Protracted development of responses to whisker deflection in rat trigeminal ganglion neurons

The rodent whisker-to-barrel pathway constitutes a major model system for studying experience-dependent brain development. Yet little is known about responses of neurons to whisker stimulation in young animals. Response properties of trigeminal ganglion (NV) neurons in 2-, 3-, and 4-week-old and adult rats were examined using extracellular single-unit recordings and controlled whisker stimuli. We found that the receptive field size of NV neurons is mature in 2-week-old animals while response latencies, magnitudes, and angular tuning continue to develop between 2 weeks of age and adulthood. At the earliest time recorded, NV neurons respond to stimulation of only one whisker and can be characterized as slowly or rapidly adapting (SA, RA). The proportion of SA and RA neurons remains constant during development. Consistent with known on-going myelination of NV axons, response latencies decrease with age, becoming adult-like during the third and fourth postnatal weeks for RA and SA neurons, respectively. Unexpectedly, we found that evoked response magnitudes increase several-fold during development becoming adult-like only during the fourth postnatal week. In addition, RA neurons become less selective for whisker deflection angle with age. Maturation of response magnitude and angular tuning is consistent with developmental changes in the mechanical properties of the whisker, the whisker follicle, and the surrounding tissues. The findings indicate that whisker-derived tactile inputs mature during the first postnatal month when whisker-related cortical circuits are susceptible to long-term modification by sensory experience. Thus normal developmental changes in sensory input may influence functional development of cortical circuits.     

Responses of rat trigeminal ganglion neurons to longitudinal whisker stimulation

Responses of rat trigeminal ganglion neurons to longitudinal whisker stimulation. Rats use their mobile set of whiskers to actively explore their environment. Parameters that play a role to generate movement dynamics of the whisker shaft within the follicle, thus activating primary afferents, are manifold: among them are mechanical properties of the whiskers (curvature, elasticity and taper), active movements (head, body, and whiskers), and finally, object characteristics (surface, geometry, position, and orientation). Hence the whisker system is confronted with forces along all three axes in space. Movements along the two latitudinal axes of the whisker (horizontal and vertical) have been well studied. Here we focus on movement along the whisker's longitudinal axis that has been neglected so far. We employed ramp-and-hold movements that pushed the whisker shaft toward the skin and quantified the resulting activity in trigeminal first-order afferents in anesthetized rats. Virtually all recorded neurons were highly sensitive to longitudinal movement. Neurons could be perfectly segregated into two groups according to their modulation by stimulus amplitude and velocity, respectively. This classification regimen correlated perfectly with the presence or absence of slowly adapting responses in longitudinal stimulation but agreed with classification derived from latitudinal stimulation only if the whisker was engaged in its optimal direction and set point. We conclude that longitudinal stimulation is an extremely effective means to activate the tactile pathway and thus is highly likely to play an important role in tactile coding on the ascending somatosensory pathway. In addition, compared with latitudinal stimulation, it provides a reliable and easy to use method to classify trigeminal first-order afferents.     

