c, Byers and Dong, 1989, Linden et al., 1994) and dental pulp (Amano et al., 1987, Yoshino et al., 1989).

The trigeminal primary afferent neurons have a common embryonic origin, but behave differently during development. The various neuronal populations that constitute the TG and MTN can be identified on the basis of their morphological characteristics, neurotransmitter contents and electrophysiological properties. Morphologically MTN neurons are considered to be very similar or even identical to the craniospinal ganglion cells (Johnston, 1909, Freeman, 1925). It is also believed that peripheral axons of the MTN neurons possess the same conduction velocity as those of low-threshold mechanoreceptive afferent neurons in the TG (Byers and Matthews, 1981, Byers and Dong, 1989, Byers, 1985). It is not known until now, however, to what extent they differ in their neurochemistry or whether they share the same neurochemical profiles. This latter issue is of key importance since the transmitter content of different neuronal populations often correlates well with their target projections (Costa et al., 1986).

The present comparative review is an updated survey of our current knowledge about the TG and MTN neuroanatomy, summarizing the available relevant background information about their morphological and synaptic organization. It concentrates on the neurochemistry of their neuronal populations both under normal conditions and following neuronal damage. Finally, we have also tried to give an integrated account of the functional significance of these characteristics for the trigeminal sensory information processing.

This overview starts with a consideration of the embryonic origins of the neuronal populations and then extends the discussion to their structure and connections. Particular emphasis is given on the connectivity patterns and projections and the possible physiological involvement of inputs in the synaptic transmission. In order to solve the puzzle of the chemical coding of trigeminal primary afferent neurons, we provide a comprehensive characterization of their neurotransmitter content. We have also surveyed the plasticity of neurotransmitters and neuropeptides in TG and MTN neurons to gain insight into their structural and functional properties in an altered neurochemical balance.