Dorsal Horn Projection Targets of On and Off Cells in the Rostral
Ventromedial Medulla.
Fields, H. L., A. Malick and R. Burstein.
Departments of Anesthesia and Neurobiology, Beth Israel Hospital and
Harvard Medical School, Boston, Massachusetts 02115. Departments of Neurology,
Physiology and the Keck Center for Integrative Neuroscience, University of
California, San Francisco, California 94143.
APStracts 2:0168N, 1995.
SUMMARY AND CONCLUSIONS
1. The rostral ventromedial medulla (RVM) participates in the modulation of
nociceptive transmission by spinal cord neurons. Previous anatomical studies
have demonstrated that RVM neurons project to laminae I, II and V of the
dorsal horn, laminae VII and VIII of the intermediate and ventral horns, the
intermediolateral column and lamina X. The RVM contains at least three
physiologically defined classes of neurons, two of which, the on and the off
cells, have been implicated in nociceptive modulation. Since these cell
classes are intermingled in the RVM, it has not been possible to determine the
spinal laminar projection targets of on and off cells by anatomical methods.
Therefore, in the current study we employed antidromic microstimulation
methods to determine the laminar projections of two of the three classes of
RVM neurons, the on and the off cells. 2. In lightly anesthetized (sodium
methohexital) rats, single unit extracellular recordings were made from 48 RVM
neurons that were physiologically characterized as on (30) or off (18) cells.
The recording locations of 45 of these neurons were recovered. Thirty-seven
were found in the nucleus raphe magnus and eight were located near its dorsal
and lateral borders. 3. Thirty-two physiologically identified RVM neurons (18
on and 14 off cells) were antidromically activated from the cervical spinal
cord using a monopolar stimulating electrode. The stimulating electrode was
moved systematically in the white matter until antidromic activation could be
produced with currents of ¯< 20 mA (6.1 ¯+ 0.7 mA; mean ¯+ S.E.). The points
from which minimum currents were required to antidromically activate the
neurons were located mainly in the ipsilateral dorsolateral funiculus (27/32).
In a few cases, lowest antidromic threshold currents were found near the
border between the dorsolateral (DLF) and ventrolateral (VLF) funiculus or,
rarely, in the VLF itself. In these cases, the cell-recordings were found to
have been near the dorsal boundary of the RVM. 4. While one electrode was used
to stimulate the parent axon in the lateral funiculus, a second was used to
explore the gray matter for the presence of collateral branches. The
identification of a branch was initially determined by an increase in
antidromic latency. At the same rostrocaudal plane of the spinal cord,
stimulation of the DLF induced an antidromic spike that invaded the neuron
earlier than the antidromic spike elicited by stimulating in the gray matter.
Collateral branches were confirmed by establishing that the location of the
minimum threshold point for antidromic activation of the neurons from the
second electrode was in the gray matter, that the minimum current required to
antidromically activate the neuron from that point was too low to activate the
parent axon in the DLF, and that a collision occurred between the spikes
induced by the two stimulating electrodes. 5. In 17 cases, physiologically
identified RVM neurons (10 on and 7 off cells) were antidromically activated
from the gray matter of the cervical spinal cord using a current of 8.4 ¯+ 2.1
[mu] A (mean ¯+ S.E.). Minimum threshold points for antidromic activation were
found in laminae I-II (3 on and 4 off cells), lamina V (5 on and 6 off cells),
and regions ventral to the lateral reticulated area (3 on and 2 off cells) of
the gray matter. As indicated by these numbers, some neurons were
antidromically activated from more than one gray matter region. In general,
all off cells and 9/10 on cells were antidromically activated from low
threshold points in either laminae I-II or lamina V. 6. In six cases, neurons
were activated from separate points located in two or three different laminae
of the gray matter. Three off cells were activated from laminae I-II and V,
one off cell and one on cell were activated from lamina V and from more
ventral points, and one on cell was activated from laminae I-II and from
points ventral to lamina V. Finally, one of these neurons, an off cell, was
activated from all three regions of the gray matter. 7. Although no systematic
attempts were made to map the parent axons of RVM neurons at each segmental
level, 25 parent axons were mapped in the rostral and caudal areas of the
cervical enlargement. In all of these cases, neurons activated from points in
the DLF at the level of C5, were also activated from the DLF at the level of
C8-T1. These data suggest that individual on and off cells innervate neurons
in several levels of the cervical spinal cord and in segments caudal to it. 8.
Since mapping all branches of each neuron was not the focus of this work, we
documented only one neuron that issued branches at 2 different rostrocaudal
levels. However, the presence of branches at each examined cervical segment
(segments C5, 6, 7, 8 and T1 contained 1, 3, 7, 4 and 2 collateral branches,
respectively.), and the average rostrocaudal distance that was explored before
finding a branch of an on (1.2 mm) or an off (2.2 mm) cell suggests that
individual RVM neurons issue collateral branches at more than one rostrocaudal
level of the cervical spinal cord. 9. The mean ( ¯+ S.E.) conduction velocity
of on cell axons was 16.4 ¯+ 2.8 m/s in the DLF and 1.1 ¯+ 0.24 m/s in the
gray matter. The mean conduction velocity of off cell axons was 11 ¯+ 2.7 m/s
in the DLF and 0.6 ¯+ 0.15 m/s in the gray matter. Thus, the conduction
velocities of the branches were an order of magnitude slower than that of
their parent axons. The differences found between the conduction velocities of
on and off axons were not significant in the DLF or the gray matter. 10. These
findings indicate that RVM on and off cells that project to the spinal cord
through the DLF issue collateral branches to laminae I-II and V of the
cervical dorsal horn. Since these laminae contain most of the nociceptive
neurons that project to supraspinal sites, this result supports the hypothesis
that RVM on and off neurons modulate nociceptive transmission by acting
directly on nociceptive neurons in the dorsal horn.
Received 13 February 1995; accepted in final form 22 May 1995.
APS Manuscript Number J104-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.