Identification of signal substances in synapses made between primary afferents and their associated axon terminals in the rat trigeminal sensory nuclei

Abstract

The relationships between primary afferent terminals (PATs) and their associated presynaptic terminals in the rat trigeminal sensory nuclear complex (TSNC) were examined with special reference to amino acid transmitters glutamate (Glu) and gamma‐aminobutyric acid (GABA). Primary afferent terminals anterogradely labeled from the trigeminal ganglion with the B subunit of cholera toxin conjugated to horseradish peroxidase (CTB‐HRP) were sectioned for electron microscopy. Serial sections from the principal nucleus (Vp), dorsomedial parts of the oral and interpolar nuclei (Vdm), and lamina III/IV of caudal nucleus (Vc) were immunostained for Glu and GABA by using a postembedding immunogold technique. The tracer, CTB‐HRP to the trigeminal ganglion, preferentially labeled myelinated primary afferents. Sections immunostained with Glu antiserum showed that most labeled PATs were enriched with immunoreactivity (IR) for Glu. The Glu‐IR PATs contained clear, round, synaptic vesicles and formed asymmetric synaptic contacts with somata or dendrites. They were frequently postsynaptic to unlabeled axon terminals filled with a mixture of clear, round, oval, and flattened vesicles (p‐endings), with symmetric synaptic junctions. The frequency of synapses onto somata or primary dendrites per Glu‐IR PAT was higher in the Vdm than in either the Vp or Vc lamina III/IV. The frequency of contacts of the p‐endings per Glu‐IR PAT was higher in the Vp than in the Vdm and Vc lamina III/IV. Sections immunostained with GABA antiserum showed that most axon terminals presynaptic to PATs were enriched with GABA in the three nuclei. The GABA‐IR axon terminals and their postsynaptic PATs had a similar ultrastructural character to p‐endings and their postsynaptic Glu‐IR PATs, respectively. The present study suggests that primary afferent neurons with large‐caliber fibers use glutamate as a neurotransmitter and are subject to presynaptic modulation by GABAergic fibers. J. Comp. Neurol. 418:299–309, 2000. © 2000 Wiley‐Liss, Inc.

Inflammatory mediator-induced modulation of GABAA currents in human sensory neurons

“…Particularly important is the gating of afferent input to the spinal cord. While data from rodent models also suggest that post-synaptic inhibitory circuitry in the spinal cord dorsal horn is likely to be important for regulation of nociceptive threshold, particularly in the presence of injury, available electrophysiological, pharmacological and morphological data suggest that pre-synaptic inhibition of afferent input is the dominant mechanism for inhibition of somatosensory input into the CNS (Eccles et al, 1962, Eccles et al, 1963, Nishi et al, 1974, Mokha et al, 1983, Hiura et al, 1998, Reeve et al, 1998, Rudomin and Schmidt, 1999, Bae et al, 2000, Olave et al, 2002, Sutherland et al, 2002, Sokal and Chapman, 2003, Vesselkin et al, 2003, Weng and Dougherty, 2005). Virtually all dorsal root ganglion (DRG) neurons from rat respond to GABA with a rapidly activating, bicuculline-sensitive anion current (Oyelese et al, 1995, Zhu et al, 2012a).…”

The transcription factor,Lmx1b, promotes a neuronal glutamate phenotype and suppresses a GABA one in the embryonic trigeminal brainstem complex

“…PrV originates the V lemniscal pathway that is the essential conduit for transmission of a whisker-related pattern to thalamic barreloids in development (Killackey and Fleming, 1985; Ding et al, 2003). PrV is also known to consist mostly of glutamatergic cells, most of which project to the contralateral thalamus, and a smaller number of GABAergic local circuit neurons (Magnusson et al, 1987; Kaneko et al, 1987; Haring et al, 1990; Clements and Beitz, 1991; Bae et al, 2000). Recent studies have begun to reveal the molecular mechanisms that govern the development of the PrV-based lemniscal pathway (reviewed in Erzurumlu et al, 2006; Jacquin et al, 2008; Xiang et al, 2010; da Silva et al, 2011), but the molecular machinery that controls the determination of a glutamatergic versus GABAergic phenotype in developing PrV neurons is unclear.…”

Central Connectivity of Transient Receptor Potential Melastatin 8-Expressing Axons in the Brain Stem and Spinal Dorsal Horn

“…Thus, while peptidergic C-afferent boutons lack axoaxonic contacts [17], [50], non-peptidergic C-afferents receive many axoaxonic contacts and form complex synaptic arrangements with multiple pre- and post-synaptic elements [18]. In addition, a considerable fraction of boutons from Aβ, low threshold mechanoreceptive afferents (40–100%; [20], [51], [52], [53]) and Aδ high-threshold mechanoreceptive afferents (20–60%; [19]) receive axoaxonic synapses in the TSN and DH. Here, the axoaxonic synapses onto TRPM8+ boutons were very rare (0–6%) in the TSN and DH, suggesting that peripheral TRPM8-mediated cold inputs may be transmitted to postsynaptic neurons at the 1 st relay nucleus with little alteration.…”