Electrophysiological responses of trigeminal root ganglion neurons in vitro

The membrane electrical properties of neurons and their responses to endogenous compounds or other neuroactive substances were investigated in vitro with intracellular recording techniques in slices of trigeminal root ganglia of guinea-pigs. The mean resting membrane potential of these neurons was -60 mV. Intracellular injections of hyperpolarizing current pulses evoked time-dependent rectification with varying degrees of dependence on membrane voltage in 107 of 110 neurons. Membrane potential oscillations were observed following the termination of the hyperpolarizing pulses and after similar injections of depolarizing current. This phenomenon appeared to be voltage-dependent at levels that were subthreshold for spike genesis; the more pronounced oscillations were evident at the more depolarized levels and were insensitive to tetrodotoxin applications. Two groups of neurons could be distinguished on the basis of certain characteristics in their action potentials. The majority exhibited short duration (0.6 ms) spikes with mean amplitude of 72 mV in response to intracellular depolarizing current. The brief (3 ms) afterhyperpolarizations that followed such spikes were blocked by intracellular injections of Cs+ or by bath applications of tetraethylammonium. Action potentials in the minority group exhibited a hump in their repolarization phase. The humped spikes had a mean peak amplitude of 78 mV and a longer duration (2 ms). Both the duration (6 ms) and the amplitude (16 mV) of the afterhyperpolarization were significantly greater in this latter group of neurons. Some fast spikes were easily blocked whereas others, including humped spikes, were resistant to tetrodotoxin (10(-6) M). Spikes which were resistant, were also not affected by perfusion with Co2+ (10(-3) M) and were reduced in amplitude during perfusion with Na+-deficient solution. Bath applications of S-glutamate (10(-4)-10(-2) M) depolarized only two of ten neurons by less than 3 mV. Similarly, 5-hydroxytryptamine produced a small depolarization in only two of thirteen neurons. Perfusion of gamma-aminobutyrate (10(-5)-10(-2) M) resulted in an increase in input conductance that waned despite continued application and was associated with a depolarization (2-14 mV) in 44/50 neurons. In some neurons, gamma-aminobutyrate application enhanced their repetitive firing ability, possibly as a result of the increased oscillatory behavior of the membrane at certain depolarized potentials. The effects of gamma-aminobutyrate were blocked by the GABAA-receptor antagonist, bicuculline (10(-4) M) but were unaffected by the GABAB-receptor agonist, baclofen (10(-4) M).(ABSTRACT TRUNCATED AT 400 WORDS)     

Multiple temporal components of optic flow responses in MST neurons

 Neurons in monkey medial superior temporal cortex (MST) respond to optic flow stimuli with early phasic, tonic, and after-phasic response components. In these experiments we characterized each response component to compare its potential contributions to visual motion processing. The early responses begin 60–100 ms after stimulus onset and last between 100 and 250 ms, the tonic responses begin 100–300 ms after stimulus onset and last for as long as the evoking stimulus persists, and the after-responses begin about 60 ms after the stimulus goes off and last for 100–350 ms. A neuron’s tonic responses were evoked by specific optic flow stimuli: over two-thirds of the 264 neurons showed tonic responses evoked by two to five stimuli, whereas only 15% responded to either all or none of the stimuli. The tonic responses continued with stimulus presentations as long as 15 s, with their directional preferences being maintained throughout stimulation. However, the tonic response to a given stimulus was seen to change in amplitude when it was presented in random sequence with different sets of other stimuli. Thus, the tonic responses might convey substantial information about optic flow patterns, which continue with prolonged stimulation, but can be modified by the visual context created by other visual motion stimuli. Only about one-third of the 264 neurons had early responses that were selective for specific stimuli. In neurons yielding at least one early response, that neuron was most often activated by all the visual motion stimuli. After-rsponses occurred in only half the neurons, but they were more often specifically related to particular optic flow stimuli, regardless of whether those stimuli had evoked tonic excitatory or tonic inhibitory responses. The presence of early and after-responses complicates the interpretation of activity evoked when one stimulus immediately follows another. However, under those conditions, early responses and after-responses might contribute to signaling changes in the ongoing pattern of optic flow. We conclude that several components of MST responses should be recognized and that they potentially play different roles in the cortical analysis of optic flow. Tonic responses show the greatest specificity for particular optic flow stimuli, and possess characteristics which make them suitable neuronal participants in self-movement perception. Received: 1 April 1996 / Accepted: 1 October 1996     

Effect of trigeminal subnucleus caudalis cold block on the cerebrovascular-evoked responses of rostral trigeminal complex neurons

The technique of reversible cold block was used to explore the possibility that the trigeminal subnucleus caudalis (Vc) influences the responses of rostral trigeminal brainstem nuclear complex (TBNC) neurons to stimulation of the cerebrovasculature. Reversible cold block of Vc was found to abolish totally the responses of many rostral TBNC neurons to stimulation of the cerebrovasculature. The remaining neurons were not affected by the cold block. These data suggest that some rostral TBNC neurons may receive an indirect input from the cerebrovasculature via Vc while other rostral TBNC neurons receive a direct input from the cerebrovasculature.     

