Corticofugal output from the primary somatosensory cortex selectively modulates innocuous and noxious inputs in the rat spinothalamic system

Abstract

Sensory maps for pain can be modified by deafferentation or injury, and such plasticity has been attributed mainly to changes in the convergence of projections in "bottom-up" mechanisms. We addressed the possible contribution of "top-down" mechanisms by investigating the functional significance of corticofugal influences from the primary somatosensory cortex (S1) to the ventroposterolateral thalamic nucleus (VPL). The strong convergence of spinal and lemniscal afferents to the VPL and the close correspondence between afferents and efferents within the VPL-S1 network suggest the existence of functionally related thalamocortical circuits that are implicated in the detection of innocuous and noxious inputs. Functional characterization of single nociceptive, wide dynamic range, and non-nociceptive VPL neurons and labeling the axons and terminal fields with the juxtacellular technique showed that all three types of cells project to a restricted area, within S1. The convergence of the terminal trees of axons from VPL neurons activated by innocuous, noxious, or both inputs suggests that their inputs are not segregated into anatomically distinct regions. Microinjections within S1 were performed for pharmacological manipulation of corticofugal modulation. Glutamatergic activation of corticofugal output enhanced noxious-evoked responses and affected in a biphasic way tactile-evoked responses of VPL cells. GABA(A)-mediated depression of corticofugal output concomitantly depressed noxious and enhanced innocuous-evoked responses of VPL neurons. Microinjections of a GABA(A) antagonist on corticofugal cells enhanced noxious-evoked responses of VPL cells. Our findings demonstrate that corticofugal influences from S1 contribute to selectively modulate somatosensory submodalities at the thalamic level.

Figure 1.

A, Digital photomicrographs of the perikaryon and proximal processes of three different functional classes of juxtacellularly stained VPL neurons (NS, NN, and WDR). For each cell, the response characteristics to peripheral cutaneous stimuli and the receptive fields are presented. Camera lucida drawings of cells with their axonal processes and terminal innervation in a common area within S1. Scale bars, 50 μm. B, Cumulative data showing the topographic distribution of dendritic arbors of juxtacellularly labeled VPL cells. Areas representing percentage of the total length of the dendrites within 30° sections show the widespread, multipolar orientation of the dendritic trees.

Figure 2.

Digital photomicrographs of labeling in coronal sections of the S1 cortex (B) after the tetramethylrhodamine-labeled dextran injection into the VPL thalamic nucleus shown in A. C shows higher magnification of the layer IV afferent labeling from the VPL and layer VI efferent labeling in the region delineated in B. Note the numerous retrogradely labeled cells in layer VI, which occupy the same area covered by the patches of anterograde labeling in layer IV. Scale bars, 500 mm. Rt, Thalamic reticular nucleus; VPM, ventroposteromedial thalamic nucleus.

Figure 3.

A, Experimental setup for the multiunit, multisite recordings and cortical microinjections. B, Summary of the histological findings from experiments during which the effects on the responses of VPL neurons of microinjections of GABA_A agonists or antagonists, the glutamate agonist DLH, and saline in layer V–VI of the S1 cortex were studied. Negative results were obtained with microinjections of muscimol or bicuculline. Location of the injection sites in S1 and rostrocaudal distribution of recordings in the VPL. Numbers indicate distance with respect to bregma. Rt, Thalamic reticular nucleus; VPM, ventroposteromedial thalamic nucleus.

Figure 4.

Examples of the effects of a microinjection of muscimol (8.7 mm, 500 nl) into layer V–VI of the S1 cortex (A) on the responses of four neurons simultaneously recorded in the VPL (B). The stimuli were brushing or noxious heat ramps applied to the extremity of the hindpaw. Note that cortical activity was depressed by the microinjection, whereas innocuous-evoked responses were enhanced (17, 37, and 56% for WDR 1, WDR 2, and NN, respectively) and noxious-evoked responses were depressed (94, 29, and 42% for NS, WDR 1, and WDR 2, respectively) in the VPL. mt, Mammillothalamic tract; VPM, ventroposteromedial thalamic nucleus.

Figure 5.

Examples of the effects of a microinjection of bicuculline (50 mm, 500 nl) into layer V–VI of the S1 cortex (A) on the responses of four neurons simultaneously recorded in the VPL (B). The stimuli were brushing or noxious heat ramps applied to the extremity of the hindpaw. Note that noxious-evoked responses in the VPL were enhanced (59, 72, and 11% for NS, WDR 1, and WDR 2, respectively), whereas innocuous-evoked thalamic responses were unaffected. mt, Mammillothalamic tract; VPM, ventroposteromedial thalamic nucleus.

Figure 6.

Summary of the experiments during which the effects on the responses of VPL neurons, of microinjections of muscimol, bicuculline, or DLH in layer V–VI of the S1 cortex were studied. Results are expressed as percentages of control responses recorded before the microinjection (*p < 0.05).