Termination zones of functionally characterized spinothalamic tract neurons within the primate posterior thalamus

Abstract

The primate posterior thalamus has been proposed to contribute to pain sensation, but its precise role is unclear. This is in part because spinothalamic tract (STT) neurons that project to the posterior thalamus have received little attention. In this study, antidromic mapping was used to identify individual STT neurons with axons that projected specifically to the posterior thalamus in Macaca fascicularis. Each axon was located by antidromic activation at low stimulus amplitudes (<30 microA) and was then surrounded distally by a grid of stimulating points in which 500-microA stimuli were unable to activate the axon antidromically, thereby indicating the termination zone. Several nuclei within the posterior thalamus were targets of STT neurons: the posterior nucleus, suprageniculate nucleus, magnocellular part of the medial geniculate nucleus, and limitans nucleus. STT neurons projecting to the ventral posterior inferior nucleus were also studied. Twenty-five posterior thalamus-projecting STT neurons recorded in lumbar spinal cord were characterized by their responses to mechanical, thermal, and chemical stimuli. Sixteen of 25 neurons were recorded in the marginal zone and the balance was located within the deep dorsal horn. Thirteen neurons were classified as wide dynamic range and 12 as high threshold. One-third of STT neurons projecting to posterior thalamus responded to noxious heat (50 degrees C). Two-thirds of those tested responded to cooling. Seventy-one percent responded to an intradermal injection of capsaicin. These data indicate that the primate STT transmits noxious and innocuous mechanical, thermal, and chemical information to multiple posterior thalamic nuclei.

FIG. 1.

Example of a single antidromically activated spinothalamic tract (STT) neuron showing the course of its axon through suprageniculate nucleus (Sg) to ventral posterior lateral (VPL). A1: photomicrograph of the lesion marking the low-threshold point (LTP) in VPL (→). A2: illustration of A1 with a superimposed grid () indicating each point at which antidromic stimulation was tested. Contour plot indicates the current amplitude required for antidromic activation. B1: the lesion marking the LTP in Sg (→) of the same axon. B2: illustration as in A2. C: recording point in the marginal zone. D: antidromic activation from VPL had a longer latency than from Sg. E: antidromic activation from VPL. Top: 3 antidromic action potentials recorded in the dorsal horn. Middle: collision of an orthodromic action potential (▾) with an antidromic action potential (▿). Bottom: train of 333-Hz stimuli at the VPL LTP (12 μA). F: antidromic activation from Sg as in E. Stimulus artifacts reduced for clarity. CL, center lateral; CM, center median; eml, external medullary lamina; L, limitans; LD, lateral dorsal; LP lateral posterior; MG, medial geniculate; MGmc, magnocellular part of medial geniculate; MD, medial dorsal; Pla, anterior pulvinar; Pli, inferior pulvinar; Pll, lateral pulvinar; Po, posterior nucleus; VMb, basal ventral medial; VPI, ventral posterior inferior; VPM, ventral posterior medial.

FIG. 2.

Example of an STT neuron projecting directly to the Po of the thalamus. A1: photomicrograph of a section 1.0 mm rostral to the LTP where stimulation with ≥500 μA was unable to generate antidromic action potentials. A2: illustration of the same section with each antidromic stimulation test site marked (). B1: photomicrograph of a lesion marking the LTP in the Po (→). B2: illustration of B1 with each stimulation test site indicated and a contour plot showing the amplitude of current required to activate the neuron antidromically. C: receptive field. D: the neuron was recorded in nucleus proprius (→). E: antidromic activation from Po: Top: series of 3 antidromic action potentials time locked to the 3 stimuli. Middle: collision between an orthodromic (▾) and blocked antidromic action potential (▿). Bottom: 333-Hz, 8-μA stimulus train.

FIG. 3.

Example of a functionally characterized STT neuron projecting directly to the Po. A, top: horizontal view of stimulating electrode penetration sites through the thalamus. The lowest amplitude of current that produced antidromic action potentials is indicated for each mediolateral position. The current amplitude of the LTP is circled (21 μA). , electrode penetrations that were unable to evoke antidromic action potentials with ≥500 μA. Bottom: coronal view corresponding to the most caudal plane above. B: photomicrograph of the coronal plane shown in A with a lesion marking the LTP in Po. Scale bar = 1.0 mm. C: characterization of the response to mechanical stimuli. B, brush; Pr, pressure; Pi, pinch; S, squeeze. This cell was classified as a high-threshold (HT) neuron. D: receptive field. E: recording point in nucleus proprius.

FIG. 4.

Receptive fields of STT neurons that projected directly to the posterior thalamus. A: receptive fields organized by mechanical classification and location of the recording site. MZ, marginal zone. black, neurons that responded to noxious heat (50°C). Receptive fields are not shown to scale. *, receptive field of neuron that responded to 52°C but not 50°C. B: size of receptive fields for each group (mean ± SD).

FIG. 5.

Mean ± SE responses to mechanical stimuli for high-threshold and wide-dynamic-range (WDR) type posterior thalamus-projecting STT neurons. Both HT and WDR type cells significantly increased their firing rates from pressure to pinch, suggesting that they can encode innocuous and noxious mechanical stimuli. One-way ANOVA with Tukey posttest (P < 0.05). WDR-Squeeze was not included in the statistical analysis because the number of tests was small (n = 3).

FIG. 6.

Responses of posterior thalamus-projecting STT neurons to thermal stimuli. A, top: an example of a response to noxious heat (50°C). Bottom: mean ± SE of all heat responsive neurons to 50°C. B, top: example of a response to cold (10°C). Bottom: mean ± SE of all cold responsive neurons to 10°C. C: responses to a range of thermal stimuli for each thermally responsive neuron. Each point represents the mean firing rate during the 5-s thermal stimulus. Note the scale change on the ordinate. Bold and dashed lines indicate data used for examples in A and B, respectively. D: mean ± SE response of all thermally responsive neurons with the baseline activity at the holding temperature subtracted.

FIG. 7.

Responses to capsaicin of posterior thalamus-projecting STT neurons. A: example of a typical response to capsaicin. ↑, the time of injection. B: mean ± SE response of each capsaicin responsive neuron calculated in 15-s bins. C: mean ± SE response to capsaicin of neurons responsive and not responsive to a ≥50°C heat stimulus. D: mean ± SE response to capsaicin of HT and WDR type neurons.

FIG. 8.

Location of all lesions in the posterior thalamus marking LTPs of functionally characterized STT neurons. Left: camera lucida tracings of four sections through the anterior-posterior extent of the posterior thalamus. Nuclei within the posterior thalamus receive input from HT and WDR type neurons located both in the marginal and the deep dorsal horn. VPI appears to receive a high percentage of its input from marginal zone neurons. Each section represents ∼750 μm. Hb, habenula; LGN, lateral geniculate nucleus; pc, posterior commissure; R, reticular nucleus.

FIG. 9.

Locations of lesions marking recording sites of 24 neurons in the lumbar dorsal horn. Top: recording sites of HT and WDR type neurons. Bottom: the recording sites of HT and WDR type neurons and to which nucleus in the posterior thalamus they project. One recording site from a WDR type cell was not recovered.