Striatal inhibition of nociceptive responses evoked in trigeminal sensory neurons by tooth pulp stimulation

The noxious evoked response in trigeminal sensory neurons was studied to address the role of striatum in the control of nociceptive inputs. In urethane-anesthetized rats, the jaw opening reflex (JOR) was produced by suprathreshold stimulation of the tooth pulp and measured as electromyographic response in the digastric muscle, with simultaneous recording of noxious responses in single unit neurons of the spinal trigeminal nucleus pars caudalis (Sp5c). The microinjection of glutamate (80 etamol/0.5 microl) into striatal JOR inhibitory sites significantly decreased the A delta and C fiber-mediated-evoked response (53 +/- 4.2 and 43.6 +/- 6.4% of control value, P < 0.0001) in 92% (31/34) of nociceptive Sp5c neurons. The microinjection of the solvent was ineffective, as was microinjection of glutamate in sites out of the JOR inhibitory ones. In another series of experiments, simultaneous single unit recordings were performed in the motor trigeminal nucleus (Mo5) and the Sp5c nucleus. Microinjection of glutamate decreased the noxious-evoked response in Sp5c and Mo5 neurons in parallel with the JOR, without modifying spontaneous neuronal activity of trigeminal motoneurons (n = 8 pairs). These results indicate that the striatum could be involved in the modulation of nociceptive inputs and confirm the role of the basal ganglia in the processing of nociceptive information.     

Sensory and motor responses of trigeminal and reticular neurons during ingestive behavior in rats

Summary Activities of 53 neurons in the brain stem were recorded with chronically implanted fine wires in freely eating and drinking rats. Twenty units were isolated from the trigeminal mesencephalic nucleus; 18 were spindle afferents and 2 periodontal afferents. The spindle units were classified into 4 types: 5 units showed rhythmical activity related only to the jaw opening phase during both licking and chewing, 8 units discharged at jaw opening phase during licking, but both at jaw opening and jaw closing phases during eating, 2 units increased phasic activity at jaw opening phase during licking, but increased tonically independent of jaw movements during eating, and the remaining 3 units responded only at jaw closing phase both in licking and eating behavior. Nine units were assumed to be alpha motoneurons isolated from the trigeminal motor nucleus; 2 innervating the temporalis muscle, 3 the masseter muscle, 2 the digastric muscle, and the remaining 2 presumably the pterygoid muscles. These units, with a mean tonic spontaneous rate of about 10 impulses/ s, showed phase-related rhythmical burst activities during licking and eating. Four units were isolated from the trigeminal main sensory nucleus. Sixteen units were isolated from the medullary reticular formation and 1 from the pontine reticular formation. Of these 16 units, 3 from the parvocellular part of the medullary reticular formation were presumably premotor interneurons, and 3 units in the intertrigeminal region, 2 units in the juxtatrigeminal region, and 8 units in the supratrigeminal region were responsive to multiple sensory modalities. These results demonstrate that almost all the units sampled showed characteristic rhythmic activities associated with the position of the tongue or mandible during rhythmical jaw movements.     

Category-specific visual responses of single neurons in the human medial temporal lobe

The hippocampus, amygdala and entorhinal cortex receive convergent input from temporal neocortical regions specialized for processing complex visual stimuli and are important in the representation and recognition of visual images. Recording from 427 single neurons in the human hippocampus, entorhinal cortex and amygdala, we found a remarkable degree of category-specific firing of individual neurons on a trial-by-trial basis. Of the recorded neurons, 14% responded selectively to visual stimuli from different categories, including faces, natural scenes and houses, famous people and animals. Based on the firing rate of individual neurons, stimulus category could be predicted with a mean probability of error of 0.24. In the hippocampus, the proportion of neurons responding to spatial layouts was greater than to other categories. Our data provide direct support for the role of human medial temporal regions in the representation of different categories of visual stimuli.     

Cross-desensitization of responses of rat trigeminal subnucleus caudalis neurons to cinnamaldehyde and menthol

Most cold-sensitive subnucleus caudalis (Vc) neurons are also excited by the TRPM8 agonist menthol and the TRPA1 agonist cinnamaldehyde (CA). We investigated how interactions among menthol, CA and noxious cooling and heating of the tongue affected responses of superficial Vc units recorded in thiopental-anesthetized rats. Units responded to 1% CA which enhanced cold- and heat-evoked responses 5 min later. They responded more strongly to 10% CA which initially depressed cold responses, followed by enhancement at 5 min without affecting responses to heat. Following 10% CA, the mean response to 1% menthol was significantly lower than when menthol was tested first. After menthol, the subsequent response to CA was significantly weaker compared to the mean CA-evoked response when it was tested first. These results demonstrate mutual cross-desensitization between CA and menthol. The response to CA was enhanced following prior application of 10% ethanol (menthol vehicle). Prior application of menthol did not prevent the biphasic effect of 10% CA on cold-evoked responses, nor did prior application of CA prevent menthol enhancement of cold-evoked responses. Responses to noxious heat were unaffected by 10% CA and menthol regardless of the order of chemical presentation. These data indicate that superficial Vc neurons receive convergent input from primary afferents expressing TRPM8 and TRPA1. The mutual cross-desensitization between CA and menthol, and differential modulation of cold- vs. heat-evoked responses, suggests a direct inhibition of TRPM8 and TRPA1 expressed in peripheral nerve endings by CA and menthol, respectively, rather than a central site of interaction.     

A cytoplasmic inclusion in mouse trigeminal neurons

Mouse trigeminal neurons contained a cytoplasmic inclusion consisting of a dense particle (diameter ～ 100 nm.) surrounded by a smooth surfaced membrane sometimes in continuity with the rough surfaced endoplasmic reticulum. The identity of the inclusion is uncertain but it may be related to intracisternal A type particles.     

Temperature neurons in the crotaline trigeminal ganglia.

1. Intrasomal recordings were made with microelectrodes from 153 warm (infrared) neurons in the trigeminal ganglia of 36 crotaline snakes, Trimeresurus flavoviridis. Background discharges were observed at room temperature. The 153 warm neurons were classified into two groups: 81 were sensitive to less than or equal to 10 mg of von Frey hair mechanical stimulation (warm T + M neuron), and 72 were insensitive to up to 100 mg or more of mechanical stimulation (warm T neuron). For T + M and T neurons the receptive fields were all located in the pit organ. The mechanically sensitive field of warm T + M neurons located within the infrared receptive field on the pit membrane was less than 1 mm in diameter, and there was only one field per neuron. 2. Electrophysiological parameters were measured. These measurements included membrane potential, action potential amplitude, time of peaking, time duration at the resting membrane potential level, afterhyperpotential (AHP) height and AHP time to half-decay, and maximum rates of depolarization and repolarization. No difference in action potential parameters between the means of these two submodality groups was observed. 3. Intracellular horseradish peroxidase (HRP) labeling was used for defining the warm neuron profile. The somata of warm T and warm T + M neurons and T- or Y-shaped bifurcations of the axon were observed in the ganglion. At the bifurcation point, nodes of Ranvier were observed, but without broad triangular expansion. Diameters of the central axons were thinner than those of the peripheral or stem axons. There were no differences between the mean diameters of the two submodalities. 4. The central axons of warm T and T + M neurons projected to the lateral descending nucleus of the trigeminal nerve (LTTD). Their synaptic boutons were found in the LTTD. No branching of the axons to the principal sensory nucleus or the descending nucleus of the trigeminal nerve was found. These results were the same for six warm T and eight warm T + M neurons. 5. Conduction velocities of the peripheral fibers were measured by stimulating superficial branches of the maxillary nerve electrically. Three groups of conduction velocity were identified in the compound potentials. The conduction velocity of the peak action potential of the warm T fibers was 6.9 +/- 1.2 (SD) m/s (n = 18), that of the T + M fibers 6.7 +/- 0.9 m/s (n = 23). These fell into the second group of the compound potentials.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of attention and stimulus interaction on visual responses of inferior temporal neurons in macaque

1. Extracellular discharges were recorded from neurons in the inferior temporal cortex (area TE) of three macaque monkeys while they performed visual fixation and pattern discrimination tasks. For the pattern discrimination task, monkey was trained to release the lever quickly at the onset of one of two pattern stimuli and to release the lever at the dimming of the other pattern. During this task, neutral light stimulus (light bar) to which the monkey was not required to respond was presented once a trial either prior to the onset of the discriminandum or during presentation of the pattern that dimmed later. The neuronal activities evoked by the neutral stimulus under these two conditions were compared. 2. When the discriminanda were located at the center or at 5 degrees in the contralateral visual field, one-half of the neurons showed significantly smaller responses to the neutral stimulus when it was presented during presentation of the dimming pattern than when it was presented prior to the onset of the discriminandum. 3. The suppressive effect depended on the location of the two stimuli. When the neutral stimulus was located in the ipsilateral visual field and the pattern was located in the contralateral visual field, the response to the neutral stimulus was suppressed. However, when the pattern was located in the ipsilateral visual field (5 degrees visual angle), still within the receptive field for many neurons, the suppressive effect of the pattern on the response to the neutral stimulus in the contralateral visual field was almost undetectable. 4. When the pattern was located nearer the fovea than was the neutral stimulus, the suppressive effect was greater than when the pattern was located more peripherally to the neutral stimulus. Different from the receptive field of more primary visual neurons, this suppressive effect did not appear to be related to the neuron's responsiveness to the patterns nor to precise stimulus location in the receptive field. 5. The magnitude of suppression by the attended pattern on the visual response during the pattern discrimination task correlated with the suppression noted in the presence of a fixation spot during the fixation tasks, while the animals did not fixate on the attended pattern. The response of some neurons to the neutral stimulus prior to pattern presentation during the pattern discrimination task was enhanced slightly compared with the response recorded during the simple fixation task.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of task demands on the responses of color-selective neurons in the inferior temporal cortex

Categorization and fine discrimination are two different functions in visual perception, and we can switch between these two functions depending on the situation or task demands. To explore how visual cortical neurons behave in such situations, we recorded the activities of color-selective neurons in the inferior temporal (IT) cortex of two monkeys trained to perform a color categorization task, a color discrimination task and a simple fixation task. Many IT neurons changed their activity depending upon the task, although color selectivity was well conserved. A majority of neurons showed stronger responses during the categorization task. Moreover, for the population of IT neurons as a whole, signals contributing to performing the categorization task were enhanced. These results imply that judgment of color category by color-selective IT neurons is facilitated during the categorization task and suppressed during the discrimination task as a consequence of task-dependent modulation of their activities.     

Sensory responses of caudal trigeminal neurons to thermal and mechanical stimuli and their behavioural correlates in the rat

Behavioural experiments in the freely moving rat were carried out to determine thermal and mechanical nociceptive thresholds to ramp stimuli applied to the face. The mean thermal escape threshold was 43.5 degrees C, and the mean mechanical escape threshold was 179.2 g/mm2. In a parallel set of experiments recordings were made from single neurons in the caudal trigeminal nucleus of the anaesthetized rat. Neurons were classified according to their responses to a range of thermal and mechanical stimuli applied to the face. Three classes of neuron responded exclusively to mechanical stimuli and four classes responded to thermal stimuli (usually in addition to responding to mechanical stimuli). The mean thermal threshold of neurons responsive to warming stimulation was 44.4 degrees C. Neurons responsive to innocuous warming were located in deeper laminae. Many of the neurons responsive to noxious heat appeared to show an exponential relation between temperature and firing rate. An argument is made for a direct role of exponentially responding neurons in thermal nociception. The distribution of all neuronal response thresholds was left-skewed compared with a normal distribution, whereas the behavioural escape thresholds approximated a normal distribution.     

Cold transduction in rat trigeminal ganglia neurons in vitro

Three sub-populations of sensory neurons may be distinguished based on responses to a decrease in temperature: one has a relatively low threshold for activation (cool fibers), a second has a high threshold for activation (cold nociceptors), and the third is unresponsive to a decrease in temperature. Results from several recent studies suggest that the ability to detect a decrease in temperature reflects an intrinsic property(ies) of sensory neurons and therefore may be characterized via the study of the sensory neuron cell body in vitro. However, while three unique ionic mechanisms of cold transduction have recently been identified (i.e. activation of the transient receptor potential channel M8 [TRPM8] or an epithelial Na(+) channel [ENaC] or inhibition of two pore K(+) channel [TREK-1]), the possibility that these "mechanisms" may be differentially distributed among sensory neurons in a manner consistent with predictions based on in vivo observations has not been investigated. To investigate this possibility, we have characterized the influence of cooling on isolated trigeminal ganglion (TG) neurons from adult rats in vitro with Ca(2+) microfluorimetry in combination with a series of pharmacological interventions. We report that neurons responded to a decrease in temperature from approximately 34 degrees C to approximately 12 degrees C in one of two ways: 1) with a low threshold (30.1+/-0.6 degrees C) for activation demonstrating an increase in fluorescence with a minimal decrease in bath temperature (12.3%); 2) with a high threshold for activation (21.5+/-0.6 degrees C), demonstrating an increase in fluorescence only after a substantial decrease in bath temperature (13.3%); 74.4% did not respond to a decrease in temperature with an increase [Ca(2+)](i). These responses also were distinguishable on the basis of their rate of activation and degree of desensitization in response to prolonged application of a cold stimulus: low threshold responses were associated with a rapid (tau=12.0+/-5.7 s) increase in [Ca(2+)](i) and a time constant of desensitization of 85.8+/-20.7 s while high threshold responses were associated with a slow (tau=38.1+/-8.2 s) increase in [Ca(2+)](i) and demonstrated little desensitization over 4 min of stimulation. We refer to low threshold and high threshold cold responsive TG neurons as LT(cool) and HT(cool) neurons, respectively. LT(cool) and HT(cool) neurons were distributed among two distinct subpopulations of TG neurons distinguishable on the basis of cell body size and isolectin B4 staining. Both ENaC and TRPM8 appear to contribute to cold transduction, but neither is sufficient to account for all aspects of cold transduction in either population of TG neurons. Furthermore, inhibition of Ba(2+) and/or Gd(3+) sensitive two-pore K(+) channels (i.e. TREK-1 and TRAAK) was insufficient to account for cold transduction in HT(cool) or LT(cool) neurons. Our results suggest that cold transduction in sensory neurons is a complex process involving the activation and inhibition of several different ion channels. In addition, there appear to be both similarities and differences between mechanisms underlying cold transduction in LT(cool) and HT(cool) neurons. Identification of specific mechanisms underlying cold transduction in LT(cool) and HT(cool) neurons may enable the development of novel therapeutic interventions for the treatment of pathological conditions such as cold allodynia.     

Effects of perceptual learning in visual backward masking on the responses of macaque inferior temporal neurons

Learning is critical for fast and efficient object recognition in primates. To understand the neuronal correlates of behavioral improvements due to training, we recorded the responses of single neurons in the inferior temporal (IT) cortex of monkeys that were trained to recognize briefly presented, backward-masked objects. First we investigated training effects that are specific to the objects shown during training and that do not transfer to untrained objects. Only one of two monkeys tested showed object-specific training effects at the behavioral level, and only this monkey showed a transient object-specific increase in object selectivity for trained compared with untrained backward-masked objects. However, in each monkey a substantial part of the training effect transferred to untrained objects. To investigate the neural correlates of these object-independent training effects, we compared the neural responses to masked objects in trained monkeys to the responses in untrained monkeys. Training was associated with a reduction of the responses to the irrelevant masking patterns. These findings suggest that extensive training in recognizing backward-masked objects results in neural changes that reduce IT responses to the interfering irrelevant masking patterns and enhance the processing of the relevant objects.     

Endomorphin-1 and endomorphin-2 modulate responses of trigeminal neurons evoked by N-methyl-D-aspartic acid and somatosensory stimuli

The present study investigated the modulation of N-methyl-D-aspartate (NMDA)-evoked and peripheral cutaneous stimulus-evoked responses of trigeminal neurons by endomorphins, endogenous ligands for the mu-opioid receptor. Effects of endomorphins, administered microiontophoretically, were tested on the responses of nociceptive neurons recorded in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized rats. Endomorphin-1 and endomorphin-2 predominantly reduced the NMDA-evoked responses, producing an inhibitory effect of 54.1 +/- 2.96% (mean +/- SE; n = 34, P < 0.001) in 92% (34/37) of neurons and 63.6 +/- 3.61% (n = 32, P < 0.001) in 91% (32/35) of neurons, respectively. The inhibitory effect of endomorphins was modality specific; noxious stimulus-evoked responses were reduced more than nonnoxious stimulus-evoked responses. Naloxone applied at iontophoretic current that blocked the inhibitory effect of [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin, reduced the peak inhibitory effect of endomorphins on the NMDA- and natural stimulus-evoked responses. We suggest that endomorphins by acting at micro-opioid receptor selectively modulate noxious stimulus-evoked responses in the medullary dorsal horn.